Hepatitis B virus-related decompensated liver cirrhosis: benefits of antiviral therapy

Following development of liver cirrhosis in patients with chronic hepatitis B, liver disease may continue to progress and decompensation or hepatocellular carcinoma (HCC) may occur, especially in those with active viral replication. Decompensation may manifest with jaundice, ascites, variceal bleeding or hepatic encephalopathy. Earlier studies have shown that the prognosis of decompensated cirrhosis is usually poor with a 5-year survival rate at 14-35% under conventional standard of care. The approval of oral antiviral agents has greatly improved the prognosis, as demonstrated in several cohort studies and randomized clinical trials involving therapy with lamivudine, adefovir dipivoxil, entecavir, telbivudine, or tenofovir disoproxil fumarate. Oral antiviral agents are effective in restoring liver function and improving survival in patients with decompensated cirrhosis especially if therapy is initiated early enough. These agents are generally well tolerated without significant side effects. However, their preventive effect in HCC development has yet to be convincingly demonstrated. Given their known resistance profiles, entecavir and tenofovir should be considered as the first-line therapy for patients with HBV-related decompensated cirrhosis.     

Efficacy of antiviral therapy with lamivudine after initial treatment for hepatitis B virus-related hepatocellular carcinoma

AIM: The aim of this study was to determine whether antiviral therapy with lamivudine is beneficial in patients after initial treatment for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: Forty-nine consecutive patients with HBV-related HCC completely treated by hepatic resection or radiofrequency ablation were retrospectively enrolled in this study. Comparison was made between 16 patients who received lamivudine therapy at a dose of 100 mg/day after treatment for HCC (lamivudine group) and 33 patients who did not (control group) in terms of changes in remnant liver function, HCC recurrence and survival. RESULTS: Cumulative recurrence rates of HCC did not significantly differ between the two groups (P = 0.622). However, median Child-Pugh score at the time of HCC recurrence was significantly different; 5 (range 5-6) in the lamivudine group versus 7 (range 5-12) in the control group (P = 0.005). All patients in the lamivudine group were able to receive curative treatment for recurrent HCC. In contrast, 10 of 15 patients in the control group were unable to receive curative optimal therapy for recurrent HCC due to deterioration of remnant liver function. The cumulative survival rates of patients in the lamivudine group tended to be higher than those of patients in the control group (P = 0.063). CONCLUSION: It is suggested that lamivudine therapy is beneficial for patients after initial treatment for HBV-related HCC because it contributes to improving remnant liver function, thus decreasing the risk of liver failure and increasing the chances of receiving available treatment modalities for recurrent HCC.     

Effects of lamivudine on outcome after liver resection for hepatocellular carcinoma in patients with active replication of hepatitis B virus

Aim:  Patients with high serum hepatitis B virus (HBV) DNA concentrations are at high risk of tumor recurrence after liver resection for HBV-related hepatocellular carcinoma (HCC).
Methods:  Among 24 patients with high serum HBV DNA concentrations who underwent liver resection for HBV-related HCC, postoperative lamivudine therapy was chosen by 14 (lamivudine group). The other 10 patients were controls.
Results:  Clinicopathologic findings did not differ between the groups. Tumor-free survival rate after surgery was significantly higher in the lamivudine than the control group ( P  = 0.0086). By univariate analysis, multiple tumors were also a risk factor for a short tumor-free survival. By multivariate analysis, lack of lamivudine therapy and multiple tumors were independent risk factors for a short tumor-free survival. In four patients YMDD mutant viruses were detected after beginning lamivudine administration; in two of them, adefovir dipivoxil was administered because of sustained serum alanine aminotransferase elevations.
Conclusion:  Lamivudine therapy improved tumor-free survival rate after curative resection of HBV-related HCC in patients with high serum concentrations of HBV DNA, although careful follow up proved necessary for the detection of YMDD mutant viruses.     

