• Clinical science

Hepatitis C

Abstract

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.

Definition

Acute HCV infection

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

References:[1]

Epidemiology

  • Prevalence: 1–2% of the US population has chronic HCV infection
    • ∼ 3% of the world's population is HCV-positive.
    • The prevalence varies greatly among geographic locations (e.g., high prevalence in Africa, the Middle East, Central and East Asia).
  • Incidence: ∼ 17,000 new infections per year in the US

References:[2][3]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

Pathogen

  • Hepatitis C virus (HCV: 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.

Transmission

  1. Parenteral
  2. Sexual: rare (in contrast to HBV and HIV)
  3. Perinatal (vertical)

High-risk groups for HCV infection

Patients with a medical history indicating a high risk for HCV infection should be tested!
References:[4][3][5]

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

References:[6][1][3][7][8]

Diagnostics

References:[7][9][10][11]

Pathology

Differential diagnoses

The differential diagnoses listed here are not exhaustive.

Treatment

Acute hepatitis C

  • Goal: prevent transition to chronic infection!
  • Treatment: interferon-α or peginterferon-α (PEG-INF) for 6 months

There is no post-exposure prophylaxis available!

Chronic hepatitis C

Interferon and ribavirin are associated with severe side effects and teratogenicity!
References:[3][5][10][12][13]

Complications

References:[14][15]

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

Special patient groups

Considerations in pregnancy

  • Vertical transmission approx. 3–5%
    • C-section does not lower risk of transmission
    • Avoid amniocentesis or the use of fetal scalp electrode (↑ risk)
    • HCV-infected patients may breastfeed as normal
  • Postpartum treatment

References:[16][17]

Regimens for chronic hepatitis C infection by genotype

Differential treatment of chronic hepatiis C: interferon-free treatment regimen
Genotype Standard treatment Alternatives and modification
1
2
  • If treatment fails, the standard treatment is then sofosbuvir + ribavirin + daclatasvir for 12 weeks.
3
4
5 & 6