214.1 ð é«åžçç
214.1.0.1 ð äžé éé»
- Virus: ssRNA Flaviviridae (hepacivirus)
- 6 genotypes (1-6); genotype 1 most common globally; 3 common Asia; genotype 4 Egypt
- Transmission:
- Blood: IDU (#1 in developed countries), transfusion (pre-1992 USA, ongoing in unscreened resource-limited)
- Healthcare: nosocomial (Egypt iatrogenic outbreak â global highest prevalence)
- Sexual: low risk overall, higher in MSM + HIV+
- Vertical: 5-10% if mother viremic; risk higher with HIV+ co-infection
- Tattoo, piercing, acupuncture: unsterile equipment
- Global Burden:
- ~ 58M chronic HCV (WHO 2024)
- 290K deaths/yr (cirrhosis + HCC)
- WHO 2030 elimination goal: 90% diagnosis + 80% treatment access + 65% mortality reduction
- Clinical:
- Acute HCV (10-20% spontaneous clearance): usually asymptomatic; sometimes mild hepatitis
- Chronic HCV (~ 80%): largely asymptomatic until cirrhosis (20-30 yr)
- Cirrhosis (20% in 20-30 yr without treatment)
- HCC (3-5% per year in cirrhotic HCV)
- Extrahepatic:
- Mixed cryoglobulinemia (5-25% of chronic HCV)
- Type II + III cryoglobulinemic vasculitis (rash, neuropathy, GN)
- Membranoproliferative GN (MPGN)
- B-cell lymphoma (NHL â splenic marginal zone, DLBCL)
- Porphyria cutanea tarda
- Sjögrenâs-like sicca
- Type 2 diabetes (insulin resistance)
- Diagnosis:
- Anti-HCV antibody (initial screening)
- HCV RNA PCR quantitative (active infection)
- Genotype (less critical now with pan-genotypic DAAs)
- Treatment:
- Direct-Acting Antivirals (DAAs):
- Sofosbuvir/Velpatasvir (Epclusa) â pan-genotypic 12 wk, > 95% SVR
- Glecaprevir/Pibrentasvir (Mavyret) â pan-genotypic 8 wk, > 95% SVR
- Sofosbuvir/Velpatasvir/Voxilaprevir (Vosevi) â salvage 12 wk
- SVR12 (Sustained Virologic Response at 12 weeks post-treatment) = cure
- No ribavirin needed for most modern regimens (except some salvage)
- No interferon needed (DAA-only era)
- Direct-Acting Antivirals (DAAs):
- WHO 2030 Elimination Strategy:
- Mass screening (especially birth cohorts in USA, high-risk groups globally)
- Universal access to DAAs (price reductions in many countries)
- Harm reduction for IDU (syringe services)
- Vertical transmission prevention
- No vaccine yet (development challenges due viral diversity); subunit + viral vector candidates in trials
214.1.0.2 1ïžâ£ Virology
214.1.0.2.1 Structure
- 55-65 nm enveloped
- ssRNA, ~ 9.6 kb
- 10 viral proteins (structural + non-structural)
- Key targets:
- NS3/4A protease (target of glecaprevir, voxilaprevir)
- NS5A (target of velpatasvir, pibrentasvir)
- NS5B polymerase (target of sofosbuvir â first DAA breakthrough)
214.1.0.3 2ïžâ£ Epidemiology
214.1.0.3.1 Global
- ~ 58M chronic HCV (WHO 2024)
- 290K deaths/yr
- Egypt: highest prevalence historically (~ 10% pre-DAA era, dropped substantially with mass treatment)
- USA: ~ 2.5M Americans
214.1.0.3.2 Transmission
- IDU: 50%+ of cases in developed countries; needle/syringe sharing
- Pre-1992 transfusion (USA): historical large cohort
- Healthcare-associated: nosocomial outbreaks (improper sterilization, contaminated multidose vials)
- Egypt iatrogenic: schistosomiasis treatment campaigns (1960s-80s) with shared injection equipment â global highest prevalence
- Sexual: low risk overall; higher in MSM (especially HIV+, drug-using contexts) + chemsex
- Vertical: 5-10% if mother viremic; ~ 20% if HIV co-infection
- Tattoo, piercing: unsterile equipment
- Hemodialysis: nosocomial historically; current strict infection control
214.1.0.4 3ïžâ£ Clinical
214.1.0.4.1 Acute HCV
- 6-7 wk incubation
- 75-85% asymptomatic
- 15-25% symptomatic: mild flu-like + mild hepatitis
- 15-20% spontaneous clearance (more likely if symptomatic acute, female, younger, certain HLA, IL-28B genotype)
- 80% develop chronic
214.1.0.4.2 Chronic HCV
- Mostly asymptomatic until cirrhosis
- Fatigue (common but non-specific)
- Cirrhosis develops in 20% over 20-30 years (faster in some â alcohol, HIV, age at infection)
- HCC in cirrhotic 3-5% per year
- ALT often mildly elevated (or normal in some)
- Liver biopsy / non-invasive fibrosis (FibroScan, FIB-4)
214.1.0.4.3 Cirrhosis Decompensation
- Ascites, variceal bleed, hepatic encephalopathy, jaundice, hepatorenal syndrome
- 5-yr mortality 50% without transplant
214.1.0.4.4 HCC
- Surveillance: liver US + AFP q6 months in cirrhotic
- Treatment: same as HBV-HCC (atezolizumab+bevacizumab, lenvatinib, etc.)
