Hepatitis C

Last updated: August 29, 2023

Summarytoggle arrow icon

Hepatitis C is an infection caused by the hepatitis C virus (HCV), which attacks liver cells and causes liver inflammation. HCV is a bloodborne pathogen commonly transmitted through needlestick injuries in health care settings or through shared drug-injection needles. Screening plays a central role in detecting HCV infection because most infected individuals are asymptomatic or mildly symptomatic. Approximately 85% of individuals with an acute infection that is not recognized and treated will develop chronic hepatitis C, which is associated with cirrhosis, hepatocellular carcinoma, and increased mortality. The presence of HCV antibodies and HCV RNA confirm the diagnosis. HCV infection can be safely and effectively treated with direct-acting antivirals (DAAs), which have cure rates of over 95%. Simplified algorithms for the use of DAAs in treatment-naive patients without decompensated cirrhosis reduce the need for specialist-guided care.

Definitiontoggle arrow icon

  • Acute hepatitis C: HCV infection that develops during the first 6 months following the exposure
  • Chronic hepatitis C: HCV infection that persists beyond 6 months following the exposure [1]

Epidemiologytoggle arrow icon

  • Prevalence: up to 2% of the US population has chronic HCV infection. [2]
  • Incidence: 1 cases per 100,000 population, > 40,000 new infections per year in the US [3]
  • Clinical progression: 75–85% of individuals with HCV infection go on to develop chronic disease [4]

Epidemiological data refers to the US, unless otherwise specified.

Etiologytoggle arrow icon


  • Hepacivirus C (Hepatitis C virus): RNA virus of the Hepacivirus genus and Flaviviridae family
  • The risk of chronic infection is multifactorial and depends on the host's ability to clear the pathogen through activation of multiple innate immunity pathways against the viral envelope. [5]
    • Flawed proofreading capability of RNA-dependent RNA polymerase (no 3′– 5′ exonuclease activity) introduces mutations into genes encoding viral glycoprotein. envelope and enabling novel antigen production.
    • Rapid replication rate produces many antigenically unique viral envelopes.
    • Infection persists because the production rate of new mutant virions exceeds the production rate of host antibodies.
  • There are six genotypes: In the US, the main ones are genotype 1 (65–80%) and genotype 2 (10–15%). [6]
  • Reinfection with another HCV genotype is possible.


Risk factors for HCV infection

  • Injection drug use (past or current, especially long-term use) [9]
  • Hepatitis B virus or HIV positivity
  • History of incarceration
  • Individuals born between 1945 and 1965 [10]
  • Individuals who received a blood transfusion or organ transplant before 1992

Patients at high risk of HCV infection should be tested.

Clinical featurestoggle arrow icon

Incubation period

  • 2 weeks to 6 months

Acute course

Symptoms are nonspecific and may be similar to those of other acute viral infections.

Chronic course

Screeningtoggle arrow icon

Individuals without risk factors for HCV infection [12][13][14]

  • All individuals aged ≥ 18 years: at least once per lifetime [13][15]
  • Pregnant individuals: once per pregnancy [14]

The CDC recommends against universal screening in settings where HCV disease prevalence is < 0.1%. [14]

Individuals with risk factors for HCV infection [14][15]

Diagnosticstoggle arrow icon

General principles [15]

Individuals with hepatitis C are often asymptomatic or minimally symptomatic. Screening plays an essential role in the diagnosis of hepatitis C infection.

Hepatitis C tests [15]

Interpretation of hepatitis C tests

Interpretation of hepatitis C tests [15]
Anti-HCV antibodies
Negative Positive
HCV RNA Negative
  • Active infection (acute or chronic)
  • Anti-HCV antibodies may take as long as 6 weeks after HCV exposure to be detectable on tests.
  • HCV RNA may take as long as 2–3 weeks after viral exposure to be detectable on tests.

Additional evaluations [12]

Obtain prior to treatment to exclude liver cirrhosis and its complications and assess for comorbidities.

Laboratory studies

Cirrhosis assessment

Liver biopsy

  • Consider when:
  • Supportive findings: See “Pathology.”

Pathologytoggle arrow icon

  • Acute Phase [17]
    • Focal areas of macrovesicular steatosis
    • Bile duct injury
    • Sinusoidal inflammation of hepatic cells
    • Lobular involvement in the form of eosinophilic single-cell necrosis
  • Chronic phase

Without treatment, the disease will ultimately progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma. See “Pathology of viral hepatitis.”

Differential diagnosestoggle arrow icon

The differential diagnoses listed here are not exhaustive.

Treatmenttoggle arrow icon

General principles [15]

Patients who are treatment-naive and have no history of decompensated cirrhosis are eligible for simplified treatment. [15]

Antiviral therapy [15]

HCV infection is always treated with a multidrug approach (no antivirals are approved as monotherapy).

DAAs have superior efficacy and safety profiles compared with interferon or ribavirin-based regimens and are thus preferred.

Acute and chronic HCV are treated with the same antiviral regimens.

Treatment regimens

Simplified treatment [12]

Simplified treatment regimens may be provided by nonspecialists.

Refer for specialty care if clinical findings and/or laboratory studies indicate hepatic decompensation (e.g., jaundice, hepatic encephalopathy, bilirubin, transaminases)

Specialist-guided treatment [15]

Posttreatment care [12][19]

Assess for sustained virologic response with a quantitative PCR for HCV RNA ≥ 12 weeks after completion of therapy.

