Makindo Medical Notes Comprehensive Medical Encyclopedia | Education for Healthcare Professionals

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MEDICAL DISCLAIMER: The contents are under continuing development and improvements and despite all efforts may contain errors of omission or fact. This is not to be used for the assessment, diagnosis, or management of patients. It should not be regarded as medical advice by healthcare workers or laypeople. It is for educational purposes only. Please adhere to your local protocols. Use the BNF for drug information. If you are unwell please seek urgent healthcare advice. If you do not accept this then please do not use the website. Makindo Ltd.

Hepatitis C

💉 PEG = polyethylene glycol, a water-soluble polymer added to interferon to make it longer-acting. The goal is to eradicate HCV, prevent fibrosis, and reduce the risk of hepatocellular carcinoma (HCC). ⚠️ HCV is curable today with modern direct-acting antivirals (DAAs).

📖 About Hepatitis C

🦠 A viral infection causing chronic hepatitis and progressive liver damage.
🌍 Affects ~185 million people worldwide.
🚨 Leads to cirrhosis, liver failure, and HCC if untreated.
🇬🇧 UK: 200,000–400,000 infected, many undiagnosed and asymptomatic.
Genotypes 1a & 1b common in Europe/US → harder to treat.

🧬 Aetiology & Pathophysiology

RNA flavivirus with 6 genotypes. Genotype 1 = most common in Europe.
80% progress to chronic hepatitis → persistently abnormal LFTs.
~30% develop cirrhosis; ~5% develop HCC.
Immune response determines outcome:
- Th1 response (γ-IFN, IL-2) → viral clearance.
- Th2 response (IL-4, IL-10, IL-13) → chronicity.

🔄 Transmission

💉 Blood transfusions/products (before screening protocols).
💊 IV drug use (most common in UK).
🤰 Maternal (vertical) transmission.
❤️ Sexual transmission (rare).
🩺 Needlestick injuries in healthcare workers.

👩‍⚕️ Clinical Features

Acute infection → usually silent/asymptomatic.
Chronic infection → fatigue, malaise, jaundice, dark urine, anorexia, nausea.
Skin/extrahepatic features: purpura, vasculitis, neuropathy, cryoglobulinaemia.
Associated with porphyria cutanea tarda & glomerulonephritis.
⚠️ Advanced disease → cirrhosis, portal hypertension, HCC.

🧪 Investigations

✅ Anti-HCV antibody (first-line screening).
✅ HCV RNA PCR (confirms infection, monitors treatment response).
🧬 Genotype testing → guides therapy choice.
📈 LFTs: mild ↑ ALT/AST (50–200).
🔬 Liver biopsy or elastography → assess fibrosis/cirrhosis.
🧫 Rheumatoid factor, cryoglobulins, low complement → extrahepatic features.
🧲 Imaging (US, CT, MRI) → cirrhosis/HCC surveillance.

⚠️ Risk Factors for Cirrhosis

🍺 Alcohol consumption.
🧑‍🦱 Male sex, age >40 at infection.
🦠 Co-infection with HIV or HBV.
💊 Immunosuppression.

🩺 Associated Conditions

Porphyria cutanea tarda.
Glomerulonephritis, diabetes, arthritis.
Sicca syndrome, non-Hodgkin lymphoma.
Lichen planus, cryoglobulinaemia.

💊 Management

🎯 Direct-acting antivirals (DAAs) → >90% cure rates.
Sofosbuvir (polymerase inhibitor, pan-genotype).
Velpatasvir (NS5A inhibitor, used with sofosbuvir).
Simeprevir (protease inhibitor).
Voxilaprevir (used in resistant cases).
Duration: 8–24 weeks depending on genotype & fibrosis.
🧪 Monitor via PCR for sustained virological response (SVR = cure).
🩺 Liver transplant if decompensated cirrhosis, but reinfection risk exists.

📌 Key Teaching Pearls

🦠 HCV is now curable → early diagnosis is essential.
🚨 Always screen at-risk patients (IV drug use, transfusions pre-1991, HIV+).
🔄 No vaccine exists → prevention relies on harm reduction (needle exchange, safe blood supply).
🧑‍⚕️ Chronic HCV → major cause of liver transplantation in the UK/US.

📊 Response to therapy = normal ALT + undetectable HCV RNA (SVR). This is equivalent to a virological cure ✅

📚 References

🧫 Hepatitis C – Clinical Cases

Case 1 – Chronic Infection Discovered Incidentally: A 44-year-old man attends for a routine insurance medical. LFTs show ALT 98 U/L and AST 85 U/L. He feels well and denies jaundice, but recalls past injecting drug use in his 20s. Ultrasound shows mild fatty change; hepatitis C antibody and RNA are both positive. FibroScan reveals F1–F2 fibrosis. Teaching point: Many HCV cases are asymptomatic until detected on screening. Assess fibrosis stage (elastography or biopsy), screen for coinfection (HIV, HBV), and start direct-acting antiviral (DAA) therapy, which now cures > 95%.

Case 2 – Extrahepatic Manifestation: Cryoglobulinaemic Vasculitis: A 55-year-old woman with known chronic hepatitis C presents with fatigue, arthralgia, and a purpuric rash on the lower legs. Urinalysis shows microscopic haematuria and proteinuria. Bloods reveal low complement C4 and positive cryoglobulins. Teaching point: HCV can trigger immune complex small-vessel vasculitis due to circulating cryoglobulins. Management requires antiviral therapy plus immunosuppression if severe (e.g. rituximab). Always consider HCV in unexplained vasculitis or membranoproliferative GN.

Case 3 – Post-Treatment Relapse and Cirrhosis: A 63-year-old man with compensated cirrhosis secondary to hepatitis C genotype 3 completed sofosbuvir-velpatasvir 12 months ago. He re-presents with malaise, ascites, and rising bilirubin. HCV RNA is again positive, indicating relapse. Teaching point: Relapse or reinfection may occur, particularly in patients with advanced fibrosis or ongoing risk factors. He requires reassessment for retreatment options, variceal screening, and hepatocellular carcinoma surveillance every 6 months by ultrasound ± AFP.

💡 Clinical pearl: Always check both HCV antibody and HCV RNA to confirm active infection. Modern DAAs (e.g. sofosbuvir, glecaprevir/pibrentasvir) achieve sustained virological response within 8–12 weeks — a remarkable shift from the interferon era. 🌟

PLEASE NOTE LEGAL ADVICE: The contents are under continuing development and improvements and may contain errors of omission or fact. Feedback vital and always welcome at drokane at gmail.com. This is not to be used for the assessment, diagnosis or management of patients. It should not be regarded as medical advice. It is only for educational purposes. Please adhere to your local protocols. If you are unwell please seek healthcare advice from your doctor. This does not replace senior or specialist advice. If you do not accept this then please do not use the website. If you need medical advice, please consult a doctor or other appropriate medical professional. If you are a medical professional and you need advice then speak to your senior or colleagues.

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