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Nonalcoholic steatohepatitis (NASH) is increasingly recognized as a serious disease that can lead to cirrhosis, hepatocellular carcinoma (HCC), and death. However, there is no effective drug to thwart the progression of the disease. Development of new drugs for NASH is an urgent clinical need. Liver biopsy plays a key role in the development of new NASH drugs. Histological findings based on liver biopsy are currently used as the main inclusion criteria and the primary therapeutic endpoint in NASH clinical trials. However, there are inherent challenges in the use of liver biopsy in clinical trials, such as evaluation reliability, sampling error, and invasive nature of the procedure. In this article, we review the advantages and value of liver histopathology based on liver biopsy in clinical trials of new NASH drugs. We also discuss the challenges and limitations of liver biopsy and identify future drug development directions.

Background & Aim Hepatitis B reactivation related to the use of immunosuppressive therapy remains a major cause of liver-related morbidity and mortality in hepatitis B endemic Asia-Pacific region. This clinical practice guidelines aim to assist clinicians in all disciplines involved in the use of immunosuppressive therapy to effectively prevent and manage hepatitis B reactivation. Methods All publications related to hepatitis B reactivation with the use of immunosuppressive therapy since 1975 were reviewed. Advice from key opinion leaders in member countries/administrative regions of Asian-Pacific Association for the study of the liver was collected and synchronized. Immunosuppressive therapy was risk-stratified according to its reported rate of hepatitis B reactivation. Recommendations We recommend the necessity to screen all patients for hepatitis B prior to the initiation of immunosuppressive therapy and to administer pre-emptive nucleos(t)ide analogues to those patients with a substantial risk of hepatitis and acute-on-chronic liver failure due to hepatitis B reactivation.

OBJECTIVES To validate the operational and diagnostic performances of a new device for transient elastography (TE), FibroTouch, for liver fibrosis in patients with chronic hepatitis B (CHB). METHODS In this prospective multicenter study, adult patients with CHB and valid liver pathological results were recruited to validate the operational and diagnostic performance of a TE device by FibroTouch for staging liver fibrosis. RESULTS In total, 517 patients with histologically proven CHB were enrolled. All had achieved at least 10 successful liver stiffness measurements (LSM), resulting in a success rate of 99.1% and reliable evaluations of 95.2%. Altogether 412 patients were included to analyze the diagnostic performance of FibroTouch. The area under the receiver operating characteristic curve for the LSM was 0.846 (95% confidence interval [CI] 0.808-0.880) for fibrosis stage ≥ F1, 0.850 (95% CI 0.811-0.883) for ≥ F2, 0.908 (95% CI 0.876-0.934) for ≥ F3 and 0.874 (95% CI 0.836-0.903) for F4. The diagnostic accuracy of LSM was superior to that of gamma-glutamyl transpeptidase-to-platelet ratio (GPR), aminotransferase-to-platelet ratio index (APRI), or fibrosis index based on 4 factors (FIB-4) index in staging fibrosis F2-F4 (P = 0.007 to

Background and Aim In China, clinical experience with direct‐acting antiviral treatments for hepatitis C virus (HCV) infection is still emerging. C‐CORAL is a phase 3, multinational, placebo‐controlled, double‐blind trial of elbasvir/grazoprevir (EBR/GZR) in participants with HCV infection from the Asia‐Pacific region and Russia. Here, we report the data from participants enrolled in China. Methods Treatment‐naive participants with chronic HCV genotype (GT) 1, GT4, or GT6 infection were randomly assigned to receive 50 mg EBR/100 mg GZR for 12 weeks (immediate‐treatment group, ITG) or placebo followed by deferred treatment with EBR/GZR (deferred‐treatment group, DTG). The primary efficacy end‐point was sustained virologic response at 12 weeks after completing treatment (SVR12), and the primary safety end‐point was a comparison of safety between participants receiving EBR/GZR and placebo (NCT02251990; Protocol PN‐5172‐067). Results A total of 152 participants in China were randomly assigned (ITG, n = 115; DTG, n = 37). SVR12 was achieved in 96.7% (146/151) participants overall and in 97.3% (142/146) of those with GT1b infection. Four participants relapsed (GT1b, n = 3; GT6a, n = 1). Drug‐related AEs were reported in 25 (21.7%) and 9 (24.3%) participants receiving EBR/GZR and placebo, respectively; no drug‐related serious adverse events (AEs) occurred. Two (1.7%) participants receiving EBR/GZR had late hepatic transaminase elevations. Patient‐reported outcomes indicate improved quality of life at follow‐up week 4 in participants receiving EBR/GZR compared to placebo. Conclusion EBR/GZR administered for 12 weeks represents a highly effective and safe treatment option for Chinese individuals with HCV GT1 infection., A sustained virologic response was achieved by 96.7% (146/151) of treatment‐naive participants with hepatitis c virus infection receiving elbasvir/grazoprevir (50 mg/100 mg) for 12 weeks. Patient‐reported outcomes indicate improved quality of life following clearance of HCV.

