2015-Journal_of_Gastroenterology_and_Hepatology (2)

P o s t e r L i v e r

Alcoholic steatohepatitis/non-alcoholic steatohepatitis

#1027Fyn tyrosine kinase can be especially associated with the development of hepatic

steatosis by taking methionine-choline-de ?cient diet that re ?ects the starvation state

Authors:S FUKUNISHI;K YOKOHAMA;K NAKAMURA;H OHAMA;A ASAI;Y TSUDA;K HIGUCHI

Affiliation:Second Department of Internal Medicine,Osaka,Japan

Aims:Fyn tyrosine kinase (Fyn)is one of the Src-family protein kinases and has been previously reported to decrease hepatic triglyceride level of ordinary diet-fed Fyn à/àmice,compared with control mice.These reports suggest a possibility that Fyn may affect hepatic function.Here,we pro-vided a methionine-choline-de ?cient diet (MCD),which increases triglyc-eride and histologically causes the expression of non-alcoholic steatosis in the liver of rodents,and high-fat diet (HFD)to Fyn à/àmice to investigate the presence or absence of histological changes in their livers.Methods:Mice were pided into three groups;standard diet (SD),HFD,and MCD were given to 8-week-old male Fyn à/àmice (n =5)and C57BL/6J Fyn +/+(Fyn+/+)mice (n =5)as controls,respectively,for 8weeks.Results:Standard diet-fed Fyn à/àmice showed the trend of the decrease in hepatic triglyceride compared with SD-fed Fyn+/+mice.However,there is no sig-ni ?cant difference in the histological ?ndings of two groups.HFD-fed mice showed a development of the same degree in hepatic steatosis be-tween the two groups.Interestingly,MCD-fed Fyn à/àmice showed sig-ni ?cantly more aggravation of hepatic steatosis,compared with MCD-fed Fyn+/+mice.MCD-fed Fyn à/àmice showed a signi ?cant increase in the expression of sterol regulatory element-binding protein (SREBP)-1c and SCD-1.These mice showed a signi ?cant decrease in the expression of PPAR-αand CPT-1a.There is no signi ?cant difference in the expres-sions of hepatic lipogenic-related gene such as ACC1,SREBP-1c,SCD-1,PPAR-α,and CPT-1a in the HFD groups.Conclusions:Fyn might be associated with the development of hepatic steatosis by taking MCD that re ?ects the starvation state.

#1031Serum alanine/aspartate aminotransferase and aspartate aminotransferase-to-platelet ratio index in Siberian adolescents with moderately elevated body mass index

Authors:S TERESHCHENKO[1];I NOVITCKII[1,2]

Affiliations:[1]Scientific Research Institute of Medical Problems of the North,Krasnoyarsk,Russian Federation [2]Krasnoyarsk State Medical University,Krasnoyarsk,Russian Federation

Introduction:Overweight and obesity among the adolescent population are coming to be of a pandemic nature and have been found to be asso-ciated with non-alcoholic fatty liver disease (NAFLD).Elevated alanine aminotransferase (ALT)is commonly used as a surrogate marker of NAFLD.Some authors state that aspartate aminotransferase (AST)may be a marker of a more aggressive course of NAFLD.Data regarding the association of body mass index (BMI)and liver enzymes in Siberian population are limited.Methods:Fifty Siberian adolescents with

BMI ≥25were paired according to age and sex with 50subjects with BMI <25.All adolescents were otherwise healthy without virus hepatitis markers.BMI was calculated by piding weight (kg)by height squared (m).ALT and AST were measured using an enzymatic rate method.Aspar-tate aminotransferase-to-platelet ratio index (APRI)was calculated by the following equation:(AST level/AST upper level of normal/platelet count)×100.Mann –Whitney test and logistic regression were used.Results:The overweight group exhibited a higher ALT and lower AST/ALT ratio levels.The multivariate logistic regression model,after adjusting for age and gender,showed that BMI >25was strongly associ-ated with abnormal (above our laboratory upper limit)AST,but not ALT,levels.Adjusted odds ratios were 5.69(95%con ?dence interval [CI]:1.43–22.7)and 1.82(95%CI:0.69–4.76)for elevated-above-upper-limits AST and ALT,respectively.APRI did not vary in accordance to BMI,and platelet count was higher in overweight adolescents.Conclusion :Both ALT and AST levels,but not APRI,are associated with moderately elevated BMI in Siberian adolescents.Only AST of abnormal level (according en-zymes upper limits)shows a signi ?cant relationship with high BMI (>25).We suggest that,in the Siberian adolescent population,NAFLD should be taken into consideration in patients with not only ALT but also AST that are persistently elevated.

#1257Fatty liver disease associated with bladder cancer

Authors:CL CHIANG;TY HSIEH;HC CHU;YL SHIH;HH HUANG;HH LIN

Affiliation:Division of Gastroenterology,Department of Internal Medicine,Tri-Service General Hospital,National Defense Medical Center,Taipei,Taiwan

Background:Fatty liver is regarded as a feature of metabolic syn-drome in the liver.Metabolic syndrome is associated with a higher risk of bladder cancer.However,the association between fatty liver and bladder cancer is unclear.Aim:The aim is to investigate the asso-ciation between fatty liver disease and bladder cancer.Material and Methods:The records of all patients (n =79)who were diagnosed with bladder cancer in our hospital between 2009and 2013were reviewed.We also randomly collected non-cancer adults (n =120)as the control group.Anthropometric measurements,biochemical tests for liver and metabolic function,and abdominal computed tomography (CT)were assessed.Fatty liver was con ?rmed by CT if the attenuation of the liver was at least 10Houns ?eld units (HU)less than that of the spleen or if the attenuation of the liver was less than 40HU.Results and Discussion:The prevalence of fatty liver was 21.5%in the bladder cancer and 6.7%in the control group (P =0.004).The cancer group had older age and was predominantly male.By using multiple logistic regression analysis to adjust these variables,fatty liver was found to be associated with an increased risk of bladder cancer (P =0.016;odds ratio, 3.53;95%con ?dence interval, 1.27–9.81).Conclusion:Fatty liver was associated with bladder cancer.Further studies are needed to con ?rm whether fatty liver is a factor for the development of blad-der cancer.

doi:10.1111/jgh.13189

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#1344Perceptions of non-alcoholic fatty liver disease—A community-based study

Authors:HH SHIM[1];GBB GOH[1,3];C KWAN[1];SY LIM[2];NKK VENKATANARASIMHA[2],RA BAKAR[2]; DSM LAU[2];TL KRISHNAMOORTHY[1];KH TAY[2,3]; WC CHOW[1,3]

Affiliations:[1]Department of Gastroenterology and Hepatology,Singapore General Hospital,Singapore

[2]Department of Diagnostic Radiology,Singapore General Hospital,Singapore[3]Duke-NUS Graduate Medical School, Singapore

Background and Aims:Non-alcoholic fatty liver disease(NAFLD)is the most common form of chronic liver disease and is associated with meta-bolic syndrome.Various epidemiological studies have reported prevalence rates between5%and30%.Local epidemiological data suggest an increas-ing prevalence of metabolic syndrome in Singapore.However,data on NAFLD are limited.We investigated the prevalence and local perceptions of NAFLD in Singapore.Methods:Attendees at a gastroenterology public forum were enrolled in a cross-sectional observational study,evaluating de-mographic,anthropometric,liver ultrasound,and clinical information.The di-agnosis of NAFLD was based on sonographic criteria.Metabolic syndrome was de?ned according to International Diabetes Federation guidelines.Per-ceptions of NAFLD were explored using a self-administered questionnaire. Results:Two hundred and twenty-seven subjects were recruited with NAFLD diagnosed in40%of the cohort.Subjects with NAFLD tended to be male(53.9%vs33.9%,P=0.007),are older(mean age57.4vs51.9years old,P=0.012),had higher mean body mass index(BMI;24.4vs21.6kg/m2, P<0.001),with larger waist circumferences(P=0.01)and more often ful-?lled criteria for metabolic syndrome(25%vs11.4%,P=0.014).Interest-ingly,subjects with NAFLD had a mean BMI(24.4kg/m2)that was within the non-obese range.The majority of subjects had heard of NAFLD,but they tended to underestimate their risk of having the disease.Receptiveness to-wards screening for NAFLD was positive.Conclusion:Our study suggests a signi?cant local prevalence of NAFLD including non-obese inpiduals. Despite general awareness about NAFLD,they tended to underestimate their risk of having the disease.Better public education is needed to improve un-derstanding.

#1393Usefulness of controlled attenuation parameter for quantifying hepatic fat content in patients with biopsy-proven non-alcoholic fatty liver disease

Authors:N FUJIMORI[1];N TANAKA[2];E TANAKA[3] Affiliations:[1]Department of Internal Medicine,Division of Gastroenterology,Shinshu University School of Medicine, Matsumoto,Japan[2]Department of Metabolic Regulation, Shinshu University Graduate School of Medicine, Matsumoto,Japan

Background and Aim:Non-invasive steatosis-quantifying methods are re-quired for non-alcoholic fatty liver disease(NAFLD)patients in order to monitor disease severity and assess therapeutic ef?cacy.Controlled attenu-ation parameter(CAP)evaluated with vibration-controlled transient elastography can predict the presence of steatosis,1–3but its application to absolute hepatic fat quantitation remains unclear.The aim of this study was to examine whether CAP is correlated to real hepatic fat content in NAFLD patients.Methods:Fifty-nine NAFLD patients underwent percu-taneous liver biopsy were enrolled.CAP was measured using FibroScan?just before liver biopsy.The percentage of fat droplet area to hepatocyte area in the biopsied specimen was determined morphometrically using a computerized optical image analyzing system.The correlation between CAP and liver histology was examined.Results:Controlled attenuation pa-rameter showed an excellent correlation to actual liver fat percentage in the NAFLD patients having body mass index(BMI)<28kg/m2(r=0.547, P<0.001),especially<25kg/m2(r=0.678,P=0.001),but the meaningful correlation disappeared in patients with BMI>28kg/m2.In patients with BMI<28kg/m2,CAP quantitativeness was affected by the presence of?bro-sis,but not hepatocyte ballooning and lobular in?ammation.Conclusions: Controlled attenuation parameter may be a promising tool for quantifying he-patic fat content in NAFLD patients having no or mild obesity without liver ?brosis.Further improvement of CAP performance is needed for the NAFLD patients having BMI>28kg/m2or hepatic?brosis.

References:

1Yoshioka K,Hashimoto S,Kawabe N.Measurement of liver stiffness as a non-invasive method for diagnosis of non-alcoholic fatty liver dis-ease.Hepatol.Res.2015;45:142–51.

2de Lédinghen V,Vergniol J,Foucher J,Merrouche W,le Bail B.Non-invasive diagnosis of liver steatosis using controlled attenuation pa-rameter(CAP)and transient elastography.Liver Int.2012;32:911–8. 3Myers RP,Pollett A,Kirsch R,Pomier-Layrargues G,Beaton M, Levstik M et al.Controlled attenuation parameter(CAP):a noninva-sive method for the detection of hepatic steatosis based on transient elastography.Liver Int.2012;32:902–10.

#1483Silymarin for the treatment of non-alcoholic steatohepatitis:Interim analysis of a randomized, double-blind,placebo-controlled trial

Authors:WAH-KHEONG CHAN[1];NIK RAIHAN NIK MUSTAPHA[2];SANJIV MAHADEVA[1]

Affiliations:[1]Department of Medicine,Faculty of Medicine, University of Malaya,Kuala Lumpur,Malaysia[2]Department of Pathology,Hospital Sultanah Bahiyah,Alor Setar,Malaysia

Background/Aims:Silymarin,derived from the milk thistle plant,Silybum marianum,has been used as a herbal remedy for diseases of the liver. Methods:This is a randomized,double-blind,placebo-controlled study of silymarin700mg t.i.d.for the treatment of non-alcoholic steatohepatitis (NASH).All included patients had biopsy-proven NASH,were given life-style advice,and received either silymarin or placebo for48weeks.A re-peat liver biopsy was performed at the end of the study.Histology was reported using the NASH Clinical Research Network scoring system. Results:A total of64patients completed the study at the time of this in-terim analysis.Mean age was50.2±11.4years and consisted of43.8% men.The baseline characteristics were comparable between the silymarin (n=30)and placebo(n=34)groups.Signi?cantly more patients in the silymarin group experienced NASH resolution(de?ned as NAS<3)com-pared with the placebo group(13.3%vs0%,P=0.043).There was also a signi?cant decrease in the?brosis stage in the silymarin group (Δ=à0.367,P=0.019).This was not observed in the placebo group(Δ= +0.147,P=0.282).A signi?cantly higher percentage of patients in the silymarin group had improvement in?brosis stage compared with the pla-cebo group(36.7%vs14.7%,P=0.043).In addition,four patients in the

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placebo group developed cirrhosis,while none of the patients in the silymarin group did.Conclusions:A signi?cantly higher percentage of pa-tients experienced NASH resolution and improvement in?brosis stage after 48weeks of treatment with silymarin compared with placebo.

#1509Fibroblast growth factor21expression during the course of mice non-alcoholic fatty liver disease and its correlation to sterol regulatory element-binding protein

Authors:YW GUO,HY GU,XY LIN

Affiliation:Department of Gastroenterology,Third Affiliated Hospital of Sun Yat-Sen University,Guangzhou,Guangdong Province,China

Aims:This study aimed to investigate the?broblast growth factor21 (FGF21)expression in liver tissue and serum from different stages of mice non-alcoholic fatty liver disease(NAFLD)and its correlation to sterol reg-ulatory element-binding protein(SREBP).Materials and Methods: C57BL/6mice were fed with chow diet and high-fat diet(HFD)for1,9, and18weeks.Expressions of FGF21and SREBP in liver tissue of mice were detected by western blot and real-time reverse transcription–polymerase chain reaction.Serum FGF21was examined using ELISA. Results:The liver of mice exhibited the typical appearance of fatty liver af-ter9weeks of HFD with a large amount of fat granule accumulation in 849853c052ea551811a68751pared with mice fed with chow diet,FGF21mRNA level in liver tissue from mice fed with HFD increased a little in the?rst week (P>0.05)and began dramatically higher in the9th and18th weeks of HFD(both P<0.05),with a positive correlation to the duration of HFD (r=0.952,P=0.000)and the SREBP mRNA level(r=0.725,P=0.000). On the other hand,FGF21protein expression in liver tissue from mice fed with HFD decreased a little in the?rst week(P>0.05)and began sta-tistically lower in the9th and18th weeks of HFD compared with mice of chow diet(both P<0.05).Opposite changes were found in the expression of SREBP protein.Furthermore,compared with mice of chow diet,serum FGF21of HFD mice became higher a little in the?rst week(P>0.05)and obviously higher in the9th and18th weeks of HFD(both P<0.05),with a positive correlation to the duration of HFD(r=0.944,P=0.000)and the FGF21mRNA level of liver tissue(r=0.910,P=0.000)and a negative correlation to the protein expression of FGF21in liver tissue(r=à0.704, P=0.000).Conclusions:In the course of mice NAFLD,the FGF21 mRNA level of liver tissue increased,protein expression decreased,and se-rum level became higher,accompanied by the elevation of SREBP in liver. This suggests a high secretion of FGF21from liver would appear with a high level of transcription and synthesis of FGF21in liver under HFD, which is closely correlated to hepatic steatosis.

