Natural history of hepatitis C

J Hepatol. 2014 Nov;61(1 Suppl):S58-68. doi: 10.1016/j.jhep.2014.07.012. Epub 2014 Nov 3.


There has long been evidence that hepatitis C can lead to persistent infection in a high proportion of infected individuals, and can progress to chronic liver disease, cirrhosis and hepatocellular carcinoma (HCC). The transition from acute to chronic hepatitis C is usually sub-clinical. Accurate studies of the time course for clearance of acute hepatitis C are difficult to carry out because of the silent onset of the acute disease. The likelihood of spontaneous HCV resolution is associated with several genetic factors, including IL28B inheritance and the DQB1*0301 allele of the major histocompatibility complex class II. Most data suggest that resolution in the acute phase without progression to chronic disease is not accompanied by significant disease, but minor histological lesions have been observed in anti-HCV positive, HCV RNA negative individuals. The risk of reinfection remains a possibility after clearance of acute hepatitis C. High rates of sexually-transmitted infection are being reported in HIV positive men who have sex with men (MSM). Chronic infection with HCV is the leading cause of end-stage liver disease, hepatocellular carcinoma (HCC) and liver related death in the Western world. The natural history of the chronic disease remains incompletely defined. It is generally a slowly progressive disease characterized by persistent hepatic inflammation, leading to the development of cirrhosis in approximately 10-20% of patients over 20-30 years of HCV infection. However, the published data indicate varying progression rates to cirrhosis. Overall, once cirrhosis has developed there is a 1-5% annual risk of HCC and a 3-6% annual risk of hepatic decompensation. Following an episode of decompensation the risk of death in the following year is between 15% and 20%. The high number of chronically infected individuals, the burden of disease, and the absence of a vaccine indicates that treatment will form part of the disease control but the impact, effectiveness and outcomes of treatment in various groups remain uncertain. Several studies and meta-analysis have concluded that eradication of HCV with antiviral therapy reduces the risk of HCC in patients with chronic hepatitis C, independent of fibrosis stage, but the risk is not eliminated.

Keywords: Acute hepatitis C; Antiviral treatment; Chronic hepatitis C; Cirrhosis; Direct acting antivirals; Hepatocellular carcinoma; Interferon; Liver transplantation; Natural history of hepatitis C.

Publication types

  • Review

MeSH terms

  • Antiviral Agents / therapeutic use
  • Carcinoma, Hepatocellular / epidemiology
  • Disease Progression*
  • Hepatitis C / complications*
  • Hepatitis C / drug therapy
  • Hepatitis C / etiology*
  • Humans
  • Liver Cirrhosis / epidemiology
  • Liver Neoplasms / epidemiology
  • Risk Factors


  • Antiviral Agents