[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Liver and gallbladder](https://durgical.com/en/general-pathology/areas/liver/) › Hepatitis C: why it becomes chronic, and its extrahepatic disease # 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. Updated Nov 12, 2026 ## Key points - Most acute infections are silent and most become chronic. - High mutation rate creates quasispecies: escape from neutralizing antibodies, no vaccine. - Biopsy hallmarks: portal lymphoid aggregates (sometimes with germinal centres), bile duct injury and macrovesicular steatosis (especially genotype 3). - Extrahepatic: mixed cryoglobulinemia, membranoproliferative glomerulonephritis, porphyria cutanea tarda, B-cell lymphoma, insulin resistance. - Diagnosis: anti-HCV antibody, confirmed by HCV RNA (antibody alone does not prove active infection). - HCC in HCV arises almost always on cirrhosis. ## 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. ## Memory aid C is for Chronic and for Cryoglobulins: a quiet, changing virus that keeps the liver busy for decades. ## 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. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/general-pathology/hepatitis-c-why-it-becomes-chronic-and-its-extrahepatic-disease/) [More Pathology questions →](https://durgical.com/en/practice/?f=pathology) ## Connections ## Related 5 - [Hepatitis viruses A to E: the comparison table](https://durgical.com/en/general-pathology/hepatitis-viruses-a-to-e-the-comparison-table/) - [Viral hepatitis on biopsy: acute and chronic](https://durgical.com/en/general-pathology/viral-hepatitis-on-biopsy-acute-and-chronic/) - [Cirrhosis: morphology](https://durgical.com/en/general-pathology/cirrhosis-morphology/) - [Hepatocellular carcinoma](https://durgical.com/en/general-pathology/hepatocellular-carcinoma/) - [Oncogenic viruses and H. pylori: the table to know](https://durgical.com/en/general-pathology/oncogenic-viruses-and-h-pylori-the-table-to-know/) ## Related conditions 7 - [Viral hepatitis](https://durgical.com/en/conditions/viral-hepatitis/) - [Cirrhosis](https://durgical.com/en/conditions/cirrhosis/) - [Hepatocellular carcinoma](https://durgical.com/en/conditions/hepatocellular-carcinoma/) - [Cryoglobulinemic vasculitis](https://durgical.com/en/conditions/cryoglobulinemic-vasculitis/) - [Membranoproliferative glomerulonephritis](https://durgical.com/en/conditions/membranoproliferative-glomerulonephritis/) - [Porphyria cutanea tarda](https://durgical.com/en/conditions/porphyria-cutanea-tarda/) - [Non-Hodgkin lymphoma](https://durgical.com/en/conditions/non-hodgkin-lymphoma/) ## Microorganisms 1 - [Hepatitis C virus](https://durgical.com/en/microbiology/hepatitis-c-virus/) [← All of general pathology](https://durgical.com/en/general-pathology/) 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](https://medlineplus.gov/ency/article/000284.htm) (MedlinePlus, US National Library of Medicine, 2026); [Hepatitis C](https://www.who.int/news-room/fact-sheets/detail/hepatitis-c) (World Health Organization, 2026). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/general-pathology/hepatitis-c-why-it-becomes-chronic-and-its-extrahepatic-disease/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/hepatitis-c-why-it-becomes-chronic-and-its-extrahepatic-disease/