Chronic Hepatitis C

Chronic hepatitis C is persistent HCV infection for more than 6 months, with progressive fibrosis.

• About 58 million people are infected worldwide; sub-Saharan prevalence 1 to 3 percent, with higher rates in people who inject drugs, haemodialysis patients, and those with HIV.
• Cirrhosis develops in 15 to 25 percent over 20 to 30 years; hepatocellular carcinoma risk is 1 to 4 percent per year once cirrhosis is established.
• Genotypes 1, 4 and 5 predominate in Africa; modern pangenotypic regimens make genotyping unnecessary for most patients.

Often asymptomatic; fatigue, arthralgia, myalgia, depression, right upper quadrant discomfort.

• Extrahepatic: cryoglobulinaemia with purpura, arthralgia and neuropathy, membranoproliferative glomerulonephritis, porphyria cutanea tarda, lichen planus, sicca syndrome, insulin resistance, B-cell lymphoma.
• Cirrhosis: spider naevi, palmar erythema, splenomegaly, ascites, jaundice, encephalopathy, variceal bleeding.
• Differential diagnosis: chronic hepatitis B and D, alcohol-related liver disease, metabolic associated fatty liver disease, autoimmune hepatitis, haemochromatosis, Wilson disease, drug-induced injury.
• Complications: decompensated cirrhosis, hepatocellular carcinoma, hepatorenal syndrome, vasculitis, renal failure and lymphoproliferative disease.

Anti-HCV antibody screens; confirm active infection with HCV RNA (quantitative).

• Fibrosis assessment: transient elastography (liver stiffness above 12.5 kPa suggests cirrhosis), a non-invasive fibrosis score using age, AST, ALT and platelets, or liver biopsy if uncertain.
• Platelets, INR, albumin, bilirubin, ALT, creatinine and eGFR; hepatitis B surface antigen and core antibody; HIV; hepatitis A and B immunity; alpha-fetoprotein and ultrasound.
• Genotype only if using a regimen that requires it; cryoglobulins and complement if vasculitis suspected.

Supportive: alcohol abstinence, weight control, vaccination against hepatitis A and B, avoid NSAIDs and herbal remedies, harm reduction.

Pharmacological (everyone with detectable HCV RNA should be treated):

• Sofosbuvir 400 mg plus velpatasvir 100 mg once daily for 12 weeks (non-cirrhotic and compensated cirrhosis).
• Glecaprevir 300 mg plus pibrentasvir 120 mg once daily with food for 8 weeks (non-cirrhotic) or 12 weeks (compensated cirrhosis); contraindicated in decompensated cirrhosis.
• Sofosbuvir 400 mg plus daclatasvir 60 mg once daily for 12 weeks (non-cirrhotic) or 24 weeks (cirrhosis, or 12 weeks with ribavirin).
• Decompensated cirrhosis: sofosbuvir plus velpatasvir with ribavirin (1000 mg daily if below 75 kg, 1200 mg if 75 kg or more, in two divided doses) for 12 weeks, under specialist transplant centre supervision; avoid protease inhibitors.
• Sofosbuvir is not advised with eGFR below 30 mL/min unless a specialist supervises (glecaprevir plus pibrentasvir is an option).
• Interactions: amiodarone with sofosbuvir (bradycardia), proton pump inhibitors, rifampicin and carbamazepine (reduce levels); adjust antiretroviral therapy (efavirenz, nevirapine) with specialist advice.
• Treatment failure: sofosbuvir plus velpatasvir plus voxilaprevir 400/100/100 mg once daily with food for 12 weeks.

Special groups: HIV and HBV coinfection (test and prophylax for HBV reactivation), children aged 3 years and above (weight based sofosbuvir plus velpatasvir or glecaprevir plus pibrentasvir), pregnancy (defer treatment), kidney disease and transplant recipients (specialist care).

Procedures: variceal screening and band ligation in cirrhosis; transplant evaluation for decompensation; hepatocellular carcinoma surveillance by ultrasound every 6 months in cirrhosis (also after cure).

Red flags: new ascites, jaundice, encephalopathy, rising alpha-fetoprotein, hepatic mass.

Follow-up: HCV RNA at 12 weeks after the end of treatment (cure); continue surveillance if cirrhotic; counsel on reinfection prevention.