Natural history of hepatitis C

Abstract

Approximately 85% of persons with acute hepatitis C de-Infection with the hepatitis C virus (HCV) is a problem of much current concern. Although acute hepatitis C is comvelop chronic hepatitis as determined by persistently abnormal serum enzymes and/or viremia (hepatitis C virus [HCV] monly an asymptomatic and seemingly mild illness, the viral infection nearly always persists, resulting in the development RNA). Both the acute and chronic illnesses are predominantly asymptomatic. For this reason and because the chronic illness of chronic hepatitis. By convention, chronic hepatitis is believed to have developed when the serum enzymes remain runs an extremely protracted course, it has been difficult to accurately define the frequency and rate of progression to abnormal for at least 6 months. An additional subgroup continue to show persistent infection (HCV RNA reactivity) in symptomatic or end-stage liver disease, specifically cirrhosis and hepatocellular carcinoma (HCC). Three evaluation strate-the absence of increased serum enzyme levels. Unfortunately, these events usually take place in an oblivious host who gies have been used. The first, prospective studies beginning from disease onset, have identified over 8 to 14 year follow-up generally continues to remain asymptomatic. Once chronicity ensues, it is believed that the disease may range through periods that morbidity (symptoms, cirrhosis) and mortality (hepatic failure, HCC) are modest in frequency. The second, incrementally advancing stages of histologically defined chronic hepatitis, progress to cirrhosis, and culminate in the prospective studies of subjects with already established chronic liver disease, have demonstrated high rates of devel-development of hepatocellular carcinoma (HCC). Some authorities believe that these sequentially progressive changes opment of cirrhosis, HCC, and mortality over relatively short follow-up periods. The third, retrospective/prospective (non-are inevitable and will occur in most chronically infected persons provided they do not die first from another lethal concurrent prospective) studies, has consisted of follow-up of recipients of HCV-contaminated immunoglobulin and of illness. Others believe that only a proportion of infected persons will develop progressive disease and that attention transfusion recipients from five enzyme-monitored transfusion studies of the early 1970s. The former study identified should therefore focus on establishing as early as possible who is likely to show advancing disease and on attempting to no mortality, trivial morbidity, and minimal cirrhosis 17 years after infection. The latter, involving hepatitis cases and define factors that might be responsible for such progression.These contradictory views can be resolved only by conductmatched nonhepatitis controls studied over a 20-year period, demonstrated no increase in all-cause but a slight increase in ing appropriate long-term studies of the natural history of the disease. liver-related mortality. Clinically evident chronic liver disease was ...

Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIF

“…P ersistent hepatitis C virus (HCV) infections are associated with cirrhosis and liver cancer and contribute significantly to liver-specific morbidity in human populations (1). Although multiple mechanisms contribute to viral persistence, the ability of the virus to evade early innate immune responses is likely to be particularly important (2).…”

Mutational Analysis of Hepatitis C Virus NS5B in the Subgenomic Replicon Cell Culture

“…Persistent infection with HCV is an important cause of chronic liver disease around the world. Infections with this hepatotropic flavivirus are associated with inflammatory liver injury, progressive fibrosis, and, in the most severely affected patients, cirrhosis and hepatocellular carcinoma (2,3). The HCV genome is a single-stranded RNA molecule 9.6 kb in length with positive-sense polarity (1,5).…”

Hepatitis C and fibrosis

“…Unfortunately, most studies are cross-sectional with only a single biopsy, and the few longitudinal studies including 2 biopsies are limited by sample size and a relative bias in patient selection. Therefore, the natural history of hepatitis is still controversial and draws much attention at consensus meetings (5)(6)(7)(8). A cross-sectional study by Poynard et al, which included 2,235 patients with chronic hepatitis C, assessed fibrosis progression (Table I).…”