Primary biliary cholangitis (PBC) patients often have concomitant extrahepatic autoimmune (EHA) diseases including Sjögren's syndrome (SS), systemic sclerosis (SSc), rheumatoid arthritis (RA), and autoimmune thyroid disease. The present study aimed to describe the prevalence of EHA diseases in PBC and explore the impact of EHA diseases on the long-term outcomes of PBC in Chinese patients.Medical records of PBC patients diagnosed in our institute were retrospectively reviewed. Patients were followed up by a standardized telephone interview. The endpoints were defined as liver-related death and/or liver transplantation.Totally 247 of the 985 (25.1%) PBC patients enrolled in the study had at least one concomitant EHA disease. Sjögren's syndrome (n = 140, 14.2%) was the most frequent one, followed by rheumatoid arthritis (RA) (n = 56, 5.7%) and Hashimoto's thyroiditis (n = 45, 4.6%). Patients with EHA diseases were more common in females (P0.001) and in those with a family history of autoimmune disease (P = 0.017). Overall, no differences were found between PBC patients with and without EHA diseases in terms of biochemical response rates to ursodeoxycholic acid, the incidence of hepatic events, or transplant-free survival. RA and EHA ≥ 2 were protective factors for hepatic events in univariate Cox analysis, but the results became insignificant in multivariate analysis.Concomitant EHA diseases were common in PBC patients but did not compromise the long-term outcomes of PBC.

The Chinese Society of Hepatology developed the current guidelines on the management of hepatic encephalopathy in cirrhosis based on the published evidence and the panelists’ consensus. The guidelines provided recommendations for the diagnosis and management of hepatic encephalopathy (HE) including minimal hepatic encephalopathy (MHE) and overt hepatic encephalopathy, emphasizing the importance on screening MHE in patients with end-stage liver diseases. The guidelines emphasized that early identification and timely treatment are the key to improve the prognosis of HE. The principles of treatment include prompt removal of the cause, recovery of acute neuropsychiatric abnormalities to baseline status, primary prevention, and secondary prevention as soon as possible.

OBJECTIVES Acute insults from viruses, infections, or alcohol are established causes of decompensation leading to acute-on-chronic liver failure (ACLF). Information regarding drugs as triggers of ACLF is lacking. We examined data regarding drugs producing ACLF and analyzed clinical features, laboratory characteristics, outcome, and predictors of mortality in patients with drug-induced ACLF. METHODS We identified drugs as precipitants of ACLF among prospective cohort of patients with ACLF from the Asian Pacific Association of Study of Liver (APASL) ACLF Research Consortium (AARC) database. Drugs were considered precipitants after exclusion of known causes together with a temporal association between exposure and decompensation. Outcome was defined as death from decompensation. RESULTS Of the 3,132 patients with ACLF, drugs were implicated as a cause in 329 (10.5%, mean age 47 years, 65% men) and other nondrug causes in 2,803 (89.5%) (group B). Complementary and alternative medications (71.7%) were the commonest insult, followed by combination antituberculosis therapy drugs (27.3%). Alcoholic liver disease (28.6%), cryptogenic liver disease (25.5%), and non-alcoholic steatohepatitis (NASH) (16.7%) were common causes of underlying liver diseases. Patients with drug-induced ACLF had jaundice (100%), ascites (88%), encephalopathy (46.5%), high Model for End-Stage Liver Disease (MELD) (30.2), and Child-Turcotte-Pugh score (12.1). The overall 90-day mortality was higher in drug-induced (46.5%) than in non-drug-induced ACLF (38.8%) (P = 0.007). The Cox regression model identified arterial lactate (P < 0.001) and total bilirubin (P = 0.008) as predictors of mortality. DISCUSSION Drugs are important identifiable causes of ACLF in Asia-Pacific countries, predominantly from complementary and alternative medications, followed by antituberculosis drugs. Encephalopathy, bilirubin, blood urea, lactate, and international normalized ratio (INR) predict mortality in drug-induced ACLF.

Liver fibrosis has been increasingly recognized as a cause for high morbidity and mortality of some diseases in humans. Herbal medicines have received great attention due to their low side effects and high safety. Herbal compound 861 (Cpd 861) has been effectively used for treating hepatic fibrosis for long time. Yet, its exact mechanism is still in fancy. Herein, we first established a liver fibrosis model by bile duct ligation (BDL), which led to the toxic accumulation of bile acids in animals, resulting in hepatic fibrosis. A serum metabonomics study on BDL-induced liver fibrosis rats after Cpd 861 treatment was performed using UHPLC-QTOF/MS. Multivariate analysis showed that Cpd 861 significantly reversed the metabolic perturbation induced by BDL to normal state, which is in agreement with the serum biochemical and histopathological findings. 15 metabolites were screened as potential biomarkers. Eight metabolic pathways were recognized as the most relevant pathways, involving dysfunction of amino acids metabolism and synthesis, fatty acid metabolism, phospholipids metabolism, and others. This is the first study to reveal the underlying mechanism of Cpd 861 based on metabonomics, which is complementary to biochemical analysis, and more importantly, a potentially powerful tool to interpret the mechanisms of extremely complex systems.

