E-ANTIGEN DEFECTIVE HEPATITIS-B VIRUS AND COURSE OF CHRONIC INFECTION

We studied the relations between HBV heterogeneity and different phases of HBV infection and disease in 145 HBsAg-positive carriers followed-up for 28 months (range 24-60 months). Viraemia was characterized for the relative prevalence of wild-type and HBeAg minus HBVs after HBV-DNA amplification by PCR using an oligonucleotide hybridization assay. HBeAg minus HBV was detected in 27% of immunotolerant HBV carriers, in 67% of patients with chronic hepatitis B (immunoelimination phase) and in 17% of HBsAg carriers with latent infection. Serum HBV-DNA and IgM anti-HBc became undectable and ALT levels normalized, either spontaneously or after interferon therapy in 12 (36.3%) of 33 patients with an exclusive wild-type viraemia, but only in two (5.7%) of 35 patients with homogeneous HBeAg minus HBV (p = 0.005). An HBeAg minus viraemia higher than 20% was associated, in both HBeAg- and anti-HBe-positive patients, with HBV-induced liver disease and an unfavourable outcome of hepatitis. These findings suggest that surgence of HBeAg defective HBV is a virus strategy to survive under peculiar conditions dictated by the interplay between HBV and the host's immune system. The HBeAg/anti-HBe serological status is determined not only by the extent of virus replication and integration of HBV-DNA into cellular DNA but also by heterogeneity of HBV. The study of HBV heterogeneity in baseline sera of patients undergoing antiviral therapy appears to have a predictive value of the outcome of HBV infection in the single patient.