Association between the early high level of serum tacrolimus and recurrence of hepatocellular carcinoma in ABO-incompatible liver transplantation

BACKGROUND Clinical factors predicting graft survival(GS)after ABO-incompatible(ABOi)liver transplantation(LT),and differences between recipients with and without hepatocellular carcinoma(HCC)are unclear.AIM To analyze the impact of serial serum tacrolimus trough concentration in recipients with or without(HCC)in ABOi living-donor liver transplantation(LDLT).METHODS We analyzed a historical cohort of 89 recipients who underwent ABOi LDLT,including 47 patients with HCC.RESULTS The 1-,3-,5-,and 10-year GS rates were 85.9%,73.3%,71.4%,and 71.4%,respectively,and there were no significant differences between HCC and non-HCC recipients.In multivariate Coxregression analyses,tacrolimus trough concentrations below 5.4 ng/mL at 24 wk post-LT,in addition to the antibody-mediated rejection(AMR)were associated with poor-graft outcomes.In HCC patients,AMR[hazard ratio(HR)=63.20,P<0.01]and HCC recurrence(HR=20.72,P=0.01)were significantly associated with poor graft outcomes.HCCs outside Milan criteria,and tacrolimus concentrations at 4 wk post-LT>7.3 ng/mL were significant predictive factors for HCC recurrence.After propensity score matching,patients with high tacrolimus concentrations at 4 wk had significantly poor recurrence-free survival.CONCLUSION Elevated tacrolimus levels at 4 wk after ABOi LDLT have been found to correlate with HCC recurrence.Therefore,careful monitoring and control of tacrolimus levels are imperative in ABOi LT recipients with HCC.

Diagnostic value of AFP-L3 and PIVKA-Ⅱin hepatocellular carcinoma according to total-AFP

AIM:To evaluate diagnostic value ofα-fetoprotein (AFP)-L3 and prothrombin induced by vitamin K absence-Ⅱ(PIVKA-Ⅱ)in hepatocellular carcinoma(HCC). METHODS:One hundred and sixty-eight patients during routine HCC surveillance were included in this study.Of the 168 patients,90(53.6%)had HCC including newly developed HCC(n=82)or recurrent HCC after treatment(n=8).Sera were obtained during their first evaluation for HCC development and at the time of HCC diagnosis before commencing HCC treatment.HCC was diagnosed by histological examination,appropriate imaging characteristics-computed tomography or magnetic resonance imaging.Control sera were collected from 78 patients with benign liver disease(BLD),which were obtained during routine surveillance with a suspicion of HCC.AFP,AFP-L3 and PIVKA-Ⅱwere measured in the same serum by microchip capillary electrophoresis and liquid-phase binding assay on a micro-total analysis system Wako i30 auto analyzer.The performance characteristics of three tests and combined tests for the diagnosis of HCC were obtained using receiver operating characteristic curves in all populations and subgroups with AFP<20 ng/mL. RESULTS:Of 90 HCC patients,38(42.2%)patients had AFP<20 ng/mL,20(22.2%)patients had AFP 20-200 ng/mL and 32(35.6%)patients had AFP>200 ng/mL.Of the 78 BLD patients,74(94.9%)patients had AFP<20 ng/mL.After adjustment for age and HBV infection status,AFP-L3 levels were higher in HCC than in BLD among patients with low AFP levels(<20 ng/mL)(P<0.001).In a total of 168 patients,areas under the curve(AUC)for HCC were 0.879,0.887,0.801 and 0.939 for AFP,AFP-L3,PIVKA-Ⅱand the combined markers,respectively.The combined AUC for three markers showed higher value than the AUCs of individual marker(P<0.05).AFP-L3 had higher AUC value than PIVKA-Ⅱfor HCC detection in entire patients(P =0.043).With combination of AFP-L3(cut-off>5%) and PIVKA-Ⅱ(cut-off>40 AU/L),the sensitivity were 94.4%and specificity were 75.6%in all patients.In 112 patients with low AFP levels(<20 ng/mL),AUCs of AFP-L3,PIVKA-Ⅱand combine AFP-L3 and PIVKA-Ⅱtests were 0.824,0.774 and 0.939,respectively. AFP-L3 with a cut-off value of 5%showed sensitivity of 71.1%and specificity of 83.8%,and PIVKA-Ⅱwith a cut-off value of 40 AU/L had sensitivity of 57.9%and specificity of 95.9%in patients with low AFP levels. The combination of AFP-L3 and PIVKA-Ⅱincreased the sensitivity and specificity up to 92.1%and 79.7%, respectively,in low AFP group.Combined markers detected 81.8%of early stage HCC(Union for Inter-national Cancer Control stageⅠ),86.7%of small sized tumor(<2 cm)and 91.7%of single tumor of HCC in the low AFP group.In multivariate analysis,AFP-L3 was correlated with AFP and tumor size,and PIVKA-Ⅱwas correlated with laboratory tests including serum aspartate aminotransferase,total bilirubin,platelets and albumin levels.PIVKA-Ⅱhad no correlation with AFP,AFP-L3 or tumor characteristics. CONCLUSION:Combined determination of AFP-L3 and PIVKA-Ⅱcould improve the diagnostic value for HCC detection in patients with or without increased AFP levels.

