Morbidity and mortality in paid Austrian plasma donors infected with hepatitis C at plasma donation in the 1970s

Background/Aims

Between 1964 and 1987 several epidemic outbreaks of hepatitis C virus infection linked to plasma donation occurred at plasmapheresis centres in Austria. Data collected by a Foundation to help the victims enabled us to study the natural history of chronic hepatitis C in this cohort.

Methods

Medical records and charts of donors accepted by the Foundation were analyzed.

Results

Four hundred and eighty-five subjects (439 males; mean age at infection: 22 years) were included. Mean follow-up was 31 years. Thirty-four percent of plasma donors had advanced liver disease; alcohol abuse and diabetes were related to progression. Twenty-one patients developed hepatocellular carcinoma; 36 underwent liver transplantation. Six donors cleared the virus spontaneously. Forty died, with death directly related to liver disease in 25 donors. Overall and transplant-free 35-year cumulative survival rates were 84% and 74%, respectively. Three hundred and nineteen patients received and 291 completed antiviral treatment. All 56 who achieved a sustained virologic response are alive and well; 14 non-responders died and nine underwent liver transplantation.

Conclusions

Thirty-one years after virus infection, advanced liver disease has developed in a third of patients, with an overall mortality of 7%. These data underline the progressive nature of chronic hepatitis C infection and the need to identify and treat infected subjects.

Introduction

Worldwide, hepatitis C virus is the major cause of chronic liver disease and hepatocellular carcinoma. Up to 85% of patients with hepatitis C virus develop chronic infection, with persistent viraemia remaining detectable over many years [1]. However, the natural course of HCV infection remains poorly understood.

Several studies have followed patient cohorts with a known onset of infection [2], [3], [4], [5], [6]. Within the first 20 years after infection, hepatitis C follows a relatively benign course. Some variability has been shown, but overall between 5% and 25% of patients have spontaneous viral clearance and the majority of adults have persistent viraemia without clinically demonstrable liver disease [2], [3], [4], [5], [6].

Although study outcomes vary widely, after more than 20 years following hepatitis C infection, the long-term sequelae have been found to be more critical. For instance, in one study, in 131 patients seen at a referral centre 20–35 years after infection post-transfusion, chronic hepatitis C was a progressive disease leading to death in 20 patients (15%) from either end stage liver failure or hepatocellular carcinoma (5%) (although referral bias is likely to have increased the apparent death rate) [7].

However, a twenty-five-year follow-up of 1833 East German women who received hepatitis C-contaminated anti-D immunoglobulin showed that, although 86% were anti-HCV positive with 46% having detectable HCV RNA, only ten (0.5%) died of hepatitis C-related complications. Also, half of these related to additional comorbidities [8]. These results may reflect that these were generally young healthy non-drinking women who seem to be at less risk than older alcohol-drinking men. A small study showed that during a 45-year follow-up, liver disease occurred in two of 17 (12%) hepatitis C-infected military recruits who had been evaluated for group A streptococcal infection and acute rheumatic fever between 1948 and 1954 [9]. Seven (including one patient with confirmed liver disease) of the 17 persons (41%) and 2226 (including 119 of liver disease) of the 8551 HCV-negative persons (26%) had died [9] – the difference in mortality was not significant and could not be attributed to HCV infection. This study, with the longest follow-up, suggests that chronic hepatitis C is a relatively benign disease. Although these studies have variable outcomes, taken together, the data suggest that HCV has a relatively benign course within the first 20 years after infection, but with longer follow-up approximately 15–20% of patients progress to potentially serious end-stage liver disease. Progression to cirrhosis is likely to occur in up to 30% of all cases and the risk of developing hepatocellular carcinoma after longstanding infection is clearly increased [10].

The current report focuses on epidemic outbreaks of hepatitis non-A, non-B in plasma donors in Austria occurring until the mid 1980s. This 31-year follow-up helps to further our understanding of the natural history of chronic hepatitis C and to clarify the long-term outcome of chronic hepatitis C in a large number of infected subjects.