State of hepatitis B virus DNA in peripheral blood mononuclear cells from persistently infected individuals: correlation with e antigen and viral DNA in the serum as well as with the activity of liver disease.

Abstract

Peripheral blood mononuclear cells (PBMC) were harvested from 76 asymptomatic carriers of hepatitis B virus (HBV) and 100 patients with type B chronic liver disease. DNA was extracted from cells and tested for the binding with radiolabeled HBV DNA probe by Southern blot hybridization technique. Among 34 asymptomatic carriers who had hepatitis B e antigen (HBeAg) and HBV DNA in the serum, HBV DNA was detected in 29 (85%) PBMC. In remarkable contrast, of the remaining 42 carriers seronegative for HBeAg, only 1 (2%) had HBV DNA in the serum, and none exhibited HBV DNA in PBMC. Among 32 patients seropositive for HBeAg, HBV DNA was detected in 28 (88%) sera, and in 24 (75%) PBMC. Of 68 patients seronegative for HBeAg, HBV DNA was found in 10 (15%) sera, and in 7 (10%) PBMC. Among 62 cases with HBV DNA in PBMC, only 1 had it integrated into the host's DNA. The remaining 61 had free HBV DNA in PBMC. Only 8 of them possessed replicative intermediate forms of HBV DNA, with molecular sizes less than 2.0 kilobases as observed in liver infected with HBV, and they all were patients with chronic active hepatitis. HBV DNA was not detectable in PBMC from 172 controls comprising 44 healthy individuals and 128 patients with non-A, non-B hepatitis. Based on these results, the state of HBV DNA in PBMC reflects the phase of HBV infection with HBeAg in the serum, and a high activity of hepatitis accompanied by active HBV replication.