Clinical manifestations and natural history of hcv infection

HCV most commonly results in a chronic infection. Acute HCV infection is not commonly diagnosed because most patients are asymptomatic. The incubation period of symptomatic acute HCV ranges from 2-12 weeks, and clinical features include fatigue, malaise, right-sided abdominal pain, and nausea. Jaundice is uncommon, occurring in fewer than 25% of patients. Fulminant hepatitis is extremely rare.

Within 1-3 weeks after exposure, HCV RNA is detectable in the blood; however, only 50-70% of patients have anti-HCV antibodies detectable by enzyme immunoassay at the onset of their symptoms, whereas 90% are proven positive by week 12. As transaminases return to reference range levels, symptoms resolve, usually over several weeks. Spontaneous clearance of HCV does occur and is usually seen in those infected at a younger age, among women, and in those with certain human leukocyte antigen (HLA) haplotypes (HLA-DRB1 and HLA-DQB1). Spontaneous clearance is uncommon if the viremia has persisted for more than 6 months. Also, evidence suggests that treatment of acute HCV infection with interferon-α2b or pegylated interferons prevents progression to chronic infection.

Studies suggest that up to 85% of individuals with HCV develop a chronic infection, defined as viremia and/or abnormal levels of hepatic transaminases persisting longer than 6 months. Patients with chronic infection are usually asymptomatic or have nonspecific symptoms such as fatigue, anorexia, or weight loss. Symptoms do not accurately predict the extent of liver disease. Most infections lead to chronic hepatitis and some degree of hepatic fibrosis; furthermore, 20-30% of infected adults develop progressive fibrosis over time that leads to cirrhosis. This development is less common in infected children. Risk factors for developing progressive fibrosis include older age at time of infection, male sex, use of alcohol, and co-infection with either chronic hepatitis B virus or HIV. Other factors may include hepatic steatosis and iron overload and use of hepatotoxins. The rate of progressive hepatic fibrosis is also higher in patients with persistently abnormal hepatic transaminase levels. African Americans appear to have a lower risk of advanced disease; however, they also have a lower response rate to available therapies.

Life-threatening complications and death usually occur in patients with cirrhosis. The lifetime risk of developing cirrhosis is approximately 15-20%. After the development of cirrhosis, HCC occurs at a rate of 0-3% per year, and HCV accounts for nearly one third of all HCC cases in the United States. The risk of developing HCC is 25 times higher in patients who are infected with HCV as compared to those who are not. Currently, end-stage liver disease due to HCV accounts for most liver transplants in the United States. Even in the absence of significant liver disease, chronic HCV has been shown to have a negative impact on health-related quality of life scores.

HCV infection accounts for 8,000-10,000 deaths annually in the United States. Predictors of death from liver failure, the development of HCC, or the need for liver transplantation include a history of hepatic decompensation (ie, ascites, jaundice, hepatic encephalopathy, variceal bleeding) or serum albumin levels less than 4.1 mg/dL.