Keywords:FGF21,non-alcoholic fatty liver disease(NAFLD),SREBP. #1510Histone deacetylase1plays an important role via sterol regulatory element-binding protein in the course of mice non-alcoholic fatty liver disease Authors:YW GUO,HY GU,XY LIN

Affiliation:Department of Gastroenterology,Third Affiliated Hospital of Sun Yat-Sen University,Guangzhou,Guangdong Province,China

Aims:This study aimed to investigate histone deacetylase1(HDAC1)expres-sion in liver tissue of mice in the course of non-alcoholic fatty liver disease (NAFLD)and its correlation to sterol regulatory element-binding protein (SREBP)and to further study the possible mechanism.Materials and Methods:C57BL/6mice were fed with chow diet and high-fat diet(HFD) for1,5,and9weeks.Expressions of HDAC1,HDAC3,and SREBP in liver tissue of mice were detected by western blot and real-time reverse transcription–polymerase chain reaction.HDAC1,HDAC3,and SREBP ex-pressions in HepG2cells were detected by western blot after the cells were treated with oleic acid for24h with or without HDAC1inhibitor pretreatment. Results:The liver of mice had the appearance of obvious steatosis after 9weeks of 849853c052ea551811a68751pared with the liver tissue of mice fed with chow diet, the liver tissue of mice fed with HFD for9weeks had statistically increased expressions of HDAC1and SREBP protein(both P<0.05),but HDAC3ap-peared to have no difference.The protein expression of HDAC1in mice liver was positively correlated to the duration of HFD(r=0.941,P<0.05).The mRNA levels of SREBP in liver tissue of mice fed with HFD for5and 9weeks were statistically higher than those of mice fed with chow diet(both P<0.05),and no differences were found in expressions of HDAC1and HDAC3.Accompanied with a large amount of fat granules accumulating in HepG2cell stained by oil red after being treated with oleic acid for24h,the protein expressions of HDAC1and SREBP in HepG2cells were dramatically increased compared with those of cells without oleic acid treatment(both P<0.05),and HDAC3had no change.After HepG2cells were pretreated with HDAC1inhibitor,the elevated of SREBP protein induced by oleic acid was obviously inhibited.Conclusions:HDAC1,but not HDAC3,plays an im-portant role in the course of NAFLD,which could at protein level accelerate the formation of NAFLD through inducing the protein and mRNA expression of SREBP.

Keywords:HDAC1,non-alcoholic fatty liver disease(NAFLD),SREBP. #1620Effects of modulation NF-E2-related factor 2expression on anti-oxidant ability and potential mechanisms in BRL-3A and HSC-T6cells Authors:ZHANG MINGXIN;LI JINGHUA;WEN QINSHENG; WANG JINGJIE

Affiliation:Department of Gastroenterology,Tangdu Hospital, Fourth Military Medical University,Xi’an,China

Background:NF-E2-related factor2(Nrf2)is an important transcription factor for cell defense against oxidative stress reaction.Nrf2may play a clearly protective role in non-alcoholic steatohepatitis(NASH),but the ex-act mechanism and target cells are still not clear.Methods:The stably transfected HSC-T6and BRL-3A cells with up/down expression of Nrf2 were constructed by lentiviral vectors.Cells were pided into normal group and oxidative stress stimulation group treated with glucose oxidase. Further,reactive oxygen species were detected by?ow cytometry.And survival rate of cells and levels of malondialdehyde,lactate dehydrogenase, and superoxide dismutase were detected by 849853c052ea551811a68751st,expression levels of p66Shc and IQGAP1protein in cells were detected by western blot. Results and Discussion:Stably transfected HSC-T6and BRL-3A with modulation Nrf2expression were successfully constructed,as con?rmed by reverse transcription–polymerase chain reaction and western blot.After oxidative stress stimulation,malondialdehyde,lactate dehydrogenase,and reactive oxygen species levels were decreased,while the survival rate and the level of superoxide dismutase increased under upregulation of Nrf2(P<0.05);and we obtained the opposite result under downregulation of Nrf2(P<0.05).Then,the p66Shc level was decreased,while the IQGAP1increased under upregulation of Nrf2in both groups(P<0.05); and we obtained the opposite result under downregulation of Nrf2

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(P<0.05).Conclusions:We successfully constructed stably transfected BRL-3A and HSC-T6cells with upregulation/downregulation of Nrf2. The oxidative stress model shows that Nrf2has anti-oxidative stress ability in both cells,and this effect may be probably through the regulation ex-pression of p66Shc and IQGAP1.

#1717Protective effect and mechanism of

NF-E2-related factor2/heme oxygenase-1pathway on the high-fat-diet-induced insulin resistance in rats

Authors:LI ZHAO;MINGXIN ZHANG;SHUGUANG ZHAO; QINSHENG WEN;JINGJIE WANG

Affiliation:Department of Gastroenterology,Tangdu Hospital, Fourth Military Medical University,Xi’an,China

Background:Our previous studies have con?rmed that curcumin can in-crease Nrf2nuclear translocation and has protective effects on oxidative stress in hepatocytes.This study aims to investigate the protective effects on insulin resistance and non-alcoholic steatohepatitis of the activation of the NF-E2-related factor2(Nrf2)/heme oxygenase-1(HO-1)pathway in-duced by curcumin.Methods:The oxidative stress model of human LO2 hepatocytes was prepared with glucose oxidase(GO).LO2hepatocytes were pided into control group,model group,curcumin-treated group, and inhibitor group.LO2hepatocytes in the control group were normally cultured,while LO2hepatocytes in the model group were treated with 100U/L GO for2h.LO2hepatocytes in curcumin-treated group were treated with30-μm curcumin for12h.And LO2hepatocytes in the inhib-itor group were treated the same as in the curcumin-treated group in the presence of0.1-μM wortmannin(PI3K inhibitor)for1h.Expressions of Nrf2,HO-1,and insulin signaling pathway were detected by western blot. Results and Discussion:For expressions of Nrf2nuclear translocation and HO-1,those in the model group were a little higher than those in the con-trol group,and those in the curcumin-treated group increased signi?cantly compared with those in the model group,but those in the inhibitor group were lower than those in the curcumin-treated group.For the expressions of phosphorylated JNK and IRS-1,those in the model group were higher than those in the control group,and those in the curcumin-treated group were lower than those in the model group,and the?gure of the inhibitor group was between those of the model group and the curcumin-treated group.There was also no signi?cant change of total IRS-1and JNK expres-sions among different groups.Conclusion:Insulin resistance caused by oxidative stress can be reduced by inducing the Nrf2/HO-1pathway,and its effect may improve the insulin signaling pathway by reducing the phos-phorylated JNK level and increasing the phosphorylated IRS-1one.

#1729Clinical application of transient elastography in the prediction of underlying liver disease in a group of patients with chronic kidney disorders

Authors:HUSI?-SELIMOVI?A[1];MESIHOVI?R[1]; VANIS N[1];SOFI?A[2];VATRENJAK S[3] Affiliations:[1]Institute for Gastroenterohepatology, University Hospital Sarajevo,Sarajevo,Bosnia and Herzegovina[2]Clinic for Radiology,University Hospital Sarajevo,Sarajevo,Bosnia and Herzegovina[3]Clinic for Anaesthesia,University Hospital Sarajevo,Sarajevo,Bosnia and Herzegovina Introduction:Non-alcoholic fatty liver disease is associated with cardio-vascular morbidity and mortality.Patients with chronic kidney disease (CKD)are in increased risk of cardiovascular deaths.Aim:This study aimed to investigate the presence of possible liver disease detected by func-tional liver tests and transient liver elastography(TE)in a group of the pa-tients with different stages of chronic kidney disease(CKD).We investigated also whether the type of disorder end length of dialysis treat-ment in patients with CKD have any effect on steatosis and?brosis grade, as documented by TE.Patients and Methods:Eighty patients with various stages of CKD were pided into subgroups in regard to etiology and dura-tion of hemodialysis treatment.Liver stiffness was used to quantify liver?-brosis.Controlled attenuation parameter(CAP)was used to quantify liver steatosis.The device used was FibroScan(Echosens,Paris).The cut-off value for liver steatosis was215dB/m,and for the presence of?brosis,it was a liver stiffness of>7kPa.Functional liver tests were measured for all patients.Results:No statistically signi?cant correlations were detected between liver enzymes and CAP value.There was a statistically signi?cant correlation detected between the value of liver enzymes and liver stiffness value(r=0.231).We did not?nd statistically signi?cant differences be-tween etiology and duration of hemodialysis in regard to the functional liver test and CAP value.There was a statistically signi?cant frequency of liver stiffness detected(P<0.05,)in regard to etiology(with a higher frequency in autoimmune kidney disease).Conclusion:Transient live elastography provides the opportunity for non-invasive screening of non-alcoholic fatty liver disease in CKD patients.

Keywords:liver steatosis,liver stiffness,transient elastography.

#1774Triglyceride regulation by leptin in alcoholic liver disease

Authors:BALASUBRAMANIYAN V[1,2];NALINI N[2] Affiliations:[1]Department of Biochemistry,Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER),Pondicherry,India[2]Department of Biochemistry and Biotechnology,Annamalai University,Chidambaram, India

Introduction:Alcohol-induced fatty liver disease is the most common and earliest response to the progression of?brosis,cirrhosis,and/or hepatocel-lular carcinoma.The mechanism by which ethanol causes fatty liver dis-ease is complex and not fully understood;however,augmented triglyceride(TG)accumulation in the hepatocyte is strongly associated with fatty liver and has been proposed as an important biochemical mech-anism.We have previously noted that the potential bene?cial effect of lep-tin on alcohol elicited toxicity in vitro.Objective:The purpose of this study was to evaluate the effect of leptin on ethanol-induced elevated hepatic TG synthesis and fatty acid composition in mice.Material and Methods:CD-1 mice(n=10/group)were studied for45days.Four groups were studied:(i) control;(ii)leptin+control(230μg/kg intraperitoneal every alternate day from day30);(iii)alcohol(6.32g/kg daily by gastric lavage,for45days); and(4)alcohol+leptin(as prior dosing).Results:Compared with naive mice,mice with ethanol supplementation had signi?cantly(P<0.05)in-creased plasma and hepatic TG levels and a key enzyme involved in TG synthesis such as acyl-CoA diacylglycerol acyltransferase(DGAT)2.Lep-tin administration to ethanol-treated mice shows signi?cantly(P<0.05) reduced hepatic and plasma TG concentrations and DGAT2enzyme pro-tein expression.Furthermore,ethanol supplementation signi?cantly (P<0.05)increased the percentage of palmitic acid(16:0),stearic acid (18:0),oleic acid(18:1),and docosapentaenoic acid(22:5)levels,whereas

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palmitoleic acid(16:1)and arachidonic acid(20:4)concentrations were de-creased signi?cantly(P<0.05)when compared with control.Leptin treat-ment to ethanol-fed mice signi?cantly corrects the aforementioned indices. Liver histology showed that mice given ethanol had macrovesicular and microvesicular steatoses.However,ethanol+leptin-treated liver showed si-nusoidal dilatation and no fatty change.Conclusion:Thus,exogenous leptin administration to ethanol-fed mice signi?cantly reduced hepatic TG synthesis and also regulates fatty acid composition,warranting further population-based mechanistic studies.

#1795Is controlled attenuation parameter with the XL probe more accurate than the M probe for estimation of hepatic steatosis in patients with non-alcoholic fatty liver disease?

Authors:WAH-KHEONG CHAN[1];NIK RAIHAN NIK MUSTAPHA[2];SANJIV MAHADEVA[1]

Affiliations:[1]Department of Medicine,Faculty of Medicine, University of Malaya,Kuala Lumpur,Malaysia[2]Department of Pathology,Hospital Sultanah Bahiyah,Alor Setar,Malaysia

Background/Aims:Controlled attenuation parameter(CAP)was intro-duced for the FibroScan XL probe recently,and this may improve the diag-nostic performance of CAP to estimate hepatic steatosis in non-alcoholic fatty liver disease(NAFLD)patients.Methods:Adult NAFLD patients who had a liver biopsy within6months were included and were examined with the FibroScan M and XL probes.Histopathological?ndings were re-ported according to the Non-alcoholic Steatohepatitis Clinical Research Network Scoring System.Subjects without fatty liver on ultrasonography were recruited as controls.Results:A total of53NAFLD patients and22 controls were included in the analysis.Mean age was41.3±16.2years old and consisted of48.0%men.Mean body mass index was27.4±6.2kg/m2.The areas under the receiver operating characteristic curve (AUROCs)of CAP for estimation of steatosis grades≥S1,S2,and S3were 0.94,0.79,and0.71,respectively,when using the M probe,and0.96,0.81, and0.70,respectively,when using the XL probe.The AUROCs of liver stiffness measurement(LSM)for estimation of?brosis stages≥F1,F2, F3,and F4were0.88,0.96,0.97,and0.97,respectively,when using the M probe,and0.88,0.92,0.94,and0.98,respectively,when using the XL probe.Overall,the XL probe gave higher CAP and lower LSM values when compared with the M probe.Conclusions:The XL probe did not fur-ther improve the accuracy of CAP and LSM for the estimation of hepatic steatosis and?brosis in NAFLD patients and gave higher CAP value and lower LSM value compared with the M probe.

#2029ZJU index:A novel model for predicting non-alcoholic fatty liver disease in a Chinese population

Authors:JINGHUA WANG,MD[1];CHENGFU XU,MD[1]; YUNHAO XUN,MD[2];ZHENYA LU,MD[3];CHAOHUI YU,MD,PHD[1];YOUMING LI,MD[1]

Affiliations:[1]Department of Gastroenterology,the First Affiliated Hospital,College of Medicine,Zhejiang University, Hangzhou,China[2]Department of Liver Diseases,Xixi Hospital of Hangzhou,Hangzhou,Zhejiang,China

[3]International Health Care Center,the First Affiliated Hospital,College of Medicine,Zhejiang University,Zhejiang, China Background:Non-alcoholic fatty liver disease(NAFLD)has been an im-portant health issue worldwide.We aim to develop a simple model to de-termine the presence of NAFLD.Methods:A cross-sectional study with 9602subjects was conducted.Potential predictors were entered into a step-wise logistic regression analysis to obtain the model.One hundred and forty-eight patients with liver biopsy were included to validate this model. Results:A model,named as ZJU index,based on body mass index,fasting blood sugar,triglycerides,and serum alanine aminotransferase-to-serum aspartate transaminase ratio was developed.The AUROC of ZJU index to detect NAFLD was0.822(95%con?dence interval[CI]:0.810–

0.834).At a value of<32.0,the ZJU index could rule out NAFLD with

a sensitivity of92.2%(95%CI:91.1–93.2%),and at a value of>38.0, the ZJU index could detect NAFLD with a speci?city of93.4%(95%CI: 92.4–94.4%).The result was similar in the validation cohort.In patients with liver biopsy,the ZJU index can detect steatosis with a good accuracy with an AUROC of0.896(95%CI:0.818–0.974).Conclusion: The ZJU index is a helpful model to detect NAFLD for community physi-cians in China.It was validated by not only a validation cohort but also pathological data.It can be utilized in the initial screening for NAFLD and lifestyle counseling.

