- Clinical science
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.
- 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)
- Membranoproliferative glomerulonephritis (more common)
- Membranous glomerulonephritis
- 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
- Autoimmune hepatitis
- See “.”
The differential diagnoses listed here are not exhaustive.
- 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
- Monitoring: regular monitoring of HCV RNA every 4–8 weeks for 6–12 months
Chronic hepatitis C 
- Treatment goals
- Chosen based on viral genotype (the most important predictive factor for response to therapy), viral load, history of antiviral treatment, and degree of liver fibrosis
- Chronic HCV infection is always treated with a multidrug approach (no antivirals are approved as monotherapy).
Combination of two direct-acting antivirals (DAAs): Antivirals target and inhibit HCV-encoded proteins that are essential for the HCV replication cycle.
- Ledipasvir PLUS sofosbuvir for 8–12 weeks (genotypes 1, 4, 5, and 6) 
- Sofosbuvir PLUS velpatasvir for 12 weeks (all 6 genotypes)
- Elbasvir PLUS grazoprevir
- Glecaprevir PLUS pibrentasvir (all genotypes)
- Sofosbuvir PLUS daclatasvir
- Sofosbuvir PLUS simeprevir
- Ombitasvir/paritaprevir/ritonavir PLUS dasabuvir
- Interferon PLUS ribavirin 
- In addition to any treatment regimen, vaccinations for hepatitis A and B should be given.
- See “ .”
Endstage liver failure
- Surgery: liver transplantation
Considerations in pregnancy 
- Vertical transmission: approx. 5–15% 
- Postpartum treatment