Recovery, Persistence, and Sequelae in Hepatitis C Virus Infection: A Perspective on Long-Term Outcome

Abstract

Hepatitis C has emerged in recent years as the most common basis for liver disease in the United States, having infected an estimated 3.9 million people in this country and an estimated 170 million worldwide.Currently, it is the predominant reason for undergoing liver transplantation.The disease it causes is characterized by silent onset in most infected individuals, a high rate of viral persistence, and the potential for development of everworsening chronic liver disease, ranging from chronic hepatitis to cirrhosis and occasionally to hepatocellular carcinoma.Such progression, when it occurs, is also most commonly a silent process that may take 20-40, and occasionally even more, years to reach its end point.Because of these characteristics, it has been exceedingly difficult to accurately assess the natural history.Efforts to accomplish this have consisted of retrospective, prospective, and cohort studies.The most concerning data have derived from the retrospective study approach, generally performed at tertiary referral centers.Because these centers commonly attract persons with existing chronic liver disease, they have tended to describe a high rate of progression to cirrhosis and cancer.This "referral bias" is avoided in the prospective and cohort study approach, and data derived from these studies indicate a lower rate of progression and a correspondingly higher rate of either recovery or minimal liver disease.In this review, we briefly describe potential mechanisms of viral persistence; present detailed information on outcomes that have derived from retrospective, prospective, and cohort studies, involving both adults and children; examine the data regarding progression of fibrosis and of progression to hepatocellular carcinoma; consider cofactors that might enhance liver disease progression; and report the emerging data that suggest that spontaneous viral clearance may be higher than is currently believed.We conclude with the view that severe, life-threatening, progressive liver disease clearly occurs in a sizable minority (perhaps 30%) of chronically infected persons but speculate that fibrosis progression is neither linear or inevitable and hence that most hepatitis C virus carriers will have either a stable nonprogressive course or such indolent pro-Objectives Upon completion of this article, the reader should recognize: 1) the influence of study design on estimates of HCV disease severity; 2) that the rate of spontaneous recovery from HCV infection is higher than previously considered; 3) that fibrosis progression is not linear and is influenced by cofactors, particularly alcohol; 4) that it is likely that the majority of HCV infected individuals will not develop cirrhosis or other life threatening complications of their infection; and 5) that although the individual risk of developing severe complications may be less than 30%, the societal burden of HCV infection is very high because of the high prevalence and global distribution of the agent. AccreditationThe Indiana University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to sponsor continuing medical education for physicians.The Indiana University School of Medicine takes responsibility for the contents, quality, and scientific integrity of this activity. CreditThe Indiana University School of Medicine designates this educational activity for a maximum of 1.0 hours credit toward the AMA Physicians Recognition Award in category one.Each physician should claim only those hours of credit that he/she actually spent in the educational activity.