Pretreatment ALT Level and Histologic Activity as Predictors of HBeAg Loss in Lamivudine Treatment for Chronic Hepatitis B

Kweon, Young Oh; Kang, Kyung Hee

Abstract

BACKGROUND/AIMS: Lamivudine is a potent inhibitor of hepatitis B virus replication, but an increased incidence of YMDD mutation may be associated with its long term use. Thus, the decision to initiate therapy should be based on variables that are predictive of lamivudine-induced HBeAg loss. The objective of this analysis was to determine patient-dependent or laboratory variables that predict HBeAg loss. METHODS: We retrospectively analyzed 99 HBeAg-positive patients with chronic hepatitis B who were treated with lamivudine and followed up for more than 52 weeks. All patients had a liver biopsy before starting lamivudine therapy. HBeAg loss and HBeAg seroconversion after 52 weeks of treatment were defined as endpoints. RESULTS: The overall rates of HBeAg loss and HBeAg seroconversion were 41.4% (41/99) and 37.4% (37/99), respectively. The rates of HBeAg loss increased as pretreatment ALT levels increased (P=0.013) and were highest among patients with pretreatment ALT levels greater than 5 times the upper limit of normal, occurring in 56.8% of those patients. The rate of HBeAg loss was higher in patients with more active histologic disease on pretreatment liver biopsy (Grade 1 and 2 vs. Grade 3 and 4, 28.3% vs 56.5%, P=0.004). Similar results were seen with HBeAg seroconversion, though seroconversion occurred less frequently than HBeAg loss. Multivariate analysis showed that elevated baseline ALT levels (P<0.05) and histologic activity (P<0.05) were the best independent predictors of HBeAg loss and seroconversion in response to lamivudine. CONCLUSIONS: Pretreatment ALT levels and histologic activity were the most important predictors for response to lamivudine.