BACKGROUND: To evaluate the impact of steatosis and/or idiopathic portal inflammation (IPI) in living donor livers on recipients’ clinical outcomes. METHODS: We assessed 305 qualified donor liver samples from June 2013 to December 2018. Donors and recipients’ clinical characteristics, including follow-up data were retrieved. The graft and overall survival with/without steatosis or portal inflammation were compared by Kaplan-Meier analysis. RESULTS: For living donors, the medium age of was 31.2 (28, 35.8) years old; liver histopathology showed macrovesicular steatosis: 0–5% 264/305 (86.6%) and 5–30% 41/305 (13.4%), IPI: no 220/305 (72.1%) and mild 85/305 (27.9%). For recipients, the medium age was 1.0 (0.6, 1.5) years old; the median pediatric-end-stage-liver-disease score was 16 (5.0, 26.0) and medium follow-up time was 32.8 (24.8, 52.0) months. Biliary atresia (69.5%) was the main indication for liver transplantation (LT). CONCLUSIONS: The presence of steatosis and portal inflammation of the donor liver did not impact the clinical outcomes including transaminase or bilirubin normalization, short-/long-term complications and recipients’ survival. However, recipients with high pediatric-end-stage-liver-disease score (>16) receiving donor liver with portal inflammation, but not steatosis, had trend negative effect on recipients’ survival. In conclusion, donor livers with mild steatosis and portal inflammation were qualified for pediatric living donor LT. However, donor liver with mild portal inflammation would better not be allocated to recipients with high pediatric-end-stage-liver-disease score. This study provided new evidence in pediatric living donor liver allocation.

Hepatic fibrosis is a reparative response of diffuse over-deposition and abnormal distribution of extracellular matrix (collagen, glycoprotein and proteoglycans) after exposure to various kinds of liver injuries, and is a key step in the developmental process of various chronic liver diseases leading to cirrhosis. Recently, many advances in our understanding of hepatic fibrosis have been obtained through basic and clinical research. Therefore, this consensus summarizes and offers 15 evidence-based recommendations on the diagnosis and evaluation of hepatic fibrosis, its treatment, drug development and applications.

Objective We aimed to estimate the optimal cut-off values of liver stiffness measurement (LSM) for diagnosing and staging fibrosis in non-obese and obese patients with nonalcoholic fatty liver disease (NAFLD). Methods NAFLD patients diagnosed by liver biopsy according to the Nonalcoholic Steatohepatitis Clinical Research Network scoring system were enrolled in this study. Non-obesity was defined as a body mass index (BMI) less than 25 kg/m2 . LSM was performed by experienced physicians within 2 weeks before or after liver biopsy. Results A total of 158 patients were included. Average BMI of the non-obese (n = 68) and obese (n = 90) groups was 23.2 ± 1.6 and 27.9 ± 2.5 kg/m2 , respectively. After adjusted for age, fibrosis stage, steatosis grade and type 2 diabetes mellitus, the obese group had a LSM of 3.522 kPa higher than the non-obese patients (P = 0.003). LSM values of the non-obese patients had a lower trend when stratified by fibrosis stage, especially in cirrhosis (F4; P = 0.021). Applying separate cut-off values for patients with NAFLD in individual fibrosis stage, 5.8 vs 7.5 kPa (≥ F1), 7.6 vs 8.5 kPa (≥ F2), 9.1 vs 11.2 kPa (≥ F3), and 12.5 vs 14.3 kPa (F4), improved their diagnostic odds ratios compared with overall cut-off values. In the non-obese NAFLD group, using a separate cut-off avoided underestimating 9.1% of patients with cirrhosis. Conclusions Non-obese NAFLD group had lower LSM than the obese group. Different cut-off values should be used to measure liver fibrosis stage in non-obese and obese NAFLD patients.

Acute-on-chronic liver failure (ACLF) is a progressive disease associated with rapid clinical worsening and high mortality. Early prediction of mortality and intervention can improve patient outcomes. We aimed to develop a dynamic prognostic model and compare it with the existing models. A total of 1402 ACLF patients, enrolled in the APASL-ACLF Research Consortium (AARC) with 90-day follow-up, were analyzed. An ACLF score was developed in a derivation cohort (n = 480) and was validated (n = 922). The overall survival of ACLF patients at 28 days was 51.7%, with a median of 26.3 days. Five baseline variables, total bilirubin, creatinine, serum lactate, INR and hepatic encephalopathy, were found to be independent predictors of mortality, with AUROC in derivation and validation cohorts being 0.80 and 0.78, respectively. AARC-ACLF score (range 5–15) was found to be superior to MELD and CLIF SOFA scores in predicting mortality with an AUROC of 0.80. The point scores were categorized into grades of liver failure (Gr I: 5–7; II: 8–10; and III: 11–15 points) with 28-day cumulative mortalities of 12.7, 44.5 and 85.9%, respectively. The mortality risk could be dynamically calculated as, with each unit increase in AARC-ACLF score above 10, the risk increased by 20%. A score of ≥11 at baseline or persisting in the first week was often seen among nonsurvivors (p = 0.001). The AARC-ACLF score is easy to use, dynamic and reliable, and superior to the existing prediction models. It can reliably predict the need for interventions, such as liver transplant, within the first week.

