Hepatitis C
Summary
Hepatitis C Virus (HCV) is a blood-borne RNA flavivirus that primarily targets the liver. Unlike Hepatitis B, HCV has a high propensity for chronicity, with ~80% of acute infections progressing to chronic hepatitis. It is a leading cause of cirrhosis and hepatocellular carcinoma (HCC) worldwide. The landscape of HCV management has been revolutionised by Direct-Acting Antivirals (DAAs), which now offer a cure (Sustained Virologic Response >95%) with a short course (8-12 weeks) of oral tablets and minimal side effects. Interferon-based therapies are now obsolete. Screening involves HCV Antibody testing, followed by HCV RNA confirmation. [1,2]
Key Facts
- Transmission: Primarily parenteral (IV Drug Use, needle stick, unsafe tattooing, blood transfusion pre-1991). Sexual transmission is rare (mostly MSM with HIV).
- The "Silent Epidemic": Most patients are asymptomatic for decades until they present with decompensated cirrhosis.
- Genotypes: There are 6 main genotypes. Genotype 1 and 3 are commonest in the West. Modern DAA regimens are "pan-genotypic" (work on all types).
- Extra-hepatic Manifestations: HCV is a systemic disease. It causes Cryoglobulinaemia (vasculitis), Porphyria Cutanea Tarda (PCT), and Glomerulonephritis.
Clinical Pearls
Antibody vs RNA:
- Antibody Positive + RNA Negative: Spontaneous clearance (lucky 20%) or Cured.
- Antibody Positive + RNA Positive: Active Chronic Infection -> TREAT.
Vaccination: There is NO vaccine for Hepatitis C. However, all HCV patients MUST be vaccinated against Hepatitis A and B, as super-infection causes fulminant liver failure.
Needlestick Risk: The risk of transmission from a known positive hollow-bore needle injury is ~1.8% (Rule of 3: HBV = 30%, HCV = 3%, HIV = 0.3%).
Re-infection: Curing HCV does NOT confer immunity. Patients can catch it again if they continue risk behaviours.
Prevalence
- Global: 71 million people.
- Risk Groups: People Who Inject Drugs (PWID), Prisoners, Homeless, Baby Boomers (US), Migrants from high prevalence areas (Egypt, Pakistan).
Mechanism
- Viral Replication: HCV replicates in hepatocytes using an RNA-dependent RNA polymerase (NS5B). It lacks proofreading, leading to high mutation rates (Quasispecies) -> Immune evasion and no vaccine.
- Liver Injury: Immune-mediated (Cytotoxic T-cells attacking infected hepatocytes) rather than direct viral cytopathicity.
- Fibrosis: Chronic inflammation activates Stellate cells -> Collagen deposition -> Cirrhosis (20% risk over 20-30 years).
Acute Infection
Chronic Infection
Extra-Hepatic Signs
- Hands: Dupuytren's, Palmar erythema, Leuconychia (Cirrhosis signs). Tattoos? Needle track marks?
- Abdomen: Hepatomegaly (early), Shrunken liver (late), Splenomegaly (Portal hypertension).
- Skin: Spider naevi, Purpura (Cryoglobulinaemia).
Diagnosis
- HCV Antibody (Anti-HCV): Screening test. Remains positive for life even after cure.
- HCV RNA (PCR): Confirmatory test. Quantitative (Viral Load).
- HCV Genotype: (Optional for pan-genotypic drugs, but useful for complex cases).
Staging Liver Disease
Essential to determine if cirrhosis is present before starting treatment.
- FibroScan (Transient Elastography): Measures liver stiffness (kPa).
- APRI / FIB-4 Score: Calculator using Platelets and AST.
- Liver Biopsy: Rarely done now.
Co-Factors
- Viral Screen: HIV, Hep B (occult co-infection).
- Alcohol: Assess intake.
Management Algorithm
HCV ANTIBODY POSITIVE
↓
CHECK HCV RNA
↓
┌─────────────┴─────────────┐
NEGATIVE POSITIVE
(Cleared/Cured) (Active Infection)
↓ │
No Action ┌───────────┴───────────┐
NON-CIRRHOTIC CIRRHOTIC
↓ ↓
TREATMENT TREATMENT
8-12 weeks + SURVEILLANCE
(HCC screening)
1. Direct Acting Antivirals (DAAs) - The "Cure"
Pan-genotypic regimens typically used:
- Sofosbuvir + Velpatasvir (Epclusa): 1 tablet OD for 12 weeks.
