Quick Answer
Hepatitis C is a NEET PG examiner favourite because DAAs turned it from a chronic disease into a curable one within a decade. The high-yield framework:
- Virology — RNA virus, Flaviviridae; six major genotypes; India dominated by genotype 3.
- Natural history — 55 to 85 percent become chronic; 20 to 30 percent develop cirrhosis over 20 to 30 years; HCC risk 1 to 4 percent per year in cirrhosis.
- Diagnosis — anti-HCV screen, confirmatory HCV RNA PCR, genotype, and fibrosis staging (Fibroscan, APRI, FIB-4).
- Modern DAAs — pan-genotypic sofosbuvir plus velpatasvir 12 weeks or glecaprevir plus pibrentasvir 8 weeks; SVR12 above 95 percent.
- Cure = SVR12 — undetectable HCV RNA 12 weeks after therapy ends.
- Screen HBV first — reactivation risk during DAA therapy; add tenofovir if HBsAg positive.
Hepatitis C prevalence in India is estimated at around 1 percent, translating to roughly 12 million infected — the largest chronic-HCV cohort outside China. The direct-acting antiviral revolution and India's low-cost generics have made elimination genuinely feasible for the first time, and NEET PG has moved accordingly from interferon-era questions to DAA sequencing, genotype-specific pitfalls, and the WHO 2030 framework.
This NEETPGAI deep dive covers epidemiology, virology, transmission, natural history, extrahepatic manifestations, diagnostic algorithm, DAA regimens, post-SVR monitoring, and India's National Viral Hepatitis Control Programme. Pair it with the Medicine subject hub and the hepatitis B guide.
Epidemiology in India
- Prevalence around 1 percent nationally; 12 million estimated infections.
- Punjab (up to 3 to 5 percent in some districts), Andhra Pradesh, Haryana, and injection-drug-user cohorts have the highest burden.
- Blood transfusion screening for HCV became mandatory in India in 2002 — pre-2002 recipients remain a high-risk cohort.
- Genotype 3 dominates (60 to 70 percent), then genotype 1.
Virology
- Enveloped, positive-sense single-stranded RNA virus.
- Family Flaviviridae, genus Hepacivirus.
- Six major genotypes and multiple subtypes; genotype affects treatment history but is less critical with modern pan-genotypic DAAs.
- No effective vaccine (high genetic variability and lack of neutralising antibody response).
Transmission
- Blood exposure — historic transfusion, injection drug use (sharing needles), unsafe healthcare (needle reuse, poorly sterilised surgical or dental equipment), tattooing, and shared razors.
- Vertical — 5 to 6 percent if maternal viraemia, higher with HIV coinfection.
- Sexual — low but non-zero, higher in men who have sex with men, especially with HIV.
- Occupational needlestick — 1.8 percent conversion risk.
Natural history
- Acute HCV — usually asymptomatic; 20 to 30 percent develop mild symptoms with jaundice.
- Spontaneous clearance in 15 to 45 percent within 6 months; more common in young women and IL28B favourable genotype.
- Chronic HCV in 55 to 85 percent.
- Cirrhosis in 20 to 30 percent over 20 to 30 years; accelerated by alcohol, HIV coinfection, HBV coinfection, obesity, insulin resistance, and older age at infection.
- Hepatocellular carcinoma 1 to 4 percent per year once cirrhosis develops.
- Decompensation (variceal bleed, ascites, encephalopathy) — indication for liver transplantation.
Presentation
- Chronic HCV is usually silent until advanced disease.
- Non-specific symptoms — fatigue, low-grade dyspepsia.
- Presentation with cirrhosis complications — ascites, variceal bleed, hepatic encephalopathy, or HCC.
- Acute HCV — jaundice, malaise, RUQ discomfort.
Extrahepatic manifestations
Chronic HCV is a systemic disease.
- Mixed cryoglobulinaemia — most classic; type II cryoglobulins; palpable purpura, arthralgia, glomerulonephritis, neuropathy.
- Membranoproliferative glomerulonephritis — usually cryoglobulinaemic.
- Porphyria cutanea tarda — HCV is the commonest secondary cause.
- Lichen planus — oral or cutaneous.
- Non-Hodgkin B-cell lymphoma — especially marginal-zone lymphoma.
- Insulin resistance and T2DM — reversal after SVR.
- Sicca syndrome and thyroid autoimmunity.