Objective Since July 1, 2011 antiviral therapy for hepatitis B virus infection has been listed as a reimbursable expense for medical insurance in Beijing. This study aimed to assess the impact of this program on liver-related death for patients with chronic hepatitis B (CHB). Methods Profiles of patients with CHB discharged between January 2008 and December 2015 were retrieved from the Beijing hospital discharge database. Liver-related deaths in these patients occurring between January 2008 and December 2017 were retrieved by linking them to the death certification database. Liver-related mortality (number of deaths divided by the observed person-years) before and after this program was launched was calculated and compared. A Poisson regression was performed to assess the strength of association (risk ratio [RR]) between the reimbursement program and liver-related mortality. Results Information on 35 943 discharged patients (17 114 patients with non-cirrhotic and 18 829 with compensated cirrhotic CHB) was retrieved. Altogether 3 832 liver-related deaths during the 190 695 person-years were observed. After the reimbursement program was launched, liver-related mortality per 100 person-years dropped from 0.38% to 0.16% for patients with non-cirrhotic CHB, and from 4.03% to 3.39% for those with compensated cirrhosis. The program was associated with a lower risk of developing liver-related death for patients with non-cirrhotic CHB (RR 0.40, 95% confidence interval [CI] 0.30-0.52) and those with compensated cirrhosis (RR 0.84, 95% CI 0.78-0.89). Conclusion Coverage of antiviral therapy by basic medical insurance reduced the risk of developing liver-related death for patients with non-cirrhotic and with compensated cirrhotic CHB.

BACKGROUND AND AIM Although treatment with direct-acting antivirals has dramatically improved morbidity and mortality attributable to chronic hepatitis C virus infection, universal access to these medicines has been slow in the Asia-Pacific region and Russia. This study evaluated efficacy and safety of elbasvir/grazoprevir in participants with hepatitis C virus infection from Asia-Pacific countries and Russia (C-CORAL). METHODS C-CORAL was a phase 3, randomized, placebo-controlled study (NCT02251990). Treatment-naive, HIV-negative, cirrhotic and non-cirrhotic participants with chronic hepatitis C genotype 1, 4, or 6 infection were randomized to elbasvir 50 mg/grazoprevir 100 mg once daily for 12 weeks (immediate-treatment group) or placebo followed by deferred treatment with elbasvir/grazoprevir (deferred-treatment group). The primary efficacy outcome was sustained virologic response at 12 weeks, and the primary safety outcome was a comparison between the immediate-treatment group and placebo phase of the deferred-treatment group. RESULTS A total of 489 participants were randomized (immediate-treatment group, n = 366; deferred-treatment group, n = 123). Sustained virologic response at 12 weeks in the combined immediate/deferred-treatment groups was 94.4% (459/486; 95% confidence interval = 92.4-96.5%). Sustained virologic response at 12 weeks was 98.2% in participants with genotype 1b, 91.9% with genotype 1a, and 66.7% with genotype 6 infection. Similar rates of adverse events and drug-related adverse events were seen in the immediate-treatment group versus placebo phase of the deferred-treatment group (51.0% vs 50.4% and 21.4% vs 21.1%). CONCLUSIONS Elbasvir/grazoprevir for 12 weeks represents an effective and well-tolerated treatment option for treatment-naive people with genotype 1 infection from Asia-Pacific countries and Russia.

Non-alcoholic steatohepatitis (NASH) is a serious form of non-alcoholic fatty liver disease (NAFLD) that can progress to advanced fibrosis, cirrhosis, and hepatocellular carcinoma. Differentiating between non-alcoholic fatty liver (NAFL) and NASH/advanced fibrosis is an important step in the management of NAFLD. Metabolic syndrome (MS) and its components are important risk factors for NAFLD, and NASH is thought to be the hepatic injury of MS. The prevalence of NASH among NAFLD patients with MS is thought to be high. In China, NAFLD is a relatively new public health concern, and the current prevalence of NASH among Chinese liver biopsy-proven NAFLD patients with and without MS is not known. This multicenter, cross-sectional study will investigate the prevalence of NASH in approximately 480 Chinese NAFLD patients. Patients will be eligible for enrollment if they have biopsy-proven NAFLD and if their liver biopsies are available for rereading. For our analysis, patients will be stratified according to the presence/absence of MS, and the prevalence of NASH in the subgroups will be compared. Other possible tests that could indicate a risk of NASH, including transient elastography, ultrasonography, cytokeratin-18, liver function tests, and others, will be studied in an effort to derive a practical, noninvasive predictive model for NASH. Patients with NAFL who have MS may also have a very high risk of developing NASH. The present study will inform about the risk of NASH in Chinese liver biopsy-proven NAFLD patients with and without MS. This study registered at http://www.chictr.org.cn (registration number: ChiCTR-OOC-16007902). Sanofi (China) Investment Co., Ltd.

