Natural course of acute hepatitis C: a long-term prospective study

Abstract

Background. Acute hepatitis C has a high chronicity rate which appears to be significantly reduced by early antiviral treatment. However, it is unclear if all acutely infected patients should be treated, and when. In this prospective study, patients with a well-documented diagnosis of acute hepatitis C were evaluated to define the natural course, the rate of chronicity, and host and virus-related factors which might predict a self-limiting or chronic evolution requiring early antiviral treatment.

Methods. From 1995 to 2000, 40 consecutive patients with a community-acquired AHC were enrolled. Liver tests, anti-hepatitis C virus antibodies and hepatitis C virus RNA levels were monitored. Median follow-up was 35 months (range 12–68).

Results. A total of 24/40 patients had symptomatic disease including 20 with jaundice; 13/40 patients had prompt serum hepatitis C virus RNA clearance and ALT normalisation within 12 weeks; in 12/13 patients this pattern remained unchanged during follow-up. Overall, 27/40 patients remained hepatitis C virus RNA positive with fluctuating ALT levels. Older age and jaundice were predictive of resolution whereas there was no correlation with other host factors, viral genotype or viral load.

Conclusions. Our data demonstrate that spontaneous resolution can occur in about 30% of AHC patients. This favourable outcome rarely occurs in patients with anicteric AHC or in those with jaundice but with persistent viremia for more than 12 weeks from onset; early antiviral treatment for these patients may avoid or reduce chronicity.

Introduction

Acute hepatitis C (AHC) is usually asymptomatic and therefore remains unrecognised in most infected individuals. Although more than 10 years have passed since the identification of hepatitis C virus (HCV), this silent onset explains why the natural history of acute hepatitis C is still poorly characterised [1]. Moreover, diagnosis of acute HCV infection is often problematic because there are no serological markers which can distinguish acute hepatitis C from an exacerbation of chronic hepatitis C. Both these issues are responsible for the difficulty in organising large patient studies which are necessary to produce guidelines for clinical management and treatment. The few reports available, mainly regarding transfusion-associated acute hepatitis C in which the onset of infection is clearly established, have demonstrated its marked propensity to progress to chronic hepatitis [2], [3], [4], which in turn can lead to cirrhosis and hepatocellular carcinoma [5], [6]. This high chronicity rate and evidence that treatment of patients with acute hepatitis C reduced the risk of chronic evolution [7], [8] emphasise the need to treat during early infection. However, if all acutely infected patients should be treated, and precisely when, is still unclear. Moreover, the epidemiological pattern of acute HCV infection has changed during recent years and the rate of chronic evolution of symptomatic community-acquired acute hepatitis C, most commonly seen at present, requires further evaluation.

Thus, in the present study we prospectively followed a cohort of patients with a well-defined diagnosis of acute hepatitis C acquired via various routes, to investigate the natural course, the rate of chronicity, and to identify host and virus-related factors which might predict which patients would spontaneously clear the virus or progress to chronic disease and therefore become candidates for antiviral treatment.