#2079Effect of allicin on cecum microbiota in alcoholic fatty liver disease mice

Authors:SURAPHAN PANYOD[1];WEI-KAI WU[1,2]; CHI-TANG HO[3];TONG-RONG JAN[4];KUAN-HUNG LU [1];YUNG-LIN CHU[5];YI-SYUAN LAI[1];WEI-CHENG CHEN[1];LEE-YAN SHEEN[1,6,7]

Affiliations:[1]Institute of Food Science and Technology, National Taiwan University,Taipei,Taiwan[2]Department of Internal Medicine,National Taiwan University Hospital, Taipei,Taiwan[3]Department of Food Science,Rutgers University,New Brunswick,NJ,USA[4]The School of Veterinary Medicine,National Taiwan University,Taipei, Taiwan[5]Department of Tropical Agriculture and International Cooperation,College of Agriculture,National Pingtung University,Pingtung,Taiwan[6]Center for Food and Biomolecules,National Taiwan University,Taipei, Taiwan[7]National Center for Food Safety Education and Research,National Taiwan University,Taipei,Taiwan Introduction:Recently,scientists have found that gut microbiota may play a role in the pathogenesis or progression of certain liver diseases, including alcoholic liver disease.Allicin is a pharmacologically active substance found in fresh aqueous extract of garlic,which has been found to have antimicrobial activity.The objectives of this study are to inves-tigate the impact of allicin on the status of gut microbiota and its rela-tionship with alcoholic fatty liver.Materials and Methods:The alcoholic fatty liver mouse experimental model was developed using male C57BL/6mice that were fed an alcohol-containing liquid diet (Lieber-DeCarli diet).Allicin was administered orally everyday for 4weeks in the treatment group.Results:The results indicated that allicin possesses potential hepatoprotective properties against alcoholic fatty liver by signi?cantly reducing relative liver weight,fatty liver score, and the accumulation of triglycerides in the liver.Next-generation se-quencing base-DNA sequencing results indicated that alcohol and allicin in?uence gut microbiota persi?cation in cecum.Allicin reduced posi-tive correlation levels in some species of the cecum microbiota that re-lated with alcohol intake,resulting in the increase of liver triglyceride

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level.In addition,the negative correlations were observed in control (36species)and alcoholic fatty liver disease groups (19species)with allicin treatment.Conclusion:Allicin exhibits a potential hepatoprotective ef-fect against alcoholic fatty liver disease possibly due to pathogenesis-inhibiting changes exerted by allicin in the gut microbiota.Therefore,fu-ture work is required to verify the relationship between cecum microbi-ota and the production of triglycerides in the gut.Keywords:alcoholic fatty liver,allicin,gut microbiota.

#2080The role of B lymphocytes in the

pathogenesis of non-alcoholic fatty liver disease Authors:FENG ZHANG;WEIWEI JIANG;ZHE WU;XIA LI;XINYUN QIU;YULAN LIU

Affiliation:Department of Gastroenterology,Peking University People ’s Hospital,Beijing,China

Aims:It is demonstrated that B lymphocytes (B cells)play a role in the path-ogenesis of obese-related diseases.However,the features of B cells in non-alcoholic fatty liver disease (NAFLD)have not been well illustrated.In this present study,we investigated the roles of intrahepatic B cells in NAFLD mice.Methods:An NAFLD mouse model was established by feeding with high-fat diet for 16weeks.The proportion of B cells was calculated by ?ow

cytometry.mRNA levels of interleukin (IL)-6,IL-10,and tumor necrosis factor (TNF)-αin liver tissue,intrahepatic lymphocytes,and intrahepatic B cells were quanti ?ed by real-time polymerase chain reaction.Cytometric Bead Array and Luminex methods were used to detect the cytokines and im-munoglobulin (Ig)levels of plasma and culture supernatant or liver homog-enate,respectively.Results and Discussion:The proportions of B cells were signi ?cantly increased in livers (P =0.03)and spleens (P =0.00)of the NAFLD group (Fig.1).Plasma IL-6levels were higher in the NAFLD group (P =0.00).Consistently,mRNA expression of IL-6was upregulated in both liver tissues (P =0.04)and intrahepatic lymphocytes (P =0.03)in NAFLD mice.However,IL-10mRNA level decreased (P =0.04)while TNF-αmRNA level increased (P =0.04)in NAFLD intrahepatic B cells.The secre-tion of IL-6(P =0.00)and TNF-α(P =0.00)was promoted by lipopolysac-charide (LPS)stimulation in the B cells from NAFLD livers.As other studies had shown that the portal vein LPS level increased during the pro-gression of NAFLD,intrahepatic B lymphocytes might promote this disease through secreting pro-in ?ammatory cytokines.Meanwhile,plasma IgA de-creased (P =0.04)while IgG2a increased (P =0.01),and IgG2a (P =0.00)was elevated in the liver homogenate of NAFLD mice.Conclusions:The intrahepatic B cells were increased in NAFLD and might promote the dis-ease by secreting IL-6,TNF-α,and IgG2a.

Keywords:B lymphocytes,cytokines,immunoglobulin,non-alcoholic fatty liver

disease.

Figure 1The percentages of B lymphocytes in CD45+cells from the livers and spleens of control and non-alcoholic fatty liver disease (NAFLD)groups.

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Hepatocellular Carcinoma and Liver Tumors

#1003Comparison of the clinical features of hepatocellular carcinoma with cryptogenic,alcohol, and viral hepatitis etiologies

Authors:PS TE,MD;SN WONG,MD

Affiliation:Chinese General Hospital and Medical Center, Manila,the Philippines

Signi?cance:In western societies,features of metabolic syndrome(MS)are in-creasingly seen in hepatocellular carcinoma(HCC)patients with cryptogenic etiology.However,it is unknown if this applies to Asians.We aimed to com-pare clinical characteristics of HCC patients pided according to etiology. Methodology:Records of HCC patients from May2006to October2013were analyzed.HCC etiology was pided into viral hepatitis,alcohol,and crypto-genic.Baseline characteristics were compared.Statistical differences were eval-uated by univariate analysis using t-test and chi-squared test for continuous and categorical variables.Results:Among334patients,viral hepatitis accounted for 61.7%,alcohol9.9%,and cryptogenic28.4%.Majority(60.4%)were overweight/obese,and47%had overt cirrhosis with no differences between the three groups(P>0.05).Cryptogenic patients were signi?cantly older than both viral and alcohol patients(68.6+12.2vs63.7+12.6vs62.0+9.0; P=0.003),were more likely to be female(25.3%vs16%vs3%;P=0.01), and tend to be diabetic(31.6%vs20.1%vs27.3%;P=0.124)and to have a family history of HCC(11.6%vs8.7%vs0%;P=0.126).Alcoholic patients, on the other hand,had larger tumors(P=0.037)and were more likely to be heavy smokers(P<0.001).Conclusions:Hepatocellular carcinoma patients with cryptogenic etiology have different demographics than hepatitis and alco-holic patients because of their higher mean age and a greater proportion of them are female.Although components of MS were not more common,there was a trend for a higher proportion of diabetic patients in the cryptogenic group.Other components of MS like body mass index and triglycerides may have been af-fected by cachexia associated with HCC.

Keywords:alcohol,cryptogenic,hepatocellular carcinoma,metabolic syn-drome,non-alcoholic fatty liver disease,non-alcoholic steatohepatitis.

#1010IGFBP1mediates pregnane X receptor-induced morphological changes and migration of hepatocellular carcinoma cells

Authors:Y YAMAZAKI[1,2];S KODAMA[1,3];

S KAKIZAKI[2];M YAMADA[2];M NEGISHI[1] Affiliations:[1]Pharmacogenetics Section,Laboratory of Reproductive and Developmental Toxicology,National Institute of Environmental Health Sciences,National Institutes of Health, Research Triangle Park,NC,USA[2]Department of Medicine and Molecular Science,Gunma University Graduate School of Medicine,Maebashi,Gunma,Japan[3]Laboratory of Pharmacotherapy of Life-Style Related Disease,Graduate School of Pharmaceutical Sciences,Tohoku University,Sendai, Miyagi,Japan

Background/Aims:Pregnane X receptor(PXR),an orphan member of the nu-clear thyroid/steroid hormone receptor superfamily,is activated in response to numerous therapeutics and xenobiotics.1The expression of PXR mRNA has been detected in highly differentiated mouse HCCs,but little is known about the role of PXR in HCCs.Methods:Utilizing human HCC HepG2-derived ShP51cells,which stably express PXR,here we have demonstrated that IGFBP1is an essential factor responsible for PXR-induced morphological changes and migration.Results and Discussion:cDNA microarrays identi?ed IGFBP1and HNF4αmRNAs to be upregulated and downregulated,respectively,in rifampicin-treated ShP51cells,and real-time polymerase chain reaction and western blot analysis con?rmed these regulations at their mRNA and protein levels,respectively.Pretreatment with an anti-IGFBP1antibody, but not with an anti-IGFBP3antibody or normal immunoglobulin G,repressed PXR-induced morphological changes and migration of ShP51cells.Con-versely,treatment with recombinant IGFBP1increased this migration in the absence of rifampicin.IGFBP1levels were upregulated in ShP51cells that were transfected with siRNA for HNF4αwithout rifampicin.Conclusion: Pregnane X receptor indirectly activated the IGFBP1gene by repressing the HNF4αgene,enabling upregulation of IGFBP1to change morphology of HCC cells and cause migration.

Reference:

1Kliewer SA,Moore JT,Wade L,Staudinger JL,Watson MA,Jones SA,McKee DD,Oliver BB,Willson TM,Zetterstr?m RH,Perlmann T,Lehmann JM.An orphan nuclear receptor activated by pregnanes de?nes a novel steroid signaling pathway.Cell.1998;92:73–82.

#1018Hepatic angiosarcoma with dyskeratosis congenita

Authors:SATORU KAKIZAKI;NORIO HORIGUCHI;SATOSHI HAGIWARA;TATSUYA OHYAMA;YUICHI YAMAZAKI; NOBUYUKI SHIBUSAWA;KEN SATO;MOTOYASU KUSANO;MASANOBU YAMADA

Affiliation:Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine,Maebashi, Gunma,Japan

Introduction:Dyskeratosis congenita is a disorder of poor telomere main-tenance and is known to increase the risk of developing multiple types of malignancy,including epithelial cancers,particularly head and neck squa-mous cell carcinoma and gastrointestinal cancers.However,there are few reports of liver tumors arising in dyskeratosis congenita patients.We herein report the second case of hepatic angiosarcoma arising from dyskeratosis congenita.Case Description:A23-year-old man was pointed out to have a liver tumor and subsequently consulted our hospital.He had a history of mental retardation.The patient was diagnosed with dyskeratosis congenita based on the following triad:(i)nail dystrophy;(ii)oral leuko-plakia;and(3)abnormal skin pigmentation at16years of age.At19years of age,hepatosplenomegaly and liver dysfunction were noted.A hepatic tumor measuring10cm in diameter was detected on a routine checkup using abdominal ultrasound at23years of age.There was no history of al-cohol consumption or smoking,and there was no reported exposure to Thorotrast,vinyl chloride,or arsenic.Hepatitis B surface antigens and HCV antibodies were negative,as were anti-nuclear antibodies and anti-mitochondrial antibodies.Abdominal computed tomography(CT)and magnetic resonance imaging revealed multiple hypervascular tumors, mainly in the hepatic right lobe.18F-Fluorodeoxyglucose positron emission tomography/CT showed increased uptake with a maximum standardized uptake value of7.8in the hepatic tumors and vertebral metastases.A nee-dle liver biopsy disclosed atypical cell in?ltration with spindle-shaped or oval-shaped nuclei,and immunohistochemistry showed positive results for vimentin,CD31,CD34,and blood coagulation factor VIII.The diagno-sis based on the needle biopsy was epithelioid hemangioendothelioma or angiosarcoma.He died4months after the?rst detection of the hepatic tu-mor as a result of tumor progression and disseminated intravascular

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coagulation.An autopsy revealed a diagnosis of angiosarcoma with metas-tasis to the lung,left adrenal gland,spleen,and vertebrae.

#1035Tolvaptan for hepatocellular carcinoma patients with poor liver function

Authors:TAKESHI ARAMAKI;EMIMA BEKKU;RUI SATO; MICHIHISA MORIGUCHI

Affiliation:Shizuoka Cancer Center,Shizuoka,Japan

Aims:The aim of this study is to evaluate the ef?cacy of tolvaptan for he-patocellular carcinoma(HCC)patients with poor liver function.Patients and Methods:Between Oct.2013and Feb.2015,we evaluate19HCC pa-tients with poor liver function treated using tolvaptan(female/male:4/15, median age;69years old).Treatment dose is7.5mg/body in all patients. We evaluate the ef?cacy(disappearance of ascites/hydrothorax or weight loss over5%),survivals,and toxicity.Results:We evaluated19patients. Child–Pugh was A/B/C=1/14/4patients.Mean Model for End-stage Liver Disease score was11.45(7.49–18.16)points.HCC stage was0/I/II/III/IVa/ IVb=1/0/2/8/5/3.Virus infection was HBV/HCV/HBV+HCV/non-HBV, non-HCV=6/7/3/3.The mean follow-up period was96.5days.Tolvaptan was considered effective in11patients(57.9%)without major complica-tions.The overall survival is90days,and median survival time of tolvaptan effective patient and non-effective patients is167and87days, respectively(P=0.0673).Prothrombin time–international normalized ratio and serum K+were pointed out as predictive factors of effect.Discussion: The treatment effect of tolvaptan appeared in57.9%of patients who had HCC with poor liver function,and the predictive factor is prothrombin time–international normalized ratio and serum K+.However,this study in-cludes only a small number of patients and is retrospective;therefore,a prospective study with a larger sample size is necessary to de?ne the treat-ment effect and the predictive factor.Conclusion:Tolvaptan may be effec-tive as palliative therapy for HCC patient.

#1057Safety and effectiveness of sorafenib in elderly patients with hepatocellular carcinoma Authors:TAKAMASA KAWAKAM[1];KENICHIRO MORI [1];ATSUSHI HIRAOKA[1];TOSHIHIKO AIBIKI[1]; TOMONARI OKUDAIRA[1];TOMOE KAWAMURA[1]; HIROKA YAMAGO[1];HIDEOMI TOMITA[1];YOSHIFUMI SUGA[1];YUJI MIYAMOTO[1];NOBUAKI AZEMOTO[1]; HIDEKI MIYATA[1];TOMOYUKI NINOMIYA[1];HIDEKI KAWASAKI[2];KOJIRO MICHITAKA[1]

Affiliations:[1]Gastroenterology Center,Ehime Prefectural Central Hospital,Matsuyama,Ehime,Japan[2]Department of Surgery,Ehime Prefectural Central Hospital,Matsuyama,Japan Aim/Background:With the progressive aging of society,the number of elderly patients with hepatocellular carcinoma(HCC)is increasing.Here,we investigated the ef?cacy and safety of sorafenib(SOR)for HCC and compared the results be-tween elderly and non-elderly patients.Materials/Methods:Elderly(≥75years old,n=15)and non-elderly(<75,n=45)HCC patients being treated with SOR in the Ehime Prefectural Central Hospital were enrolled,and their clinical features were retrospectively evaluated.Results:There were no signi?cant differ-ences in age(79.4±2.6vs65.2±7.0years,P=0.026),performance status (0:1:2:3:4)(11:4:0:0:0vs43:1:0:0:1,P=0.017),total bilirubin(0.62±0.18vs 0.85±0.40mg/dL,P=0.017),creatinine(0.76±0.09vs0.86±0.32mg/dL, P=0.008),and epidermal growth factor receptor(69.5±5.4vs76.6±27.4mL/ min/1.73m2,P=0.009),while gender,body mass index,etiology,Child–Pugh class,tumor markers(α-fetoprotein[AFP],AFP-L3,and des-γ-carboxyprothrombin),maximum intrahepatic tumor size,intrahepatic tumor number,TNM stage,and starting dose of SOR did not show signi?cant differ-ences between elderly and non-elderly groups.There were no differences be-tween the elderly and non-elderly groups for time to progression(median10.2 vs5.7months,P=0.332),rate of stopping SOR(3and6months:35.7%and 59.8%vs46.4%and65.0%,P=0.936),and overall survival(6months and1 and2years:84.8%,66.0%,and28.3%vs59.8%,43.0%,and23.9%, P=0.983).Conclusion:Sorafenib is safe and effective regardless of age.

