Hepatitis B-associated fibrosis and fibrosis/cirrhosis regression with nucleoside and nucleotide analogs

Hepatitis B virus (HBV) infection currently accounts for approximately 600,000 deaths per year resulting from progression of liver fibrosis to cirrhosis and hepatocellular carcinoma. Treatment of chronic hepatitis B with antiviral agents aims to improve survival through the reduction of HBV DNA to undetectable levels and the resultant prevention of disease progression. In recent years, observations in various disease areas have shown that liver fibrosis can be reversed if the underlying cause of the liver damage is effectively addressed. In line with these observations, there is now considerable evidence to suggest that effective sustained suppression of HBV replication with long-term anti-HBV treatment can result in measurable improvements in liver fibrosis over time, even in patients with advanced cirrhosis. This review article provides an overview of currently available data on regression of fibrosis and cirrhosis in patients with chronic hepatitis B treated with nucleoside and nucleotide analog inhibitors of HBV.     

Managing hepatitis B to prevent liver cancer: recent advances

Chronic hepatitis B (CHB) infection is a major cause of human mortality worldwide. The majority of people with CHB are infected early in life, and 20–40% of men and 15% of women with chronic infection will develop hepatocellular carcinoma (HCC). Antiviral therapy is recommended for patients with CHB who have cirrhosis or active disease with the aims of reducing disease progression to cirrhosis, liver failure and liver cancer, thereby preventing death. Evidence that treatment with interferon or with early nucleos(t)ide analogue therapy reduces HCC has been somewhat conflicting, however evidence is emerging to support a significant role in HCC prevention of the more effective antivirals, entecavir and tenofovir. Older patients, those with cirrhosis, and those undergoing curative treatments for HCC derive the greatest medium-term benefit in terms of HCC reduction, but HCC can still occur and long-term surveillance is recommended.     

Improving clinical outcomes of chronic hepatitis B virus infection

Chronic hepatitis B virus (HBV) infection is a global health problem, leading to cirrhosis, hepatocellular carcinoma (HCC) and liver-related deaths. Universal hepatitis B vaccination is the most cost–effective way to eradicate HBV infection with the remarkable reduction of chronic carriage, neonatal fulminant hepatitis and childhood HCC. The introduction of highly effective antiviral agents, including lamivudine, adefovir dipivoxil, entecavir, telbivudine, tenofovir disoproxil fumarate and pegylated interferons further improve short-, medium- and long-term outcomes of chronic HBV infection, such as ALT normalization, HBV DNA suppression, HBeAg seroconversion, HBsAg seroclearance, fibrosis regression, reduction of cirrhosis, HCC, liver-related deaths and the need for liver transplantation. Above all, sustained and profound viral suppression is the key to improve the clinical outcomes of chronic hepatitis B.     

Efficacy and safety of prophylaxis with entecavir and hepatitis B immunoglobulin in preventing hepatitis B recurrence after living‐donor liver transplantation

Aim: Hepatitis B recurrence after liver transplantation can be reduced to less than 10% by combination therapy with lamivudine (LAM) and hepatitis B immunoglobulin (HBIG). The aim of this study was to evaluate the efficacy and safety of prophylaxis with entecavir (ETV), which has higher efficacy and lower resistance rates than LAM, combined with HBIG in preventing hepatitis B recurrence after living‐donor liver transplantation (LDLT). Methods: Twenty‐six patients who received ETV plus HBIG (ETV group) after LDLT for hepatitis B virus (HBV)‐related end‐stage liver disease were analyzed by comparing with 63 control patients who had received LAM plus HBIG (LAM group). Results: The survival rates of the patients treated with ETV plus HBIG was 73% after both 1 and 3 years, and there was no statistical difference between the patients in the ETV group and LAM group. No HBV recurrence was detected during the median follow‐up period of 25.1 months in the ETV group, whereas the HBV recurrence rate was 4% at 3 years and 6% at 5 years in the LAM group. No patients had adverse effects related to ETV administration. Conclusion: ETV combined with HBIG provides effective and safe prophylaxis in preventing hepatitis B recurrence after LDLT.     