Partial Virological Response after 2 Years of Entecavir Therapy Increases the Risk of Hepatocellular Carcinoma in Patients with Hepatitis B Virus-Associated Cirrhosis

Background/AimsThe clinical significance of partial virological response (PVR) in patients undergoing antiviral therapy is not well known. This study investigated whether PVR after 2 years of entecavir (ETV) therapy is associated with hepatocellular carcinoma (HCC) development in cirrhotic patients.MethodsA total of 472 naïve patients with hepatitis B virus (HBV)-associated cirrhosis who were treated with ETV for at least 2 years were retrospectively enrolled. Clinical characteristics, laboratory data, PVR, and noninvasive fibrosis markers (aspartate aminotransferase to platelet ratio and FIB-4 index) at 2 years after ETV commencement were analyzed for HCC risk.ResultsAfter excluding those who developed HCC within 2 years of ETV therapy, 359 patients (mean age, 51±10 years; male 64.3%) were examined. During a median follow-up of 82 months, 80 patients developed HCC. In the univariate analysis, older age (hazard ratio [HR], 1.056; p<0.001), PVR (HR, 2.536; p=0.002), higher aspartate aminotransferase (HR, 1.018; p=0.005), lower albumin level (HR, 0.463; p<0.001), lower platelet count (HR, 0.993; p=0.01), and higher FIB-4 index (HR, 1.141; p<0.001) at 2 years after ETV commencement were risk factors for HCC. In the multivariate analysis, older age (HR, 1.046; 95% confidence interval [CI], 1.022 to 1.072; p<0.001), PVR (HR, 2.358; 95% CI, 1.310 to 4.245; p=0.004), and higher FIB-4 index (HR, 1.103; 95% CI, 1.035 to 1.177; p=0.003) were independent risk factors.ConclusionsPVR and higher FIB-4 index after 2 years of ETV therapy were independent risk factors for HCC. Therefore, efforts to accomplish a complete virological response and reduce the FIB-4 index should be made. (Gut Liver 2021;15-439)     

Hepatitis B virus-related cirrhosis: natural history and treatment

In patients with compensated hepatitis B virus (HBV) cirrhosis, active viral replication correlates significantly with the risk of hepatic flare, decompensation, and the development of hepatocellular carcinoma (HCC). The 5-year survival of patients with compensated cirrhosis was reported to be 80 to 85%, and is significantly lower in patients with replicative HBV. Both interferon and maintenance lamivudine therapy have been shown to reduce the risk of decompensation or HCC and prolong survival in responders. A finite course of interferon is recommended as the first-line agent. For patients who had a contraindication for or who have failed interferon therapy, direct antiviral(s) can be considered for long-term treatment. Once decompensation occurs, mortality increases remarkably. Early treatment with nucleoside analogues should be instituted. Lamivudine therapy is associated with rapid viral suppression, improvement in Child-Pugh scores, and improved survival, but drug resistance is a major problem and is associated directly with a poor clinical outcome. Adefovir or entecavir is preferred in patients with decompensated cirrhosis who require long duration of treatment, due to the lower rate of development of resistance.     

Hepatocellular carcinoma progression in hepatitis B virus-related cirrhosis patients receiving nucleoside (acid) analogs therapy: A retrospective cross-sectional study

BACKGROUNDAntiviral therapy cannot completely block the progression of hepatitis B to hepatocellular carcinoma (HCC). Furthermore, there are few predictors of early HCC progression and limited strategies to prevent progression in patients with HBV-related cirrhosis who receive nucleos(t)ide analog (NA) therapy.AIMThe study aim was to clarify risk factors and the diagnostic value of alpha-fetoprotein (AFP) for HCC progression in NA-treated hepatitis B virus (HBV)-related cirrhosis patients.METHODSIn this retrospective cross-sectional study, we analyzed the clinical data of 266 patients with HBV-related cirrhosis who received NA treatment between February 2014 and April 2020 at Zhejiang Provincial People’s Hospital. The patients were divided into two groups, 145 who did not progress to HCC (No-HCC group), and 121 who progressed to HCC during NA treatment (HCC group). The logistic regression analysis was used to analyze the risk factors of HCC progression. The diagnostic value of AFP for HCC was evaluated by receiver operating characteristic (ROC) curve analysis.RESULTSUnivariate analysis showed that age ≥ 60 years (P = 0.001), hepatitis B and alcoholic etiology (P = 0.007), smoking history (P < 0.001), family history of HBV-related HCC (P = 0.002), lamivudine resistance (P = 0.011), HBV DNA negative (P = 0.023), aspartate aminotransferase > 80 U/L (P = 0.002), gamma-glutamyl transpeptidase > 120 U/L (P = 0.001), alkaline phosphatase > 250 U/L (P = 0.001), fasting blood glucose (FBG) ≥ 6.16 (mmol/L) (P = 0.001) and Child-Pugh class C (P = 0.005) were correlated with HCC progression. In multivariate analysis, age ≥ 60 years [hazard ratio (HR) = 3.089, 95% confidence interval (CI): 1.437-6.631, P = 0.004], smoking history (HR = 4.001, 95%CI: 1.836-8.716, P < 0.01), family history of HBV-related HCC (HR = 6.763, 95%CI: 1.253-36.499, P < 0.05), lamivudine resistance (HR = 2.949, 95%CI: 1.207-7.208, P = 0.018), HBV DNA negative (HR = 0.026, 95%CI: 0.007-0.139, P < 0.01), FBG ≥ 6.16 mmol/L (HR = 7.219, 95%CI: 3.716-14.024, P < 0.01) were independent risk factors of HCC progression. ROC of AFP for diagnosis of HCC was 0.746 (95%CI: 0.674-0.818). A cutoff value of AFP of 9.00 ug/L had a sensitivity of 0.609, and specificity of 0.818 for diagnosing HCC.CONCLUSIONAge ≥ 60 years, smoking history, family history of HCC, lamivudine resistance, HBV DNA negative, FBG ≥ 6.16 mmol/L were risk factors of HCC progression. Serum AFP had limited diagnostic value for HCC.     

