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Dilemma of the natural history of hepatitis C

natural history of hepatitis C and the controversy that has emerged. Non-A, non-B hepatitis (NANB) was first recognized in the early 1970s through a series of enzyme-monitored prospective studies seeking hepatitis in transfusion recipients. Another 15 years would elapse before hepatitis C would be identified as the predominant cause of the infection. The illness in these early transfusion studies seemed mild as judged by the paucity of symptoms, the low frequency of jaundice and the mild elevations of serum aminotransferases and, hence, early views held the condition to be relatively insignificant. Only when it became evident that approximately 50% of the NANB hepatitis cases persisted with raised serum enzymes for periods exceeding 6 months, establishing, by definition, evolution to chronic hepatitis, did concern about the infection begin to develop. This was reinforced by the evidence that as many as 20% of those biopsied for continuing enzyme abnormalities showed the presence of cirrhosis, and that HCC appeared to be a potential sequel to chronic NANB hepatitis. The relationship to HCC was further strengthened after discovery of HCV, which also permitted recognition that, while enzyme elevations persisted in approximately one-half of acutely infected persons, more than 80% of them remained viraemic. With this background, anxiety about chronic HCV infection spiralled, fuelled by several important prospective studies detailing high morbidity and mortality rates attributable to liver disease, which showed that HCV-related end-stage liver disease comprised the bulk of cases subjected to liver transplantation, and showed links between HCV and HCC. Based on these observations, progressive liver disease among HCV-infected persons seemed almost inevitable. Other studies, two in particular, presented a somewhat different picture. One, a multicentre follow-up study of transfused patients, reported that all-cause mortality approximately 18 years after transfusion was the same among those who had developed NANB/C hepatitis as among a matched control group of transfuSee article on page 269.