Efficacy of entecavir in chronic hepatitis B patients with mildly elevated alanine aminotransferase and biopsy‐proven histological damage

Current guidelines for management of chronic hepatitis B recommend treatment for patients presenting with elevated hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT) >2 × upper limit of normal (ULN) or histological evidence of liver disease. Retrospective analyses have demonstrated that significant hepatic necroinflammation and fibrosis were present in a substantial proportion of patients with ALT 1 to 2 × ULN. To assess therapeutic efficacy in this clinical setting, we retrospectively examined treatment endpoints among the subset of nucleoside‐naïve chronic hepatitis B (CHB) patients treated in phase 3 clinical trials of entecavir who had both screening and baseline serum ALT 1.3 to 2 × ULN. A total of 1347 patients were randomized to treatment with entecavir or lamivudine. Three hundred thirty‐six patients, constituting 25% of the total study population, had screening and baseline ALT 1.3 to 2 × ULN. Clinically significant necroinflammation (Knodell necroinflammation score ≥7) was observed in 60% and 72% of hepatitis B e antigen (HBeAg)‐positive and HBeAg‐negative patients, respectively, whereas marked fibrosis (Ishak fibrosis score ≥4) was observed in 8% and 15% of HBeAg‐positive and HBeAg‐negative patients, respectively. Among entecavir‐treated HBeAg‐negative patients, the proportions of patients achieving histological improvement, HBV DNA 2 × ULN. However, entecavir‐treated HBeAg‐positive patients with mildly elevated ALT had lower response rates for histological improvement, HBV DNA less than 300 copies/mL, ALT normalization, and HBeAg seroconversion than those with ALT greater than 2 × ULN. Conclusion: This retrospective analysis demonstrated that HBeAg‐negative CHB patients treated with entecavir responded similarly irrespective of baseline ALT level. However, HBeAg‐positive patients with mildly elevated ALT responded less well to treatment with entecavir than did those with ALT greater than 2 × ULN. (HEPATOLOGY 2010.)