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Hepatitis C

SNOMED: 50711007788 words•Updated 03/03/2026
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Exam Tips

  • In UK exams, state diagnosis as a two-step process: HCV antibody (exposure) then HCV RNA PCR (current infection).
  • Quote key numbers: spontaneous clearance 15-45%, chronicity 55-85%, cirrhosis 10-30% by 20 years, HCC 1-3% per year once cirrhotic.
  • High-yield risk group to mention first: people who inject drugs; then transfusion before 1991 and blood products before 1986.
  • Do not say routine universal antenatal screening in the UK; test in pregnancy when risk factors are present.
  • Safety station favorite: avoid NS3/4A protease-inhibitor regimens (for example glecaprevir-containing) in decompensated cirrhosis; check interaction lists (strong enzyme/P-gp inducers can cause treatment failure).
  • If asked about counselling, include confidentiality, insurance disclosure implications for positive tests, and reinfection risk despite antibody positivity after clearance.

Definition

Hepatitis C is a blood-borne viral hepatitis caused by hepatitis C virus (HCV), an RNA flavivirus that primarily infects hepatocytes and can produce acute then persistent liver inflammation. In clinical practice, acute infection is within 6 months of acquisition and is often asymptomatic, while chronic infection is persistence of HCV beyond 6 months with risk of progressive fibrosis, cirrhosis, liver failure, and hepatocellular carcinoma.

Pathophysiology

HCV enters hepatocytes and replicates in the cytoplasm with high mutation rates, generating quasispecies that help immune escape and persistence. Liver injury is largely immune mediated (cytotoxic T-cell and inflammatory cytokine driven), causing chronic necroinflammation, stellate-cell activation, collagen deposition, and fibrosis progression to cirrhosis in a subset. Portal hypertension and synthetic dysfunction then drive decompensation (ascites, variceal bleeding, encephalopathy). Extrahepatic disease can occur via immune dysregulation/immune-complex mechanisms (for example mixed cryoglobulinaemia) and metabolic effects (including insulin resistance/diabetes).

Risk Factors

  • Ever injected drugs (highest UK risk; sharing needles/paraphernalia)
  • Transfusion before 1991 or blood products before 1986
  • Birth/upbringing in higher-prevalence regions (>=2% chronic HCV prevalence)
  • HIV infection, especially MSM with high-risk sexual exposure
  • HBV coinfection or other blood-borne virus exposure
  • Needlestick/sharps injuries (including healthcare exposure)
  • Unsterile tattooing, piercing, acupuncture, or medical/dental/cosmetic procedures
  • Prison exposure, homelessness/hostel residence, sex work, looked-after young people
  • Household blood contact (shared razors/toothbrushes)
  • Maternal HCV infection (vertical transmission risk increased with maternal HIV coinfection)
  • Excess alcohol intake, smoking, BMI >25 kg/m2, and immunosuppression (key progression risks once infected)

Clinical Features

Symptoms

  • Often asymptomatic (both early acute and chronic phases)
  • Fatigue, malaise, reduced concentration
  • Anorexia, nausea, right upper quadrant discomfort
  • Jaundice is uncommon in acute infection
  • Pruritus or nonspecific systemic symptoms in chronic liver disease
  • Features of decompensation in advanced disease: abdominal distension, confusion, GI bleeding

Signs

  • May have no abnormal signs initially
  • Mild hepatomegaly or right upper quadrant tenderness
  • Jaundice (uncommon, more likely in significant hepatitis/decompensation)
  • Stigmata of chronic liver disease (spider naevi, palmar erythema, muscle wasting)
  • Signs of portal hypertension/decompensation (ascites, splenomegaly, encephalopathy, caput medusae)