#1061Colonoscopy in the diagnosis of graft-versus-host disease and cytomegalovirus enteritis Authors:JOJI TANI;HISAAKI MIYOSHI;HIROHITO YONEYAMA;ASAHIRO MORISHITA;TSUTOMU MASAKI Affiliation:Department of Gastroenterology and Neurology, Kagawa University Faculty of Medicine,Takamatsu,Kagawa, Japan

Introduction:Graft-versus-host disease(GVHD)and cytomegalovirus(CMV) enteritis are important complications following allogeneic hematopoietic stem cell transplantation(allo-HSCT).We explored the role of colonoscopy in the di-agnosis of GVHD and CMV enteritis following allo-HSCT to identify the en-doscopic manifestations of GVHD and CMV enteritis.Aims and Methods: From2006to2013,57patients have undergone allo-HSCT.A retrospective analysis of the colonoscopic manifestations of GVHD,CMV enteritis,and GVHD with concurrent CMV enteritis(GconC)and their related clinical issues. Results:Twenty patients underwent colonoscopies with diagnoses of13 GVHD,4CMV enteritis,and3GconC.Both GVHD and CMV enteritis had colonic mucosal lesions with various manifestations under colonoscopy.Deep ulcers(0of4)were not speci?c endoscopic manifestations for CMV enteritis, but tortoise shell-like changes of the mucosa(11of13)were speci?c for GVHD,while mucosal edema,erythema,congestion,erosion,and shallow ul-cers could not be used to differentiate GVHD from CMV enteritis.GconC pa-tients have no speci?c endoscopic manifestations but colonic mucosal lesions with various manifestations.All GVHD and CMV enteritis were de?ned histo-logically as the presence of gland apoptosis and CMV immunostaining. Conclusion:Endoscopy may play a signi?cant role in early diagnosis of GVHD and CMV enteritis in patients following allo-HSCT,and histologic ex-amination of gastrointestinal biopsies is needed to con?rm the?nal diagnosis.

#1086Alternative implication of serum vascular endothelial growth factor in living donor liver transplantation for hepatocellular carcinoma Authors:KING-WAH CHIU[1,2];TOSHIAKI NAKANO[1,2]; KUANG-DEN CHEN[1];LI-WEN HSU[1];CHIA-YUN LAI[1]; CHING-YIN HUANG[1];YU-FAN CHENG[1,2];SHIGERU GOTO[1];CHAO-LONG CHEN[1,2]

Affiliations:[1]Liver Transplant Program,Kaohsiung Chang Gung Memorial Hospital,Kaohsiung,Taiwan[2]College of Medicine,Chang Gung University,Taoyuan,Taiwan Background:This study aimed to clarify the level of vascular endothelial growth factor(VEGF)on patients with hepatocellular carcinoma(HCC)who underwent living donor liver transplantation(LDLT);it is possibly related to the recurrence of HCC or possibly came from the rapid regeneration of the liver graft after LDLT.Methods:Data from50recipients who underwent LDLT for HCC were collected in this2-year study.Three serum VEGF time factors were

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analyzed.VEGF_1was de?ned as pre-LDLT day1,and VEGF_2as post-LDLT day1.VEGF_3was pided into VEGF_3N,which is1month post-LDLT without HCC recurrence(n=41),and VEGF_3P,which is the day of HCC recurrence(n=9).The time to HCC recurrence was90–1352days. Wilcoxon signed-rank test and mixed-model repeated-measure analysis were used to investigate.Results:The data pro?le was presented as Table1.There was statistical signi?cance only between VEGF_1and VEGF_3N and between VEGF_1and VEGF_2(P=0.022and0.012),but there was no signi?cant differ-ence between VEGF_2and VEGF_3N,between VEGF_1and VEGF_3P,be-tween VEGF_2and VEGF_3P,and between VEGF_3N and VEGF_3P(all were P>0.05).Discussion:For both HCC recurrence and liver graft regener-ation after LDLT,angiogenesis and the VEGF receptor pathways might be acti-vated,possibly resulting in the loosening of intercellular junctions of endothelial cells and promoting angiogenesis.The VEGF receptor pathway plays a physio-logical role that may not differentiate between HCC recurrence and liver graft re-generation after LDLT.Liver graft regeneration requires signi?cant blood?ow and leads to the activation of this pathway.Conclusions:The implication of VEGF in case of LDLT should be that liver graft regeneration may play a major role in the clinical investigation.

#1093Malignant peripheral nerve sheath tumor of the liver

Authors:NORIO HORIGUCHI[1,2];SATORU KAKIZAKI[1]; TOSHIYUKI OTSUKA[1];DAICHI TAKIZAWA[2];YUICHI YAMAZAKI[1];KEN SATO[1];YOSHIHIRO OHNO[3]; MOTOYASU KUSANO[4];MASANOBU YAMADA[1] Affiliations:[1]Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine,Maebashi, Gunma,Japan[2]Department of Internal Medicine,Tone-Chuo Hospital,Numata,Gunma,Japan[3]Department of Pathology, Tone-Chuo Hospital,Numata,Gunma,Japan[4]Department of Endoscopy and Endoscopic Surgery,Gunma University Hospital,Maebashi,Gunma,Japan

Introduction:Malignant peripheral nerve sheath tumor(MPNST)of the liver is rare.Most cases of MPNST are accompanied by neuro?bromatosis 1(von Recklinghausen’s disease).Materials and Methods:We herein report a case of a72-year-old woman with MPNST without neuro?broma-tosis1,which was diagnosed by an autopsy.In addition,we review the per-tinent literature of MPNST of the liver.Results:The tumor occupied the entire lobe of the liver and was18cm in maximum diameter.The tumor re-vealed necrosis and cystic changes with hemorrhage and metastasized to the peritoneum.Microscopically,it was composed of pleomorphic spindle cells with hyperchromatic nuclei and mitogenic?gures.The spindle cells stained positive for both S-100and vimentin antibodies,which suggests this is an autopsy case of MPNST of the liver.

#1126Novel function of eltrombopag as an antitumor agent for hepatocellular carcinoma Authors:TOMOHIRO KUROKAWA;SOICHIRO MURATA; YUN-WEN ZHENG;KENICHI IWASAKI;KIYOSHI FUKUNAGA;NOBUHIRO OHKOHCHI

Affiliation:Department of Surgery,Division of Gastroenterological and Hepatobiliary Surgery and Organ Transplantation,Faculty of Medicine,University of Tsukuba, Tsukuba,Ibaraki,Japan

Introduction:Sorafenib is the only available chemotherapeutic agent for ad-vanced hepatocellular carcinoma(HCC)at present,but it cannot be used in pa-tients with liver cirrhosis(LC)nor thrombocytopenia.In our previous studies,it was revealed that LC can be reduced by an increment of platelets with administra-tion of thrombopoietin(TPO).Eltrombopag(EP),TPO receptor agonists,has an-titumor effects on several kinds of cancers in spite of lack of the TPO receptor.It is still unclear whether EP has an antitumor effect on HCC.The aim of this study was to clarify the antitumor effect of EP on HCC in vitro.Materials and Methods: To verify the antitumor effects of EP in vitro with HepG2,Hep3B,and Huh7,the assays were carried out for cell proliferation with WST8,DNA synthesis with BrdU,?ow cytometry,and western blot.To clarify the antitumor mechanism of EP,iron preloading into HCC was performed and determined the effect of iron chelator deferoxamine.In addition,the combination effect of EP and sorafenib were investigated.Results:It was revealed that EP had a strong antitumor effect on HCC by suppression of cell cycle-related protein cyclin D1and resulted in cell cycle arrest in the G0/G1phase.Iron preloading into HCC cells resulted in an in-hibition of the anti-proliferative effects of EP.Antitumor effect of EP did not com-pete with sorafenib.Conclusion:Our results suggest that EP would be a good candidate for chemotherapy of HCC in patients with LC and thrombocytopenia. Keywords:cell cycle,cirrhosis,eltrombopag,hepatocellular carcinoma, Huh7,iron chelate,thrombocytopenia,thrombopoietin,liver cancer,liver cirrhosis,sorafenib.

#1157Active tumor treatment versus supportive care for patients with Barcelona Clinic Liver Cancer stage D hepatocellular carcinoma Authors:WING-YEE KWOK;CHIN-LIN LIN;KUAN-YANG CHEN;LI-YING LIAO;CHUNG-KWE WANG

Affiliation:Department of Gastroenterology,Ren-Ai Branch, Taipei City Hospital,Taipei,Taiwan

Background:Patients with Barcelona Clinic Liver Cancer(BCLC)stage D he-patocellular carcinoma(HCC)often have poor clinical outcomes.The purpose of this study was to compare the effect of active tumor treatment and supportive care for patients with BCLC stage D HCC.Methods:We conducted a retrospective study.There were a total of138patients who were diagnosed as BCLC stage D HCC at Taipei City Hospital Ren-Ai Branch from1999to2013.The duration

Table1Descriptive statistics

N Mean Standard

deviation Minimum Maximum

VEGF_150249.7374188.3295342.64640.73 VEGF_250356.4950325.48200 3.201150.26 VEGF_3N41418.5220378.23687à51.981226.99 VEGF_3P9229.701185.27579174.17378.25

Table2Test statistics(Wilcoxon signed-rank test)

VEGF_ 3N–VEGF_1

VEGF_

3P–

VEGF_1

VEGF_

3N–

VEGF_2

VEGF_

3P–

VEGF_2

VEGF_

2–

VEGF_1

VEGF_

3P–

VEGF_3N

Zà2.289?à0.889?à0.305?à1.599?à2.506?à1.125?

Asymptotic

signi?cance

(two-tailed)

0.0220.3740.7610.1100.0120.260

?Based on negative ranks.?Based on positive ranks.

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of patients ’survival was calculated from the date of diagnosis to death or the date of last follow-up.Survival analysis was performed by the Kaplan –Meier method,and a comparison was made by log –rank test.Factors associated with survival rate were analyzed by Cox ’s regression analysis.Results:There were 46(33.3%)patients who underwent different kinds of tumor treatment including op-eration,percutaneous ethanol injection,radiofrequency ablation,and radiother-apy.The remaining 92(66.7%)patients received supportive care.Patients with active tumor treatment had a signi ?cantly higher survival rate of 1–3years com-pared with those treated with supportive care (26.1%,20.9%,and 6.3%vs 3.1%,1.6%,and 0%,P =0.001).Multivariate Cox regression analysis revealed that male gender (hazard ratio [HR]: 2.059,95%con ?dence interval [CI]:1.315–3.224,P =0.002),tumor number >3(HR:1.511,95%CI:1.009–2.263,P =0.045),and supportive care (HR:2.758,95%CI:1.749–4.348,P <0.001)were independent risk factors associated with poor survival.Conclusions:The overall survival of patients with BCLC stage D HCC is quite poor.Active tumor treatment provides superior survival bene ?t than supportive care for patients with BCLC stage D HCC.Further studies with a large patient number are required to prove these preliminary ?ndings.

#1163Evaluation of laparoscopic multipolar radiofrequency ablation for small hepatocellular carcinoma

Authors:N MORIMOTO;N ISODA;Y T AKAOKA;

S WA T ANABE;T OT AKE;K MURA Y AMA;T HIROSAWA;T FUJIEDA;H Y AMAMOTO

Affiliation:Division of Gastroenterology and Hepatology,Department of Internal Medicine,Jichi Medical University,Shimotsuke,Tochigi,Japan

Background:Radiofrequency ablation (RFA)has played a key role in the management of small hepatocellular carcinoma (HCC)worldwide.We have performed laparoscopic RFA (LRA)using a multipolar RFA system (CelonPOWER System,Olympus Medical Systems,Japan)for treatment of HCCs since 2014.We assessed the ef ?cacy and safety of multipolar LRA by short-term results.Methods:We performed LRA under general anesthesia in patients with HCCs ≤4cm and ≤3nodules.An RFA needle applicator was inserted under laparoscopic ultrasonography guidance,re-gardless of tumor location.It aimed at the parallel insertions based on “do-simetry table ”and no-touch ablation as much as possible.Results and Discussion:Fifty-nine patients with 100HCCs were treated by multipolar LRA.The maximum diameter of tumor averaged 22.7±6.3mm (10–42).Operative time was 145±40min.The median follow-up time was 6.5months (0.7–16.6).In all cases,suf ?cient ablated area as planned was obtained,and there was no procedural complication and local recurrence.The laparoscopic approach offers parallel insertion of multiple applicators without limitation by echo window and/or the ribs.Especially in case of HCC in hepatic surface,it is highly useful to avoid thermal injury to adja-cent organs by maintaining the space with pneumoperitoneum and immer-sion (Fig.1).There was no local recurrence in the short-term results.To attempt at no-touch ablation may lead to obtainment of a suf ?cient safety margin.Conclusions:Although multipolar LRA required some proper skills,it is ef ?cacious in treatment for localized HCCs by gaining a good ablated area

safely.

Figure 1ARFI to predict signi ?cant ?brosis

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#1165FIB-4index is a predictor of background liver?brosis and overall survival after curative resection of hepatocellular carcinoma

Authors:YUKIYASU OKAMURA;KATSUHIKO UESAKA; RYO ASHIDA;YUSUKE YAMAMOTO;TAKAAKI ITO; TEIICHI SUGIURA

Affiliation:Shizuoka Cancer Center Hospital,Shizuoka,Japan

Background and Objectives:The FIB-4index is a simple formula for predicting liver?brosis.This study aimed to examine the relationship be-tween the preoperative FIB-4index and background liver?brosis in non-tumor regions of surgical specimens and investigate whether the FIB-4in-dex is a useful predictor in hepatocellular carcinoma(HCC)patients after curative resection.Methods:A total of493HCC patients treated with cu-rative resection were retrospectively analyzed.We assessed the utility of the FIB-4index as a predictor of advanced liver?brosis(F4).The cut-off value for the FIB-4index was determined using a receiver operating char-acteristic curve analysis,and the impact of the FIB-4index on overall sur-vival after surgery was evaluated.Results:F4was found in236patients (47.9%).The FIB-4index was signi?cantly higher in the patients with F4than in those with F0–F3(P<0.001).An FIB-4index of2.87was the best cut-off point for predicting F4.In the multivariate analysis,the FIB-4index was found to be an independent prognostic factor for overall survival after curative resection(hazard ratio:1.71,95%con?dence inter-val: 1.18–2.47,P=0.004).Additionally,elevated des-γ-carboxyprothrombin(P=0.011)andα-fetoprotein(P=0.011)levels,the presence of microsatellite lesions(P=0.014),and a serum albumin level lower than40g/L(P=0.016)were also signi?cant predictors of overall sur-vival.Conclusions:The present study showed the FIB-4index to be a pre-dictor of background liver?brosis and overall survival in patients treated with hepatectomy for HCC with curative intent.

