- Clinical science
Hepatitis C is an infection caused by the hepatitis C virus (HCV), which attacks liver cells and leads to 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 present with fever, malaise, fatigue and jaundice. Transition to chronic infections occurs in up to 85% of cases since asymptomatic patients are rarely diagnosed and treated. Chronic infections may lead to cirrhosis and hepatocellular carcinoma as well as increased mortality. Diagnosis usually occurs via the detection of anti-HCV antibodies and HCV RNA. Acute HCV infection is treated with interferon-α, while a combination of two direct-acting antivirals (e.g., ledipasvir, sofosbuvir) is usually recommended in cases of chronic infection. With adequate treatment, up to 90% of patients can be cured.
Acute HCV infection
- HCV infection acquired in the past 6 months
- Acute hepatitis C: acute HCV infection + impaired liver function
Chronic HCV infection
- HCV infection persisting for more than 6 months
- Frequency: affects 50–85% of HCV-positive individuals
- Chronic hepatitis C: chronic HCV infection + impaired liver function + potential extrahepatic manifestations
- Prevalence: 1–2% of the US population has chronic HCV infection
- Incidence: ∼ 17,000 new infections per year in the US
Epidemiological data refers to the US, unless otherwise specified.
- RNA virus, flavivirus) ( :
Chronic infectious risk is multifactorial and ultimately derives from the host's inability to achieve true immunity despite the production of neutralizing antibodies against the viral envelope
- Flawed proofreading capability of RNA dependent RNA polymerase introduces mutations into genes encoding viral glycoprotein envelope, allowing for continuous novel antigen production
- Rapid replication rate produces many antigenically unique viral envelopes
- Consequently, the production of host antibodies is delayed relative to the production of new mutant virions so infection continues
- 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 even after previous infection.
- 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
- 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
- Asymptomatic in 80% of cases
- Symptomatic (see also )
Symptoms are nonspecific and may be similar to those of other acute viral infections!
- Findings often mild, nonspecific (e.g., fatigue)
- Liver cirrhosis (30% of cases) within 20 years of infection
- Extrahepatic features (common)
- EIA/ELISA 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” below for findings)
- If diagnosis is unclear
- For evaluating fibrosis in patients with chronic hepatitis C
- Evaluation of response to therapy
- Ultrasound: detection of cirrhosis and neoplasia, e.g., HCC
- Rule out coinfections: HIV, hepatitis A virus (HAV), hepatitis B virus (HBV) serology necessary
- See .
- Goal: prevent transition to chronic infection!
- Treatment: interferon-α or peginterferon-α (PEG-INF) for 6 months
There is no post-exposure prophylaxis available!
- Treatment goals
- Chosen based on viral genotype, history of antiviral treatment, and degree of liver fibrosis
- Combination of two direct-acting antivirals (DAAs)
- Interferon + ribavirin
- In addition to any treatment regimen, give vaccinations for hepatitis A and B
Interferon and ribavirin are associated with severe side effects and teratogenicity!
Considerations in pregnancy
- Vertical transmission approx. 3–5%
- Postpartum treatment
|Differential treatment of chronic hepatiis C: interferon-free treatment regimen|
|Genotype||Standard treatment||Alternatives and modification|
|5 & 6|