Isa K. Mushahwar

Pathogenesis of chronic liver disease in patients with chronic hepatitis B virus infection without serum HBeAg

Chronic hepatitis B in patients lacking hepatitis B e antigen has been attributed to a hepatitis B virus variant (G-to-A mutation at nucleotide 1896 in the precore region of the genome). We therefore assessed the frequency and significance of this variant among 43 United States patients (10 with chronic hepatitis B seropositive for e antigen, 19 seronegative for e antigen, and 14 healthy carriers). Sera were tested for HBV DNA by polymerase chain reaction and branched DNA assay. The A1896 variant was detected by direct sequencing and ligase chain reaction. Serum HBV DNA was more frequently found among patients with e antigenpositive than e antigen-negative chronic hepatitis B. Viral titers were generally higher in those with e antigen. None of the e antigen-positive and only 24% of e antigen-negative patients harbored the A1896 variant. Patients infected with the variant were more often Asian, had had hepatitis B for longer and had higher levels of viral DNA than HBeAg-negative patients with the wild-type virus. The A1896 variant was found exclusively in patients infected with HBV genotypes C and D. Thus, the A1896 variant is uncommon in the United States. The activity of liver disease appears to be more closely related to the level of HBV replication than the presence of mutations at nucleotide 1896 in the genome.

The Molecular Biology of GB Viruses

Following the development of specific and sensitive assays for the detection of the five recognized human hepatotropic viruses, it became apparent that additional human hepatitis viruses must exist as 5–20% of community-acquired and parenterally transmitted hepatitis cases could not be attributed to the known viruses. Further evidence for the existence of such viruses included varying incubation periods prior to disease onset (1), multiple disease episodes (2), chronic or fulminant hepatitis of cryptogenic origin (3, 4), and the visualization of virus-like particles (5, 6, 7). Finally, serial passage of the filterable GB agent was described in non-human primates (8, 9). This agent, originally obtained from a surgeon experiencing acute hepatitis, was inoculated into tamarins that later developed acute biochemical hepatitis. Although the disease could be further passaged in these animals, isolation of the putative agent remained elusive.