HBV DNA levels predict significant liver histology for HBeAg-negative chronic hepatitis B patients

Abstract

Background: Current treatment guidelines recommend liver biopsies for hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) patients with a high viral load but an alanine aminotransferase (ALT) less than 2 times the upper limit of normal before considering antiviral therapy. Aim: To determine any association between high HBV DNA levels and significant liver histology in both HBeAg-positive and HBeAg-negative patients. Methods: From 1994 to 2008, liver biopsy was performed on 313 treatment-naïve CHB patients. Histological assessment was based on the Knodell histologic activity index (HAI) for necroinflammation and the Ishak fibrosis staging for fibrosis. Pre-biopsy liver function, HBeAg status and HBV DNA levels were checked. Results: 205 HBeAg positive and 108 HBeAg negative patients were recruited, with a median age of 31 (range: 16-60) and 46 (range 18-63) respectively. An elevated HBV DNA was predictive of significant fibrosis (Ishak fibrosis stage ≥3, p<0.001) and significant necroinflammation (Knodell HAI ≥8, p=0.002) for HBeAgnegative CHB. While older age is associated with significant fibrosis for all CHB patients (p=0.001), a high viral load predicted significant fibrosis in HBeAg-negative patients with age <40 years (p<0.001) or ≥40 years (p=0.009). HBV DNA levels failed to predict liver histology in HBeAg-positive patients. An elevated ALT was associated with significant necroinflammation (p=0.002), but was not predictive of significant fibrosis for both HBeAg-positive and -negative patients. Conclusion: High HBV DNA levels were predictive of advanced liver histology in HBeAg- negative CHB but not in HBeAg-positive CHB, and may guide decisions regarding antiviral therapy for HBeAg-negative patients.