AIM To assess daclatasvir plus asunaprevir (DUAL) in treatment-naïve patients from mainland China, Russia and South Korea with hepatitis C virus (HCV) genotype 1b infection. METHODS Patients were randomly assigned (3:1) to receive 24 wk of treatment with DUAL (daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily) beginning on day 1 of the treatment period (immediate treatment arm) or following 12 wk of matching placebo (placebo-deferred treatment arm). The primary endpoint was a comparison of sustained virologic response at posttreatment week 12 (SVR12) compared with the historical SVR rate for peg-interferon plus ribavirin (70%) among patients in the immediate treatment arm. The first 12 wk of the study were blinded. Safety was assessed in DUAL-treated patients compared with placebo patients during the first 12 wk (double-blind phase), and during 24 wk of DUAL in both arms combined. RESULTS In total, 207 patients were randomly assigned to immediate (n = 155) or placebo-deferred (n = 52) treatment. Most patients were Asian (86%), female (59%) and aged < 65 years (90%). Among them, 13% had cirrhosis, 32% had IL28B non-CC genotypes and 53% had baseline HCV RNA levels of ≥ 6 million IU/mL. Among patients in the immediate treatment arm, SVR12 was achieved by 92% (95% confidence interval: 87.2-96.0), which was significantly higher than the historical comparator rate (70%). SVR12 was largely unaffected by cirrhosis (89%), age ≥ 65 years (92%), male sex (90%), baseline HCV RNA ≥ 6 million (89%) or IL28B non-CC genotypes (96%), although SVR12 was higher among patients without (96%) than among those with (53%) baseline NS5A resistance-associated polymorphisms (at L31 or Y93H). During the double-blind phase, aminotransferase elevations were more common among placebo recipients than among patients receiving DUAL. During 24 wk of DUAL therapy (combined arms), the most common adverse events (≥ 10%) were elevated alanine aminotransferase and upper respiratory tract infection; emergent grade 3-4 laboratory abnormalities were infrequently observed, and all grade 3-4 aminotransferase abnormalities (alanine aminotransferase, n = 9; aspartate transaminase, n = 6) reversed within 8-11 d. Two patients discontinued DUAL treatment; one due to aminotransferase elevations, nausea, and jaundice and the other due to a fatal adverse event unrelated to treatment. There were no treatment-related deaths. CONCLUSION DUAL was well-tolerated during this phase 3 study, and SVR12 with DUAL treatment (92%) exceeded the historical SVR rate for peg-interferon plus ribavirin of 70%.

Objective: To identify the species and abundance of microbes in the bile of patients with biliary injury after liver transplantation. To explore the potential microbial involvement, we evaluated the differences in biliary microbiota in patients with and without biliary injury after liver transplantation. Methods: Bile was collected by percutaneous transhepatic cholangiography drainage from 5 liver transplant recipients with biliary injury (case group) and from the T-tube in 4 liver transplant recipients without biliary injury (control group). 16S rRNA sequencing was performed on the bile samples. Results: The biliary bacterial phyla in patients after liver transplantation were Firmicutes, Proteobacteria, Actinobacteria, Bacteroidetes, and Acidobacteria in order of abundance from highest to lowest. There were differences in genus Prevotella (P = 0.03), Porphyromonas (P = 0.02), and Fusobacterium (P = 0.02) between the two groups, which were significantly abundant in the case group. There was no significant difference in the diversity analysis between the two groups (P > 0.05). The terpenoid backbone biosynthesis pathway and the histidine degradation pathway were significantly enriched in the bile samples in the case group. Compared with the control group, the pyruvate ferredoxin oxidoreductase pathway was depleted in the samples from the case group. Conclusion: This is the first bile microbiota report using high-throughput 16S rRNA gene sequencing of bile material in liver transplant recipients. There were significant differences in bacterial abundance between patients with and without biliary tract injury after liver transplantation but no significant differences in the diversity. KEGG analysis showed that there were differences in metabolic pathways between the two groups.

Six analogous two-dimensional (2D) [Tp*WS3Cu3]-based (Tp* = hydridotris(3,5-dimethylpyrazol-1-yl)borate) networks, namely, {[(Tp*WS3Cu3)2L3](μ3-N3)}n (2: L = 5-methyltetrazolate (Mtta); 3a: L = 5-ethyltetrazolate (Etta)) and {[(Tp*WS3Cu3)2L3]BF4}n (3b: L = Etta; 4: L = 5-propyltetrazolate (Ptta); 5: L = 5-butyltetrazolate (Btta); 6: L = 5-pentyltetrazolate (Petta)) were synthesized by reactions of [Et4N][Tp*WS3] (1), [Cu(CH3CN)4]BF4, NaN3, and NH4BF4 in different nitrile solvents (CH3(CH2)nCN, n = 0, 1, 2, 3, and 4) under solvothermal conditions. In the structures of 2–6, each alkyl tetrazolate L as a bridging ligand was generated in situ from the “click” reaction between azide and nitrile. These 2D (6,3) networks support two types of voids wherein the pendant alkyl groups are accommodated. A tetrahedron cage-like cluster [Tp*W(μ3-S)3(μ3-S′)Cu3]4 (7) was also formed in some of the above reactions and can be readily separated by solvent extraction. The proportion of 7 increased with the elongation of the a...

