Natural history of hepatitis C infection: a concise review.

Chronic hepatitis C virus (HCV)b infection is a major public health problem, affecting over 2.7 million individuals in the U.S. and over 170 million worldwide [1, 2]. In the United States, HCV infection is the most common cause of chronic liver disease, accounts for 8,000 to 10,000 deaths annually, and is the leading indication for liver transplantation [3]. Since the initial discovery of HCV virus as the causative agent of non-A, non-B (NANB) hepatitis by Choo and colleagues in 1989 [4], significant advances have been made in our understanding of its epidemiology, pathogenesis, diagnosis, and therapy. Increased understanding of the natural history of chronic infection will be essential in any effort to further elucidate pathogenetic mechanisms, predict clinical outcomes, and identify those patients for whom treatment is beneficial. Acute infection with HCV virus is usually asymptomatic, and therefore infrequently diagnosed during this early period. Although up to one-third of patients may develop mild flu-like symptoms or jaundice, fulminant liver failure is very rare [5]. Despite vigorous humoral and cellmediated immune responses by the host, approximately 85 percent of patients fail to achieve spontaneous recovery and thus develop chronic infection, defined as a positive HCV antibody and RNA at six months. Chronic infection is typically characterized by a prolonged asymptomatic period, but will eventually lead to chronic hepatitis, cirrhosis, and hepatocellular carcinoma in 70 percent, 20 percent, and 4 percent of cases, respectively [6]. Mechanisms for HCV persistence remain unclear, but may involve viral mutation during replication, persistence in extrahepatic tissues, or formation of quasispecies that escape host immune response [7-8]. The natural history of HCV infection has been difficult to study. Accurate determination requires a well-defined time of disease onset and frequent, prospective monitoring of clinico-pathologic outcomes over the course of infection without therapeutic intervention, ideally with a matched control group for comparison.