Family history influences the early onset of hepatocellular carcinoma

AIM: To evaluate the relationship between a positive family history of primary liver cancer and hepatocellular carcinoma (HCC) development in Korean HCC patients. METHODS: We studied a total of 2242 patients diagnosed with HCC between January 1990 and July 2008, whose family history of primary liver cancer was clearly described in the medical records.positive family history of HCC and 2077 (92.6%) did not. The male to female ratio was 3.6:1, and the major causes of HCC were chronic hepatitis B virus (HBV) infection in 75.1%, chronic hepatitis C virus infection in 13.2% and alcohol in 3.1%. The median ages at diag- nosis in the positiveand negative-history groups were 52 years (range: 29-79 years) and 57 years (range: 18-89 years), respectively (P < 0.0001). Furthermore, among 1713 HCC patients with HBV infection, the number of patients under 45 years of age out of 136 patients with positive family history was 26 (19.1%), whereas those out of 1577 patients with negative family history was 197 (12.5%), suggesting that a positive family history may be associated with earlier development of HCC in the Korean population (P = 0.0028). CONCLUSION: More intensive surveillance maybe recommended to those with a positive family history of HCC for earlier diagnosis and proper management especially when HBV infection is present.

Predictive value of ^(18)F-fluorodeoxyglucose PET/CT for transarterial chemolipiodolization of hepatocellular carcinoma

Myeong Jun Song,Si Hyun Bae,Chung-Hwa Park,Jeong Won Jang,Jong Young Choi,Seung Kew Yoon,Department of Internal Medicine,College of Medicine,The Catholic University of Korea,Seoul 137-040,South Korea Ie Ryung Yoo,Department of Nuclear,Medicine College of Medicine,The Catholic University of Korea,Seoul 137-040,South Korea Ho Jong Chun,Byung Gil Choi,Hae Giu Lee,Department of Radiology,College of Medicine,The Catholic University of Korea,Seoul 137-040,South

Durability of viral response after off-treatment in HBeAg positive chronic hepatitis B

AIM:To evaluate the durability in hepatitis B e antigen (HBeAg) positive chronic hepatitis B patients who discontinued antiviral treatment. METHODS:A total of 48 HBeAg positive chronic hepatitis B patients who were administered nucleoside analogues and maintained virological response for ≥ 6 mo [hepatitis B virus (HBV) DNA < 300 copies/mL and HBeAg seroconversion] before cessation of treatment were enrolled between February 2007 and January 2010. The criteria for the cessation of the antiviral treatment were defined as follows:(1) achievement of virological response; and (2) duration of consolidation therapy (≥ 6 mo). After treatment cessation, the patients were followed up at 3-6 mo intervals. The primary endpoint was serologic and virologic recurrence rates after withdrawal of antiviral treatment. Serologic recurrence was defined as reappearance of HBeAg positivity after HBeAg seroconversion. Virologic recurrence was defined as an increase in HBV-DNA level > 104 copies/mL after HBeAg seroconversion with previously undetectable HBV-DNA level. RESULTS:During the median follow-up period of 18.2 mo (range:5.1-47.5 mo) after cessation of antiviral treatment, the cumulative serological recurrence rate was 15 % at 12 mo. The median duration between the cessation of antiviral treatment and serologic recurrence was 7.2 mo (range:1.2-10.9 mo). Of the 48 patients with HBeAg positive chronic hepatitis, 20 (41.6%) showed virological recurrence. The cumulative virologic recurrence rates at 12 mo after discontinuing the antiviral agent were 41%. The median duration between off-treatment and virologic recurrence was 7.6 mo (range:4.3-27.1 mo). The mean age of the virological recurrence group was older than that of the non-recurrence group (46.7 ± 12.1 years vs 38.8 ± 12.7 years, respectively; P = 0.022). Age (> 40 years) and the duration of consolidation treatment (≥ 15 mo) were significant predictive factors for offtreatment durability in the multivariate analysis [P = 0.049, relative risk (RR) 0.31, 95% CI (0.096-0.998) and P = 0.005, RR 11.29, 95% CI (2.054-65.12), respectively]. Patients with age (≤ 40 years) who received consolidation treatment (≥ 15 mo) significantly showed durability in HBeAg positive chronic hepatitis B patients (P = 0.014). These results suggest that additional treatment for more than 15 mo after HBeAg seroconversion in patients who are ≤ 40 years old may be beneficial in providing a sustained virological response. CONCLUSION:Our data suggest that HBeAg seroconversion is an imperfect end point in antiviral treatment. Long-term consolidation treatment (≥ 15 mo) in younger patients is important for producing better prognosis in HBeAg positive chronic hepatitis B.

