Hepatitis C: why it becomes chronic, and its extrahepatic disease
- Topic
Hepatitis C quietly stays in the liver for decades in most people, slowly scarring it, unless it is treated.
What it is
Hepatitis C virus is an RNA flavivirus spread mainly by blood. Its error-prone RNA polymerase produces many variants (quasispecies) that escape antibodies, so most infections become chronic. Chronic hepatitis C is usually mild and slowly progressive, but over decades a proportion of patients develop cirrhosis and hepatocellular carcinoma. Direct-acting antivirals now cure most patients, which has changed the natural history.
Structure
- Portal tracts with dense lymphoid aggregates or follicles; mild interface hepatitis.
- Bile duct epithelial injury inside the aggregates.
- Macrovesicular steatosis in many cases.
Step by step
- HCV enters the bloodstream (shared needles, unscreened transfusion, unsafe procedures; less often sex or birth).
- It replicates in hepatocytes in the cytoplasm; it does not integrate into host DNA.
- Its polymerase makes errors, producing many variants that escape antibodies.
- Persistent T-cell inflammation causes chronic hepatitis with portal lymphoid aggregates.
- Fibrosis progresses slowly over decades, faster with alcohol, HIV, obesity and older age.
- Cirrhosis develops in a part of patients and carries a yearly risk of hepatocellular carcinoma.
Clinical notes
- Most patients are found by screening or by abnormal ALT; symptoms are vague fatigue.
- Cryoglobulinemic vasculitis: palpable purpura, arthralgia, glomerulonephritis, low complement.
Test yourself
Think of the answer, then tap the question to see it.
Why has a vaccine against HCV been so hard to make?
Its error-prone RNA polymerase generates many variants (quasispecies) that escape neutralizing antibodies.
Which portal finding is typical of chronic hepatitis C on biopsy?
Dense portal lymphoid aggregates, sometimes with germinal centres, with bile duct injury.
Which extrahepatic diseases are linked to chronic HCV?
Mixed cryoglobulinemia with vasculitis and membranoproliferative glomerulonephritis; also porphyria cutanea tarda and B-cell lymphoma.
A patient is anti-HCV positive but HCV RNA negative. What does that mean?
Past infection that has cleared (spontaneously or with treatment), or a false-positive antibody; there is no active viremia.
Connections
Microorganisms1
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Hepatitis C: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Hepatitis C (World Health Organization, 2026).
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Representative model, for educational purposes only.