Detection of hepatitis B virus in the liver by in situ hybridization (ISH) in HBsAg seropositive and seronegative patients.

The presence of hepatitis B virus (HBV) DNA in the liver of 119 patients was studied to assess the diagnostic value of in situ hybridization (ISH) and its relationship with viral replication and histological liver damage. Liver biopsies of 119 patients (55 hepatitis B surface antigen -HBsAg- seropositive and 64 HBsAg seronegative) were studied retrospectively. Among the HBsAg seropositive patients, the ISH was positive in 26 cases (47%) and negative in 29 (53%) and the former group had higher levels of serum transaminases. The hepatocyte number with positivity for HBsAg and hepatitis B core antigen (HBcAg) in the liver were similar in both ISH-positive and -negative patients. The histological activity index (Knodell) was higher in ISH-positive patients (11 vs 7, p < 0.001). Six patients out of 12 were positive by PCR. In the HBsAg seronegative patients, the ISH was negative in 57 cases and positive in 7. These 7 were positive for anti-HBs (5 cases) and/or anti-HBc (6 cases); 4 were confirmed by PCR. Thus, our data suggest that the ISH technique is useful for detecting viral nucleic acid in the liver, but that the HBV-DNA cannot always be considered as a replication marker, because we also show that some HBsAg seronegative patients with chronic liver disease do have HBV-DNA in their liver cells.