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Hepatitis C virus infection

Hepatitis C is an infectious disease caused by HCV that is characterized by progressive liver damage and polymorphous extrahepatic manifestations.
HCV, an RNA virus of the Flaviviridae family, infects hepatocytes and evades the immune system, causing oxidative stress, inflammation and fibrosis, which can progress to cirrhosis, hepatic decompensation, HCC, and death.
The prevalence of hepatitis C in the US adult population is estimated at 1.0% (current infection) and 1.7% (current or past infection).
Disease course
Approximately 15-20% of patients who are infected will progress to cirrhosis over a 20-year period. The risk of HCC in cirrhotic patients (without successful treatment) is 3% per year.
Prognosis and risk of recurrence
The mortality rate ratio of patients with HCV infection, as compared with the general population, is estimated at 2.3 (95% CI, 2.2-2.5). Cure rates with modern antiviral therapy are > 90% for chronic HCV infection.
Key sources
The following summarized guidelines for the evaluation and management of hepatitis C are prepared by our editorial team based on guidelines from the Center for Disease Control (CDC 2023), the European Association for the Study of the Liver (EASL 2023), the World Health Organization (WHO 2022), the Kidney Disease: Improving Global Outcomes Foundation (KDIGO 2022), the American College of Emergency Physicians (ACEP 2021), the Infectious Diseases Society of America (IDSA/AASLD 2020), the American College of Gastroenterology (ACG 2016), and the U.S. Preventive Services Task Force (USPSTF 2013).


1.Screening and diagnosis

Indications for screening: as per AASLD 2020 guidelines, obtain one-time, routine opt-out HCV testing in all persons ≥ 18 years of age.
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2.Diagnostic investigations

Initial laboratory tests: as per WHO 2022 guidelines, obtain quantitative or qualitative nucleic acid testing directly following a positive HCV antibody serological test result for the detection of HCV RNA as the preferred strategy to diagnose viremic infection.
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  • Viral genotyping

  • Evaluation for liver fibrosis

  • Evaluation for other co-infections

  • Evaluation of renal function

  • Pretreatment evaluation

  • Resistance-associated substitution testing

3.Diagnostic procedures

Kidney biopsy: consider managing patients with HCV infection with a typical presentation of immune-complex proliferative glomerulonephritis without a confirmatory kidney biopsy. Consider performing a biopsy in certain clinical circumstances.

4.Medical management

General principles: as per WHO 2022 guidelines, initiate any of the following pangenotypic direct-acting antiviral regimens in all adult,
and ≥ 3 years old pediatric patients with chronic hepatitis C infection, regardless of the disease stage:
sofosbuvir/daclatasvir for 12 weeks
sofosbuvir/velpatasvir for 12 weeks
glecaprevir/pibrentasvir for 8 weeks.

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  • Antiviral therapy, genotype 1a

  • Antiviral therapy, genotype 1b

  • Antiviral therapy, genotype 2

  • Antiviral therapy, genotype 3

  • Antiviral therapy, genotype 4

  • Antiviral therapy, genotype 5 or 6

  • Antiviral therapy, prior failures

  • Indications for treatment discontinuation

5.Specific circumstances

Pediatric patients, laboratory testing, CDC: obtain testing for hepatitis C in all infants and children born to pregnant patients with current (detectable HCV-RNA) or probable (reactive anti-HCV testing while HCV-RNA results are not available) HCV infection.
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  • Pediatric patients (preventative measures and counseling)

  • Pediatric patients (antiviral therapy)

  • Pediatric patients (follow-up)

  • Patients contemplating pregnancy

  • Pregnant patients (indications for screening)

  • Pregnant patients (laboratory tests)

  • Pregnant patients (general principles of management)

  • Pregnant patients (antiviral therapy)

  • Pregnant patients (invasive procedures)

  • Pregnant patients (delivery)

  • Pregnant patients (postpartum evaluation)

  • Pregnant patients (breastfeeding)

  • MSM

  • Patients injecting drugs

  • Patients in jails and prisons

  • Patients with CKD (screening for HCV infection)

  • Patients with CKD (screening for other infections)

  • Patients with CKD (liver testing)

  • Patients with CKD (antiviral regimens)

  • Patients with CKD (management of glomerular disease)

  • Patients with CKD (kidney transplantation)

  • Patients with CKD (follow-up)

  • Kidney transplant recipients

  • Patients receiving organs of HCV-infected patients

  • Patients with acute HCV infection

  • Patients with HBV co-infection

  • Patients with HIV co-infection

6.Patient education

General counseling: provide education and interventions in all patients with HCV infection aimed at reducing liver disease progression and preventing HCV transmission.
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7.Preventative measures

Administer vaccination against hepatitis A and hepatitis B in all susceptible patients with HCV infection.
Administer vaccination against pneumococcal infection in all patients with cirrhosis.

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  • Prevention of transmission in hemodialysis units

8.Follow-up and surveillance

Treatment monitoring
As per ACEP 2021 guidelines:
Consider limiting laboratory monitoring to the beginning and end of the treatment in adult patients without cirrhosis or with compensated cirrhosis.
Obtain closer monitoring in patients with decompensated cirrhosis.

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  • Post-treatment follow-up (patients achieved sustained virologic response)

  • Post-treatment follow-up (patients failed sustained virologic response)

  • Management of recurrence after liver transplantation