Natural disappearance of serum HCV RNA: prospective study in a hyperendemic area
Introduction
Patients with chronic hepatitis C often progress to liver cirrhosis and hepatocellular carcinoma 1, 2, 3. Few patients show natural recovery. However, 20–30% of anti-HCV antibody positive cases lack serum hepatitis C virus (HCV) RNA 4, 5. This data imply that natural disappearance of HCV RNA occurs in some individuals infected with HCV. There have been no reports concerning the factors involved in the natural recovery or disappearance of serum HCV RNA.
H town, Fukuoka Prefecture in northern Kyushu, Japan, which has an adult population of approximately 7400, distributed in four districts (S, 1800; K, 1800; H, 2600 and M, 1200) with a high HCV infection rate. Most inhabitants are engaged in agriculture. Living and educational status correspond to the national averages. The area has experienced little migratory activity, with most families residing there for many generations. This town is not known for practising folk remedies. Previously, we tried to clarify the transmission route of HCV in H town, but we could not get clear results [6]. In the present study we conducted mass screenings twice in this town to analyze factors related to the natural disappearance of HCV RNA. The results obtained in this study will be useful for clarification of the mechanism of natural clearance of HCV infection and for selecting patients eligible for interferon (IFN) therapy.
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Materials and methods
Sera from 3708 subjects (1504 males and 2204 females) from H town were first screened during 1990 to 1994 for serum levels of aspartate aminotransaminase (AST, normal, <40 IU l−1), alanine aminotransaminase (ALT, normal, <30 IU l−1), zinc turbidity (ZTT, normal, <12 Kunkel Units) [7], anti-HCV antibody and HBsAg. Subjects positive for anti-HCV antibody were further analyzed for serum HCV RNA and if positive for HCV RNA, HCV genotypes and serum HCV RNA levels. They were also analyzed by
Changes in anti-HCV antibody and HCV RNA levels
In the first screening of 3708 subjects (1504 males and 2204 females), the prevalence of anti-HCV antibody was 20% (743/3708) and HCV RNA was positive in 69.6% (517/743) of those who were positive for anti-HCV antibody. An elevated ALT was observed in 40.5% (301/743) of those positive for anti-HCV antibody. In the second screening, 270 subjects (58.1 mean age, 26–85 range; 156 males and 238 females) of the original 517 subjects positive for HCV RNA could be examined again. At the second
Discussion
The natural disappearance rate of serum HCV RNA has been reported to be as low as 0.2–0.3% per year, indicating that most patients with chronic hepatitis C do not spontaneously recover. The results of this study showed that the natural disappearance rate was 2.8% per year, a result higher than those of other studies 3, 15. The selection bias in other studies that the subjects were limited in symptomatic patients, may explain the difference. The results of the multivariate analysis showed that
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