#1181Transcatheter arterial chemoembolization combined with sorafenib versus sorafenib for hepatocellular carcinoma:A retrospective study Authors:MIN-KAI LIAO;CHE-KUANG LIN;CHIH-LIN LIN; TSUNG-JUNG LIN;KUAN-YANG CHEN;LI-YING LIAO; CHUNG-KWE WANG

Affiliation:Liver Center,Department of Gastroenterology, Ren-Ai Branch,Taipei City Hospital,Taipei,Taiwan

Background/Aims:Sorafenib,which is an orally administered target ther-apy,inhibits multiple protein kinases.At present,sorafenib is the only ap-proved systemic therapy for patients with advanced stage(BCLC-C)HCC. Sorafenib combined with transarterial chemoembolization(TACE)is now more widely applied to treat unresectable HCC.The purpose of our study is to compare the overall survival of patients with HCC who were treated with sorafenib combined with TACE compared with sorafenib monother-apy.Methods:We collected baseline characteristics of HCC patients who ever received sorafenib treatment and were recruited from Ren-Ai Branch, Taipei City Hospital,during April2010to March2014.Survival analysis was performed by the Kaplan–Meier method,and a comparison was made by log–rank test.Factors associated with survival rate were analyzed by Cox’s regression analysis.Results:There were106patients(84men and 22women)who had ever received sorafenib treatment.The mean age was65±11.8years(range,38–90years).Among them,54patients (50.9%)received sorafenib monotherapy,and21patients(19.8%)received combination therapy of sorafenib with TACE.There were no signi?cant differences in terms of sex,age,tumor size,number of tumor,prevalence of HBV/HCV infection,child classi?cation,and BCLC stage between pa-tients treated with sorafenib alone and sorafenib+TACE.However,pa-tients receiving sorafenib alone had a signi?cantly higher ratio ofα-fetoprotein(AFP)>400ng/mL(60%vs30%,P=0.034)and shorter soraf-enib treatment period(<2months sorafenib treatment,70%vs38%, P=0.009).Patients receiving combination therapy of sorafenib with TACE had a signi?cantly longer mean and median survival period compared with those receiving sorafenib alone(15.0±3.4and10.9±2.9vs5.2±1.1and 2.6±0.6,respectively,P<0.001).Multivariate Cox’s regression analysis revealed that an AFP level of>400ng/mL(hazard ratio[HR]:3.150, 95%con?dence interval[CI]:1.644–6.035,P=0.001)and a sorafenib treatment period of<2month(HR: 3.966,95%CI: 2.118–7.466, P<0.001)were independent risk factors associated with poor prognosis. Conclusions:Our results indicated that survival rate is signi?cantly longer in patients receiving sorafenib+TACE than in those with sorafenib alone. However,as most of our patients(88%)received sorafenib therapy for less than6months,the effect of sorafenib may be underestimated.Thus,further prospective randomized trials are required to con?rm our?ndings.

#1190Translational study for liver carcinogenesis and developing personalized targeted

treatment Authors:HP XIA[1,2];KM HUI[2];MH HU[1] Affiliations:[1]Department of Surgery,Yijishan Hospital of Wannan Medical College,Wuhu,China[2]Division of Cellular and Molecular Research,National Cancer Center, Singapore

Background/Aims:Hepatocellular carcinoma(HCC)is the most com-mon type of primary liver cancer and the second leading cause of cancer-related death worldwide.Most of the liver cancer cases occur in15Asian countries.China has more than half of the newly diagnosed liver cancer cases in the world.Recurrence,metastasis,and chemoresistance are major obstacles to improving the prognosis of HCC.Methods:Combining gene expression pro?les of HCC samples with or without early recurrence and established cell lines with epithelial or mesenchymal phenotype,some key factors like EDIL3were identi?ed as a novel regulator of epithelial–mesenchymal transition,which contrib-utes to angiogenesis,metastasis,and recurrence of HCC.The expression of EDIL3was evaluated by quantitative polymerase chain reaction, western blotting,and immunohistochemistry.The function of EDIL3 and targeted treatment strategies were investigated in liver cancer cells in vitro and orthotopic xenograft mouse model of HCC in vivo.Results and Discussion:EDIL3induces epithelial–mesenchymal transition and promotes HCC migration,invasion,and angiogenesis in vitro.Mechanis-tically,overexpression of EDIL3,which was regulated by downregula-tion of miR-137in HCC,triggered the activation of extracellular signal-regulated kinase(ERK)and transforming growth factor(TGF)-βsignaling through interactions withαvβ3integrin.Blocking ERK and TGF-βsignaling overcomes EDIL3-induced angiogenesis and invasion. Using the orthotopic xenograft mouse model of HCC,we demonstrated that EDIL3enhanced the tumorigenic,metastatic and angiogenesis po-tential of HCC in vivo.Conclusions:Therefore,it is promising for com-bating liver cancer through translation study and personalized therapy. EDIL3-mediated activation of TGF-βand ERK signaling could provide personalized therapeutic implications for HCC.

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#1209α-Fetoprotein-L3and simpli?ed hepatocellular carcinomaα-fetoprotein routine test for early detection of hepatocellular carcinoma in Egyptians with liver cirrhosis Authors:AHMED KHAIRY[1];DOAA SOLIMAN[1]; NAGLAA ZAYED[1];MONA ZAKY[2];WAFAA EL-AKEL[1]; EMAN MEDHAT[1];HOSNY SALAMA[1]

Affiliations:[1]Department of Endemic Medicine,Faculty of Medicine,Cairo University,Cairo,Egypt[2]Department of Clinical and Chemical Pathology,Faculty of Medicine,Cairo University,Cairo,Egypt

Hepatocellular carcinoma(HCC)is a common disorder worldwide with a rising incidence in Egypt due to high prevalence of HBV-related and HCV-related chronic liver disease.α-Fetoprotein(AFP)-L3and simpli?ed HCC-α-fetoprotein routine test(HCC-ART)could help in early detection of HCC.However,their diagnostic accuracy was not previously compared among Egyptian patients.Aim:This study aimed to compare the diagnostic role of simpli?ed HCC-ART and AFP-L3in Egyptian patients with HCC. Methods:Serum levels of AFP and AFP-L3were determined in47patients with HCC and17patients with liver cirrhosis admitted to Kasr Al-Aini

Hospital–Cairo University.All HCC patients were diagnosed by the non-invasive criteria applied to cirrhotic patients according to2012EASL guidelines.AFP and AFP-L3were assessed by the ELISA technique in all participants.AFP-L3%was de?ned as the percentage of AFP-L3over the total AFP.A simpli?ed HCC-ART was calculated(age[years]×log AFP×AAR[AST/ALT]×ALP/albumin[g/L]).The performance charac-teristics for the diagnosis of HCC were obtained using receiver operating characteristic(ROC)curves in study populations with a special emphasis on patients with20200ng/mL,and28(59.6%) patients had an AFP of20–200ng/mL,while15/17(88.2%)non-HCC pa-tients had AFP≤200ng/mL.Among the whole study population(n=64), ROC yielded that the simpli?ed HCC-ART and AFP at cut-off values of 634and62.5ng/mL were able to diagnose HCC patients with higher sen-sitivity and speci?city for HCC-ART(83%and53%)compared with se-rum AFP(78.7%and47%),respectively.Areas under the curve of AFP, simpli?ed HCC-ART,and AFP-L3were0.7(P<0.05),0.64(P<0.01), and0.49(P>0.05),respectively,with a signi?cant difference between AFP-L3and simpli?ed HCC-ART(P<0.05).On the other hand,among the subset of patients with AFP ranging from20to200ng/mL(liver cirrho-sis±HCC,n=43),areas under the curve of AFP-L3and HCC-ART for HCC were0.72(P=0.017)and0.59(P>0.05),respectively.At a cut-off value of10.9%for AFP-L3,HCC was diagnosed with82%sensitivity and67%speci?city(Fig.1).However,there was no signi?cant difference between AFP-L3and HCC-ART for HCC diagnosis among this subgroup. Conclusion:Simpli?ed HCC-ART could be a helpful score in HCC diag-nosis.AFP-L3could improve the diagnostic performance particularly in patients with AFP below the diagnostic cut-off level for HCC,that is, 200ng/mL.

Keywords:α-Fetoprotein L3,diagnosis,Egypt,hepatocellular carcinoma, simpli?ed HCC-ART,tumor marker.#1211Comparison of radiofrequency ablation with surgical resection in patients with intermediate-stage hepatocellular carcinoma:A single-center experience

Authors:YC TSENG;MC LIN;CT CHEN;PJ CHEN;HH LIN;HH HUANGE;TY HUANG;TY HSIEH;WK CHANG; YL SHIH

Affiliation:Division of Gastroenterology,Department of Internal Medicine,Tri-Service General Hospital,National Defense Medical Center,Taipei,Taiwan

Background/Aims:Hepatocellular carcinoma(HCC)is a common pri-mary liver cancer in Asia.Radiofrequency ablation(RFA)or surgical re-section(SR)are both well-established treatments for early-stage HCC. However,the management of intermediate-stage or advanced-stage HCC was not well recognized.In this scenery,RFA is an alternative consideration.Material and Methods:In a single medical center,we carried out a retrospective study of patients with HCC meeting strict in-clusion criteria who received RFA or SR from September2009to Au-gust2013.Results and Discussion:In all,37and120patients with intermediate-stage to advanced-stage HCC who underwent RFA or SR were analyzed,respectively.The median size of HCC was3.5(range 1.7–5.8)cm for the RFA group and7.1(range3.1–24)cm for the SR group.The average age of HCC diagnosis for each group was62.1±10.6(range43–79)years for RFA and55.9±12.4(range21–77)years for SR.The days of hospital stays were6.5±6.1(range3–37)days for RFA and16.6±12.7(range4–98)days for SR.The recurrence rate was 81.1%(30/37)for RFA groups but only53.3%(64/120)for SR groups. Conclusion:For intermediate-stage to advanced-stage HCC,RFA could be applied to older patients and has short hospital stay but higher recur-rence rate than the SR group.RFA may be considered as a safe and ef-fective salvage treatment strategy for intermediate-stage to advanced-stage HCC patients,especially those patients who have a high risk for SR.Further studies are needed to compare RFA and SR in patients with more-advanced-stage cancers.

Figure1ROC curve for AFP-L3and simpli?ed HCC-ART score in diagnosis of HCC in patients with AFP of20–200ng/mL.

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#1227Nucleos(t)ide analog therapy is associated with reduced hepatocellular carcinoma recurrence after radiofrequency ablation

Authors:TENG-YU LEE[1];JAW-TOWN LIN[2];YI-SIOU ZENG[1];YI-JU CHEN[3];MING-SHIANG WU[4];

CHUN-YING WU[1,3]

Affiliations:[1]Division of Gastroenterology and Hepatology, Taichung Veterans General Hospital,Taichung,Taiwan [2]School of Medicine,Fu Jen Catholic University,New Taipei City,Taiwan[3]Faculty of Medicine,School of Medicine,National Yang-Ming University,Taipei,Taiwan [4]Department of Internal Medicine,National Taiwan University Hospital,Taipei,Taiwan

Efforts should be made to reduce the risk of tumor recurrence after radiofre-quency ablation(RFA)for hepatocellular carcinoma(HCC).We aimed to in-vestigate the association between nucleos(t)ide analog(NA)therapy for hepatitis B virus(HBV)and the risk of HCC recurrence following 849853c052ea551811a68751ing the Taiwan National Health Insurance Research Database between July1, 2004,and December31,2012,we screened48807patients with newly diag-nosed HBV-related HCC.We identi?ed850patients(200patients who used NAs for more than90days and650patients who never used NA after RFA) who received RFA as a potentially curative treatment.Patients in the NA-treated cohort were randomly matched1:2with patients in the untreated cohort by age,gender,cirrhosis,and the time period between RFA and initiation of NA therapy.Finally,148patients were recruited in the NA-treated group and296in the untreated group.The HCC recurrence rate of the NA-treated group was signi?cantly lower than that of the untreated group(2-year recur-rence rate:43.0%,95%con?dence interval[CI]:34.5–51.4%vs55.2%,95% CI:49.2–61.1%;P<0.01).In a modi?ed Cox regression analysis,NA therapy was independently associated with a decreased risk of HCC recurrence(hazard ratio0.68,95%CI:0.50–0.92;P=0.01).Multivariate strati?ed analyses veri-?ed the association of NA therapy and decreased HCC recurrence in all patient subgroups.Conclusion:Nucleos(t)ide analog therapy was associated with a decreased risk of HCC recurrence among patients with HBV-related HCC fol-lowing RFA.

#1238Ultrasound-guided biopsy of hepatic cystic lesions with a thick wall

Authors:DY YANG;J QU*;H WANG;GQ SUI Affiliation:Department of Ultrasound,Third Hospital of Jilin University,Changchun,China

Aims:This study aimed to assess the security and accuracy of US-guided biopsy of cystic lesions with a thick wall in liver.Methods:Fifteen patients with hepatic cystic masses were enrolled in this study from June2012to April2015.We compared the pathology by US-guided biopsy with the postoperative.Patient selection included the following criteria:(i)the thickness of the cystic mass wall is more than1cm;(ii)the puncture path should be through normal hepatic tissues;and(iii)the thick wall of cystic masses should be parallel with the ultrasonic sound beam.In the process of US-guided biopsy,we performed the following:(i)detect the internal tex-ture and adjacent tissue of the tumor in different sections;(ii)select those cyst walls that have a different blood supply to puncture;(iii)according to the direction of the cyst wall,select puncture site and approach;(iv)de-tect blood vessels in the tumor and peripheral blood vessels and bile duct; and(v)use color Doppler to detect whether there is bleeding.A coagulant was used in the cystic cavity to stop bleeding.Results:(i)US-guided biopsy of liver was performed in15patients successfully.(ii)The bleeding of one patient was stopped by using a coagulant in the cystic cavity.(iii) There was no serious complications after the implantation in other patients. (iv)The pathological results of US-guided biopsy agreed with postopera-tive pathologic results.Conclusion:(i)US-guided biopsy is less invasive, safe,and effective for tumor,especially for cystic tumor.(ii)Complications after US-guided biopsy can be treated in time.

*corresponding author

Correction added on5December2015,after Online publication.Corre-sponding author is J QU.

