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Background/Aims : To determine the correlation between hepatic hepatitis C virus (HCV) RNA and histological lesions, viral genotype or response to alpha interferon therapy. Methods : Forty-three patients with chronic hepatitis C (14 sustained responders (SR) and 29 non-sustained responders (NSR)) were studied. A liver tissue sample was obtained before and 1 year after treatment. Quantitation of hepatic HCV-RNA was performed by competitive PCR. Results : Before treatment, HCV-RNA was detectable in all liver samples. There was no association between hepatic HCV-RNA and the severity of liver lesions. There was a significant association between old age and hepatic HCV-RNA ( P =0.03). There was an association, at the limit of significance, between genotype 1 and high hepatic HCV-RNA amounts (15×10 6 and 4.1×10 6 copies/g, P =0.05). Pre-treatment hepatic HCV-RNA amounts were lower in SRs than in others (0.65×10 6 and 13.2×10 6 copies/g, P =0.0002). After treatment, no liver HCV-RNA was detectable in the SRs while in the NSRs, the HCV-RNA amounts were unchanged. Conclusions : The amount of hepatic HCV-RNA is correlated to genotype and response to interferon therapy but not to histologic lesions. Hepatic HCV-RNA clearance is observed in SRs, suggesting viral eradication.

Background/Aims: The aim of this study was to determine the predictors for sustained response to alpha interferon therapy in a large population of patients with chronic hepatitis C, using multivariate analysis. Methods: Two hundred and ninety-six patients were included in four controlled trials of alpha interferon. Pretreatment serum HCV RNA levels were assessed by the branched DNA version 2.0 assay and HCV genotypes by the reverse hybridization assay (LiPA). Results: Sustained responses were observed in 37%, 14% and 6% of the patients with low, mediumand high pretreatment serum HCV RNA levels, respectively ( p −4 ). Sustained responses were observed in 5%, 4%, 32% and 27% of the patients with genotype 1a, 1b, 2a and 3a, respectively ( p −4 ). The multivariate analysis showed that a non-transfusional source of HCV infection, low serum HCV RNA levels and HCV genotypes non-1 (2a or 3a) were independent factors associated with sustained response to interferon therapy. Conclusion: Virological factors (flow pretreatment serum HCV RNA level and HCV genotype non-1a and non-1b), when adjusted in a large population of patients, using improved technology, are the main independent predictors of sustained response to alpha interferon therapy.

Background/Aims: The natural history of chronic hepatitis C infection during pregnancy has not been clearly established, and thus our aim was to assess serum alanine aminotransferase levels and serum HCV RNA levels during pregnancy. Methods: Twenty-six pregnant women with chronic hepatitis C were studied. Serum alanine aminotransferase was assessed within the 3 months before, monthly during and within the 3 months after pregnancy. In 12 women, serum HCV RNA levels were quantified by the branched DNA assay. Twenty-six age-matched non-pregnant women with chronic hepatitis C were followed up for 1 year, and used as a comparison group. Results: During pregnancy, serum alanine aminotransferase levels decreased in the second and third trimesters. The third trimester levels were significantly lower than serum alanine aminotransferase levels before pregnancy ( p =0.0001). Seventy-seven percent of the pregnant women with increased pre-pregnancy levels had normalization of serum alanine aminotransferase levels. In the second or third trimesters, serum HCV RNA levels increased. The third trimester serum HCV RNA levels were significantly higher than levels before pregnancy ( p =0.01). No significant change in serum alanine aminotransferase or HCV RNA levels was observed in the control group. Conclusion: In pregnant women with chronic hepatitis C, serum alanine aminotransferase levels decrease, and serum HCV RNA levels increase during the second and third trimesters.

Background/Aims: The aims of the study were to determine, in patients with chronic hepatitis C treated with alpha interferon: (i) changes in the morphometric evaluation of liver fibrosis at the end of treatment and 6, 12 and 18 months after treatment; (ii) the predictive value of histologic lesions for the response to treatment, in particular the predictive value of morphometric evaluation of liver fibrosis. Methods: Seventy patients with chronic hepatitis C who participated in two trials of recombinant interferon alpha 2b treatment were studied. Liver specimens were obtained before and at the end of treatment and 6, 12 or 18 months later. Histologic lesions were assessed according to the Knodell system. Quantitative study of total fibrosis and of Disse space collagen was done by the computerized automated morphometric method. Results: A significant decrease in morphometric Disse space collagen was observed at the end of treatment and 6 months later. This decrease was also observed, although it was not significant, 12 and 18 months after treatment. There was no relationship between this decrease and the biochemical and virological responses or the dose of interferon. The pretreatment Knodell activity score, but not the morphometric evaluation of fibrosis, was a significant predictor of sustained response. Conclusion: A decrease in Disse space collagen, as assessed by the sensitive morphometric method, was observed at the end of and 6 months after treatment. This observation is consistent with an anti-fibrogenetic effect of alpha interferon. Mild or moderate histologic activity was associated with a sustained response to therapy.