Elsevier

Hepatology Research

Volume 9, Issues 2–3, December 1997, Pages 144-151
Hepatology Research

Natural disappearance of serum HCV RNA: prospective study in a hyperendemic area

https://doi.org/10.1016/S1386-6346(97)00090-9Get rights and content

Abstract

We examined the clinical and laboratory factors related to natural disappearance of hepatitis C virus (HCV) RNA by multiple logistic analysis after two rounds of testing in H town (3708 subjects) from 1990 to 1996. Liver function parameters, HBsAg and anti-HCV antibodys were determined in sera. In HCV seropositive individuals, abdominal ultrasonography, HCV RNA testing and where appropriate, HCV genotype and RNA level determinations were performed. Among 517 HCV RNA-positive subjects in the first screening, 270 subjects could be tested after an average interval of 4.3 years. Of these, 235 (87%) were RNA-positive at the second screening (positive persisted) and 35 (13%) had become negative (seroconversion to negative). The natural disappearance rate of serum HCV RNA was estimated as 2.8% per year. Significant independent factors related to disappearance were: serum HCV RNA levels (below 1.0 Meq ml−1); alanine aminotransferase (below 30 IU l−1) and zinc turbidity test (below 7.9 KU). These factors should help in elucidating mechanisms of HCV exclusion from the host, in predicting prognostication and in patient selection for interferon therapy.

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.

Section snippets

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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