214.1.0.4.5 Extrahepatic Manifestations
214.1.0.4.5.1 Mixed Cryoglobulinemia
- 5-25% of chronic HCV have detectable cryoglobulins (most asymptomatic)
- Symptomatic cryoglobulinemic vasculitis:
- Palpable purpura (lower extremities)
- Arthralgia
- Peripheral neuropathy
- Glomerulonephritis
- Treatment: DAAs (HCV eradication often resolves cryo)
214.1.0.4.5.2 Membranoproliferative Glomerulonephritis (MPGN)
- HCV + cryoglobulinemia association
- Hematuria, proteinuria, hypertension
- ACEi/ARB + HCV treatment
214.1.0.4.5.3 B-cell Lymphoma
- Splenic marginal zone (most strongly associated)
- DLBCL
- Treatment of HCV may regress lymphoma
214.1.0.5 4ïžâ£ Diagnosis
214.1.0.5.1 Anti-HCV Antibody
- Screening test
- ELISA, > 95% sens/spec
- Positive in chronic + past resolved (cannot distinguish active vs resolved)
214.1.0.5.2 HCV RNA PCR (Quantitative)
- Confirms active infection
- Cutoff > 12 IU/mL (sensitive)
- Quantitative viral load (less critical for DAA decisions)
214.1.0.5.3 Genotype
- Less critical now (most DAAs pan-genotypic)
- May guide salvage / specific regimens
- Reflex testing in some labs
214.1.0.5.4 Resistance-Associated Substitutions (RAS)
- Test in retreatment / salvage
- Particularly NS5A polymorphisms
214.1.0.6 5ïžâ£ Treatment
214.1.0.6.2 Treatment Goals
- SVR12 (Sustained Virologic Response 12 weeks post-treatment completion) = cure
95% achievable with first-line DAAs
- Re-evaluation 12 weeks post: undetectable HCV RNA = cure
214.1.0.6.3 Re-Infection
- After cure, re-infection possible if continued risk (IDU, MSM with risk)
- Counseling on harm reduction
- Re-treatment if re-infected
214.1.0.6.4 Special Populations
214.1.0.6.4.1 Cirrhotic Decompensated (Child B/C)
- Adjust regimen (avoid protease inhibitors in severe decompensation)
- Sofosbuvir/velpatasvir + ribavirin à 12-24 weeks
- Bridge to transplant in some
214.1.0.6.4.2 HIV/HCV Co-Infection
- Same DAA regimens
- Drug interactions with ART (especially boosted PIs + glecaprevir)
- Refer to interaction checker
214.1.0.6.4.3 Pregnancy
- DAAs not approved in pregnancy yet (limited data)
- Sofosbuvir/velpatasvir + similar â under study; safety encouraging
- Treat post-pregnancy + breastfeeding
214.1.0.6.4.4 Vertical Transmission
- 5-10% if maternal viremic
- 20% in HIV co-infection
- Treat post-delivery
- Pediatric HCV treatment approved (Mavyret 3+ yr, Epclusa 6+ yr)
214.1.0.7 6ïžâ£ Prevention
214.1.0.7.1 Harm Reduction
- Sterile injection equipment (syringe services programs)
- Opioid agonist therapy (methadone, buprenorphine) â reduces injection
- Education
- Naloxone access
214.1.0.7.2 Screening
- Universal adult screening (USA 2020+)
- Pregnant women
- High-risk groups regardless
214.1.0.7.3 Treatment as Prevention
- Cure stops transmission
- WHO 2030 elimination needs treatment scale-up
214.1.0.7.4 No Vaccine
- Development challenges:
- Viral diversity (quasispecies)
- Weak natural immunity (most donât clear)
- Multiple genotypes
- Candidates: chimpanzee adenovirus + MVA-vectored (Phase 2)
- Subunit vaccines in trial