恩替卡韦治疗慢加急性乙型肝炎肝衰竭疗效的Meta分析

目的 系统评价恩替卡韦治疗慢加急性乙型肝炎肝衰竭的疗效和安全性。方法 应用计算机检索PubMed、Cochrane Library、CBMdisc、CNKI、维普、万方等数据库公开发表的文献,检索年限均从2006年1月至2014年9月。纳入恩替卡韦与拉米夫定相比较治疗慢加急性乙型肝炎肝衰竭的随机对照试验。由两名评判员对纳入试验独立进行质量评价和资料提取,采用RevMan5.1软件进行Meta分析。结果 经筛选共纳入7个随机对照试验,合计823例患者。Meta分析结果显示,恩替卡韦治疗6月以上的患者其病死率显著低于拉米夫定治疗患者[RR=0.75,95%CI（0.60,0.95）,P＜0.05];在治疗2～3 m和6 m以上评价,恩替卡韦治疗患者HBV DNA转阴率也显著高于拉米夫定治疗患者[RR=1.47,95%CI（1.29,1.68）,P＜0.05;RR=1.48,95%CI（1.30,1.67）,P＜0.05],病毒学突破率也显著低于拉米夫定治疗组[RR=0.07,95%CI（0.01,0.54）,P＜0.05],且未出现严重不良反应。结论 恩替卡韦治疗慢加急性乙型肝炎肝衰竭患者的远期病死率和病毒学突破率均显著低于拉米夫定,适合于长期抗病毒治疗。     

Management of severe acute to fulminant hepatitis B: to treat or not to treat or when to treat?

Despite a decline in cases of acute hepatitis B and the low hepatitis B virus (HBV) chronicity rates in adults, still some patients progress to HBV-related fulminant liver failure. In this review, we discuss treatment options that may prevent the progression of severe acute hepatitis B to fulminant liver failure and death. In severe acute HBV with prolonged prothrombin time and increased bilirubin, interferon failed to be effective while antiviral treatment, particularly with lamivudine, appears to improve survival (mean survival almost 80%). Outcome without antiviral therapy has remained considerably poor, whereas there is no convincing evidence of amelioration of HBV-targeted immunity. Of note, most patients who died or required transplantation despite lamivudine therapy, were started on lamivudine at advanced stages compared with those survived. This suggests that prompt and timely antiviral therapy is crucial. Owing to the abovementioned results the design of randomized placebo-control trials in the setting of severe acute hepatitis B seems unethical. On the contrary, the design of multicentre double-blind randomized trials to compare the efficacy between lamivudine and entecavir or even tenofovir in acute severe HBV cases is ideally needed, but these studies appear to be very difficult to perform considering that these cases are not frequent and therefore, it is almost impossible to have two arms adequately numerous and homogenous for statistical evaluation. Thus, in the absence of solid evidence based data, the hepatologists could treat their patients with severe acute hepatitis B with lamivudine or the most potent antivirals entecavir or tenofovir.     

