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Hepatitis B virus (HBV) with X gene mutations has been a putative pathogen of chronic hepatitis without serological markers of known hepatitis viruses. The aim of this study was to reconfirm whether the HBV with the X gene mutation is associated with these serologically "silent" non-B, non-C (NBNC) chronic hepatitis, alcoholic liver disease (ALD) and autoimmune hepatitis (AIH). HBV DNA was amplified from serum and sequenced in 30 patients with NBNC chronic hepatitis in comparison with 20 patients with ALD and 5 patients with AIH. HBV DNA was identified in 21 patients (70%) in NBNC chronic hepatitis by nested polymerase chain reaction while only one patient (5%) in ALD and none in AIH showed HBV DNA. Eighteen (85.7%) of the 21 identified HBV DNAs had an identical 8-nucleotide deletion mutation at the distal part of the X region. This mutation affected the core promoter and the enhancer II sequence of HBV DNA and created a translational stop codon which truncated the X protein by 20 amino acids from the Cterminal end. All the HBV DNAs had a precore mutation at the 83rd nucleotide resulting in disruption of HBe antigen synthesis. These results indicate that HBV mutants are closely associated with the majority of serologically "silent" NBNC chronic hepatitis cases and the population of such mutant HBV DNAs is not uniform.

To investigate the relationship between intrahepatic cytokine expression and interferon (IFN) response in chronic hepatitis C [CH(C)], interleukin (IL)‐1ß,‐2,‐4,‐6,‐8, interferon (IFN)‐γ, tumor necrosis factor (TNF)‐α and TNF‐ß mRNAs were investigated semiquantitatively by reverese transcription polymerase chain reaction using serial liver biopsies taken before and after IFN‐α treatment from 24 patients with CH(C), including 12 responders and 12 non‐responders. Before IFN treatment, IL‐2, TNF‐ß, IFN‐γ and IL‐8 mRNA were associated with severe hepatitis activity whereas IL‐4 mRNA was associated with weak hepatitis activity, regardless of IFN response. IL‐2, TNF‐ß and IFN‐γ mRNAs were significantly greater in IFN non‐responders. After IFN treatment a complete response to IFN was significantly associated with the disappearance of these pro‐inflammatory cytokines, whereas non‐responders retained the expression of cytokine mRNA as before IFN treatment. Our results indicated that IFN‐α treatment may modulate the intrahepatic cytokine network, and this may be one mechanism of IFN‐α that reduces hepatitis activity, aside from an anti‐viral effect. A difference in cytokine network may be involved in IFN response in CH(C).

To investigate whether interferon-alpha receptor (IFN-alpha Rc) expression was related to the effectiveness of interferon therapy in hepatitis C virus (HCV)-associated chronic liver disease (CLD). IFN-alpha Rc mRNA was investigated by reverse transcription polymerase chain reaction (RT-PCR) in liver biopsies and peripheral blood mononuclear cells (PBMCs) from 40 patients with HCV-associated CLD who subsequently received IFN-alpha therapy. IFN-alpha Rc mRNA in the liver was detected in 18 of 20 (90%) responders to IFN and in 5 of 20 (25%) non-responders (P < 0.01). In PBMCs, IFN-alpha Rc mRNA was detected in all patients regardless of response to IFN. Increased histological hepatitis activity and liver fibrosis were significantly related to the absence of IFN-alpha Rc mRNA. The HCV-RNA genotype showed no significant relationship to IFN-alpha Rc mRNA expression. Our results suggest that IFN-alpha Rc mRNA expression in the liver, but not in PBMCs, is closely associated with the effectiveness of IFN-alpha therapy in HCV-associated CLD.