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Referral and warning signs
When to refer
Refer ALL patients with positive Anti-HCV and detectable HCV RNA to a specialist (Gastroenterologist/Hepatologist/Infectious Diseases) for: Confirmation of diagnosis, Genotyping, Fibrosis staging, Selection and prescription of appropriate DAA therapy, Management of complex cases (cirrhosis, co-infections, treatment failure).
Red flags
- Signs of liver decompensation (jaundice, ascites, encephalopathy, variceal bleeding)
- Signs suggestive of HCC (weight loss, palpable liver mass, rising AFP)
- Extrahepatic manifestations (e.g., vasculitic rash, peripheral neuropathy, renal failure)
Signs and symptoms
- Usually asymptomatic for many years.
- May have non-specific fatigue, malaise.
- Can present later with complications of cirrhosis (jaundice, ascites, variceal bleeding, encephalopathy) or HCC (weight loss, RUQ pain).
- Extrahepatic manifestations may occur (e.g., cryoglobulinemia - rash, arthralgia, neuropathy; glomerulonephritis, porphyria cutanea tarda).
Risk factors
- Injecting drug use (past or present, sharing needles/equipment) - major risk factor.
- Receipt of unscreened blood/blood products (primarily before early 1990s).
- Needlestick injuries / Occupational exposure.
- Haemodialysis.
- Birth to an HCV-infected mother.
- Sharing personal items contaminated with blood (razors, toothbrushes).
- Tattoos/piercings with non-sterile equipment.
- High-risk sexual behaviour (less efficient transmission than HBV/HIV, but risk increased with multiple partners, HIV co-infection, MSM).
- Incarceration.
Diagnosis
Clinical assessment
Suspect in individuals with risk factors or unexplained elevated LFTs, or presentation with cirrhosis/HCC. Often identified through screening.
Investigations
- Anti-HCV Antibody Test: Initial screening test. Positive result indicates exposure (current or past infection).
- HCV RNA (Viral Load) Test: Confirms active/current infection if positive. Essential before treatment.
- HCV Genotype Testing: Determines HCV genotype (1-6) and potentially subtypes. Important for choosing appropriate DAA regimen and duration (though pan-genotypic regimens increasingly used).
- Liver Function Tests (LFTs): ALT/AST may be normal or elevated.
- Assessment of Fibrosis/Cirrhosis:
- - Non-invasive markers (APRI, FIB-4).
- - Transient Elastography (FibroScan).
- - Liver Biopsy (rarely needed for diagnosis/staging now).
- Screening for Co-infections: HBsAg (HBV), HIV test.
- Renal function (required before starting some DAAs).
Diagnostic criteria
Positive Anti-HCV antibody test AND detectable HCV RNA.
Management
Non-pharmacological management
- Avoid alcohol (accelerates liver disease progression).
- Maintain healthy weight, manage metabolic factors (diabetes, lipids).
- Vaccination against Hepatitis A and Hepatitis B (if not immune).
- Counseling on preventing transmission (avoid sharing sharps, safe sex practices).
Pharmacological treatment
- Goal: Eradicate HCV infection (Sustained Virologic Response - SVR), prevent progression to cirrhosis/HCC.
- Direct-Acting Antiviral (DAA) Therapy: Standard of care. Highly effective (>95% cure rates), well-tolerated, oral regimens.
- - Choice of DAA regimen and duration (typically 8-12 weeks) depends on: HCV genotype, presence/absence of cirrhosis, prior treatment history, potential drug interactions, renal function.
- - Pan-genotypic regimens (effective against all common genotypes) simplify treatment: e.g., Sofosbuvir/Velpatasvir; Glecaprevir/Pibrentasvir.
- - Genotype-specific regimens also exist.
- - Requires specialist assessment and prescribing.
- Management of Complications:
- - Treat cirrhosis complications (ascites, encephalopathy, varices) as appropriate.
- - Continue HCC surveillance (Ultrasound +/- AFP every 6 months) even after HCV cure IF cirrhosis was present before treatment.
- - Ribavirin: Older drug, sometimes used in combination with DAAs in specific difficult-to-treat populations (e.g., decompensated cirrhosis, prior treatment failure - specialist use, significant side effects).
- - Interferon-based therapies: Largely obsolete due to lower efficacy and high side effect burden.
Monitoring
- During DAA Therapy: Monitor for adherence and rare side effects. Routine LFT/viral load monitoring during therapy often not needed with simple regimens.
- Post-Treatment: Check HCV RNA 12 weeks after completing therapy to confirm Sustained Virologic Response (SVR12) = Cure.
- Long-term: If cirrhosis present pre-treatment, continue HCC surveillance indefinitely. Monitor LFTs periodically.
Complications
- Liver Cirrhosis
- Portal Hypertension
- Hepatocellular Carcinoma (HCC)
- Decompensated liver disease (ascites, encephalopathy, variceal bleeding)
- Extrahepatic manifestations (Cryoglobulinemic vasculitis, renal disease, lymphoma, etc.)
- Increased mortality
Prevention
- Screening of blood supply.
- Safe injection practices / Harm reduction for IVDU.
- Avoid sharing personal items (razors, toothbrushes).
- Infection control in healthcare settings.
- Safe sex practices (condom use reduces risk).
Patient education
- Explain chronic HCV infection and potential for cure with DAAs.
- Mode of transmission and prevention.
- Importance of alcohol abstinence.
- Need for HAV/HBV vaccination.
- DAA regimen details: duration, importance of adherence, potential interactions.
- Need for post-treatment testing (SVR12) to confirm cure.
- Long-term monitoring/HCC screening if cirrhosis present.
- Screening recommendations for contacts.
Uganda-specific notes
HCV prevalence significant, especially among PLHIV and potentially PWID. Access to HCV RNA testing, genotyping, and especially DAA therapy is improving but remains a major challenge due to cost and availability. Screening based on risk factors important. Linkage to care and treatment programs crucial.
References
- Uganda Clinical Guidelines (UCG) 2023
Chapter 6, Section 6.5.3
- National Hepatitis C Guidelines, MOH Uganda
(Refer to specific MOH guidelines)