Low frequency of cirrhosis in a hepatitis C (genotype 1b) single-source outbreak in germany: A 20-year multicenter study

Abstract

batches of anti-D immune globulin contaminated with hepatitis C virus (HCV) genotype 1b (20,000-480,000 copies/dose) from a single erythrocyte donor had been administered for prophylaxis of rhesus isoimmunization throughout East Germany. All 2,867 women involved had been recalled after January 12, 1979 for repeated screening of alanine transaminase (ALT). They were prospectively followed in regional centers. We have reexamined a cohort of 1,018 women (median age 24, range 16-38 years at infection) on follow-up for 20 years in 9 representative centers. Within 6 months after anti-D administration, 10% of these women had no evidence of disease and 90% had acute hepatitis C (n ‫؍‬ 917) including 49% with symptomatic and 22% with icteric course. After 20 years, 85% of the 917 affected women still tested positive for HCV antibodies (among them 3% responded to interferon treatment) and 55% were positive for HCV RNA (among them 7% were nonresponders to interferon and 3% were apparent HCV carriers). Only 4 (0.4%) had overt cirrhosis. Two (0.2%) died of superinfected fulminant hepatitis B or alcoholism and cirrhosis, respectively. Histology obtained in 44% of the viremic women showed hepatitis of minimal to moderate grade in 96%, portal fibrosis in 47%, and septal fibrosis in 3% of the cases.

Hemophilic Siblings With Chronic Hepatitis C: Familial Aggregation of Spontaneous and Treatment-Related Viral Clearance

“…These rates of viral clearance are consistent with other reports in nonhemophilic populations (1), although somewhat less than reported in children and young women infected through contaminated blood products (4,43). In the hemophilia cohort, repeatedly exposed to unsterilized blood products, it is possible that single episodes of spontaneous viral clearance were overshadowed by reinfection during subsequent exposures, as has been demonstrated in thalassemic patients who developed repeated episodes of acute hepatitis C following multiple exposures (44).…”

“…Population-based studies in the United States indicate that approximately 75% of patients remain chronically infected with hepatitis C (1). In contrast, up to 50% of patients have been reported to spontaneously resolve hepatitis C infection when exposure occurred in children undergoing cardiac surgery or cancer chemotherapy, in young women after a common-source outbreak of contaminated anti-D immunoglobulin, or in healthcare workers after needlestick exposures (2)(3)(4).…”

“…Attempts to define the natural history of hepatitis C have yielded conflicting results and indicate that the outcome is neither uniformly fatal nor predictable. Fewer than 10% of European women infected with hepatitis C from anti-D immunoglobulin, progressed to cirrhosis, and the majority had only mild chronic hepatitis, after two decades of observation (2,4,6). Similarly, patients with hepatitis C viremia may have persistently normal ALT activities during prolonged monitoring with minimal histologic changes (7,8).…”

Liver disease progression in hepatitis C virus carriers with normal alanine aminotransferase levels

“…Whereas some studies showed that HCV carriers with normal ALT have mild and stable disease, others reported a significant progression of fibrosis in approximately 20%-30% of such patients. 3 In their first study 4 describing the 20-year follow-up of over 1,000 women infected in East Germany in January 1979 by contaminated anti-D immune globulin, the researchers reported that 26 patients should be considered as true healthy carriers (i.e., normal liver, normal ALT, and persistent HCV viremia). At 25-year follow-up, 5 only 11 women had remained in a healthy state, whereas the others had progressed to chronic hepatitis C (CHC).…”

“…1. Of the original 26 HCV carriers which we described at 20 years after infection, 4 HCV inhouse polymerase chain reaction (PCR) emerged as false-positive in three patients, unraveling a spontaneous resolution of HCV infection in these patients. Among the remaining HCV carriers, seven patients developed chronic hepatitis C as determined by elevated transaminases and clinical or histological signs of liver damage.…”