Baseline hepatitis B core antibody predicts treatment response in chronic hepatitis B patients receiving long‐term entecavir

Studies regarding the clinical significance of quantitative hepatitis B core antibody (anti‐HBc) in patients with chronic hepatitis B receiving first‐line nucleos(t)ide analogues is limited. The aim of this study was to determine the performance of anti‐HBc as a predictor for hepatitis B e antigen (HBeAg) seroconversion in HBeAg‐positive CHB patients treated with entecavir. This was a retrospective cohort study consisting of 139 Chinese patients enrolled in a multicenter clinical trial treated with entecavir or entecavir maleate for up to 240 weeks. Anti‐HBc evaluation was conducted for all the available samples using a newly developed double‐sandwich anti‐HBc immunoassay. At week 240, 35 (25.2%) patients achieved a serological response (HBeAg seroconversion) and these patients at week 240 had significantly higher levels of anti‐HBc (P<.01). We defined 4.65 log₁₀ IU·mL^?1, with a maximum sum of sensitivity and specificity, as the optimal cut‐off value of baseline anti‐HBc level to predict seroconversion. Patients with baseline anti‐HBc ≥4.65 log₁₀ IU·mL^?1 had 28.0% (26/93) and 35.5% (33/93) chance of seroconversion at weeks 144 and 240, respectively. The baseline anti‐HBc level was the strongest predictor for seroconversion at week 144 (OR: 5.78, 95% confidence interval [CI]: 2.05‐16.34, P=.001). The baseline anti‐HBc level was a strong predictor for seroconversion at week 240 (OR: 5.36, 95% CI: 2.17‐13.25, P<.001). Hence, baseline anti‐HBc titre is a useful predictor of long‐term entecavir therapy efficacy in HBeAg‐positive CHB patients, which could be used to optimize antiviral therapy.     

Effects of antiviral therapy in patients with chronic hepatitis B and cirrhosis

Introduction: Hepatitis B virus (HBV) infection is the major cause of cirrhosis worldwide. The ultimate goal of current antiviral treatments for chronic hepatitis B (nucleos(t)ide analogs and interferon-α) is to prevent the development of end-stage liver diseases.

Areas covered: We present a review of the current literature on antiviral therapy in patients with chronic hepatitis B and cirrhosis. Medline search was performed to identify relevant literature from 1993 through January of 2017.

Expert commentary: One randomized controlled trial and a number of observational studies have shown that nucleos(t)ide analogs can decrease the incidence of hepatocellular carcinoma (HCC) in chronic hepatitis B patients with advanced fibrosis. Data from clinical trials of entecavir and tenofovir have shown that histological improvement and regression of fibrosis can be achieved in the majority of patients with chronic hepatitis B by successful viral suppression. Entecavir and tenofovir are the preferred antiviral agents for treatment of chronic hepatitis B in patients with cirrhosis due to their high antiviral potency and high genetic barrier to resistance. Pegylated interferon-α is another therapeutic option for chronic hepatitis B patients with well-compensated cirrhosis. However, interferon therapy is contraindicated in patients with decompensated cirrhosis, and evidence for reduced HCC is currently insufficient.     

Stratified management based on surface antibody for the prevention of hepatitis B virus reactivation in lymphoma patients

This study aimed to investigate a stratified approach based on hepatitis B virus (HBV) surface antibody (anti-HBs) for managing HBV reactivation (HBVr) in lymphoma patients with serological protection against HBV. A retrospective analysis was conducted on 209 lymphoma patients with a baseline anti-HBs titre of ≥10 iu/L, who were either positive or negative for HBV core antibody (anti-HBc). The results revealed that 15.7% of patients lost serological protection following 6-month anti-lymphoma therapy. With a median follow-up of 28.1 months, the cumulative rates of HBVr at 6 months, 2 years and 4 years were 2.9%, 4.7% and 6.3% respectively. Without intervention, the overall rate of reactivation was 2.0% for patients with isolated anti-HBs and 10.5% for those with positive anti-HBs and anti-HBc. To identify patients at high risk of losing seroprotection and susceptible to HBVr, a predictive model was developed. The high-risk group had significantly higher rates of serological protection loss (27.8% vs. 2.2%) and cumulative incidence of HBVr (22.0% vs. 0%) compared to the low-risk group. Overall, this study highlights the risk of HBVr in lymphoma patients with positive anti-HBs, with or without positive anti-HBc, and recommends periodic monitoring for low-risk patients and early intervention for high-risk patients.     

恩替卡韦治疗慢性乙型肝炎的临床观察

目的评价恩替卡韦治疗慢性乙型肝炎（CHB）的疗效和安全性。方法72例慢性乙型肝炎（CHB）患者随机分为治疗组和对照组,治疗组（30例）予恩替卡韦0.5mg/d;对照组（42例）予拉米夫定100mg/d,疗程均48周,基础治疗相似。结果治疗组和对照组在治疗24周、48周时：血清HBV-DNA水平比基线值（log10copies/ml）平均下降分别为5.48、6.87和2.84、5.38;病毒应答率分别为53%、67%和21%、43%,两组差异均有统计学意义（P〈0.001）。ALT复常率分别为67%、77%和60%、67%,血清HBeAg阴转率、HBsAg消失率、不良事件发生率,均P〉0.05,差异无统计学意义。无严重不良反应发生。结论恩替卡韦治疗慢性乙型肝炎,可在病毒学及生物化学方面取得显著疗效,且安全性良好。