Diagnosis
- Anti-HCV antibody — screening; positive means past or current infection.
- HCV RNA PCR quantitative — confirms current infection and gives viral load.
- Genotype — historically guided regimen choice; less critical with pan-genotypic DAAs but still needed for some special populations.
- Fibrosis staging — Fibroscan (transient elastography), APRI (AST-to-platelet ratio), FIB-4, or liver biopsy in complex cases.
- HBV screen — HBsAg, anti-HBs, anti-HBc — mandatory before DAA (reactivation risk).
- HIV screen — coinfection changes management and drug interactions.
Direct-acting antivirals — the modern era
DAAs replaced interferon-ribavirin regimens after 2013 and turned HCV into a curable disease. They target three viral proteins:
- NS3/4A protease inhibitors — "-previr" (grazoprevir, glecaprevir, voxilaprevir).
- NS5A inhibitors — "-asvir" (velpatasvir, pibrentasvir, ledipasvir, daclatasvir).
- NS5B polymerase inhibitors — "-buvir" (sofosbuvir, the backbone of most modern regimens).
First-line pan-genotypic regimens
| Regimen | Duration | Notes |
|---|
| Sofosbuvir + velpatasvir (Epclusa) | 12 weeks | All genotypes; add ribavirin for decompensated cirrhosis |
| Glecaprevir + pibrentasvir (Mavyret) | 8 weeks | Treatment-naive without cirrhosis; 12 weeks with compensated cirrhosis |
| Sofosbuvir + daclatasvir | 12 weeks | India commonest low-cost generic combination |
| Sofosbuvir + velpatasvir + voxilaprevir (Vosevi) | 12 weeks | For DAA treatment failures |
Special populations
- Compensated cirrhosis (Child-Pugh A) — standard pan-genotypic regimens; may extend duration or add ribavirin.
- Decompensated cirrhosis (Child-Pugh B or C) — protease inhibitors (glecaprevir, voxilaprevir, grazoprevir) are contraindicated; use sofosbuvir plus velpatasvir plus ribavirin for 12 to 24 weeks; consider transplantation.
- Renal impairment (CrCl under 30) — glecaprevir plus pibrentasvir is safe; older sofosbuvir data was limited but current guidance allows sofosbuvir in dialysis with monitoring.
- HIV coinfection — pan-genotypic regimens work; check antiretroviral interactions (avoid efavirenz with sofosbuvir-velpatasvir; efavirenz reduces velpatasvir levels).
- HBV coinfection — screen first; add tenofovir if HBsAg positive; monitor LFTs.
- Pregnancy — DAAs not recommended; treat postpartum.
Defining cure — SVR12
Sustained virologic response at 12 weeks (SVR12) — undetectable HCV RNA 12 weeks after the last dose — is the endpoint of therapy. SVR12 correlates almost perfectly with long-term virologic cure. Modern DAAs achieve SVR12 above 95 percent across all genotypes and populations.
Post-SVR monitoring
- Non-cirrhotic — discharged; re-test only if re-exposure risk.
- Cirrhotic — continue biannual USG plus AFP for hepatocellular carcinoma surveillance for life; SVR reduces but does not eliminate HCC risk.
- Portal hypertension surveillance — continued endoscopic screening for varices in cirrhotic SVR patients.
- Lifestyle — abstain from alcohol; treat comorbid NAFLD, obesity, and T2DM.
Prevention
- No vaccine — unlike hepatitis A and B, no HCV vaccine is available because of extreme genetic diversity and lack of neutralising antibody response.
- Blood-supply screening — universal since 2002 in India; look-back exercises target pre-2002 recipients.
- Harm reduction — clean needle programmes and opioid substitution therapy for people who inject drugs remain the highest-yield public-health interventions.
- Safe injection practices — no reuse of single-use syringes; sterilisation of reusable instruments; safe tattoo and dental practices; scaling up autodisable syringes in the public sector.
- Post-exposure — no post-exposure prophylaxis; monitor with HCV RNA at 4 to 6 weeks and anti-HCV at 3 to 6 months; treat with DAAs if seroconversion.
- Screening high-risk populations — pregnant women, prisoners, people who inject drugs, HIV-positive patients, patients on maintenance haemodialysis, and health-care workers with a percutaneous injury.
