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

Abstract

UNLABELLED:

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 x 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 x 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 x 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 x ULN. Clinically significant necroinflammation (Knodell necroinflammation score > or =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 > or =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 <300 copies/mL, and ALT normalization were similar between patients with mildly elevated ALT and those with ALT >2 x 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 x 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 x ULN.

• Authors: I-Chin Wu, Ching-Lung Lai, Steven-Huy Bui Han, Kwang-Hyup Han, Stuart C Gordon, You-Chen Chao, Chee-Kiat Tan, William Sievert, Tawesak Tanwandee, Dong Xu, Boon-Leong Neo, Ting-Tsung Chang
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 51 Issue 4 Pg. 1185-9 (Apr 2010) ISSN: 1527-3350 [Electronic] United States
• PMID: 20044806 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• Antiviral Agents
• Hepatitis B e Antigens
• entecavir
• Guanine
• Alanine Transaminase

Topics

• Adult
• Alanine Transaminase (blood)
• Antiviral Agents (therapeutic use)
• Biopsy
• Female
• Guanine (analogs & derivatives, therapeutic use)
• Hepatitis B e Antigens (analysis)
• Hepatitis B, Chronic (drug therapy, physiopathology)
• Humans
• Liver (physiopathology)
• Male
• Middle Aged
• Retrospective Studies