Long-term beneficial outcome of Chinese asymptomatic patients with HBeAg-positive chronic hepatitis B on continuous lamivudine therapy: 7-year experience

Abstract

AIM: To determine whether long-term lamivudine treatment in asymptomatic patients can reduce the risk of hepatocellular carcinoma (HCC) and cirrhosis-related complications. Patients and METHOD: Two hundred and sixty-six HBeAg-positive patients (140 with lamivudine and 126 without treatment serving as controls) were recruited from the Hepatitis Clinic, Queen Mary Hospital, Hong Kong. They included all patients who participated in 3 controlled trials of lamivudine (NUCB 3009, 3018, 4003) and all the other patients who fulfilled the inclusion criteria but were not included in the trials seen at the same period of time (1994-1997). All lamivudine-treated patients were maintained on lamivudine throughout follow-up irrespective of HBeAg seroconversion. RESULTS: There were no differences in the baseline characteristics and liver biochemistry between the 140 treated patients (M:F 105:35; median age 33.9 years) and the 126 controls (M:F 92:34; median age 33.3 years). The follow-up duration was significantly longer in controls compared to that of lamivudine-treated patients (median 106.2 vs. 90 months respectively, p0.004). There were no differences in the cumulative rates of HBeAg seroconversion and hepatitis flare between the two groups (pNS). However lamivudine-treated patients had a slower decline in albumin levels during the follow-up period compared to controls (median drop 3 vs. 4 g/L respectively, p0.025). 93 (66.4%) lamivudine-treated patients and 81 (64.3%) controls had normal ALT level at the last follow-up. HCC occurred in 1 lamivudine-treated patient and 3 controls. Cirrhosis developed in 6 lamivudine-treated patients and 15 controls. Using Kaplan-Meier analysis, lamivudine-treated patients had a significantly lower cumulative risk of development of complications compared to controls (log rank test, p0.035). At the time of writing, YMDD mutations were determined in 38 lamivudine-treated patients with elevated transaminases during follow-up. 36 had YMDD mutations. At the last follow-up, there were no differences in the liver biochemistry between patients with YMDD mutations and controls; 24 (66.7%) of patients with YMDD mutations had normal ALT levels. CONCLUSIONS: Long-term lamivudine treatment can reduce the risk of complications from CHB in asymptomatic HBeAg-positive patients. Development of YMDD mutations was not associated with more serious disease when compared to untreated patients.