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.
- Prevalence: up to 2% of the US population has chronic HCV infection. 
- Incidence: 1 cases per 100,000 population, > 40,000 new infections per year in the US 
- Clinical progression: 75–85% of individuals with HCV infection go on to develop chronic disease 
Epidemiological data refers to the US, unless otherwise specified.
- 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. 
- 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%). 
- Reinfection with another HCV genotype is possible.
- Organ transplantation
- Sexual: rare (in contrast to HBV and HIV)
- Perinatal (vertical)
High-risk groups for HCV infection
- IV drug users (especially long-time users) 
- Hepatitis B virus (HBV) or HIV-positive individuals
- Prison inmates
- Individuals born between 1945–1965 
- Recipients of blood transfusions or organ transplants before 1992
- 2 weeks to 6 months
- Asymptomatic in 80% of cases
- Symptomatic (see “ ”)
Symptoms are nonspecific and may be similar to those of other acute viral infections.
- Seen especially in asymptomatic individuals (up to 85%), as the disease may go undiagnosed and treatment may be delayed or never initiated (carrier state). 
- Findings often mild, nonspecific (e.g., fatigue)
- Liver cirrhosis (up to 25% of cases) within 20 years of infection 
Extrahepatic features (common)
- Vascular: leukocytoclastic vasculitis
- Others: sialadenitis
Detection of antibodies 
- EIA/ELISA: standard immunoassay tests for anti-HCV antibodies (positive in cases of acute, chronic, and previous HCV infection)
- PCR for HCV RNA if antibodies are positive.
- Liver function tests
- Inflammation markers: leukocytosis, ↑ ferritin 
- Liver biopsy indications (see “Pathology”)
- Ultrasound: detection of cirrhosis and neoplasia, e.g., HCC
- Rule out coinfections: HIV, hepatitis A virus (HAV), hepatitis B virus (HBV) serology necessary
- Acute Phase 
- Chronic phase
- Avoid hepatotoxic drugs (e.g., acetaminophen) and alcohol use.
- Refer to an addiction specialist to treat substance use.
Acute hepatitis C 
- 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
Chronic hepatitis C 
- Treatment goals
- Chronic HCV infection is always treated with a multidrug approach (no antivirals are approved as monotherapy).
- Chosen based on the history of antiviral treatment, degree of liver fibrosis, viral genotype, and viral load
- Combination of two direct-acting antivirals (DAAs): Antivirals target and inhibit HCV-encoded proteins that are essential for the HCV replication cycle.
- Interferon PLUS ribavirin 
- Vaccinations for hepatitis A and B should be given in addition to any treatment regimen.
- See “ .”
Treatment algorithm for all genotypes in treatment-naive patients
|Simplified Pangenotypic algorithm for the treatment of HCV|
With compensated cirrhosis (Child-Pugh class A)
Treatment algorithm for patients with decompensated cirrhosis (Child-Pugh class B or C)
- Refer to a medical professional with expertise and/or liver transplant center
- Interferon is contraindicated (high risk of worsening cirrhosis decompensation)
- Endstage liver failure: liver transplantation
Retreatment algorithm for treatment-experienced patients
- Failed glecaprevir PLUS pibrentasvir treatment (all genotypes)
- Failed sofosbuvir PLUS velpatasvir PLUS voxilapravir (all genotypes) with or without compensated cirrhosis
Screening recommendations 
- 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
- IV drug users
- Long-term hemodialysis patients
- One-time testing is indicated in individuals exposed to (potentially) HCV-positive blood, especially: 
- Universal hepatitis C screening
- Screening protocol
Special patient groups
Considerations in pregnancy 
- Vertical transmission: approx. 5–15% 
- Prenatal screening ( testing): recommended for all pregnant women during the initial examination (∼ 10 weeks of gestation)
- Postpartum treatment