NEET PG MCQ traps
- Cure = SVR12 — not end-of-treatment response, not seroconversion. Anti-HCV antibody often remains positive lifelong even after cure.
- HBV reactivation risk during DAA — always screen HBsAg and anti-HBc before therapy.
- Protease inhibitors are hepatotoxic — contraindicated in decompensated cirrhosis (Child-Pugh B or C).
- Genotype 3 is commonest in India — the historic hard-to-treat genotype, now cured with pan-genotypic DAAs.
- Cryoglobulinaemia — most classic extrahepatic manifestation; type II cryoglobulins.
- Porphyria cutanea tarda — HCV is the commonest secondary cause.
- No effective vaccine — HCV has too much genetic variability.
- HCC surveillance continues after SVR in cirrhotics — do not tell a cirrhotic SVR patient they are "cured and can stop follow-up".
- Interferon is off the list — modern practice is interferon-free.
- Ribavirin is not routine — reserved for decompensated cirrhosis or select retreatment.
India-specific programme
- National Viral Hepatitis Control Programme (NVHCP) launched in 2018 by the Ministry of Health and Family Welfare.
- Free DAA testing and treatment at government facilities.
- State leaders — Punjab's Mukh Mantri Punjab Hepatitis-C Relief Fund, Kerala, and Gujarat have run large-scale mass treatment programmes.
- Generic prices — sofosbuvir plus daclatasvir 12 weeks around 1500 to 3000 rupees; branded equivalents cost 20 to 40 times more in the private market.
- Medicines Patent Pool — Cipla, Mylan, Natco, and Hetero manufacture generic DAAs licensed by Gilead and others.
- Compared internationally — Egypt achieved near-elimination through mass screening and generic DAAs; Georgia's national programme is another benchmark. India's coordinated push, if scaled, could achieve WHO 2030 targets.
Frequently asked questions
What is the first-line direct-acting antiviral regimen for hepatitis C?
Pan-genotypic regimens are preferred first-line. Sofosbuvir plus velpatasvir (Epclusa) for 12 weeks and glecaprevir plus pibrentasvir (Mavyret) for 8 weeks in treatment-naive patients without cirrhosis both achieve sustained virologic response above 95 percent. In India, sofosbuvir plus daclatasvir is widely used because of low-cost generics. Sofosbuvir plus velpatasvir plus voxilaprevir (Vosevi) is reserved for DAA treatment failures.
What defines a cure of hepatitis C?
Cure is defined as sustained virologic response at 12 weeks after completing therapy (SVR12) — an undetectable HCV RNA 12 weeks after the last dose. Modern DAA regimens achieve SVR12 above 95 percent across all genotypes. SVR12 correlates almost perfectly with long-term virologic cure and reduces the risks of cirrhosis progression, hepatocellular carcinoma, and liver-related mortality.
Which HCV genotype dominates in India?
Genotype 3 is the commonest HCV genotype in India (60 to 70 percent), followed by genotype 1. Genotype 3 was historically the hardest to treat and drove the need for pan-genotypic DAAs. Modern regimens like sofosbuvir plus velpatasvir and glecaprevir plus pibrentasvir cure genotype 3 as effectively as other genotypes. Ribavirin is no longer routinely required for genotype 3 with these regimens.
Why must HBV status be checked before HCV treatment?
HCV DAAs can trigger HBV reactivation in patients with untreated chronic HBV coinfection. All patients starting DAAs must be screened with HBsAg and anti-HBc. If HBsAg is positive, add prophylactic tenofovir before or during DAA therapy and continue until at least 12 weeks after DAA completion. If anti-HBc is positive but HBsAg negative, monitor LFTs during DAA therapy.
What is India's role in the WHO 2030 hepatitis elimination target?
The WHO 2030 target is a 90 percent reduction in new HCV infections and a 65 percent reduction in HCV mortality. India launched the National Viral Hepatitis Control Programme in 2018, offering free DAAs at government facilities. Punjab, Kerala, and Gujarat lead state-level elimination programmes. Low-cost sofosbuvir plus daclatasvir generics (about 1500 to 3000 rupees for 12 weeks) have made mass treatment feasible.
This content is for educational purposes for NEET PG exam preparation. It is not a substitute for professional medical advice, diagnosis, or treatment. Clinical information has been reviewed by qualified medical professionals.
Written by: NEETPGAI Editorial Team
Reviewed by: Pending SME Review
Last reviewed: September 2026