Prevention of hepatocellular carcinoma in hepatitis B virus infection

Chronic hepatitis B is the main risk factor for hepatocellular carcinoma (HCC) in Asia. The most important preventive strategy's adoption of the universal hepatitis B vaccination program is now in its third decade. There is a clear reduction in both chronic hepatitis B virus (HBV) infection (hepatitis B surface antigen "carriage") but also in childhood HCC in Taiwan. An outstanding concern is variability in vaccine coverage between countries. For patients with chronic hepatitis B, serum HBV DNA levels have emerged as the key risk factor for development of HCC. The initial treatment for chronic hepatitis B was interferon. One randomized control trial, and several case–control or cohort studies have shown benefits for preventing HCC, particularly in cirrhotic patients who responded to therapy. With nucleos(t)ide analogs, the most important study has been the Asian Cirrhosis Lamivudine multicenter randomized controlled trial. This showed that lamivudine can reduce disease progression in HBV-related cirrhosis, including an approximately 50% decrease in HCC incidence. Such efficacy was achieved despite emergence of drug resistance in approximately 50% of cases. Case–control studies have suggested that hepatitis B cases without cirrhosis may also benefit. In conclusion, it is now possible to prevent HBV-related HCC. The most effective method is hepatitis B vaccination, which prevents chronic HBV infection and chronic liver disease resulting therefrom. Interferon therapy appears to confer benefit but the evidence is weaker. First-generation oral antiviral (lamivudine) reduces HCC risk, particularly in cirrhotics. Long-term outcome data with newer, more potent HBV antivirals that have a higher genetic barrier to drug resistance are eagerly awaited.     

Impact of antiviral therapy on post-hepatectomy outcome for hepatitis B-related hepatocellular carcinoma

The outcome after curative resection for hepatocellular carcinoma (HCC) remains unsatisfactory due to the high recurrence rate after surgery. In patients with hepatitis B virus (HBV)-related HCC, which is the majority of patients with HCC in Asia, a high viral load is a strong risk factor for HCC recurrence. It is logical to believe that antiviral therapy may improve the post-operative outcome by promoting viral clearance and hepatocyte regeneration, as well as improving residual liver volume in HCC patients with hepatitis B. However, the effect of antiviral therapy on clinical outcomes after liver resection in patients with HBV-related HCC remains to be established. There are two main groups of antiviral treatment for HBV-oral nucleos(t)ide analogues and interferon. Interferon treatment reduces the overall incidence of HBV-related HCC in sustained responders. However, side effects may limit its long-term clinical application. Nucleos(t)ide analogues carry fewer side effects and are potent in terms of viral suppression when compared to interferon and are typically implemented for patients with more advanced liver diseases. They may also improve the outcome after curative resection for HBV-related HCC. There are increasing evidence to suggest that antiviral therapy could suppress HBV, decrease the perioperative reactivation of viral replication, reduce liver injury, preserve the liver function before and after operation, and may lower the risk of HCC recurrence. After all, antiviral therapy may improve the survival after liver resection by reducing recurrence and delaying the liver damage by the virus, resulting in a higher chance of receiving aggressive salvage therapy during HCC recurrence.     

Effects of antiviral therapy on long-term outcome after liver resection for hepatitis B virus-related hepatocellular carcinoma

Background/purpose

We investigated the effects of nucleos(t)ide analogues (NAs) on long-term outcome in patients following curative treatment for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).

Methods

This study involved 70 of the 76 patients who had undergone liver resection for HBV-related HCC in our department; 6 patients were excluded due to non-curative resection or advanced cancer. The 70 patients were divided into three groups, as follows: 13 patients with high serum concentration of HBV DNA (≥4?log₁₀?copies/mL) and no antiviral therapy (high viral group); 46 patients who received antiviral therapy during the serial follow up (antiviral therapy group) because of high viral concentration (≥4?log₁₀?copies/mL); and 11 patients with low serum concentration of HBV DNA (<4?log₁₀?copies/mL) and no antiviral therapy (low viral group).

Results

Tumor-free survival rate was significantly higher in the low viral group than in the high viral group (P?=?0.0058). Multivariate analysis revealed that a high serum concentration of HBV DNA (≥4?log₁₀?copies/mL) (risk ratio 6.717, 95% confidence interval 1.435–31.434, P?=?0.0156) was an independent risk factor for a short tumor-free survival time. Tumor-free survival rate was significantly higher in the antiviral therapy group than in the high viral group (P?=?0.0478). Multivariate analysis revealed that presence of multiple tumors (risk ratio 2.857, 95% confidence interval 1.403–5.816, P?=?0.0038) was an independent risk factor for a short tumor-free survival time. The cumulative survival rate was significantly higher in the antiviral therapy group than in the high viral group (P?=?0.0025). Multivariate analysis revealed that not undergoing antiviral therapy (risk ratio 0.121, 95% confidence interval 0.024–0.608, P?=?0.0104) was an independent risk factor for a short survival time.