If hepatocellular enzymes remain elevated after achieving SVR, test for other etiologies of liver disease. [19]

Supportive care

Monitor for complications of HCV infection in individuals who decline antiviral treatment or do not achieve SVR.

Complicationstoggle arrow icon

We list the most important complications. The selection is not exhaustive.

Preventiontoggle arrow icon

Spontaneous resolution of HCV and successful treatment of infection do not confer immunity to reinfection.

Special patient groupstoggle arrow icon

Considerations in pregnancy [23]

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Referencestoggle arrow icon

  1. Hepatitis C. Updated: July 1, 2016. Accessed: March 27, 2017.
  2. Hofmeister MG, Rosenthal EM, Barker LK, Rosenberg ES, Barranco MA, Hall EW, Edlin BR, Mermin J, Ward JW, Ryerson AB. Estimating Prevalence of Hepatitis C Virus Infection in the United States, 2013-2016.. Hepatology. 2018.
  3. How many new HCV infections occur annually in the United States?. Updated: April 9, 2019. Accessed: June 7, 2019.
  4. Hepatitis C Questions and Answers for the Public. Updated: November 2, 2018. Accessed: July 2, 2019.
  5. Kwon et al.. Hepatitis C virus infection: establishment of chronicity and liver disease progression.. EXCLI journal. 2014; 13: p.977-96.
  6. Jeffrey J Germer, Jayawant N Mandrekar, Jordan L Bendel, P Shawn Mitchell, Joseph D C Yao. Hepatitis C virus genotypes in clinical specimens tested at a national reference testing laboratory in the United States. Journal of Clinical Microbiology. 2011.
  7. Elise M. Beltrami, Ian T. Williams, Mary E. Chamberland. Risk and Management of Blood-Borne Infections in Health Care Workers. Clinical Microbiology Reviews. 2000.
  8. Ronald E. Engle, Jens Bukh, Robert H. Purcell. Transfusion-associated hepatitis before the screening of blood for hepatitis risk factors. Transfusion. 2014.
  9. Edlin et al.. Managing Hepatitis C in Users of Illicit Drugs.. Current hepatitis reports. 2007; 6 (2): p.60-67.
  10. Recommendations for the Identification of Chronic Hepatitis C Virus Infection Among Persons Born During 1945–1965. Updated: August 17, 2012. Accessed: July 3, 2019.
  11. The ABCs of Hepatitis. Updated: January 1, 2016. Accessed: March 27, 2017.
  12. HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. Updated: August 27, 2020. Accessed: December 3, 2020.
  13. Bhattacharya D, Aronsohn A, Price J, et al. Hepatitis C Guidance 2023 Update: American Association for the Study of Liver Diseases– Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Clin Infect Dis. 2023.doi: 10.1093/cid/ciad319 . | Open in Read by QxMD
  14. Maheshwari A, Ray S, Thuluvath PJ. Acute hepatitis C.. Lancet. 2008; 372 (9635): p.321-32.doi: 10.1016/S0140-6736(08)61116-2 . | Open in Read by QxMD
  15. Dhingra S. Liver pathology of hepatitis C, beyond grading and staging of the disease. World Journal of Gastroenterology. 2016; 22 (4): p.1357.doi: 10.3748/wjg.v22.i4.1357 . | Open in Read by QxMD
  16. Clark V, Nelson DR. The role of ribavirin in direct acting antiviral drug regimens for chronic hepatitis C. Liver Int. 2012; 32 (Suppl 1): p.103-107.doi: 10.1111/j.1478-3231.2011.02711.x . | Open in Read by QxMD
  17. Ghany MG, Morgan TR. Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases–Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Hepatology. 2020; 71 (2): p.686-721.doi: 10.1002/hep.31060 . | Open in Read by QxMD
  18. Chu C-J, Lee S-D. Hepatitis B virus/hepatitis C virus coinfection: epidemiology, clinical features, viral interactions and treatment. J Gastroenterol Hepatol. 2008; 23 (4): p.512-520.doi: 10.1111/j.1440-1746.2008.05384.x . | Open in Read by QxMD
  19. Tsoulfas G, Goulis I, Giakoustidis D, et al. Hepatitis C and liver transplantation. Hippokratia. 2009; 13 (4): p.211-215.
  20. Owens DK, Davidson KW, et al. Screening for Hepatitis C Virus Infection in Adolescents and Adults. JAMA. 2020; 323 (10): p.970.doi: 10.1001/jama.2020.1123 . | Open in Read by QxMD
  21. Schillie S, Wester C, Osborne M, Wesolowski L, Ryerson AB. CDC Recommendations for Hepatitis C Screening Among Adults — United States, 2020. MMWR Recomm Rep. 2020; 69 (2): p.1-17.doi: 10.15585/mmwr.rr6902a1 . | Open in Read by QxMD
  22. Yeung CY, Lee HC, Chan WT, Jiang CB, Chang SW, Chuang CK. Vertical transmission of hepatitis C virus: Current knowledge and perspectives. World J Hepatol. 2014; 6 (9): p.643-651.doi: 10.4254/wjh.v6.i9.643 . | Open in Read by QxMD
  23. Chung RT, Ghany MG, et al. Hepatitis C Guidance 2018 Update: AASLD-IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Clinical Infectious Diseases. 2018; 67 (10): p.1477-1492.doi: 10.1093/cid/ciy585 . | Open in Read by QxMD
  24. Workowski KA, Bachmann LH, Chan PA, et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR. Recommendations and Reports. 2021; 70 (4): p.1-187.doi: 10.15585/mmwr.rr7004a1 . | Open in Read by QxMD

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