Hepatitis C natural history

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Yazan Daaboul, Serge Korjian, Javaria Anwer M.D.[2]


The majority of individuals infected with HCV will become chronic carriers. The primary and most severe complications of HCV are hepatic, namely liver cirrhosis years after the onset of infection and the consequent development of hepatocellular carcinoma. Other classical extra-hepatic manifestations (e.g., cryoglobulinemia, lichen planus, membranoproliferative glomerulonephritis, and porphyria cutanea tarda) are also complications of chronic HCV infection. Treatment is necessary for patients with chronic stable HCV infection; otherwise, the prognosis is poor and progression of the disease is potentially fatal.

Natural History

Upon exposure, HCV causes an acute phase that is asymptomatic in approximately 80% of cases. Acute HCV persists for less than 6 months. In 15-45% of cases, HCV is an isolated acute infection with almost no chronic sequelae, even in the absence of treatment. Patients exposed to HCV will subsequently develop anti-HCV antibodies but will demonstrate undetectable viral levels and negative HCV RNA.

In the majority of cases, however, HCV persists beyond 6 months and individuals become chronic carriers of HCV. Chronic HCV occurs in approximately 55-85% of patients. These patients will have positive anti-HCV antibodies and positive nucleic acid test (NAT) for HCV RNA, demonstrating the persistence of HCV and the inability of the body to appropriately clear the infection.[1][2]

Natural History of HCV - Source: http://www.who.int/en/


Hepatic Manifestations

A major complication of chronic HCV infection is cirrhosis, which ultimately leads to a decompensated state or transforms into a malignant hepatocellular carcinoma (HCC).[3] Not all patients develop cirrhosis at the same rate; exposure to other risk factors of cirrhosis, such as alcohol, HBV, or HIV infection, or immunocompromised status may hasten fibrosis of the liver and the development of HCC.[4]

Chronic HCV often eventually progresses to cause cirrhosis of the liver due to persistence of tissue inflammation and necrosis, along with fibrogenesis and deposition of components in the extracellular matrix. In the absence of treatment, 15-30% of patients with chronic HCV develop cirrhosis within 20 years.[3]

Similarly, hepatocellular carcinoma (HCC) is a known complication of chronic HCV infection. Patients with HCV develop HCC when the liver reaches its cirrhotic stage. The annual risk of developing hepatocellular carcinoma in a patient with cirrhosis is approximately 2-4%.

Extrahepatic complications of HCV infection

Extrahepatic complications of HCV infection include:[5][3]


Acute HCV Infection[7]

Chronic HCV Infection[7]


  1. Thomson EC, Fleming VM, Main J, Klenerman P, Weber J, Eliahoo J; et al. (2011). "Predicting spontaneous clearance of acute hepatitis C virus in a large cohort of HIV-1-infected men". Gut. 60 (6): 837–45. doi:10.1136/gut.2010.217166. PMC 3095479. PMID 21139063.
  2. Gerlach JT, Diepolder HM, Zachoval R, Gruener NH, Jung MC, Ulsenheimer A; et al. (2003). "Acute hepatitis C: high rate of both spontaneous and treatment-induced viral clearance". Gastroenterology. 125 (1): 80–8. PMID 12851873.
  3. 3.0 3.1 3.2 "Guidelines for the screening, care, and treatment of persons with HCV infection" (PDF). WHO. WHO. April 2014. Retrieved July 27, 2014.
  4. Freeman AJ, Law MG, Kaldor JM, Dore GJ (2003). "Predicting progression to cirrhosis in chronic hepatitis C virus infection". J Viral Hepat. 10 (4): 285–93. PMID 12823595.
  5. Fletcher NF, McKeating JA (2012). "Hepatitis C virus and the brain". J Viral Hepat. 19 (5): 301–6. doi:10.1111/j.1365-2893.2012.01591.x. PMID 22497808.
  6. 6.0 6.1 6.2 6.3 6.4 6.5 Cacoub, Patrice; Longo, Dan L.; Saadoun, David (2021). "Extrahepatic Manifestations of Chronic HCV Infection". New England Journal of Medicine. 384 (11): 1038–1052. doi:10.1056/NEJMra2033539. ISSN 0028-4793.
  7. 7.0 7.1 Chen SL, Morgan TR (2006). "The natural history of hepatitis C virus (HCV) infection". Int J Med Sci. 3 (2): 47–52. PMC 1415841. PMID 16614742.