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Hepatitis C

Last updated: May 25, 2021

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Hepatitis C is an infection caused by the hepatitis C virus (HCV), which attacks liver cells and causes liver inflammation. The virus is mainly transmitted parenterally, especially through IV drug use or needlestick injuries in healthcare settings. Most patients are asymptomatic in the acute phase, but may develop fever, malaise, fatigue, or jaundice. Transition to chronic infections occurs in up to 85% of cases since asymptomatic patients are rarely diagnosed and treated. Chronic infection is associated with increased mortality due to cirrhosis and hepatocellular carcinoma. Suspicion of HCV infection due to exposure, clinical presentation, or elevated aminotransferase levels should be followed up with HCV antibody and HCV RNA testing to confirm the diagnosis. HCV infection is treated with a combination of two direct-acting antivirals (e.g., ledipasvir, sofosbuvir). More than 90% of patients are cured with adequate treatment.

  • 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]
  • 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.

Pathogen

Transmission

High-risk groups for HCV infection

  • IV drug users (especially long-time users) [9]
  • Hepatitis B virus (HBV) or HIV-positive individuals
  • Prison inmates
  • Individuals born between 1945–1965 [10]
  • Recipients of blood transfusions or organ transplants before 1992

Patients with a medical history indicating a high risk for HCV infection should be tested.

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

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

The differential diagnoses listed here are not exhaustive.

General recommendations

Acute hepatitis C [15][16]

  • Treatment goal: prevent transition to chronic infection
  • Antiviral therapy: the same regimens as for chronic HCV infection (see “Chronic hepatitis C” below)
  • Monitoring: regular monitoring of HCV RNA every 4–8 weeks for 6–12 months

There is neither a pre-exposure or postexposure prophylaxis nor a vaccine for HCV.

Chronic hepatitis C [15][16]

Interferon and ribavirin are associated with severe adverse effects (e.g., arthralgias, thrombocytopenia, leukopenia, depression, and anemia) and teratogenicity.

Treatment algorithm for all genotypes in treatment-naive patients

Simplified Pangenotypic algorithm for the treatment of HCV
Elegibility criteria Regimens Contraindications

Without cirrhosis

With compensated cirrhosis (Child-Pugh class A)

Treatment algorithm for patients with decompensated cirrhosis (Child-Pugh class B or C)

Retreatment algorithm for treatment-experienced patients

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

  • Screening recommendations [22]
    • Universal hepatitis C screening
      • All individuals aged 18–79 years; should be screened at least once in their lifetimes.
      • All women should be screened at each pregnancy.
    • Periodic testing is indicated in individuals with ongoing high-risk of exposure
    • One-time testing is indicated in individuals exposed to (potentially) HCV-positive blood, especially: [23]
      • Infants born to HCV-positive mothers
      • Healthcare personnel with percutaneous or parenteral exposure to blood with known HCV-positive or unknown HCV status
  • Screening protocol

Considerations in pregnancy [24]

  1. Hepatitis C. http://www.who.int/mediacentre/factsheets/fs164/en/. 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?. https://www.cdc.gov/hepatitis/hcv/hcvfaq.htm#a2. Updated: April 9, 2019. Accessed: June 7, 2019.
  4. Hepatitis C Questions and Answers for the Public. https://www.cdc.gov/hepatitis/hcv/cfaq.htm. 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. https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6104a1.htm. Updated: August 17, 2012. Accessed: July 3, 2019.
  11. The ABCs of Hepatitis. https://www.cdc.gov/hepatitis/Resources/Professionals/PDFs/ABCTable.pdf. Updated: January 1, 2016. Accessed: March 27, 2017.
  12. Barrera JM, Bruguera M, Ercilla MG, Gil C, Celis R, Gil MP, del Valle Onorato M, Rodés J, Ordinas A. Persistent hepatitis C viremia after acute self-limiting posttransfusion hepatitis C.. Hepatology. 1995 .
  13. Kowdley KV, Belt P, Wilson LA, et al. Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease. Hepatology. 2011; 55 (1): p.77-85. doi: 10.1002/hep.24706 . | Open in Read by QxMD
  14. 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
  15. HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. https://www.hcvguidelines.org/sites/default/files/full-guidance-pdf/AASLD-IDSA_HCVGuidance_August_27_2020.pdf. Updated: August 27, 2020. Accessed: December 3, 2020.
  16. Initial Treatment of HCV Infection. https://www.hcvguidelines.org/treatment-naive. Updated: August 27, 2020. Accessed: December 3, 2020.
  17. Hepatitis C FAQs for Health Professionals. https://www.cdc.gov/hepatitis/hcv/hcvfaq.htm. Updated: January 27, 2017. Accessed: March 27, 2017.
  18. Yasir Waheed. Ledipasvir and sofosbuvir: Interferon free therapy for hepatitis C virus genotype 1 infection. World Journal of Virology. 2015 .
  19. 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
  20. 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
  21. Tsoulfas G, Goulis I, Giakoustidis D, et al. Hepatitis C and liver transplantation. Hippokratia. 2009; 13 (4): p.211-215.
  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. Hepatitis C Virus Infection in Adolescents and Adults: Screening. https://www.uspreventiveservicestaskforce.org/uspstf/document/RecommendationStatementFinal/hepatitis-c-screening. Updated: March 2, 2020. Accessed: January 28, 2021.
  25. CDC Recommendations for Hepatitis C Screening Among Adults in the United States. https://www.cdc.gov/hepatitis/hcv/guidelinesc.htm#:~:text=CDC%20Recommendations%20for%20Hepatitis%20C,is%20less%20than%200.1%25*. Updated: July 29, 2020. Accessed: January 28, 2021.