Epidemiology
Etiology
- Parenteral
- Needle sharing among individuals who use injection drugs
- Needlestick injury (e.g., health care workers)
- Blood transfusion
- Dialysis
- Organ transplantation
- Sexual: rare (in contrast to HBV and HIV)
Pathophysiology
Pathogen
- 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.
Clinical features
Incubation period
- 2 weeks to 6 months
Chronic course
- 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 of HCV (common)
- Hematological
- Mixed cryoglobulinemia
- Lymphoma (especially B-cell non-Hodgkin lymphoma)
- ITP
- Autoimmune hemolytic anemia
- Monoclonal gammopathies
- Renal
- Membranoproliferative glomerulonephritis (more common)
- Membranous glomerulonephritis
- Dermatological
- Porphyria cutanea tarda
- Lichen planus
- Endocrine
- Diabetes mellitus
- Autoimmune thyroiditis (may lead to hypothyroidism)
- Vascular: leukocytoclastic vasculitis
- Hematological
Diagnostics
Treatment
Antiviral therapy
- Direct-acting antivirals (DAAs)
- Antivirals target and inhibit HCV-encoded proteins that are essential for the HCV replication cycle.
- Example regimens
- Glecaprevir PLUS pibrentasvir (all 6 genotypes)
- Sofosbuvir PLUS velpatasvir (all 6 genotypes)
- Ledipasvir PLUS sofosbuvir (genotypes 1, 4, 5, and 6)
- Interferon PLUS ribavirin
- Was the preferred treatment before the development of DAAs
- Associated with severe adverse effects (e.g., arthralgias, thrombocytopenia, leukopenia, depression, anemia) and teratogenicity
- Contraindicated in patients with decompensated cirrhosis (high risk of worsening cirrhosis decompensation)
- Ribavirin
- Mechanism of action
- Guanosine analogue (nucleoside inhibitor)
- Competitive inhibition of IMP dehydrogenase → prevention of guanine nucleosides synthesis
- Adverse effects
- Hemolytic anemia
- Highly teratogenic
- Mechanism of action
Tip
DAAs have superior efficacy and safety profiles compared with interferon or ribavirin-based regimens and are thus preferred.