Long-term lamivudine therapy reduces the risk of long-term complications of chronic hepatitis B infection even in patients without advanced disease.

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.

One-year entecavir or lamivudine therapy results in reduction of hepatitis B virus intrahepatic covalently closed circular DNA levels.

Entecavir and lamivudine are potent nucleoside analogues that can suppress hepatitis B virus (HBV) replication. However, the effects of these two antiviral agents on intrahepatic total HBV DNA and covalently closed circular DNA (cccDNA) are not known. In this study, we aimed to assess the effect of 48 weeks of entecavir/lamivudine therapy on intrahepatic total HBV DNA and cccDNA levels. Forty chronic hepatitis B patients, participating in two Phase III entecavir trials at our centre, were randomized to receive 48 weeks of either 0.5 mg once daily of entecavir (n = 21) or 100 mg once daily of lamivudine (n = 19). Their serological, virological and biochemical responses, as well as intrahepatic HBV DNA levels were monitored. There was no significant difference between entecavir and lamivudine therapy in terms of post-treatment serological, virological and biochemical responses. Both nucleoside analogues reduced serum viral load, intrahepatic total HBV DNA, and cccDNA by about 4.8 logs, 2 logs, and 1 log respectively. An increase in the proportion of intrahepatic HBV DNA in the form of cccDNA was seen after 48 weeks of therapy. In conclusion, both entecavir and lamivudine can successfully reduce intrahepatic HBV DNA and cccDNA. CccDNA becomes the dominant form of HBV DNA during viral suppression and is possibly responsible for viral rebound after short-term antiviral therapy.