Role of hepatitis C and delta viruses in the termination of chronic hepatitis B surface antigen carrier state: a multivariate analysis in a longitudinal follow-up study.

Influences of hepatitis delta (HDV) or C virus (HCV) superinfection on the spontaneous clearance of hepatitis B virus (HBV) surface antigen (HBsAg) were investigated in 992 patients. Patients were infected with HBV alone (group 1), HBV and HDV (group 2), HBV and HCV (group 3), or all three viruses (group 4). They were followed for 6.2 +/- 3.7 years. Thirty-six patients (3.6%) had spontaneous serum HBsAg clearance. There was an increasing linear trend in the annual incidence from 0.43% (group 1) to 0.64% (group 2), 2.08% (group 3), and 2.33% (group 4; P < .0001). Relative risk (RR) of group 3 to 1 was 4.8 (P < .001) and of group 4 to 1 was 5.1 (P < .02). RR was significantly higher in group 3 than 2 (P < .02). By Cox multivariate regression analysis, only HCV superinfection and age at entry were significant influencing factors. Moreover, there was a significant interaction between HCV and age. Patients > 35 years old with HCV had a higher HBsAg clearance rate. Results suggest that HCV is the most important hepatotropic virus that enhances HBsAg clearance in chronic hepatitis B.