Quantification of intrahepatic hepatitis B virus (HBV) DNA in patients with chronic HBV infection

No data are available about the amount of hepatitis B virus (HBV) genomes i n liver of patients with chronic HBV infection. The aim of this study was t o quantify the intrahepatic HBV DNA in hepatitis B surface antigen (HBsAg)- positive patients with either active or suppressed viral replication and in HBsAg-negative subjects with occult HBV infection. We optimized the Roche "Amplicor HBV Monitor" kit for quantifying liver HBV DNA and analyzed hepat ic DNA extracts and serum samples from 19 HBs-Ag-positive and 43 HBsAg-nega tive individuals. Eight of the HBsAg carriers had active HBV replication, a nd for 3 of them we analyzed samples obtained before and at the end of 1 ye ar of lamivudine treatment. Five hepatitis Delta virus (HDV) coinfected pat ients and 6 healthy HBsAg carriers had inhibited HBV activity. Among the HB sAg-negative subjects 21 had occult HBV infection and 22 had no evidence of HBV infection. The median of HBV genomes per microgram of liver DNA millil iter of serum was 34,500 to 2,620,000 in patients with active viral replica tion, 20,000 to 3,900,000 before and 10,000 to 2,800 at the end of therapy in lamivudine-treated individuals, 9,800 to 600 in HDV-infected individuals , and 7,450 to 17,400 in healthy HBsAg carriers. These data indicate that c ases with suppressed HBV activity, despite the very low levels of viremia, maintain a relatively high amount of intrahepatic viral genomes. This virus reservoir is likely involved in HBV reactivation, which is usually observe d after stopping lamivudine treatment. Finally, the analysis of cases with occult HBV infection showed that the assay we used was able to specifically detect and quantify as few as 100 copies of viral genomes per microgram of liver DNA.