#1255Assessment of percutaneous radiofrequency ablation treatment with Soloist and LeVeen needles for hepatocellular carcinoma patients

Authors:HANG DAO[1,2];LONG DAO[1,2] Affiliations:[1]Internal Medicine Department,Hanoi Medical University,Hanoi,Vietnam[2]Gastroenterology Department,Bach Mai Hospital,Hanoi,Vietnam Introduction:Hepatocellular carcinoma(HCC)is a common disease in the world as well as in Vietnam.Radiofrequency ablation(RFA)is a local ther-apy to destroy tumor tissue by heat.Materials and Methods:This is an in-terventional longitudinal study on HCC patients having≤3tumors with each tumor being≤3cm in size or with a single tumor of up to5cm and having Child Pugh A or B.The study was conducted in the Gastroenterol-ogy Department of Bach Mai Hospital from November2011to April2015. Results:One hundred and twenty-seven patients with a mean age of58.1±10.3underwent368times of RFA with the mean ablation times being 2.9±1.5in which81were treated only by RFA and46patients were treated by RFA combined with transarterial chemoembolization.HBV was the predominant cause of HCC with a rate of67.7%.Eight patients underwent arti?cial ascites with a mean volume of2125±231mL of5% glucose,and two patients underwent arti?cial pleural effusion with a mean volume of1100±141mL of5%glucose due to dif?cult locations.The procedure was safe with the complication rate being1.1%including hemo-thorax,ascites,pleural effusion,and hypervagal reaction,which were treated well by internal medicine.Fever and abdominal pain were recorded in13.6%ablation times.After1month of the?rst RFA,117patients had complete and partial responses according to modi?ed Response Evaluation Criteria in Solid Tumors(92.1%);after9months,105patients had com-plete and partial responses(82.7%).Forty-nine patients(38.6%)had better clinical response with gain weight and less fatigue.During follow-up time (18.1±7.5months),5patients died(3.9%),22patients had a new lesion (17.3%),3patients had portal vein thrombosis(2.3%),1patient had ab-dominal lymph node(0.8%),and1patient had tract seeding(0.8%). Conclusion:Radiofrequency ablation with Soloist and LeVeen needles is a safe technique and effective in improving treatment response and quality of life of HCC patients.

Keywords:hepatocellular carcinoma(HCC),radiofrequency ablation (RFA).

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#1260Expression of endoglin(CD105)in hepatocellular carcinoma with its clinicopathological and prognostic signi?cance analysis

Authors:MING-TSUNG LIN;YI-HAO YEN;PO-LIN TSENG; KUO-CHIN CHANG;TSUNG-HUI HU

Affiliation:Division of Hepato-Gastroenterology, Department of Internal Medicine,Kaohsiung Chang Gung Memorial Hospital and Chang Gung University,College of Medicine,Kaohsiung,Taiwan.

Background and Aims:Hepatocellular carcinoma(HCC)is a highly vascularized tumor with intense angiogenesis,but the molecular mechanisms regulating angiogenesis have not been fully understood.We clari?ed the rela-tion of CD105expression with HCC and explored its importance with HCC prognosis comprehensively.Methods:A total of112hepatocellular carcinoma patients were analyzed.Immunohistochemical staining for the CD105was per-formed in tumor and non-tumor specimens.We further compared the relation of CD105with clinicopathological parameters by immunohistochemical stain-ing.We also analyzed30pairs of fresh tissue specimens including a tumor part and a non-tumor part in30hepatocellular carcinoma patients using the quanti-tative real-time polymerase chain reaction and western blot and analyzed the expression of endoglin with clinicopathological parameters.Results:We dem-onstrated that CD105was more abundant in the non-tumor part of liver in HCC patients.And the well-differentiated HCC and early-stage HCC and lower serumα-fetoprotein level had higher microvessel density of CD105ex-pression.And a higher CD105expression had a lower tumor recurrent rate af-ter operation.In western blot,the early-stage and smaller HCCs had a higher CD105expression.The quantitative real-time polymerase chain reaction also showed a higher CD105expression in the non-tumor part than in the tumor part.Conclusions:CD105has an important role in HCC angiogenesis,and this study provides evidence for HCC prognosis related with CD105expres-sion.We obtained similar results and validated them by immunohistochemical staining and quantitative real-time polymerase chain reaction and western blot.

#1265Fighter or genomics?Surviving a decade of liver cancer conservatively

Authors:BH OOI[1];MR HASSAN[1];Z ZALWAN[1];

MS FIRDAUS[1];CH LOO[2];KK KIEW[1]

Affiliations:[1]Department of Internal Medicine,Hospital Sultanah Bahiyah,Alor Setar,Kedah,Malaysia

[2]Department of Internal Medicine,Hospital Sultan Abdul Halim,Sungai Petani,Kedah,Malaysia

Introduction:An estimated695900liver cancer deaths occurred world-wide in2008.Based on US statistics,the5-year survival rate is only 15%.The low survival rate is attributable to concomitant liver cirrhosis, which in itself is fatal.Case Description:We present a case of a65-year-old lady who survived a decade despite being diagnosed with liver cancer in a cirrhotic liver.She had chronic hepatitis C infection but achieved sustained viral response following therapy with pegylated inter-feron and ribavirin in2005.A year later,she was diagnosed with liver can-cer during surveillance.The cancer measured2.2×2.6×1.7cm in segment 2.Surgery was not an option because of her poor liver reserve.She was not keen on further treatment and opted for conservative therapy.A repeated computed tomography scan after5years revealed the tumour had doubled in size to4.2×5.8×4.2cm with other new lesions.Regular monitoring of α-fetoprotein showed a steady rise from the initial hundreds to thousands and?nally>10000ng/mL.She remained asymptomatic until her10th year when she started experiencing liver decompensation.Despite a known poor survival outcome,she de?ed all odds to live a decade with a European Cooperative Oncology Group score of1despite no cancer treatment. Conclusion:Liver cancer is highly heterogeneous,and cancer genomics may hold the key to explaining the aggressiveness and indolence of certain cancer subtypes.By unlocking this,we may one day inpidualize liver cancer treatment.Some may not require aggressive treatment regimes where the bene?ts and risks need to be weighed against survival prognosis.

References:

1Jemal A,Bray F,Center MM,Ferlay J,Ward E,Forman D.Global cancer statistics.CA Cancer J.Clin.2011;61:69–90.

2Takai A,Dang HT,Wang XW.Identi?cation of drivers from cancer genome persity in hepatocellular carcinoma.Int.J.Mol.Sci.2014;

15:11142–60.

#1290Building of a scoring model based on preoperative plasma?brinogen level for predicting tumor recurrence after liver transplantation for hepatocellular carcinoma

Authors:WANG GUO-YING;ZENG KAI-NING;YANG YANG;CHEN GUI-HUA

Affiliation:Liver Transplantation Center of the Third Affiliated Hospital,Sun Yat-sen University,Guangzhou,China

Objective:Elevated plasma?brinogen(FBG)level is associated with tumor pro-gression and poor patient outcomes in several cancers.However,the prognostic value of FBG in hepatocellular carcinoma(HCC)patients undergoing liver trans-plantation(LT)is unclear.The aim of this study was to investigate the prognostic value of preoperative plasma FBG level in HCC patients after LT and build a scoring model based on FBG for predicting tumor recurrence after LT.To our knowledge,this is the?rst report discussing the prognostic value of preoperative plasma FBG level in HCC patients after LT.Methods:We analyzed the outcome of99patients who underwent LT for HCC at our institution.Clinical and path-ological factors were evaluated by Kaplan–Meier analysis,and survival curves were compared using the log–rank test.Cox multiple-regression analysis was performed to determine the parameters predicting HCC recurrence and patient survival.The optimal cut-off value for elevated level of preoperative FBG was determined by using a receiver operating characteristic curve analysis.A scoring model was built by giving a value of0or1to independent risk factors selected by Cox regression analysis.Results:Preoperative FBG levels were signi?cantly higher in patients with tumor recurrence(3.27g/L)compared with those in pa-tients without recurrence(2.34g/L)(P<0.001).A cut-off value for elevated FBG level of2.68g/L was de?ned using receiver operating characteristic curve analysis.There were signi?cant differences in disease-free survival between the elevated FBG group and normal FBG group(78.4%vs37.2%,P=0.001).Pa-tients with macrovascular invasion andα-fetoprotein>400ng/mL also had sig-ni?cantly higher preoperative plasma FBG concentration than the others. Macrovascular invasion,tumor number>3,and FBG≥2.68g/L were indepen-dent risk factors of HCC recurrence after LT.A scoring model was built to pre-dict the risk of tumor recurrence,with a sensitivity of68.3%and a speci?city of 87.5%.Conclusion:Pretransplant elevated plasma FBG level signi?cantly in-creases the risk of tumor recurrence in patients after LT for HCC.The scoring model we built based on FBG level and tumor number strongly correlates to tu-mor recurrence and may aid in the selection of patients that would most bene?t from transplantation for HCC.

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#1385Prognostic factors of transarterial chemoembolization/transarterial embolization for hepatocellular carcinoma patients with prolonged survival of more than3years

Authors:G SARVESH[1,2];CM JENG[3,4];WM TSAI[5]; YW HUANG[1,6–8];JT HU[1,4];SS YANG[1,4] Affiliations:[1]Liver Unit,Cathay General Hospital Medical Center,Taipei,Taiwan[2]Bhaktapur Cancer Hospital, Bhaktapur,Nepal[3]Department of Radiology,Cathay General Hospital,Taipei,Taiwan[4]School of Medicine,

Fu-Jen Catholic University,New Taipei City,Taiwan

[5]Department of Radiology,Sijhih Cathay General Hospital, Sijhih,New Taipei City,Taiwan[6]Health Management Center,Cathay General Hospital Medical Center,Taipei, Taiwan[7]School of Medicine,Taipei Medical University College of Medicine,Taipei,Taiwan[8]Division of Gastroenterology,Department of Internal Medicine,National Taiwan University College of Medicine,Taipei,Taiwan Background:The advancements in transarterial management of non-resectable hepatocellular carcinoma,including transarterial embolization (TAE)and transarterial chemoembolization(TACE),are used as palliative ther-apies.The aim of this study is to evaluate the survival rate of patients subjected to TAE/TACE and to propose a new opinion.Method:A total of112patients of hepatocellular carcinoma,who were managed with TAE/TACE and radiofre-quency ablation(RFA)and/or ultrasound-guided alcohol injection(USGAI) and survived for3years or more till the year2014,were studied.To explore fac-tors in?uencing their survival,age,number of procedures(including RFA and USGAI)in1year,the frequency of procedures in1year,Barcelona Clinic Liver Cancer stage,Model for End-stage Liver Disease scores,spleen size,and all blood data related to liver were analyzed.Results:The survival rate was statis-tically signi?cantly higher if patients were younger than70years old(log–rank test,P=0.028)and have had more than three times of TAE/TACE procedures within1year(P=0.019),prothrombin time of≤12s(P=0.010),international normalized ratio of≤1.2(P=0.012),alkaline phosphatase of≤95U/L (P=0.037),Barcelona Clinic Liver Cancer staging of A(P=0.007),and an av-erage interval between each procedure of>8months(P=0.034).Conclusion: The survival outcomes of patients presenting with early staging,less severe co-agulopathy and liver dysfunction,and increasing number of procedures within the given time frame showed comparable improvements.

#1490A pilot safety study of natural killer cells from sibship to treat the recurrence of hepatocellular carcinoma after liver transplantation

Authors:WANG GUO-YING;YANG YANG;CHEN GUI-HUA Affiliation:Liver Transplantation Center,the Third Affiliated Hospital of Sun Yat-Sen University,Guangzhou,China

Objective:Natural killer(NK)cells have been thought to play a pivotal role in innate immunity.However,the safety and ef?cacy of NK cells for the treatment of hepatocellular carcinoma(HCC)recurrence after liver trans-plantation(LT)are unknown.In this study,we investigated whether the in-jection of activated NK cells(CD3àCD56+cells)from a sibship with the same blood type is safe for the treatment of HCC recurrence after LT. Methods:Six patients with HCC recurrence after LT were eligible and en-rolled in this study.The patients received injections of5×109NK cells from the sibship with the same blood type four times at a frequency of once every2weeks.Lymphocytes were extracted from the peripheral blood mononuclear cells and cultured with interleukin-2and other cytokines for 2weeks.The purity of lymphocytes was assessed by?ow cytometric anal-ysis,and only the CD3àCD56+cells greater than70%were used.The ad-verse effects,laboratory tests,and overall survival were assessed.Results: No serious adverse effects and laboratory abnormalities were identi?ed as related to the treatment of NK cells.Five patients were alive in the follow-up period of2–6months,while one died of liver failure due to tumor pro-gression after2months of NK cell infusion.There was no graft-versus-host disease in all six patients during follow-up.Conclusion:In this study,we have demonstrated for the?rst time to our knowledge that NK cells from sibships with the same blood type can be used safely as adoptive immuno-therapy for the treatment of HCC recurrence after LT.

#1511Expression of I2-arrestin1in the course of mice non-alcoholic fatty liver disease progressing to hepatocellular carcinoma

Authors:YW GUO;HB MIAO;XY LIN

Affiliation:Department of Gastroenterology,Third Affiliated Hospital of Sun Yat-Sen University,Guangzhou,Guangdong Province,China

Aims:This study aimed to investigate the expression ofβ-arrestin1and its possi-ble function in the course of non-alcoholic fatty liver disease(NAFLD) progressing to hepatocellular carcinoma.Materials and Methods:C57BL/6mice were fed with chow diet and high-fat diet(HFD)for9,24,and48weeks,and the incidence of hepatocellular carcinoma was observed at the end of48weeks.Ex-pressions ofβ-arrestin1in the liver tissue of mice were detected by western blot and real-time reverse transcription–polymerase chain reaction.Results:The liver of mice exhibited the typical appearance of fatty liver after9weeks of HFD.At the48th week or the end-point of study,the incidence of hepatocellular carcinoma was0/23in the chow diet group and4/22in the HFD group with a statistically signi?cant difference(P<0.05).Compared with the chow diet group,the HFD group had statistically increasedβ-arrestin1protein expression of liver tissue at 9weeks(P<0.05),and the level ofβ-arrestin1protein was positively correlated to the duration of HFD(r=0.949,P=0.000).Furthermore,the expressions ofβ-arrestin1protein in tumor tissue was dramatically higher than that of fatty liver tis-sue from the same period of HFD(P<0.05).The change ofβ-arrestin1mRNA exhibited the same tendency.The order from lowest to highest in mRNA level of β-arrestin1was liver tissue from mice fed with chow diet for9weeks,liver tissue from mice fed with HFD for9,24,and48weeks,and tumor tissue from hepato-cellular carcinoma(all P<0.05).Conclusions:It is easy to develop NAFLD in mice fed with HFD,and there is a higher incidence of hepatocellular carcinoma in NAFLD mice.β-Arrestin1might play an important role in the course of NAFLD progressing to hepatocellular carcinoma.

Keywords:β-Arrestin1;hepatocellular carcinoma;non-alcoholic fatty liver disease(NAFLD).

