THE NATURAL HISTORY OF CHRONIC HEPATITIS C VIRUS INFECTION

Within a short time of the recognition of acute non-A, non-B (NANB) hepatitis, identified in the course of enzyme-monitored transfusion studies conducted during the early 1970s, it became clear that, despite a paucity of symptoms, the illness failed to resolve in approximately half of those affected. The evidence for disease persistence was the fact that the serum enzymes, specifically alanine aminotransferase (ALT), continued to remain abnormal for periods in excess of 6 months. Now labeled chronic hepatitis by convention, liver biopsy examination confirmed this clinical diagnosis through the identification of histologically-defined chronic hepatitis of graded severity in about 50% to 60% of instances and of cirrhosis in another 20%. Despite these findings, most affected persons remained oblivious to these outcomes because of continued lack of symptoms.

The detection almost a decade and a half later of the hepatitis C virus (HCV) provided a further tool for identifying chronicity. With the development of the highly sensitive polymerase chain reaction (PCR), it was possible to identify the persistence of HCV RNA in an additional group, even in the absence of raised ALT values. Currently, it is believed that approximately 85% of acutely infected individuals fail to recover fully following acute HCV infection.

Short-term prospective, point-prevalence, and retrospective studies have since shown that, once chronically infected with HCV, such persons are at risk of progressing from histologically defined chronic hepatitis to cirrhosis and, in some instances, to hepatocellular carcinoma (HCC). More often than not, these events can continue to occur in the complete absence of symptoms which may emerge only when end-stage liver disease is reached. The true frequency and rate of these progressive changes have represented an area of uncertainty and have led to conflicting views on the subject. Some authorities have suggested that progression to severe end-stage liver disease is inevitable, provided the infected person does not succumb first to another lethal illness; others have concluded that disease progression is restricted to a limited few and that the challenge is to define factors that might account for wide differences in outcome. These opposing views can be accounted for, at least in part, by the extraordinarily insidious nature of the process and the almost snails' pace rate of its progression.

Efforts to resolve this controversy are required for two obvious reasons: (1) the need to inform HCV carriers of what to anticipate in their future in the hope of reassuring them about potential sequelae; and (2) the need to make prudent decisions regarding therapy with drugs that are currently of only limited therapeutic benefit. The only means of resolving the conflict is to conduct appropriate long-term studies of the natural history of the disease.