Abstract

In 1996 we initiated a retrospective-prospective study in 184 untreated women infected in 1977 with chronic hepatitis C virus (HCV). To provide insight into the natural history of HCV, we determined liver fibrosis outcomes and any predictors of such. Baseline 1994 biopsy specimens (size, >or=15 mm; portal areas, >or=5) and sequential biopsy specimens were assessed by Ishak score for grade change (increase or decrease of >or=2 points) and stage progression or regression (increase or reduction of >or=1 point), the latter correlated with digital quantification of fibrosis percentage. No baseline biopsy specimens had cirrhosis, therefore all could potentially progress. Grade and stage scores decreased or increased significantly in 28% and 18% and 24% and 27% of patients, respectively. There was a positive correlation between baseline and sequential grade/stage scores (r = .39, P < .001), and between semiquantitative Ishak scores and fibrosis percentage (Spearman rho = .85; P < .01). Baseline alanine transaminase values (mean, 49 U/L; range, 23-363 U/L) correlated positively with changes in grade (r = .41, P < .01) and stage (r = .39, P < .01), and regression analyses indicated that baseline alanine transaminase value was a good predictor of such changes. Confounding variables (alcohol, smoking, and herbal and paracetamol [acetaminophen] use) did not correlate with histologic outcomes. In a follow-up study, 49% of patients showed no change in fibrosis, 24% showed regression, and only 27% showed progression, including 4 patients (2.1%) who developed stage 6 cirrhosis. Unidirectional sequential grade/stage concordance attested to biopsy sample reliability. Given the current age of these women in their fifth decade, some still may have a risk for more advanced liver disease, but for most of these patients it appears unlikely.

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