Conclusions

A high serum concentration of HBV DNA (≥4?log₁₀?copies/mL) was a strong risk factor for HCC recurrence after resection of HBV-related HCC. Antiviral therapy with NAs improved the long-term outcome after resection of HBV-related HCC in patients with high serum concentrations of HBV DNA.     

恩替卡韦抗病毒治疗对乙型肝炎相关肝细胞癌肝动脉化疗栓塞术预后的影响

目的探讨恩替卡韦抗病毒治疗对乙型肝炎相关肝细胞癌肝动脉化疗栓塞术(TACE)预后的影响。方法选取2011年1月—2018年3月在南方医院肝肿瘤中心首次接受TACE治疗的HCC患者170例,包括恩替卡韦治疗组114例,对照组(未抗病毒治疗)56例。记录治疗前基线的人口学资料,ALT、AST、TBil、Alb、PLT和Child-Pugh分级,HBeAg和HBV DNA水平,AFP、BCLC分期,以及治疗后4~8周的HBV DNA水平,ALT、AST、TBil、Alb和Child-Pugh分级变化和治疗后长期的生存状况。观察患者的短期和长期临床获益(总生存期)。计量资料两组间比较采用t检验或Mann-Whitney U检验;计数资料两组间比较采用χ2检验。对治疗前临床相关指标进行多因素logistic分析,以发现与乙型肝炎再活动的相关危险因素。Kaplan-Meier法分析总生存期的生存曲线,log-rank检验生存曲线间差异性。结果恩替卡韦治疗组患者乙型肝炎再活动的发生率与对照组比较无差异(15.79%vs 16.07%,χ2=0.002,P=0.962)。PLT水平在乙型肝炎再活动组与无乙型肝炎再活动组间差异有统计学意义(Z=-2.183,P=0.029)。多因素分析结果显示,HBV DNA水平是乙型肝炎再活动的独立危险因素(HR=1.000,P=0.015)。恩替卡韦组的1、3和5年生存率分别是56.20%、30.30%和13.20%,对照组的1、3和5年生存率分别是60.60%、27.20%和16.30%,两组在总体生存率上差异无统计学意义(χ2=0.049,P=0.755)。结论抗病毒治疗可以抑制乙型肝炎相关HCC患者TACE术后HBV复制,从而减少TACE治疗的肝毒性。     

Predisposing factors for recurrence of HBV-related small hepatocellular carcinoma after percutaneous radiofrequency ablation

Abstract

Background. Radiofrequency ablation (RFA) as a curative therapy for hepatocellular carcinoma (HCC) is widely used. The aim of this study was to investigate predisposing factors for HCC recurrence in patients with hepatitis B virus (HBV)-related small HCC after RFA. Methods. A total of 170 patients underwent percutaneous RFA for HBV-related small HCC (≤3 cm in diameter) from January 2008 to December 2010 at Samsung Medical Center. We analyzed the risk factors for recurrence of HCC after RFA. Results. The median follow-up duration was 27.0 months. A total of 89 patients (52%) experienced recurrence after percutaneous RFA. Cumulative recurrence-free rates after RFA at 1-, 3-, and 5 years were 81.3%, 47.2% and 35.7%, respectively. Univariate analysis showed that predisposing factors for HCC recurrence were the multinodularity (hazard ratio (HR) 2.22, p = 0.005), pre-RFA HBV DNA levels ≥2000 IU/mL (HR 1.61, p = 0.025), and Barcelona Clinic Liver Cancer stage A (HR 1.54, p = 0.046). The independent risk factors for recurrence by multivariate analysis were the multinodularity (HR 1.94, p = 0.026) and pre-RFA HBV DNA levels ≥2000 IU/mL (HR 1.57, p = 0.039). Conclusion. Multinodularity and HBV DNA levels were associated with the recurrence of HBV-related small HCC after RFA.     