- Glecaprevir + Pibrentasvir (Maviret): 3 tablets OD for 8 weeks.
- Efficacy: SVR12 (Cure) rates >95-98%.
- Side Effects: Headache, fatigue (minimal). No psychiatric effects (unlike Interferon).
2. Monitoring
- Check PCR at 12 weeks post-treatment (SVR12). If negative = CURED.
3. Cirrhosis Management
- Even if cured of HCV, a cirrhotic liver remains cirrhotic.
- HCC Surveillance: Ultrasound Liver + AFP every 6 months Lifelong.
- Varices: Gastroscopy screening.
4. Public Health
- Needle Exchange Programs.
- Opioid Substitution Therapy (Methadone).
- "Micro-elimination" strategies.
- Cirrhosis: Decompensation (Ascites, Encephalopathy).
- Hepatocellular Carcinoma (HCC): Annual risk 1-4% in cirrhotics.
- Cryoglobulinaemic Vasculitis: Membranoproliferative glomerulonephritis.
- Untreated: 20-30% develop cirrhosis over 20 years.
- Treated: Mortality reduced significantly. Regression of fibrosis possible.
- Re-infection: Common in ongoing IVDU group (5-10%).
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Hepatitis C | EASL / AASLD | Treat ALL patients with chronic HCV (Treatment for Prevention). Use Interferon-free DAA regimens. |
| Testing | CDC / PHE | Opt-out testing in prisons and drug services. One-time screening for all Baby Boomers (USA). |
Landmark Knowledge
1. Discovery (1989)
- Previously known as "Non-A Non-B Hepatitis". Discovery led to blood screening and massive drop in transfusion cases. Nobel Prize 2020 (Alter, Houghton, Rice).
2. The DAA Revolution (2014)
- Launch of Sofosbuvir. Transformed HCV from a chronic managed condition (with terrible Interferon side effects) to a curable disease.
What is Hepatitis C?
It is a virus that lives in the blood and attacks the liver. It causes inflammation that slowly scars the liver (fibrosis) over 20-30 years.
How did I get it?
It is passed through blood. Common ways are sharing needles (even once, decades ago), unsterile tattoos abroad, or blood transfusions before 1991. It is not easily passed by hugging, kissing, or sharing cups.
Can it be cured?
YES. This is one of the few viral diseases we can completely cure.
- Old Treatment: Injections for months that made you feel like you had severe flu.
- New Treatment: One or three tablets a day for 8-12 weeks. Very few side effects. Cure rate is nearly 100%.
Does the liver heal?
If we catch it early, the liver can repair itself completely. If you already have severe scarring (cirrhosis), the tablets will stop it getting worse and kill the virus, but the scar might remain. You will need scans to check for liver cancer in the future.
Primary Sources
- European Association for the Study of the Liver (EASL). Clinical Practice Guidelines on the management of hepatitis C virus infection. J Hepatol. 2018/2020.
- AASLD-IDSA. HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. hcvguidelines.org.
- Manns MP, et al. Hepatitis C virus infection. Nat Rev Dis Primers. 2017;3:17006.
Common Exam Questions
- Hepatology: "Best test to confirm active HCV infection?"
- Answer: HCV RNA (PCR). (Antibody only shows exposure).
- Dermatology: "Blistering rash on hands, worse in summer, in patient with Hep C?"
- Answer: Porphyria Cutanea Tarda (PCT).
- Virology: "Why is there no vaccine?"
- Answer: High mutation rate of envelope proteins (Hypervariable region).
- Public Health: "Risk of transmission from needlestick?"
- Answer: 3% (approx 1 in 30).
Viva Points
- SVR12: Define it. Undetectable HCV RNA 12 weeks after completion of therapy. Considered a functional cure.
- Cryoglobulinaemia: Mechanism? Chronic immune stimulation produces abnormal IgM that binds IgG (Rheumatoid Factor activity) and precipitates in cold. Vasculitis.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.