Polyarteritis nodosa related to hepatitis B virus. A prospective study with long-term observation of 41 patients.

Extrahepatic manifestations of chronic hepatitis B.

Hepatitis B virus (HBV) has been reported to exist in peripheral blood mononuclear cells (PBMC), but it is not clear whether it replicates there. A precondition for replication should be the formation of covalently closed viral DNA and transcription of all essential viral mRNAs. The mRNAs of HBV form a nested box with common 3' ends. In order to detect even low levels of potential replication, we developed a quantitative reverse transcription-PCR method for detection of a smaller HBV mRNA species in the presence of the larger ones. All three highly viremic patients tested so far had mRNAs for the large and the small surface proteins and the X protein of the virus within PBMC but not in the virus from their sera. Furthermore, we detected by PCR covalently closed viral DNA in their PBMC. These data suggest that HBV may be not only taken up but also replicated by mononuclear blood cells and that these cells may be an extrahepatic site of viral persistence. X mRNA was detected in the largest amount. Possibly, X protein interferes with functions of the mononuclear cells during the immune response against the virus.

Transcription of hepatitis B virus in peripheral blood mononuclear cells from persistently infected patients.

Scleritis: Immunopathogenesis and molecular basis for therapy.

Current information on the immunologic status of occult hepatitis B infection.

We have investigated hepatitis B virus (HBV) infection in systemic necrotizing vasculitis (SNV). Our approach included the detection of the viral surface antigen (HBsAg) with a radioimmunoassay employing monoclonal anti-HBs (m-RIA); in addition, HBV DNA was looked for in serum and peripheral mononuclear blood cells. Among 28 subjects with SNV, 12 were found to be positive for HBsAg with the conventional test (p-RIA) and 7 additional subjects had anti-HBc and/or anti-HBs. From the 16 HBsAg negative individuals, 9 had HBsAg epitopes identified in serum with the m-RIA test and 1 had a low amount of circulating viral DNA. In contrast, only 1 among 6 subjects with other systemic vasculitis showed a positive test for m-RIA and HBV DNA assays; this individual had acquired HIV infection through transfusions which were also probably the source of his HBV infection. HBV DNA sequences were identified in peripheral mononuclear blood cells of 9 from the 37 tested, including 2 individuals who were HBsAg positive only with m-RIA. Therefore, our study indicates a much higher rate of HBV infection in patients with polyarteritis nodosa than previously suspected.

Latent hepatitis B virus (HBV) infection in systemic necrotizing vasculitis.

. Hepatitis B virus (HBV) DNA sequences have been detected in leucocytes from HBV-infected individuals. The aim of this study was to assess the specificity of HBV for a special leucocyte subset in nine healthy chronic HBV carriers, nine HBs antigen-positive patients with chronic active hepatitis, 16 HBs antigen-negative haemophiliacs with HBc and/or HBs antibodies, and 10 patients with HBV-related systemic necrotizing vasculitis. HBV-DNA sequences were found by Southern blot hybridization in the leucocytes of 15 out of the 44 (34%) patients. The prevalence was not significantly different between the four groups. HBV-DNA was found in the CD4+ cells (9/11) as well as in the CD8+ cells (4/11), B cells (4/12) and monocytes (2/12). In conclusion, leucocytes, and particularly CD4+ lymphocytes, are frequently infected by HBV in patients with HBV serum markers.

Distribution of hepatitis B virus DNA sequences in different peripheral blood mononuclear cell subsets in HBs antigen-positive and negative patients.

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Latent hepatitis B virus (HBV) infection in systemic necrotizing vasculitis.

Distribution of hepatitis B virus DNA sequences in different peripheral blood mononuclear cell subsets in HBs antigen-positive and negative patients.