Suppressive effects of entecavir on hepatitis B virus and hepatocellular carcinoma

Background and Aim: We investigated the efficacy and effectiveness of entecavir in hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) patients. Methods: We enrolled 231 nucleoside‐naïve chronic hepatitis B (CHB) patients primarily treated with entecavir 0.5 mg/day for at least 6 months in our institution. Of these, 71 patients had HCC at the start of entecavir treatment (HCC group) and 160 did not (non‐HCC group). We compared antiviral responses to entecavir in the two groups, and evaluated the effects of entecavir on the clinical outcomes of curatively‐treated HCC patients. Results: The HCC and non‐HCC groups had similar cumulative rates of HBV‐DNA negativity, alanine aminotransferase normalization, and hepatitis e antigen loss in year 2 (100% vs 95.4%, 94.7% vs 97.3%, and 40.8% vs 41.8%, respectively; P > 0.05). Entecavir treatment for 12 months decreased mean Model for End‐Stage Liver Disease scores in patients with cirrhosis and HCC (7.2 vs 5.6, P < 0.001). Of the 71 HCC patients, 16 underwent curative therapies concurrently with entecavir; hepatectomy in six and radiofrequency ablation in 10, and the 55 remaining patients received transarterial chemoembolization or conservative treatment. In a subgroup of 16 HCC patients receiving curative treatments, patients who became serum HBV DNA negative by week 24 had better overall survival (P = 0.039), but not recurrence‐free survival (P = 0.961), than those who did not. Conclusions: First‐line entecavir monotherapy is comparably effective in CHB patients with and without HCC, and improves hepatic function in HBV‐related HCC patients. An early virological response to entecavir is prognostic of improved survival following curative therapy against HBV‐related HCC.     

初始联合拉米夫定与阿德福韦酯在乙肝肝硬化治疗中的进展

慢性乙型肝炎在我国是一种常见疾病,每年约有2.0%~5.5%的患者进展为肝硬化,而一旦进入肝硬化失代偿阶段,治疗难度加大,生存率低。大量研究证实,早期有效的抗病毒治疗可以延缓肝硬化的进程,改善肝功能,延长生存期。目前抗病毒药物主要是干扰素和核苷(酸)类似物,但对于病毒载量相对较高的乙肝肝硬化患者,使用干扰素应答率低,单用一种核苷(酸)类似物疗效不稳定,耐药率高,进而导致抗病毒治疗失败。近年来大量临床研究表明,初始联合无交叉耐药的核苷(酸)类似物治疗乙肝肝硬化不仅能够快速抑制病毒复制,提高远期疗效,还能预防耐药的发生,为乙肝肝硬化的治疗提供了新的治疗方案。     

Hepatitis E virus superinfection impairs long-term outcome in hospitalized patients with hepatitis B virus-related decompensated liver cirrhosis

Introduction and objectivesHepatitis E virus (HEV) superinfection is a common excerbating event in patients with chronic hepatitis B, but the impact on the long-term prognosis is not clear. This study investigates the specific role of HEV superinfection in the long-term outcome of hepatitis B virus (HBV) patients with liver cirrhosis.Patients and methodsA retrospective, observational cohort study was conducted using clinical, laboratory, and survival data collected from patients suffering from hepatitis B cirrhosis with or without HEV superinfection. Disease progression and mortality rates were analyzed.ResultsAfter a two-year follow-up, HEV superinfection was identified in 27 of 811 patients. The transplantation-free mortality was significantly increased (51.9% vs. 14.3%, p< 0.001) in HEV superinfection compared to that in hepatitis B cirrhosis patients without HEV superinfection. Logistic regression analysis demonstrated that elderly people were independent host risk factors for hepatitis B cirrhosis patients with HEV superinfection before and after propensity score matching (PSM). Moreover, HEV superinfection was a risk factor for patients with hepatitis B cirrhosis with new acute decompensation (AD) and acute-on-chronic liver failure (ACLF) during hospitalization. A multivariate Cox proportional hazards regression model demonstrated that acute HEV co-infection is associated with two-year mortality (hazard ratio [HR]: 2.49; 95% CI: 1.40–4.43; p= 0.002; and HR: 5.79; 95% CI: 1.87–17.87; p= 0.002) in patients with hepatitis B cirrhosis before and after PSM.ConclusionsElder patients with hepatitis B cirrhosis are susceptible to HEV superinfection, accelerating disease progression and increasing long-term mortality in hospitalized patients with HBV-related decompensated liver cirrhosis.     