Outcome of transarterial chemoembolization-based multi-modal treatment in patients with unresectable hepatocellular carcinoma

AIM:To investigate the efficacy and safety of transarterial chemoembolization(TACE)-based multimodal treatment in patients with large hepatocellular carcinoma(HCC).METHODS:A total of 146 consecutive patients were included in the analysis,and their medical records and radiological data were reviewed retrospectively.RESULTS:In total,119 patients received TACE-based multi-modal treatments,and the remaining 27 received conservative management.Overall survival(P<0.001)and objective tumor response(P=0.003)were significantly better in the treatment group than in the conservative group.After subgroup analysis,survival benefits were observed not only in the multi-modal treatment group compared with the TACE-only group(P=0.002)but also in the surgical treatment group compared with the loco-regional treatment-only group(P<0.001).Multivariate analysis identified tumor stage(P<0.001)and tumor type(P=0.009)as two independent pre-treatment factors for survival.After adjusting for significant pre-treatment prognostic factors,objective response(P<0.001),surgical treatment(P=0.009),and multi-modal treatment(P=0.002)were identified as independent post-treatment prognostic factors.CONCLUSION:TACE-based multi-modal treatments were safe and more beneficial than conservative management.Salvage surgery after successful downstaging resultedin long-term survival in patients with large,unresectable HCC.

Epirubicin,Cisplatin,5-FU combination chemotherapy in sorafenib-refractory metastatic hepatocellular carcinoma

AIM:To evaluate the clinical efficacy and safety of epirubicin,cisplatin,and 5-FU combination chemotherapy for the sorafenib-refractory metastatic hepatocellular carcinoma(HCC).METHODS:From April 2009 to June 2012,31 patients who were diagnosed with metastatic and progressive HCC after sorafenib treatment were retrospectively reviewed.Patients were treated with the combination of epirubicin(50 mg/m2Ⅳ;day 1),cisplatin(60 mg/m2Ⅳ;day 1),and 5-FU(1000 mg/m2Ⅳ;day 1-3)[Epirubicin,cisplatin,5-FU combination(ECF)],repeated every 4 wk.RESULTS:The overall response rate was 12.9%.Patients who responded to ECF chemotherapy showed a longer overall survival(OS)and time to progression(TTP)relative to those in the non-responder group(OS:20.4 mo vs 4.9 mo,P<0.001,TTP:9.4 mo vs 2.2 mo,P<0.001).Patients with a stable primary liver mass also exhibited a longer OS and TTP relative to those with progressive disease(OS:13.4 mo vs 5.3 mo,P=0.003;TTP:9.4 mo vs 2.3 mo,P=0.003).The most common hematologic toxicity was thrombocytopenia(87.2%),and the incidence of grade 3-4 neutropenia was 53.9%.Age older than 60,a stable primary mass,and a good response to chemotherapy were prognostic factors for OS and TTP.CONCLUSION:This combination cytotoxic chemotherapy can serve as another treatment option after sorafenib failure for the subset of patients with advanced metastatic HCC.

Hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis

AIM: To evaluate the prognostic factors and efficacy of hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis. METHODS: Fifty hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) were treated using hepatic arterial infusion chemotherapy (HAIC) via a subcutaneously implanted port. The epirubicin-cisplatin-5-fluorouracil (ECF) chemotherapeutic regimen consisted of 35 mg/m 2 epirubicin on day 1, 60 mg/m 2 cisplatin for 2 h on day 2, and 500 mg/m 2 5-fluorouracil for 5 h on days 1-3. The treatments were repeated every 3 or 4 wk. RESULTS: Three (6%) of the 50 patients achieved a complete response (CR), 13 (26%) showed partial responses (PR), and 22 (44%) had stable disease (SD).The median survival and time to progression were 7 and 2 mo, respectively. After 2 cycles of HAIC, CR was achieved in 1 patient (2%), PR in 10 patients (20%) and SD in 26 patients (52%). Significant pre-treatment prognostic factors were a tumor volume of < 400 cm 3 (P = 0.01) and normal levels of protein induced by vitamin K absence or antagonist (PIVKA)-Ⅱ (P = 0.022). After 2 cycles of treatment, disease control (CR + PR + SD) (P = 0.001), PVTT response (P = 0.003) and α-fetoprotein reduction of over 50% (P = 0.02) were independent factors for survival. Objective response (CR + PR), disease control, PVTT response, and combination therapy during the HAIC were also significant prognostic factors. Adverse events were tolerable and successfully managed. CONCLUSION: HAIC may be an effective treatment modality for advanced HCC with PVTT in patients with tumors < 400 cm 3 and good prognostic factors.

Risk factors of biliary intervention by imaging after livingdonor liver transplantation

AIM:To determine the risk factors of biliary intervention using magnetic resonance cholangiopancreatography(MRCP) after living donor liver transplantation(LDLT).METHODS: We retrospectively enrolled 196 patients who underwent right lobe LDLT between 2006 and 2010 at a single liver transplantation center. Direct duct-to-duct biliary anastomosis was performed in all 196 patients. MRCP images routinely taken 1 mo after LDLT were analyzed to identify risk factors for biliary intervention during follow-up, such as retrograde cholangiopancreatography or percutaneous transhepatic biliary drainage. Two experienced radiologists evaluated the MRCP findings, including the anastomosis site angle on three-dimensional images, the length of the filling defect on maximum intensity projection, bile duct dilatation, biliary stricture, and leakage.RESULTS: Eighty-nine patients underwent biliary intervention during follow-up. The anastomosis site angle [hazard ratio(HR) = 0.48; 95% confidence interval(CI), 0.30-0.75, P < 0.001], a filling defect in the anastomosis site(HR = 2.18, 95%CI: 1.41-3.38,P = 0.001), and biliary leakage(HR = 2.52, 95%CI: 1.02-6.20, P = 0.048) on MRCP were identified in the multivariate analysis as significant risk factors for biliary intervention during follow-up. Moreover, a narrower anastomosis site angle(i.e., below the median angle of 113.3°) was associated with earlier biliary intervention(38.5 ± 4.2 mo vs 62. 1 ± 4.1 mo, P < 0.001). Kaplan-Meier analysis comparing biliary intervention-free survival according to the anastomosis site angle revealed that lower survival was associated with a narrower anastomosis site angle(36.3% vs 62.0%, P < 0.001).CONCLUSION: The biliary anastomosis site angle in MRCP after LDLT may be associated with the need for biliary intervention.

Low skeletal muscle mass is associated with non-alcoholic fatty liver disease in Korean adults： the Fifth Korea National Health and Nutrition Examination Survey

BACKGROUND： Sarcopenia and non-alcoholic fatty liver dis- ease （NAFLD） share similar pathophysiological mechanisms, and the relationship between sarcopenia and NAFLD has been recently investigated. The study investigated whether low skel- etal muscle mass is differentially associated with NAFLD by gender in Korean adults. METHODS： We conducted a cross-sectional analysis of the data from the Fifth Korea National Health and Nutrition Examination Survey. The skeletal muscle index （SMI） was obtained by the appendicular skeletal muscle mass divided by the weight. NAFLD was defined as a fatty liver index （FLI） 〉60 in the absence of other chronic liver disease. RESULTS： Among the included subjects, 18.3% （SE： 1.4%） in men and 7.0% （SE： 0.7%） in women were classified as having FLI-defined NAFLD. Most of the risk factors for FLI-defined NAFLD showed a significant negative correlation with the SMI in both genders. Multiple logistic regression analysis showed that low SMI was associated with FLI-defined NAFLD, inde- pendent of other metabolic and lifestyle parameters in both genders [males： odds ratio （OR）=1.35; 95% confidence inter- val （CI）： 1.17-1.54; females： OR=1.36; 95% CI： 1.18-1.55]. The magnitude of the association between FLI-defined NAFLD and low SMI was higher in middle aged to elderly males （OR-1.50; 95% CI： 1.22-1.84） than in males less than 45 years of age （OR=1.25; 95% CI： 1.02-1.52） and in premenopausal females （OR=l.50; 95% CI： 1.12-2.03） than in postmenopausal females （OR-1.36; 95% CI： 1.20-1.54）.CONCLUSIONS： Low SMI is associated with the risk of FLI- defined NAFLD independent of other well-known metabolic risk factors in both genders. This association may differ ac- cording to age group or menopausal status. Further studies are warranted to confirm this relationship.