Despite decreasing prevalence, new cases of hepatitis C in China are increasing recently with growing percentage of patients who are with advanced disease, aging, or not eligible for interferon-based treatments. Hepatitis C infection represents a serious public health burden. This review was based on expert's consensus during a medical forum on hepatitis sponsored by the Beijing Wu Jie-Ping Medical Foundation. The literature searches were conducted in PubMed and critical publications in Chinese journals. Data on hepatitis C prevalence, risk factors, viral or host features, and treatment modalities were extracted and reviewed. Recent large-scale surveys reported reducing prevalence of hepatitis C to approximately 0.4% in China, partly because of regulation changes to safer medical practices and illegalizing commercial blood donations. Patient demographics evolved from being dominated by former paid blood donors to include intravenous drug users and others. Although hepatitis C genotype 1 is the most common, other genotypes are emerging in prevalence. The current standard of care is interferon-based without direct acting antivirals. However, many patients failed therapy because of high treatment costs, substantial needs to manage side effects, difficulties with treatment monitoring in the rural areas, and growing populations of elderly and cirrhotic patients. The lack of high efficacy therapies with good safety profile and low disease awareness in China resulted in increasing public burden of advanced hepatitis C disease. Despite significant reduction of hepatitis C prevalence, iatrogenic, nosocomial, and community transmissions are still significant. In addition to promoting disease awareness, interferon-free regimens are needed to reduce the public health burden.

Hepatic epithelioid hemangioendothelioma (HEHE) is a rare tumor of vascular origin. Whether HEHE in Chinese patients exhibits similar characteristics compared with Western patients is not well known. The aim of the present study was to summarize the characteristics of HEHE in Chinese patients and identify its prognostic factors. In total, six patients diagnosed with HEHE at the Beijing Friendship Hospital between 2000 and 2012 were combined with 44 previously reported cases in China, retrieved from the literature between 1989 and mid-2012. These 50 cases from China were compared with 402 patients from Western populations. Prognostic factors were identified by the χ2 test and Cox regression analysis. The male to female ratio of the Chinese patients was 1:2.1 with the mean age of 44.2 years (range, 22–86 years). The percentage of asymptomatic Chinese patients was significantly higher than in the Western patients (40.0 vs. 24.8%; P=0.026), and that of extrahepatic metastasis (16.0 vs. 36.6%; P=0.005) was significantly lower in Chinese patients. On imaging study, capsular retraction (59.5%) and calcification (26.0%), as well as positivity of CD34 (93.5%) and CD31 (80.6%), were more frequently found in the Chinese patients. Management for the Chinese patients included liver resection (LRx; 45.7%), liver transplantation (LTx; 5.7%), trans-catheter arterial chemoembolization (14.3%) and palliative treatment (34.3%). Chinese patients with larger-sized tumor nodules [relative risk (RR), 1.58; 95% confidence interval (CI), 1.032–2.422; P=0.035) and diffuse type (RR, 12.17; 95% CI, 1.595–92.979; P=0.016) exhibited unfavorable outcomes. In contrast to Western patients with HEHE, a larger number of Chinese patients were asymptomatic with less extrahepatic metastasis. In China, LRx is widely adopted rather than LTx. Chinese patients with large tumor size or diffuse type may encounter a poorer prognosis.

Aims: Asian Pacific Association for the Study of Liver (APASL) acute-on-chronic liver failure (ACLF) Research Consortium (AARC) proposed new prognostic scoring system of ACLF in cluding lactate. However, lactate is not routinely checked in clinical practice of patient with ACLF in Korea. Therefore, we aimed to investigate the predictive accuracy of lactate-free AARC-ACLF score for predicting short-term mortality in patients with alcoholic liver disease. Methods: A total of 749 ALD patients who had liver failure (bilirubin≥5mg/dL and INR≥1.5) in AARC database were in vestigated. Diagnostic performances for short-term mortality were compared according to the area under receiver operating characteristic (AUROC) curve. Predictive accuracy of lactate-free AARC-ACLF score were compared with other prognostic scores in 143 ALD patients with liver failure and 60 ALD patients with ACLF according to AARC definition in Korean ACLF cohort. Results: Among 749 patients, 30-day and 90-day mortality were 40.3% and 51.5%. There were no significant differences in AUROC for predicting 30-day and 90-day mortality between AARC-ACLF score and lactate-free AARC-ACLF score (30-day mortality: 0.752 vs. 0.751, P=0.918, 90-day mortality: 0.728 vs. 0.736, P=0.346). In Korean ACLF cohort, the AUROCs of lactate-free AARC-ACLF score for predicting 28-day and 90- day mortality were 0.861 and 0.846 in ALD with liver failure, and 0.884 and 0.874 in ALD patients with ACLF according to AARC definition, respectively. In Korean ALD patients with liver failure and ACLF according to AARC definition, diagnostic per formance of lactate-free AARC-ACLF score for predicting 28- day and 90-day mortality was comparable to those of Model for End-stage Liver Disease (MELD), MELD-Na, Chronic Liver Failure-Sequential Organ Failure Assessment score. Conclusions: Lactate-free AARC-ACLF score is as excellent as AARC-ACLF score in predicting short-term mortality in ALD patients with liver failure of AARC database and Korean ACLF cohort.