Investigations

HCV antibody (serology):Positive indicates current or previous infection; may remain positive after spontaneous or treatment-related clearance
HCV RNA PCR:Detectable RNA confirms current viraemic infection; can be positive from about 1-3 weeks post exposure
Repeat testing in window period:If recent high-risk exposure and initial tests negative, repeat based on exposure timing because antibodies may not yet be detectable
Liver blood tests (ALT/AST, bilirubin, albumin, INR, platelets):ALT may be persistently raised; synthetic dysfunction and thrombocytopenia suggest advanced fibrosis/cirrhosis
Fibrosis staging (transient elastography/FIB-4/APRI as locally used):Quantifies fibrosis and helps identify cirrhosis/decompensation risk
Liver ultrasound +/- AFP surveillance when cirrhotic:Screens for hepatocellular carcinoma in patients with cirrhosis
Baseline coinfection screen (HBsAg, HIV; immunity to HAV/HBV):Identifies coinfections and vaccination needs; HBV reactivation risk must be considered before DAAs
Pregnancy test when relevant:Essential before ribavirin-containing therapy because ribavirin is highly teratogenic

Management

Lifestyle Modifications

  • Harm-reduction advice: never share injecting equipment; support needle and syringe programmes/opioid substitution treatment
  • Avoid alcohol (or strict minimisation) to reduce fibrosis progression
  • Weight, metabolic, and smoking risk-factor optimisation
  • Vaccinate against hepatitis A and hepatitis B if non-immune
  • Transmission counselling (blood-contact precautions; do not share razors/toothbrushes)
  • Mental health and comorbidity support (depression, diabetes, CKD are common in HCV cohorts)

Pharmacological Treatment

Pan-genotypic direct-acting antiviral combinations (first-line specialist treatment)

  • Sofosbuvir 400 mg/velpatasvir 100 mg orally once daily for 12 weeks
  • Glecaprevir 300 mg/pibrentasvir 120 mg orally once daily (as 3 tablets together with food), usually 8 weeks in non-cirrhotic treatment-naive disease

SVR (cure) rates exceed 90% in most groups. Regimen and duration depend on genotype, prior treatment, fibrosis/cirrhosis stage, renal function, and drug interactions.

Adjunct in selected difficult-to-treat cases

  • Ribavirin (typically weight-based, often 1000 mg/day if <75 kg or 1200 mg/day if >=75 kg in divided doses, with specialist adjustment)

Major safety warning: teratogenic; contraindicated in pregnancy and in male partners of pregnant women. Effective contraception is required during treatment and for 6 months after exposure.

Surgical / Interventional

  • Liver transplantation for end-stage liver disease or selected hepatocellular carcinoma, with ongoing hepatology follow-up post-transplant

Complications

  • Chronic hepatitis with progressive fibrosis
  • Cirrhosis (approximately 10-30% over 20 years if untreated)
  • Decompensated liver disease: ascites, variceal haemorrhage, encephalopathy
  • Hepatocellular carcinoma (around 1-3% per year in cirrhosis)
  • Fulminant hepatitis (rare, <1%; risk increased with HAV coinfection)
  • Extrahepatic manifestations: mixed cryoglobulinaemia, CKD, lichen planus, Sjogren-like disease, arthritic syndromes, depression, diabetes

Prognosis

Acute infection is usually silent; about 15-45% clear spontaneously within 6 months, while 55-85% progress to chronic infection. Without treatment, a proportion develop cirrhosis and then annual HCC risk rises if cirrhosis is present. Prognosis worsens with older age, male sex, alcohol excess, obesity, smoking, HIV/HBV coinfection, and immunosuppression. Modern DAA therapy achieves cure in the large majority of patients and markedly reduces long-term liver-related morbidity.

Sources & References

🏥BMJ Best Practice(1)

💊BNF Drug References(1)

✅NICE Guidelines(1)

📖Textbook References(20)

  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 735)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 745)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 742, 743)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 734, 735)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1833)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 854)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1614)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 744)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1614)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1515)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 729)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 743, 744)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1615)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 857)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1606)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1644)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 747)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1579, 1580)[context]
  • Emergencies in - Obstetrics and Gynaecology, Second Edition (Stergios K. Doumouchtsis, S. Arulkumaran) (Z-Library).pdf(pp. 78, 79)[context]
  • [Williams, Bailey and Love's Short Practice of Surgery] Norman Williams, Christopher Bulstrode, P Ronan O'Connell - Bailey & Love's Short Practice of Surgery 26E (2013, CRC Press) - libgen.li.pdf(pp. 181)[context]

Sources

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