Changes in liver histology as a "surrogate" end point of antiviral therapy for chronic HBV can predict progression to liver complications

Abstract

BACKGROUND: The modified histology activity index (HAI) score has been extensively used as an additional primary or secondary end point in most phase III pivotal therapeutic clinical trials on chronic hepatitis B. Improvement in modified HAI after antiviral therapy has usually been defined as a 2-point reduction in modified HAI score. AIM: We studied whether a 2-point change in modified HAI score after antiviral therapy for chronic hepatitis B is associated with progression to liver complications (decompensated cirrhosis or hepatocellular carcinoma). METHOD: Eighty-nine patients treated with interferon-α with liver biopsy before and at 6 to 12 months after the end of therapy were followed-up for a median 119.4 months. RESULTS: At the time of analysis, 11 patients (12.4%) had liver complications. Liver complications were higher in patients with a 2-point increase in modified HAI score [8 of 19 patients (42.1%) vs. 3 of 70 patients (4.3%), P=0.0002] and in those with severe fibrosis at end of therapy [6 of 19 patients (31.6%) vs. 5 of 70 patients (7.1%), P=0.010]. On Cox regression analysis, a 2-point increase in modified HAI score was associated with increased liver complications (relative risk 5.564, P=0.036). CONCLUSIONS: A 2-point increase in modified HAI score after antiviral therapy is associated with increased progression to liver complications. © 2008 Lippincott Williams & Wilkins, Inc.