Comparative study of rendezvous techniques in post-liver transplant biliary stricture

AIM:To investigate the usefulness of a new rendezvous technique for placing stents using the Kumpe(KMP) catheter in angulated or twisted biliary strictures.METHODS:The rendezvous technique was performed in patients with a biliary stricture after living donor liver transplantation(LDLT) who required the exchange of percutaneous transhepatic biliary drainage catheters for inside stents.The rendezvous technique was performed using a guidewire in 19 patients(guidewire group) and using a KMP catheter in another 19(KMP catheter group).We compared the two groups retrospectively.RESULTS:The baseline characteristics did not differ between the groups.The success rate for placing inside stents was 100% in both groups.A KMP catheter was easier to manipulate than a guidewire.The mean procedure time in the KMP catheter group(1012 s,range:301-2006 s) was shorter than that in the guidewire group(2037 s,range:251-6758 s,P = 0.022).The cumulative probabilities corresponding to the procedure time of the two groups were significantly different(P = 0.008).The factors related to procedure time were the rendezvous technique method,the number of inside stents,the operator,and balloon dilation of the stricture(P < 0.05).In a multivariate analysis,the rendezvous technique method was the only significant factor related to procedure time(P = 0.010).The procedural complications observed included one case of mild acute pancreatitis and one case of acute cholangitis in the guidewire group,and two cases of mild acute pancreatitis in the KMP catheter group.CONCLUSION:The rendezvous technique involving use of the KMP catheter was a fast and safe method for placing inside stents in patients with LDLT biliary stricture that represents a viable alternative to the guidewire rendezvous technique.

Short-term overlap lamivudine treatment with adefovir dipivoxil in patients with lamivudine-resistant chronic hepatitis B

AIM:To evaluate the efficacy of short-term overlap lamivudine therapy with adefovir in patients with lamivudine-resistant and nave chronic hepatitis B,we compared patients receiving overlap therapy with those receiving adefovir alone. METHODS:Eighty patients who had received lamivudine treatment for various periods and had a lamivudine- resistant liver function abnormality were enrolled.Forty of these patients received adefovir treatment combined with lamivudine treatment for≥2 mo,while the other 40 received adefovir alone.We assessed the levels of hepatitis B virus(HBV)DNA at 0,12 and 48 wk and serum alanine aminotransferase(ALT)levels after 0,12, 24 and 48 wk of adefovir treatment in each group. RESULTS:We found serum ALT became normalized in 72(87.5%)of the 80 patients,and HBV DNA decreased by≥2 log10 copies/mL in 60(75%)of the 80 patients at the end of a 48-wk treatment.HBV DNA levels were not significantly different between the groups.The improvements in serum ALT were also not significantly different between the two groups. CONCLUSION:These findings suggest short-term overlap lamivudine treatment results in no better virological and biological outcomes than non-overlap adefovir monotherapy.

Severe thrombocytopenia before liver transplantation is associated with delayed recovery of thrombocytopenia regardless of donor type

