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.