To identify the risk factors for new-onset seizures after pediatric LT and to assess their clinical implications and long-term prognosis. The clinical and laboratory data of 27 consecutive children who underwent LT from January 2007 to December 2010 in our center were analyzed retrospectively. Patients were divided into seizures group and a non-seizures group. Pre-operative, intra-operative, and post-operative data were collected. Seizures occurred in four children, an incidence of 14.8%. All exhibited generalized tonic-clonic seizures within the first two wk after LT. Univariate analysis showed that the risk factors associated with seizures after pediatric LT included gender, pediatric end-stage liver disease score before surgery, Child-Pugh score before surgery, serum total bilirubin after surgery, and trough TAC level. Multivariate analysis showed that trough TAC level was the only independent risk factor associated with the seizures. All children who experienced seizures survived with good graft function and remained seizure-free without anti-epileptic drugs over a mean follow-up period of 33.7 ± 14.6 months. High trough TAC level was the predominant factor that contributed to seizures in the early post-operative period after pediatric LT. High PELD and Child-Pugh scores before LT and high post-operative serum Tbil may be contributory risk factors for TAC-related seizures.

Systemic inflammatory response syndrome (SIRS) is an early marker of sepsis and ongoing inflammation and has been reported in large proportion of acute-on-chronic liver failure (ACLF) patients. Whether sepsis is the cause or the result of liver failure is unclear and is vital to know. To address this, the study investigated the course and outcome of ACLF patients without SIRS/sepsis.Consecutive ACLF patients were monitored for the development of SIRS/sepsis and associated complications and followed till 90 days, liver transplant or death.Of 561 patients, 201 (35.8%) had no SIRS and 360 (64.2%) had SIRS with or without infection. New onset SIRS and sepsis developed in 74.6% and 8% respectively in a median of 7 (range 4-15) days, at a rate of 11% per day. The cumulative incidence of new SIRS was 29%, 92.8%, and 100% by days 4, 7, and 15. Liver failure, that is, bilirubin 12 mg/dL (odds ratio [OR] = 2.5 [95% confidence interval {CI} = 1.05-6.19], P = 0.04) at days 0 and 4, and renal failure at day 4 (OR = 6.74 [95%CI = 1.50-13.29], P = 0.01), independently predicted new onset SIRS. Absence of SIRS in the first week was associated with reduced incidence of organ failure (20% vs 39.4%, P = 0.003), as was the 28-day (17.6% vs 36%, P = 0.02) and 90-day (27.5% vs 51%,P = 0.002) mortality. The 90-day mortality was 61.6% in the total cohort and that for those having no SIRS and SIRS at presentation were 42.8% and 65%, respectively (P 0.001).Liver failure predicts the development of SIRS. New onset SIRS in the first week is an important determinant of early sepsis, organ failure, and survival. Prompt interventions in this 'golden window' before development of sepsis may improve the outcome of ACLF.

Summary The Asia-Pacific region has disparate hepatitis C virus (HCV) epidemiology, with prevalence ranging from 0·1% to 4·7%, and a unique genotype distribution. Genotype 1b dominates in east Asia, whereas in south Asia and southeast Asia genotype 3 dominates, and in Indochina (Vietnam, Cambodia, and Laos), genotype 6 is most common. Often, availability of all-oral direct-acting antivirals (DAAs) is delayed because of differing regulatory requirements. Ideally, for genotype 1 infections, sofosbuvir plus ledipasvir, sofosbuvir plus daclatasvir, or ombitasvir, paritaprevir, and ritonavir plus dasabuvir are suitable. Asunaprevir plus daclatasvir is appropriate for compensated genotype 1b HCV if baseline NS5A mutations are absent. For genotype 3 infections, sofosbuvir plus daclatasvir for 24 weeks or sofosbuvir, daclatasvir, and ribavirin for 12 weeks are the optimal oral therapies, particularly for patients with cirrhosis and those who are treatment experienced, whereas sofosbuvir, pegylated interferon, and ribavirin for 12 weeks is an alternative regimen. For genotype 6, sofosbuvir plus pegylated interferon and ribavirin, sofosbuvir plus ledipasvir, or sofosbuvir plus ribavirin for 12 weeks are all suitable. Pegylated interferon plus ribavirin has been replaced by sofosbuvir plus pegylated interferon and ribavirin, and all-oral therapies where available, but cost and affordability remain a major issue because of the absence of universal health coverage. Few patients have been treated because of multiple barriers to accessing care. HCV in the Asia-Pacific region is challenging because of the disparate epidemiology, poor access to all-oral therapy because of availability, cost, or regulatory licensing. Until these problems are addressed, the burden of disease is likely to remain high.

There has been much progress in antiviral therapy for chronic hepatitis B; however, antiviral therapy for hepatitis B in special populations is still very challenging. Here, we review antiviral therapy for hepatitis B in special populations, including children and pregnant patients, patients with hepatitis-B-related cirrhosis, patients with acute hepatitis B and chronic hepatitis B surface antigen carriers who receive immunosuppressive or cytotoxic therapy. Major advances have been made in antiviral therapy for hepatitis B in these special populations because of recent increasing availability of oral nucleoside/nucleotide analogues that are well-tolerated and highly effective; however, the findings are mostly based on small uncontrolled short-term studies. More well-designed clinical studies on antiviral therapy for hepatitis B in these special populations are urgently needed to obtain more evidence-based high-quality data.