Current clinical evidence for nucleos(t)ide analogues in patients with HBV-related hepatocellular carcinoma

Introduction: Hepatocellular carcinoma (HCC) is a leading cause of death globally and is frequently seen following Hepatitis B virus (HBV) or Hepatitis C virus infection. Areas with high HBV infection rates, such as Asia and sub-Saharan Africa, are therefore also high-risk areas for HCC.

Areas covered: This review identifies and discusses the current evidence from robust clinical trials which have investigated the benefits of Nucleos(t)ide analogue (NA) antiviral therapy in HBV-related HCC patients, including HCC patients that underwent liver transplantation and HCC patients with or without curative treatment. In addition, we assess how this evidence has influenced current clinical practice, with a particular focus on those areas of high HBV infection rates.

Expert commentary: A number of studies have assessed whether NA antiviral treatment can improve the prognosis of HBV-related HCC patients. In this review we evaluate the current evidence, including that from trials in Asia, for antiviral NA treatments in HBV-related HCC patients. We also focus on those NAs with a high genetic barrier to resistance (i.e. ETV or TDF), on different therapeutic approaches, and on the future evidence that is required in this field.     

Expression of IL-26 predicts prognosis of patients with hepatocellular carcinoma after surgical resection

BackgroundThere is no data regarding prognostic impact of interleukin (IL)-26 on outcomes of patients with hepatocellular carcinoma (HCC). The present study aimed to evaluate the prognostic impact of IL-26 on HCC patients undergoing liver resection.MethodsFrom 2003 to 2008, 122 patients with HCC who received surgical curative resection were enrolled. Patients were stratified into IL-26-upper and -lower groups according to the median expression level from immunohistochemical staining of resected specimens. Prognostic impact of IL-26 was estimated using Kaplan–Meier curves. Univariate and multivariate analyses were performed to evaluate time-dependent prognostic impact and independency of IL-26. Demographic and clinical factors that were associated with IL-26 were comprehensively identified.ResultsPrognosis of the patients with high level of IL-26 revealed to be significantly unfavorable in both cumulative recurrence-free survival (P < 0.001) and overall survival (P = 0.002). Upper expression of IL-26 (HR: 1.643; 95% CI: 1.021 to 2.644; P = 0.041) and microvascular invasion (HR: 3.303; 95% CI: 1.255 to 8.696; P = 0.016) were identified as significant independent prognostic factors for overall survival in the multivariable analysis.ConclusionsIL-26 is a novel prognostic factor for HCC after resection. Evaluation of IL-26 expression may be potentially valuable in clinical therapy when planning individualized follow-up schedule and evaluating candidates for prophylactic adjuvant treatment to prevent recurrence.     

Meta-analysis of prophylactic entecavir or lamivudine against hepatitis B virus reactivation

Introduction and aim. Studies suggest that entecavir and lamivudine are useful as prophylactics against hepatitis B virus (HBV) reactivation in patients undergoing chemotherapy or immunosuppressive therapy, but which drug is more effective is unclear. Here we meta-analyzed available evidence on relative efficacy of prophylactic entecavir or lamivudine therapy in patients with chronic or resolved hepatitis B infection who were undergoing chemotherapy or immunosuppressive therapy.Material and methods. Two reviewers searched PubMed, EMBASE and Google Scholar as well as reference lists in relevant articles to find studies published between January 2005 and May 2015 that met inclusion and exclusion criteria. Data on HBV reactivation, HBV-related hepatitis and all-cause mortality were extracted from the studies and meta-analyzed.Results. A total of eight studies involving 593 patients were included in the meta-analysis, which was performed using a fixed-effect model since no significant heterogeneity was found. Entecavir was associated with significantly lower risk of HBV reactivation than lamivudine (RR 0.29, 95% CI 0.17 to 0.52) as well as lower risk of HBV-related hepatitis (RR 0.11, 95% CI 0.03 to 0.40). The two drugs were associated with similar risk of all-cause mortality (RR 1.12, 95% CI 0.54 to 2.35). Egger’s test suggested no significant publication bias in the meta-analysis.Conclusions. The available evidence suggests that entecavir is more effective than lamivudine for preventing HBV reactivation and HBV-related hepatitis in patients with chronic or resolved HBV infection who are undergoing chemotherapy or immunosuppressive therapy.