• Clinical science

Hepatitis C

Summary

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. Acute HCV infection is treated with interferon-α, while a combination of two direct-acting antivirals (e.g., ledipasvir, sofosbuvir) is recommended in cases of chronic infection. More than 90% of patients are cured with adequate treatment.

Definition

Epidemiology

  • 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.

Etiology

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.

Clinical features

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

Diagnostics

Pathology

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

Differential diagnoses

The differential diagnoses listed here are not exhaustive.

Treatment

General recommendations

  • Avoid hepatotoxic drugs (e.g., acetaminophen) and alcohol use.
  • Refer to an addiction specialist to treat substance use.

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 for 12–16 weeks is recommended before initiation.
      • Treatment should be started if HCV is not cleared.
      • No treatment is necessary if HCV is cleared.
  • 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]

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

Endstage liver failure

Complications

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

Special patient groups

Considerations in pregnancy [22]

  • Vertical transmission: approx. 5–15% [23]
    • C-section does not lower risk of transmission
    • Avoid amniocentesis or the use of fetal scalp electrode (due to increased risk of transmission)
    • HCV-infected patients (without HIV coinfection) may breastfeed as normal
  • Postpartum treatment
  • 1. World Health Organization. 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. url: https://pubmed.ncbi.nlm.nih.gov/30398671/.
  • 3. CDC -Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention. 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: pp. 977–96. pmid: 26417315.
  • 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. url: https://pubmed.ncbi.nlm.nih.gov/21613437/.
  • 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. url: https://pubmed.ncbi.nlm.nih.gov/10885983/.
  • 8. Ronald E. Engle, Jens Bukh, Robert H. Purcell. Transfusion-associated hepatitis before the screening of blood for hepatitis risk factors. Transfusion. 2014. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498987/.
  • 9. Edlin et al. Managing Hepatitis C in Users of Illicit Drugs. Current hepatitis reports. 2007; 6(2): pp. 60–67. pmid: 23801897.
  • 10. Bryce et al. 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. Centers for Disease Control and Prevention. 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. url: https://www.ncbi.nlm.nih.gov/pubmed?term=7533121.
  • 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): pp. 77–85. doi: 10.1002/hep.24706.
  • 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.
  • 15. AASLD/IDSA. HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. https://www.hcvguidelines.org/sites/default/files/full-guidance-pdf/HCVGuidance_May_24_2018b.pdf. Updated May 18, 2018. Accessed April 23, 2019.
  • 16. The American Association for the Study of Liver Diseases and the Infectious Diseases Society of America. Initial Treatment of HCV Infection. https://www.hcvguidelines.org/treatment-naive. Updated September 21, 2017. Accessed March 27, 2017.
  • 17. Centers for Disease Control and Prevention. 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. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4308526.
  • 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): pp. 103–107. doi: 10.1111/j.1478-3231.2011.02711.x.
  • 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): pp. 512–520. doi: 10.1111/j.1440-1746.2008.05384.x.
  • 21. Tsoulfas G, Goulis I, Giakoustidis D, et al. Hepatitis C and liver transplantation. Hippokratia. 2009; 13(4): pp. 211–215. pmid: 20011084.
  • 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): pp. 643–651. doi: 10.4254/wjh.v6.i9.643.
  • 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): pp. 1477–1492. doi: 10.1093/cid/ciy585.
last updated 10/09/2020
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