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#1533Increased risk of hepatocellular carcinoma in chronic hepatitis C patients with new-onset diabetes:A nationwide cohort study

Authors:YW HUANG[1–3];TC WANG[4];SC FU[1];

JT HU[1,5];DS CHEN[3,6–8];SS YANG[1,5] Affiliations:[1]Liver Center,Cathay General Hospital Medical Center,Taipei,Taiwan[2]School of Medicine,Taipei Medical University College of Medicine,Taipei,Taiwan [3]Division of Gastroenterology,Department of Internal Medicine,National Taiwan University College of Medicine, Taipei,Taiwan[4]Department of Medical Research,Cathay General Hospital Medical Center,Taipei,Taiwan[5]School of Medicine,Fu-Jen Catholic University College of Medicine, Taipei,Taiwan[6]Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine,Taipei, Taiwan[7]Hepatitis Research Center,National Taiwan University Hospital,Taipei,Taiwan[8]Genomics Research Center,Academia Sinica,Nankang,Taipei,Taiwan Background:The impact of diabetes for hepatocellular carcinoma(HCC) development in chronic hepatitis C(CHC)patients remains controversial. We aimed to investigate the risk of HCC in CHC patients who develop new-onset diabetes.Methods:We conducted a nationwide cohort study by using the Taiwanese National Health Insurance Research Database, which comprised data from>99%of the entire population.Among the randomly sampled one million enrollees,6251adult CHC patients were identi?ed from1997to2009.Diabetes was de?ned as new onset in patients who were given the diagnosis in the years1999–2009but not in1997–1998.The cohorts of CHC with new-onset diabetes(n=1100)and1:1ratio age-matched,gender-matched,and inception point(onset date of diabetes)-matched non-diabetes(n=1087)were followed up from the inception point until the development of HCC,withdrawal from insurance,or De-cember2009.Results:After adjustment for competing mortality,patients with new-onset diabetes had a signi?cantly higher cumulative incidence of HCC(relative risk=1.544,95%con?dence interval[CI]=1.000–2.387,modi?ed log–rank test,P=0.047)as compared with those without. After adjustment for age,gender,cirrhosis,hyperlipidemia,CHC treat-ment,diabetes treatment,comorbidity index,obesity,and statin therapy by the Cox proportional hazard model,diabetes was still an independent predictor for HCC(hazard ratio[HR]=1.906,95%CI=1.102–3.295, P=0.021).The risk for HCC was increased in those who were 40–59years old,independent of other variables(HR=3.086,95% CI=1.045–9.112,P=0.041)and after adjustment for competing mortality (modi?ed log–rank test,P=0.009).Conclusions:Chronic hepatitis C patients who develop diabetes are at an increased risk of HCC over time.#1547The NIACE score:An additional prognostic tool that applies to any hepatocellular carcinoma treatment modality

Authors:XAVIER ADHOUTE[1];GUILLAUME PENARANDA[1];JEAN LUC RAOUL[1];JEAN FREDERIC BLANC[1];JULIEN EDELINE[1];GUILLAUME CONROY[1]; EMILIE BOLLON[1];HERVE PERRIER[2];BERNARD POL[2]; OLIVIER BAYLE[2];OLIVIER MONNET[2];PATRICK BEAURAIN[2];CYRIL MULLER[2];PAUL CASTELLANI[2]; JEAN HARDWIGSEN[1];YVES PATRICE LETREUT[1]; JEAN PIERRE BRONOWICKI[3];MARC BOURLIERE[2] Affiliations:[1]Centre Hospitalo-Universitaire Conception, Marseille,France[2]H?pital Saint-Joseph,Marseille,France [3]CHU de Nancy,Vandoeuvre-lès-Nancy,France Background:Nowadays,therapeutic options in hepatocellular carcinoma (HCC)are based on the Barcelona Clinic Liver Cancer(BCLC)staging system algorithm.However,each BCLC stage comprises a wide spectrum of tumors,and patients’prognosis is variable after treatment.Aim of the Study:This study aimed to re?ne the strati?cation of patients after curative or palliative treatment of HCC,by establishing a new,simple prognostic score.Methods:The score was de?ned by a regression model based on an advanced HCC BCLC C population(n=161)and validated with several cohorts at different stages(BCLC C n=377,BCLC B n=104,and BCLC A n=128).It was then assessed with HCC patients according to the admin-istered treatment(surgery n=248/RFA,TACE n=321,sorafenib n=285). Five centers took part in this study.Results:Five variables had indepen-dent prognostic values:the number of nodules,the in?ltrating nature of the HCC,α-fetoprotein serum level,Child–Pugh score,and European Co-operative Oncology Group performance status grade.They were integrated into a new score(NIACE)ranging from0to7,correlated to survival,what-ever the BCLC stage of the HCC(A,B,or C)and the administered treat-ments are.Through the use of different threshold values,this score allows us to de?ne two populations having different survivals within each HCC treatment modality.Conclusion:The NIACE score is a simple addi-tional tool that allows us to de?ne different prognostic subgroups after cu-rative or palliative treatment of HCC.This?nding could have clinical implications for the management of patients with HCC.

#1553The Child–Turcotte–Pugh numeric score of 6or more has in?uence on survival in patients with hepatocellular carcinoma after curatively hepatic resection

Authors:WEI-FAN HSU[1,2];KUO-HSIN CHEN[3];KUO-SHYANG JENG[3];CHIEN-CHEN TSAI[4];TZONG-HSI LEE[1] Affiliations:[1]Division of Gastroenterology and Hepatology, Department of Internal Medicine,Far Eastern Memorial Hospital,New Taipei City,Taiwan[2]Institute of Clinical Medicine,National Yang-Ming University,Taipei,Taiwan [3]Department of Surgery,Far Eastern Memorial Hospital,New Taipei City,Taiwan[4]Department of Anatomical Pathology,Far Eastern Memorial Hospital,New Taipei City,Taiwan Background/Aims:Surgery is one of the preferred methods for curative in-tervention of HCC.Risk factors of mortality and tumor recurrence are ma-jor issues after curative hepatectomy.Child–Turcotte–Pugh(CTP)score is a scoring system to assess the severity of liver cirrhosis and a part of the

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Barcelona Clinic Liver Cancer staging system.Most patients who underwent surgical resection of HCC belong to CTP classi?cation A or early B.However,few articles discussed the role of the CTP numeric score in these patients.This study aimed to investigate the prognostic factors of HCC after liver resection in the Far Eastern Memorial Hospital.Methods: From March2006to January2011,178patients who underwent curative hepatectomy(for HCC)in the Far Eastern Memorial Hospital were in-cluded and followed till January2014.CTP scores were assessed in spite of liver cirrhosis or not.We used the Kaplan–Meier method to analyze their survival and recurrence.Demographics,CTP scores,tumor factors,and pathologic characteristics were tested by log–rank test.Variables in univar-iate analyses with P<0.1were subjected to multivariate Cox regression modeling.Because the biochemical variables,including albumin,total bil-irubin,prothrombin time,and ascites,are parameters of CTP,we analyzed CTP score and parameters of CTP by different methods in multivariate analysis.In method1,variables including CTP score and classi?cation were analyzed,but the parameters of CTP were excluded.In method2,pa-rameters of CTP and other variables were evaluated excluding CTP score and classi?cation.Results:Of the178patients,135patients were male, and43patients were female.The median age was60.38years,and the me-dian follow-up duration was40months(1–95months).One hundred twenty-seven patients(71.35%)had liver cirrhosis.One hundred?fty-?ve (87.08%)and21(11.80%)patients belonged to Child classi?cations A and B,and the highest CTP score was9in3patients.Hepatitis B/C virus and both infections were detected in95(53.37%),44(24.72%),and9(5.2%) patients.The multivariate analysis of variants that predict recurrence and survival were in Tables1and 2.Conclusions:(i)Child–Turcotte–Pugh≥6was a poor survival factor in patients after curative resection of HCC.Albumin≤3.5g/dL,the major component of CTP≥6,was a poor prognostic factor in survival.Major branch portal venous thrombosis,in only three patients in our study,was a poor recurrent prognostic factor.

#1652Hepatocellular carcinoma,NIACE score: An aid to the decision-making process before the ?rst transarterial chemoembolization

Author:XAVIER ADHOUTE[1];GUILLAUME PENARANDA [2];JEAN LUC RAOUL[3];HERVE PERRIER[1];PAUL CASTELLANI[1];GUILLAUME CONROY[4];BERNARD POL [1];OLIVIER BAYLE[1];OLIVIER MONNET[1];PATRICK BEAURAIN[1];CYRIL MULLER[1];JEAN PIERRE BRONOWICKI[4];MARC BOURLIERE[1]

Affiliations:[1]H?pital Saint-Joseph,Marseille,France [2]AlphaBio Laboratory,Marseille,France[3]Institut

Paoli-Calmette,Marseille,France[4]Centre Hospitalo-Universitaire de Nancy,Vandoeuvre-les Nancy,France

Background:NIACE score(which stands for nodules[N],in?ltrative tu-mor[I],α-fetoprotein[A],Child–Pugh[C],European Cooperative On-cology Group performance status[E])(American Association for the Study of Liver Diseases2014[P1329]and EASL2015[P0376])de?nes two populations with different survival.Transarterial chemoembolization (TACE)is recommended for intermediate-stage HCC(Barcelona Clinic Liver Cancer[BCLC]B).In clinical practice,it is used to treat more ad-vanced HCC or earlier stages not suitable for surgery/radiofrequency ab-lation or recurrent after surgery.Aim of the Study:This study aimed to evaluate the NIACE score as an aid to the decision-making process be-fore the?rst TACE in order to determine the patients who may not ben-e?t from TACE.Patients and Methods:Patients treated with TACE as the main treatment in our institution between01/2007and12/2013were included,including HCC with segmental portal vein thrombosis.Patients who had additional treatment after TACE(surgery/radiofrequency abla-tion and transplantation),involved in the establishment of the NIACE

Table1Multivariate analysis of variants that predict recurrence Variables Hazard ratio95%con?dence interval P-value

Portal venous

thrombosis

23.562 4.225–131.416<0.001 Stage1 1.00

Stage2 1.5970.873–2.9210.129 Stage3or4 3.713 2.003–6.885<0.001?The1-year,3-year,and5-year recurrence rates are55.24%,63.74%, and65.04%,respectively.

?Portal venous thrombosis(P=0.02)and tumor size>5cm(P=0.042) were factors for very early recurrence(recurrence<1year).Table2Multivariate analysis of variants that predict survival

Variables Hazard ratio95%con?dence interval P-value

Method1

Child score5 1.00

Child score≥6 2.948 1.774–4.899<0.001 Stage1 1.00

Stage2 3.543 1.632–7.6930.003 Stages3+4 6.633 3.16–13.903<0.001 Indocyanine green,

15min>10%

1.713 1.015–

2.8900.044

Method2

Albumin3.5 2.255 1.306–3.8930.004 Stage1 1.000

Stage2 2.839 1.330–6.0600.007 Stages3+4 5.868 2.835–12.146<0.001?The1-year,3-year,and5-year survival rates are74.50%,56.38%,and 39.46%,respectively.

?Of the61patients with CTP≥6,most of the patients(n=35,57.38%) had albumin≤3.5g/dL(ascites in50.82%,total bilirubin≥2.0mg/dL in 14.75%patients).

?The CTP classi?cation(A vs B)did not reach statistical signi?cance (P=0.485,univariate).

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score,and had metastatic HCC and HCC with main portal vein thrombo-sis were excluded.The results were con?rmed in an external cohort treated with TACE during the same period.Likelihood ratio,Akaike in-formation criterion,and area under the receiver operating curves were used to determine the best model.Results:The internal cohort included 230patients,with a median age of67(58.5–74)years and European Co-operative Oncology Group performance status of0/1(100%);patients were mainly cirrhotics(95%),classi?ed as Child–Pugh A(66%)or Child–Pugh B(29%),related to a viral etiologies(48%)or alcohol 33%,and classi?ed as BCLC A(39%),B(40%),or C(21%).HCCs were multi-nodular(41%)or in?ltrating tumors(19%).Thirty-three per-cent of the patients had an elevatedα-fetoprotein level of≥200ng/mL, and58%had esophageal varices.The median overall survival(OS)of the group was22.3(10.2–36.5)months.The score’s variation was corre-lated to survival.With a threshold value<3,the score distinguished be-tween two populations having different median OS:NIACE<3 (n=160),28(26–35)months versus NIACE≥3(n=70),9.6(7–12) months,P<0.0001.Concerning the external cohort including91BCLC A and B HCC patients from Nancy,treated by TACE,the median OS of the group was24.9(20.9–32.5)months.By applying a NIACE<3 threshold,the median OS of the NIACE<3group was27(23–26) months versus13(13–23)months for the NIACE≥3group, P=0.0015.Conclusion:In this multicentric study involving HCC pa-tients treated with TACE as the main treatment,NIACE score can distin-guish two groups with different survival.Patients with a score of NIACE>3do not seem to bene?t from TACE treatment.These results should be con?rmed in a prospective study.

#1667How to guide sorafenib for advanced hepatocellular carcinoma?Usefulness of NIACE score Author:XAVIER ADHOUTE[1];GUILLAUME PENARANDA[2];JEAN LUC RAOUL[3];JEAN FREDERIC BLANC[4];JULIEN EDELINE[5];GUILLAUME CONROY[6]; HERVE PERRIER[1];PAUL CASTELLANI[1];BERNARD POL [1];JEAN PIERRE BRONOWICKI[6];MARC BOURLIERE[1] Affiliations:[1]H?pital Saint-Joseph,Marseille,France [2]AlphaBio Laboratory,Marseille,France[3]Institut Paoli-Calmette,Marseille,France[4]Centre Hospitalo-Universitaire Saint-André,Bordeaux,France[5]Centre

Eugène Marquis,Rennes,France[6]Centre Hospitalo-Universitaire de Nancy,France

Background:Sorafenib is the?rst Food and Drug Administration-approved therapy for patients with advanced HCC.It is a treatment option for intermediate-stage HCC(Barcelona Clinic Liver Cancer[BCLC]B)not suitable or refractory to transarterial chemoembolization(Bruix J et al.,J. Hepatol.,2012).The prognosis of patients treated with sorafenib is vari-able.The NIACE score(American Association for the Study of Liver Dis-eases2014[P1329]and European Association for the Study of the Liver 2015[P0376]),ranging from0to7,is correlated to survival,whatever the BCLC stage of the HCC(A,B,or C)are.It includes parameters such as the in?ltrating nature of the HCC at any stage of the disease and the AFP level(±200ng/mL).Aim of the Study:This study aimed to de?ne among HCC patients treated with sorafenib subgroups with different prog-noses using the NIACE score.Patients and Methods:All patients treated with sorafenib as the main therapeutic modality between01/2008and 12/2013in four institutions(Marseille n=139,Nancy n=83,Bordeaux n=119,and Rennes n=83)were included.We excluded patients involved in the development of the score and patients who had additional treatment (transarterial chemoembolization,surgery/radiofrequency ablation,or transplantation)with sorafenib.Results:The four cohorts,that is,424pa-tients,had common characteristics:age,male sex,majority of Child–Pugh A cirrhosis,in?ltrating nature of HCC,portal vascular invasion,elevatedα-fetoprotein level≥200ng/mL in50%of cases.The median duration of so-rafenib administration in the four cohorts varied from3.7(1.3–8.1)to6.9 (3.8–11.3)months;less than20%of patients stopped the treatment during the?rst month.By applying the score,there were subgroups of different prognoses,and the score’s variation was correlated to survival.The NIACE score with a threshold value<3corresponded to two groups with different median overall survival into the three external cohorts:Nancy,NIACE<3 (n=28),16(14–25)months versus NIACE≥3(n=55),6(4–8)months, P<0.0001;Rennes,NIACE<3(n=37),10.6(4.1–17.1)months versus NIACE≥3(n=46),5.1(2.9–7.4)months,P<0.0001;and Bordeaux, NIACE<3(n=44),11.3(8.1–15.9)months versus NIACE≥3(n=75), 6.0(4.3–7.6)months,P<0.0001.The median duration of sorafenib ad-ministration in the four cohorts varied from2.2(0.7–4.1)months to4.2 (2.6–7.1)for patients with a NIACE score>3versus 6.0(3.9–13.1) months to9.9(6.8–21.5)months for patients with a NIACE score<3. The median survival of patients with NIACE score>3was similar to a group of untreated patients.Conclusion:In this multicenter series of HCC treated with sorafenib as a main treatment,NIACE score distin-guishes subgroups with different prognoses.Patients with a NIACE score>3do not seem to bene?t from treatment with sorafenib.

