Purpose: Patterns of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg) –negative, antihepatitis B core antigen antibody (anti-HBc) –positive patients with lymphoma receiving rituximab-containing chemotherapy have not been well described. Patients and Methods: HBsAg-negative, anti-HBc–positive Chinese patients with undetectable serum HBV DNA (< 10 IU/mL), diagnosed with hematologic malignancies and receiving rituximab-containing chemotherapy, were prospectively monitored every 4 weeks for up to 2 years. Entecavir was started when HBV reactivation (defined as detectable HBV DNA) was encountered. Results: Among 260 patients receiving rituximab-containing chemotherapy, 63 patients (24.2%) who were HBsAg negative and anti-HBc positive underwent follow-up for a median of 70 weeks (range, 6 to 104 weeks). The 2-year cumulative rate of HBV reactivation was 41.5%, occurring at a median of 23 weeks (range, 4 to 100 weeks) after rituximab treatment. The median HBV DNA level at reactivation was 43 IU/mL (range, 14 to 920 IU/mL). A baseline undetectable antibody to HBsAg (anti-HBs; < 10 mIU/mL) was the only significant risk factor that was positively associated with HBV reactivation (hazard ratio, 3.51; 95% CI, 1.37 to 8.98; P = .009). Patients with negative baseline anti-HBs, compared with those with positive anti-HBs, had a significantly higher 2-year cumulative rate of HBV reactivation (68.3% v 34.4%; P = .012). At HBV reactivation, all patients had normal ALT, and all patients but one were HBsAg negative. Entecavir successfully controlled HBV reactivation in all patients. Conclusion: A high rate of HBV reactivation was observed in HBsAg-negative, anti-HBc–positive patients undergoing rituximab-containing chemotherapy, with the risk of reactivation significantly higher in anti-HBs–negative patients. Periodic HBV DNA monitoring was an effective strategy in preventing HBV-related complications.

Background: Long-term effects of lamivudine treatment on chronic hepatitis B patients without advanced disease remain unknown. Our aim was to investigate the effects of long-term lamivudine treatment and lamivudine-resistant virus (YMDD) on the development of cirrhosis and hepatocellular carcinoma (HCC) in asymptomatic patients without advanced disease. Methods: One hundred and forty-two hepatitis B e antigen (HBeAg)-positive patients (median age: 33.9 years) on long-term lamivudine (median treatment duration: 89.9 months) and 124 HBeAg-positive controls (median age: 33.4 years) were prospectively followed up. Patients were monitored for the development of cirrhosis and HCC, liver biochemistry, hepatitis B virus (HBV) DNA levels, HBeAg seroconversion and hepatitis flares. YMDD mutations (YMDD-MT) were determined annually. Results: Lamivudine-treated patients had a significantly lower cumulative rate of development of cirrhosis and/or HCC compared with controls ( P=0.005). YMDD-MT occurred in 76.3% of patients after 8 years of lamivudine treatment. When compared with controls and patients with YMDD-MT, patients without YMDD-MT had the greatest reduction of HBV DNA and bilirubin levels, slowest decline of albumin level, highest rate of HBeAg seroconversion and lowest risk of hepatitis flare. Patients with YMDD-MT still had a lower risk for developing cirrhosis and/or HCC ( P=0.024) and a greater HBV DNA reduction ( P=0.001) in comparison with controls. Patients with YMDD-MT and controls had a similar chance of hepatitis flares and hepatic decompensation. Conclusions: Long-term lamivudine treatment was associated with a reduced chance of developing cirrhosis and HCC in patients without advanced disease. Although YMDD-MT reduced the benefits from lamivudine therapy, the outcome of these patients was still better than untreated patients.

The current available agents for the treatment of chronic hepatitis B (CHB) include immunomodulatory agents, such as interferon-α and pegylated interferon-α, and oral nucleoside/nucleotide analogues (NAs), including lamivudine, adefovir, telbivudine, entecavir and tenofovir. The NAs work mainly by inhibiting hepatitis B virus (HBV) DNA polymerase activity and thus suppress HBV replication. Oral NAs have become the mainstay of CHB treatment, mainly due to their profound viral suppressive effects and also due in part to the ease of single daily dosing and lack of significant side effects. One major drawback of NA therapy is the development of drug resistance mutations with long-term treatment. Lamivudine, the first oral NA approved for CHB patients, is associated with high rates of drug resistance, with resultant virological relapse and biochemical flare. Fortunately, newer and more potent NAs, such as entecavir and tenofovir, have very low resistance rates, with potent and durable viral suppression. This review is aimed at the current developments in NAs for CHB treatment, detailing the mechanisms of antiviral activity of the different agents, the efficacy of viral suppression, the achievement of treatment endpoints, the development of drug resistance and the optimal strategies for using these drugs.

We investigated the efficacy of entecavir, a cyclopentyl guanosine nucleoside analogue, as monoprophylaxis in patients with chronic hepatitis B who received a liver transplant. We studied data from 80 consecutive patients who received a liver transplant (47 from living donors and 33 from deceased donors) for hepatitis B-related disease and entecavir monotherapy as prophylaxis. None of the patients received hepatitis B immunoglobulin. Indications for transplant included decompensation from cirrhosis (27.5%), acute-on-chronic hepatitis B (47.5%), and hepatocellular carcinoma (25%). The median follow-up time was 26 months (range, 5-40 months). Before transplant, 33 patients were not on antiviral therapy and 47 were on oral therapy (18 had received less than 3 months of treatment). At the time of transplant, the median log HBV DNA level was 3.5 copies/mL (range, 1.54-8.81); 21 patients (26%) had undetectable levels of HBV DNA. The cumulative rate of hepatitis B surface antigen (HBsAg) loss was 86% and 91% after 1 and 2 years, respectively. Ten patients had reappearance of HBsAg. Eighteen patients (22.5%) were HBsAg positive at the time of their last examination; 17 of these had undetectable levels of HBV DNA, and the remaining patient had a low level of HBV DNA (217 copies/mL). There was no evidence of mutations at sites that confer resistance to entecavir among patients who were HBsAg positive. Although only 26% of patients had complete viral suppression at the time of transplant, 91% lost HBsAg, with 98.8% achieving undetectable levels of HBV DNA. A hepatitis B immunoglobulin-free regimen of entecavir monotherapy is effective after liver transplantation for chronic hepatitis B.