[Clinical studies on the detection of hepatitis C virus genome in the serum and the liver].
Hepatitis C virus (HCV) is the major cause of non-A, non-B hepatitis worldwide. Since the HCV viral genome was molecularly cloned and antibody detection systems were established, a considerable amount of information on HCV has been accumulated. In the present study, I have examined the sera and liver tissues of the patients of type C chronic liver disease using molecular biological methods and tried to correlate the data obtained with the clinical, pathological and therapeutic outcomes. A reverse transcription-polymerase chain reaction (RT-PCR) method using radiolabeled nucleotides provided constant results in genome amplification, and could be shown to be a reliable method for quantifying the levels of HCV genome. The amount of HCV RNA in the serum tended to increase as a function of the duration of the disease and the progression of histopathologic changes of the liver. In addition, the serum HCV RNA titers correlated well with those of liver tissues, which showed that the amount of circulating HCV genome reflected the intrahepatic amount of HCV. HCV, a positive-stranded RNA virus, is likely to make a negative strand during viral replication. In studies to detect the positive and negative strands of HCV RNA separately using strand specific primers, the existence of both strands in the liver was demonstrated, confirming viral replication in the liver. The ratio of negative to positive strands ranged from 0.03% to 30%, being 3.7% in chronic persistent hepatitis, 4.8-6.0% in chronic aggressive hepatitis and 6.7% in liver cirrhosis. The viral factors influencing the interferon (IFN) response were also examined. Individuals who had low titers of HCV genome tended to respond well to IFN. Moreover, IFN was more effective for patients with HCV type III than for those with HCV type II. Thus, IFN response was shown to depend both on virus titers and genotypes. However, mean levels of HCV RNA were almost the same between the patients with HCV type II and those with HCV type III before the treatment, there were significant differences in the disappearance of HCV and the effects of IFN therapy. It is suggested that the susceptibility to IFN is different for each genotype. Hokkaido J Med Sci 69 (6), 1382-1398, 1994.
Hige
S
S
Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
D000328:Adult; D000368:Aged; D001483:Base Sequence; D005260:Female; D016679:Genome, Viral; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000175:diagnosis* / Q000628:therapy; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis* / Q000097:blood
D012367:RNA, Viral; D007372:Interferons