Background: Currently, hepatitis B immunoglobulins (HBIg) and/or lamivudine have become the main options for prevention of hepatitis B recurrence after liver transplantation. Aim: To assess the benefits of HBIg and/or lamivudine for prevention of hepatitis B recurrence after liver transplantation. Methods: We conducted a search of electronic databases and a manual search of bibliographical lists of relevant articles. All randomized clinical trials and non-randomized studies that meet the pre-specified criteria were included. However, results of non-randomized studies were reported under ‘exploratory analyses’ in the result section. The outcome measure was hepatitis B recurrence. Results: Two randomized and 44 non-randomized studies were included. Meta-analysis of two randomized studies shows one week HBIg combined with lamivudine regimen had equivalent effect compared with long-term high-dose HBIg regimen for preventing hepatitis B recurrence (RR 1.23; 95% CI 0.38–4.03; P = 0.73). For 44 non-randomized studies, only qualitative systematic review was performed. With long-term HBIg prophylaxis, hepatitis B recurrence rate ranged from 3.7% to 65%; with lamivudine prophylaxis, hepatitis B recurrence rate varied from 3.8% to 40.4%; Long-term high-dose HBIg plus lamivudine prophylaxis can reduce the risk of HBV recurrence to less than 10%. Conclusions: Long-term HBIg prophylaxis or lamivudine prophylaxis can reduce the risk for hepatitis B virus recurrence. Long-term high-dose HBIg combined with lamivudine can further reduce HBV recurrence to less than 10%.

Introduction: The Asian Pacific Association for the Study of the Liver (APASL) convened an international working party on the management of hepatocellular carcinoma (HCC) in December 2008 to develop consensus recommendations. Methods: The working party consisted of expert hepatologist, hepatobiliary surgeon, radiologist, and oncologist from Asian-Pacific region, who were requested to make drafts prior to the consensus meeting held at Bali, Indonesia on 4 December 2008. The quality of existing evidence and strength of recommendations were ranked from 1 (highest) to 5 (lowest) and from A (strongest) to D (weakest), respectively, according to the Oxford system of evidence-based approach for developing the consensus statements. Results: Participants of the consensus meeting assessed the quality of cited studies and assigned grades to the recommendation statements. Finalized recommendations were presented at the fourth APASL single topic conference on viral-related HCC at Bali, Indonesia and approved by the participants of the conference. © 2010 Asian Pacific Association for the Study of the Liver., link_to_OA_fulltext

The emergence of antiviral resistance can negate the benefits of antiviral therapy in patients with chronic hepatitis B (CHB). This study aimed to assess how physicians in Asia manage suspected antiviral resistance.Randomly selected CHB-treating physicians in Mainland China, South Korea, Taiwan, and Thailand underwent a face-to-face interview. A standardized questionnaire was used to assess how physicians identify, monitor, and manage suspected resistance and its associated medical costs.We interviewed 575 physicians from January to May 2008. Most physicians preferred a "prevention-of-antiviral resistance" strategy over a "rescue-once-resistance-develops" strategy. Physicians had encountered lamivudine resistance most frequently (96-100% of respondents), followed by the resistance to adefovir (18-58%) and entecavir (3-7%). While physicians in South Korea and Taiwan have access to resistance testing, physicians in Mainland China and Thailand have limited access to resistance testing but rely on HBV DNA and alanine aminotransferase (ALT) tests to identify resistance. Once resistance is suspected, 60% of the physicians in Mainland China, South Korea, and Thailand monitored these patients quarterly and the remaining 40% opted for monthly follow-up. In comparison, 70% of the Taiwanese physicians monitored these patients monthly. The average total direct medical costs, excluding antiviral costs, to manage a patient during the first year after suspected resistance is identified ranged from USD $319 to USD $709.Limited access to HBV resistance tests causes physicians in Asia to manage suspected resistance by various HBV DNA assays and ALT tests. This raises concerns that resistance may not be detected early enough to be rescued efficiently.

Chronic hepatitis B infection is a very important health problem in China, which is carrying an enormous economic and social burdens. The major routs of chronic hepatitis B infection in China are mother-infant vertical transmission and early childhood horizontal transmission. After more than 10 years implementation of universal vaccination against hepatitis B in newborns and safety injection in health care settings, the prevalence of HBsAg in general population has decreased from 9.75% to around 7%. In China, patients with hepatitis are cared by either hepatologists or physicians of infectious diseases. The Chinese Society of Hepatology, and Chinese Society of Infectious Diseases jointly issued an evidence-based guideline on the prevention and treatment of chronic hepatitis B in 2005. This guideline concisely describes the virology, epidemiology, natural history and prevention, as well as diagnosis and management of chronic hepatitis B. It also highlights the importance of active viral replication in disease progression in chronic HBV infection and explicitly states the necessity of antiviral therapy in patient care. The cornerstone of anti-hepatitis B therapy is optimal use of interferons or nucleos(t)ide analogs in those patients with active viral replication and elevated serum transaminase levels. Through an independent continue medical educational agency, a panel of selected speakers were trained to give well-formatted talks on the key points of the guideline in over 60 major cities across China. This educational campaign among health care providers has greatly improved the awareness and the stand of care for antiviral therapy.