AIM: To compare the recovery of thrombocytopenia and splenomegaly during long-term follow-up after liver transplantation in patients receiving a living donor transplant or a cadaveric donor transplant. METHODS: This was a retrospective cohort study of 216 consecutive liver transplant patients who survived for > 6 mo after transplantation; 169 received a liver transplant from a living donor and 47 from a cadaveric donor. The platelet counts or spleen volumes were examined before transplant, 1, 6, and 12 mo after transplant, and then annually until 5 years after transplant. RESULTS: The mean follow-up period was 49 mo (range, 21-66). Platelet counts increased continu-ously for 5 years after orthotopic liver transplant. The restoration of platelet counts after transplant was sig-nificantly slower in patients with severe pretransplant thrombocytopenia (< 50 000/μL) until 4 years after transplant (P = 0.005). Donor type did not significantly affect the recovery of platelet count and spleen vol-ume in either patient group. In multivariate analysis, pretransplant severe thrombocytopenia (< 50 000/μL) was an independent factor associated with sustained thrombocytopenia (P < 0.001, odds ratio 6.314; con-fidence interval, 2.828-14.095). Thrombocytopenia re-appeared after transplant in seven patients with portal flow disturbance near the anastomosis site. CONCLUSION: Our study suggests that severe throm-bocytopenia before transplant is closely associated with delayed recovery of platelet count after transplant and donor type did not affect the recovery of throm-bocytopenia. The reappearance of thrombocytopenia after transplant should be considered a possible indica-tor of flow disturbance in the portal vein.

Transarterial chemoembolization in Barcelona Clinic Liver Cancer Stage 0/A hepatocellular carcinoma

AIM:To evaluate the clinical characteristics of patients with Barcelona Clinic Liver Cancer(BCLC)stage 0 and A hepatocellular carcinoma(HCC)after transarterial chemoembolization(TACE).METHODS:Between January 2001 and September2011,129 patients with BCLC stage 0 and stage A HCC who underwent TACE were retrospectively enrolled.Patient characteristics,routine computed tomography and TACE findings,survival time and 1-,5-,and 10-year survival rates,risk factors for mortality,and survival rates according to the number of risk factors were assessed.RESULTS:The mean size of HCC tumors was 2.4±1.1 cm,and the mean number of TACE procedures performed was 2.5±2.1.The mean overall survival time and 1-,5-,and 10-year survival rates were 80.6±4.9 mo and 91%,63%and 49%,respectively.In the Cox regression analysis,a Child-Pugh score>5(P=0.005,OR=3.86),presence of arterio-venous shunt(P=0.032,OR=4.41),amount of lipiodol used(>7 mL;P=0.013,OR=3.51),and female gender(P=0.008,OR=3.47)were risk factors for mortality.The 1-,5-,and 10-year survival rates according to the number of risk factors present were 96%,87%and 87%(no risk factors),89%,65%,and 35%(1 risk factor),96%,48%and unavailable(2 risk factors),and 63%,17%,and 0%(3 risk factors),respectively(P<0.001).CONCLUSION:TACE may be used as curative-intent therapy in patients with BCLC stage 0 and stage A HCC.The Child-Pugh score,arterio-venous shunt,amount of lipiodol used,and gender were related to mortality after TACE.

A Decade-old Change in the Screening Rate for Hepatocellular Carcinoma Among a Hepatitis B Virus-infected Population in Korea

Background： Evaluating a change in the screening rate for hepatocellular carcinoma （HCC） is critical for understanding screening implementation, and whether targeted population groups are receiving proper screening. This study examined recent nationwide changes in HCC screening use among hepatitis B virus （HBV）-infected populations after the introduction of the Korean National Cancer Screening Program and predictors of screening adherence. Methods： We analyzed 165 and 276 participants 〉40 years of age who were hepatitis B surface antigen-positive fiom 2001 （14,936 participants） to 2010-2011 （9159 participants） Korea National Health and Nutrition Examination Surveys, respectively. Demographic data, socioeconomic factors, and HCC screening use were collected by means of self-reported questionnaires. Results： The rate of HCC screening within the previous 2 years increased significantly from 17.5% in 2001 to 40.3% in 2010- 20I 1 （P〈 0.0001 ）. The rate of HCC screening use increased from 2001 to 2010-2011 in all study populations. Subjects who had a higher income staius and were aware of their infection were more likely to have undergone recent HCC screening. Conclusions： This study showed a substantial increase in HCC screening in high-risk HBV-infected subjects from 2001 to 2010-2011. However, the HCC screening participation rate remained suboptimal despite the introduction of the nationwide screening program. Efforts should be made to identiry high-risk individuals and increase attendance at HCC screening events among high-risk groups.

Relative skeletal muscle mass and non-alcoholic fatty liver disease: from association to causation

The prevalence of nonalcoholic fatty liver disease(NAFLD)and its associated metabolic risk factors,including obesityand metabolic syndrome,have increased over the lastdecade in both developed and developing countries(1).NAFLD is considered to be the hepatic manifestation ofmetabolic syndrome and insulin resistance which is oneof multiple hits leading to NAFLD(2).