#1673Increasing incidence of and mortality by hepatocellular carcinoma and decreasing mortality by liver diseases in Korea:Nationwide

whole-population data analyses

Author:JIHYUN AN;YOUNG-SUK LIM;HYUNG DON KIM;GI-AE KIM

Affiliation:Department of Gastroenterology,Asan Liver Center,Asan Medical Center,University of Ulsan College of Medicine,Seoul,Korea

Background and Aims:The annual mortality rate by chronic liver diseases and hepatocellular carcinoma(HCC)that are associated with hepatitis B and C has been shown to be reduced by antiviral treatments.However, the prolonged life expectancy of patients with chronic viral hepatitis may in-crease the cumulative incidence of and mortality by HCC.Methods:Data on incidence rates of HCC were obtained from the Korea Central Cancer Registry,which compiles nationwide data on all newly diagnosed cancers. Data on cause-speci?c mortality and on liver transplantation were obtained from the Korean National Death Registry(Statistics Korea)and Korea Na-tional Organ Sharing,respectively.Results:The mean age at death by liver diseases and HCC signi?cantly increased between1998and2013(56.3vs 64.8years;β=0.65,P<0.001,and60.0vs63.9years;β=0.30, P<0.001,respectively).Between1998and2013,the mortality rate by liver diseases and viral hepatitis signi?cantly decreased(25.4/100000peo-ple vs14.7/100000people;β=à0.77,P<0.001).The incidence rate of and mortality rate by HCC signi?cantly increased during the same period (28.2/100000people vs32.9/100000people;β=0.45,P<0.001,and 20.0/100000people vs22.6/100000people;β=0.11,P=0.01).The trends in mortality rates by liver diseases and HCC were consistently observed af-ter adjusting for liver transplantation and mortality by alcoholic disease. Conclusions:During the recent15years when the antiviral treatments for hepatitis B and C have been introduced,life expectancy of patients with

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chronic liver disease has increased in Korea,a hepatitis B virus endemic area,which may be associated with the increasing cumulative incidence and mortality rates by HCC.These results suggest that HCC is becoming the main cause of death in patients with chronic viral hepatitis.

#1683Hepatocellular carcinoma,NIACE score:A simple tool to better distinguish patients at risk of relapse after surgery

Author:XAVIER ADHOUTE[1];GUILLAUME PENARANDA [2];JEAN LUC RAOUL[3];BERNARD POL[1];EMILIE BOLLON[4];HERVE PERRIER[1];PAUL CASTELLANI[1];JEAN HARDWIGSEN[4];YVES PATRICE LETREUT[4];MARC BOURLIERE[1]

Affiliations:[1]H?pital Saint –Joseph,Marseille,France [2]AlphaBio Laboratory,Marseille,France [3]Institut Paoli-Calmette,Marseille,France [4]Centre Hospitalo-Universitaire Conception,Marseille,France

Background:Surgery is the reference treatment of HCC.Despite patient selection being linked to underlying cirrhosis and late detection,patients ’prognosis is variable after surgery.NIACE score (which stands for nodules [N],in ?ltrative tumor [I],α-fetoprotein [AFP][A],Child –Pugh [C],Euro-pean Cooperative Oncology Group performance status [E])(American As-sociation for the Study of Liver Diseases 2014[P1329]and EASL 2015[P0376])allows us to de ?ne subgroups with different prognoses whatever the BCLC stage of HCC (A,B,or C)are.Aim of the Study:This study aimed to identify among operated HCC or HCC treated by radiofrequency ablation subgroups with different prognoses,using the NIACE score.Patients and Methods:We selected Barcelona Clinic Liver Cancer (BCLC)A,B,and C HCC patients treated by surgical resection in our ser-vice between 01/2007and 12/2013.We excluded patients who participated in the development of the NIACE score and those who are transplanted pa-tients.The results were con ?rmed in an external cohort treated exclusively by surgery.Likelihood ratio,Akaike information criterion,and area under the receiver operating curves were used to determine the best model.Results:Internal cohort included 104patients,with a median age of 71(58;75)years;patients were mostly cirrhotic (70%);related to viral etiol-ogies (40%),alcohol 19%,and metabolic syndrome 28%;and classi ?ed as Child –Pugh A (64%)and B (6%)and BCLC A (64%),B (28%),and C (8%).The median size of operated tumors was 30mm (25;57);7%of HCC were multi-nodular;20%of patients had an elevated AFP of ≥200ng/mL.The mean overall survival (OS)was 55.4±3.0months.The NIACE ≤1threshold is the one with the best likelihood ratio (13.2423,P =0.0003).Application of this threshold makes it possible to

discriminate between two groups having different mean OS (NIACE ≤1,66.3±2.6months,vs NIACE >1,25.7±2.9months,P <0.0001)and dif-ferent mean time until progression (NIACE ≤1,26.9±16.3months,vs NIACE >1,9.2±9.7months,P <0.0001).External cohort was made of 144BCLC A,B,and C HCC patients;the mean OS was 51.6±3.9months.By Applying a NIACE ≤1threshold,the mean OS of the NIACE ≤1group was 66±6versus 41±5months for the NIACE >1group,P <0.0001.The score also distinguished between two BCLC B HCC patient populations having signi ?cantly different median OS:50(27–78)versus 16(9–36)months,P =0.0002.Conclusion:There was a signi ?cant difference sur-vival between patients having a low score,which include not only BCLC A HCC but also BCLC B HCC,and the others patients.Without referring to the stage of the disease,survival is probably in ?uenced by the in ?ltrating nature of the tumor and a signi ?cantly high AFP level.NIACE is a simple score,which is able to distinguish between subgroups with different prog-noses,within an HCC population treated by surgery.

#1688Hepatectomy for malignancy con ?ned to segment VII

Author:CHIAH YANG CHAI[1];CHEN CHIA CHE[2];LI HUNG CHAI[3];CHOU CHIA CHENG[3];HSIEH YEI SAM [3];LIN MING HUI[3];HUANG CHIA HSUN[3];HSU KUEI[3]Affiliations:[1]Tao Yuan General Hospital,Taoyuan,Taiwan [2]Taipei Medical University Hospital,Taipei,Taiwan [3]Taoyuan General Hospital ,Ministry of Health and Welfare,Taoyuan,Taiwan

Introduction:Despite advancement in surgical technique,resection of he-patic malignancy located in Couinaud ’s segment VII remains challenging because of its deep location.Full mobilization of the right liver is necessary to facilitate resection.The most common surgical procedure for HCC is posterior sectionectomy and wedge resection for metastasis.Material and Method:Between August 2008and March 2015,127consecutive pa-tients received hepatectomy for HCC,metastasis,cholangiocarcinoma,and others.Twenty-seven patients received hepatectomy for malignancy con-?ned to segment VII.The operation procedure selected was based on back-ground liver function,tumor size,and tumor number.Result:Fifteen patients with HCC received posterior sectionectomy,and two patients with huge HCC had right hepatectomy.The remaining 10patients with metasta-sis received either wedge resection or posterior sectionectomy.Conclusion:For malignancy located in segment VII,full mobilization of the right liver is essential for safe hepatectomy.The procedure may range from wedge resection,posterior sectionectomy to right hepatectomy de-pending upon the background liver function.

Keywords:hepatectomy,posterior sectionectomy,segment VII.

#1690The effect of con ?uent hepatic ?brosis on hepatectomy

Author:LI HUNG CHAI[1];CHEN CHIA CHE[2];CHIAH YANG CHAI[3];CHOU CHIA CHENG[1];WANG CHI

CHAO[1];CHENG SHENG FANG[1];LAI CHUN YING[1];CHEN CHI FENG[1];LIU CHENG HUNG[1]

Affiliations:[1]Taoyuan General Hospital,Ministry of Health and Welfare,Taoyuan,Taiwan [2]Taipei Medical University Hospital,Taipei,Taiwan [3]Tao Yuan General Hospital,Taoyuan,

Taiwan

Figure 1

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Journal of Gastroenterology and Hepatology 2015;30(Suppl.4):323–407

?The Authors.Journal of Gastroenterology and Hepatology ?2015Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd

Introduction:Con?uent hepatic?brosis(CHF)is a mass-like?brosis seen in some patients with advanced?brosis.The morphological changes were attributed to selective volume reduction,especially middle hepatic venous (MHV)drainage area.The long length of MHV with its relatively large drainage area may account for the selective volume reduction.The topo-graphical change in the surface anatomy of such liver may cause confusion in major hepatectomy.Material and Method:Between August2008and March2015,127consecutive patients received hepatectomy for hepatocel-lular carcinoma(HCC),metastasis,cholangiocarcinoma,and others.Seven patients(5.5%)demonstrated CHF.All cases with CHF occur in HCC pa-tients.The correlation of preoperative imaging and the resected specimen was investigated.Result:The surface anatomy of the liver showed atrophic change with capsular retraction.It is mostly seen in the MHV drainage area.Conclusion:Topographic confusion may occur for hepatectomy of liver with CHF.Preoperative imaging study may provide useful informa-tion for distinction of surgical boundaries.

Keywords:con?uent hepatic?brosis,hepatectomy.

#1723The relationship of survival time and histopathologic diagnosis for hepatocellular carcinoma in a real-world practice

Authors:CHIEN-YUAN HUNG[1];TSANG-EN WANG[1,2]; CHING-CHUNG LIN[1,2];CHENG-HSIN CHU[2];

SHOU-CHUAN SHIH[2]

Affiliations:[1]Department of Medicine,MacKay Medical College,New Taipei,Taiwan[2]Division of Gastroenterology, Department of Internal Medicine,MacKay Memorial Hospital,Taipei,Taiwan

Background:Hepatocellular carcinoma(HCC)could be diagnosed with-out histopathology in certain circulation.The biopsy was suggested for atypical nodule by the American Association for the Study of Liver Dis-eases guideline.However,the correction of image diagnosis is not100%; some tumor may be mistaken and treated as HCC.Whether to perform bi-opsy became a debate issue in clinical practice.Did the biopsy for liver tu-mor affect the survival times in the patients?Aims:This study aimed to compare the relationship of survival time and histopathologic diagnosis in a real-world practice.Methods:Retrospectively,we reviewed patients who were diagnosed with primary HCC between2009and2012.The can-cer stage depended on the American Joint Committee on Cancer.The HCCs proven by surgical resection were excluded.Clinical data and sur-vival times of patients were analyzed by SPSS.Results:Five hundred and ninety-six patients were enrolled:group A(508,clinic diagnosis)and group B(88,histopathology).The mean age of patients was65.8±3.4years old.Patients’TNM stages were I(130),II(108),III(184), and IV(86)in group A and I(25),II(16),III(25),and IV(22)in group

B.The month of median survival time in groups A and B were I(48and

39),II(21and30),III(4and5)and IV(3and5),respectively. Conclusions:In this report,we found better survival in stage I without tis-sue diagnosis.We propose there were some patients with non-HCC tumor, which were treated as HCC.In contrast,middle-stage and later-stage pa-tients had prolonged survival time in biopsy group.They might have less comorbidity diseases and have tension to receive aggressive therapy.De-pending on this?nding,we suggested tissue diagnosis might be more im-portant in HCC diagnosis in the early stage.#1752Unusual presentation of metastatic thymic carcinoma in liver:A case report

Authors:HAO-WEN DAI[1];CHING-WEI CHANG[1–4]; CHIA-HSIEN WU[5];CHIA-YUAN LIU[1–4];MING-JEN CHEN[1–3];TSANG-EN WANG[1–3];CHENG-HSIN CHU [1–3];SHOU-CHUAN SHIH[1–3];CHIA-CHI TSAI[6]; WEN-CHIEN HUANG[7]

Affiliations:[1]Division of Gastroenterology,Department of Internal Medicine,MacKay Memorial Hospital,Taipei, Taiwan[2]Mackay Junior College of Medicine,Nursing,and Management,New Taipei City,Taiwan[3]Department of Medicine,MacKay Medical College,New Taipei City,Taiwan [4]Institute of Traditional Medicine,National Yang-Ming University,Taipei,Taiwan[5]Division of Gastroenterology, Department of Internal Medicine,MacKay Memorial Hospital,Taitung,Taiwan[6]Division of General Surgery, Department of Surgery,Mackay Memorial Hospital,Taipei City,Taiwan[7]Division of Thoracic Surgery,Department of Surgery,Mackay Memorial Hospital,Taipei City,Taiwan

A thymic carcinoma,basaloid type,is a rare neoplasm and also an unusual case with extra-thoracic metastasis.Most patients presented with dyspnea, chest pain,and cough initially.Asymptomatic patients account for less

than

Figure1Abdominal ultrasonography revealed one mix to hyperechoic tumor lesion around4.8×5.0cm in the right lobe of the liver,S5–S8.There is no obvious blood?ow in the liver tumor un-der Doppler

ultrasonography.

Figure2Abdominal CT revealed a5.5×4.4cm heterogeneous le-sion with central high density at hepatic subphrenic area.

Poster liver

342Journal of Gastroenterology and Hepatology2015;30(Suppl.4):323–407?The Authors.Journal of Gastroenterology and Hepatology?2015Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd

one-third in all cases.The clinical outcome for advanced stage of thymic carcinoma depends on complete resection.However,complete surgical re-section is not always possible in cases of advanced-stage thymic carcinoma because of local regional invasion.

We reported a 61-year-old man who had a medical history of neuro ?broma involving the thoracolumbar spine and underwent resection because of paraplegia in 2008and 2010.One hepatic mass was found accidentally by abdominal ultrasound on November 2014.

On abdominal ultrasonography,this huge mass was homogeneous hyperechogenicity (Fig.1).Computed tomography (CT)of the abdomen (Fig.2)presented that this metastatic mass had soft tissue density with

central calci ?cation.Fluorodeoxyglucose (FDG)positron emission tomog-raphy was performed to search for the primary site of malignancy,and lob-ulated FDG hypermetabolic lesions were located in the anterior mediastinum (Fig.3).Chest CT presented a lobulated soft tissue density mass with central necrosis,and perifocal lymphadenopathy occupied ante-rior mediastinum.The patient underwent resection of the thymic tumor followed by curative partial hepatectomy.It was proved to be thymic basaloid carcinoma with liver metastasis (Fig.4).After surgical interven-tion,he received concomitant chemoradiotherapy 1month later.The pa-tient was still alive 6months after the appearance of the liver

metastasis.

Figure 3Fluorodeoxyglucose positron emission tomography showing prominent thymus with cystic lesion in the left side and hypermeta-bolic lesions in the inner portion of the anterior

mediastinum.

Figure 4Photomicrograph showing

Poster liver

343

Journal of Gastroenterology and Hepatology 2015;30(Suppl.4):323–407

?The Authors.Journal of Gastroenterology and Hepatology ?2015Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd

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