Makindo Medical Notes

Related Subjects: | Chronic liver disease | Cirrhosis | Alkaline phosphatase (ALP) | Liver Function Tests | Ascites Assessment and Management | Budd-Chiari syndrome | Autoimmune Hepatitis | Primary Biliary Cirrhosis | Primary Sclerosing Cholangitis | Wilson disease | Hereditary Haemochromatosis | Alpha-1 Antitrypsin (AAT) deficiency | Nonalcoholic steatohepatitis (NASH) | Spontaneous Bacterial Peritonitis | Alcoholism and Alcoholic Liver Disease |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

• EASL Recommendations on Treatment of Hepatitis C 2018
• Hepatitis C: Diagnosis and Treatment

🧫 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. 🌟