Outcome in a hepatitis C (genotype 1b) single source outbreak in Germany—a 25-year multicenter study

Background/Aims

The natural course of the hepatitis C virus genotype 1b (HCV-1b) infection is still unclear but important for therapeutic decisions. There are few unbiased long-term follow-up studies with known dates of infection.

Methods

Between August 1978 and March 1979, 14 HCV-1b contaminated batches of anti-D immunoglobulin had been administered to 2867 women for prophylaxis of rhesus isoimmunization throughout East Germany. We reexamined 1980 women, representing 70% of the total cohort of 15 centers.

Results

After application of the contaminated anti-D, 93% of the recipients developed an acute hepatitis C. After 25 years, 86% of the 1833 affected women still tested positive for hepatitis C virus antibodies and 46% for HCV RNA. Only nine (0.5%) had overt liver cirrhosis, 30 women (1.5%) developed precirrhotic stages and one HCC was diagnosed. Ten (0.5%) died of HCV related complications, half of these related to additional comorbidity. In the last 5 years, a continuous, but low increase of fibrotic scores was observed.

Conclusions

Young women without comorbidity may clear HCV (1b) infection in more than half of the cases, or develop mild chronic hepatitis C. We confirmed the low risk of progression to cirrhosis in this cohort within 25 years.

Introduction

Hepatitis C virus (HCV) infection is rated by the World Health Organization (WHO) and international consensus conferences as a global health problem, based on its prevalence, the high rate of chronicity, the rate of severe complications such as cirrhosis and HCC as well as the high costs of antiviral therapy and liver transplantation [1], [2], [3]. Screening measures by transfusion organizations as well as preventive measures have indeed led to a decreasing incidence of HCV infections in the industrialized world. However, the prevalence of fully-developed illnesses caused by HCV, and the subsequent mortality due to HCV are rising [4]. An evaluation of the risk of progression to cirrhosis and HCC is highly important in relationship to the need for therapy, not only for the general welfare of society but also for the individual patient. In order to make a decision for the appropriate therapy, studies of the natural course of the disease are necessary. This applies especially to aggressive and very expensive forms of therapy which are frequently burdened with side effects, e.g. interferon–ribavirin-therapy for chronic hepatitis C.

Retrospective studies on the natural history of hepatitis C assumed that HCV would lead to cirrhosis over the course of 20 years. However, more recent studies show that the progression of hepatitis C is usually slow and that only a proportion of cases develop rapidly into advanced forms of liver disease [1], [5], [6], [7]. Existing studies differ widely in design with the particular concern that specialized clinics, which are the sources of some of the studies, are more likely to see patients with advanced chronic liver disease and less likely to see those without any symptoms. International consensus conferences have therefore called for further prospective studies as well documented populations, indicating that natural history studies should begin with the onset of HCV infections. Especially interesting are the rare instances in which infection begins at a known time, such as the hepatitis C outbreak in East Germany in 1978/79 [8], [9], [10], [11], [12]. An earlier report regarding this cohort [11] showed the lowest ever reported cirrhosis rate of only 0.4% after 20 years.