Genotype Identification
HCV genotype shapes which DAA regimen will cure the infection.
- 6: HCV genotypes worldwide (plus many subtypes)
- GT1: Most common genotype (~46% of cases globally)
- RT-PCR: Test method (RNA sequencing assay)
- 2–5 days: Result turnaround (reference lab standard)
Why genotype matters
Genotypes differ genetically, affecting drug susceptibility.
Genotype 3 caveat
GT3 responds least well to standard DAA regimens.
GT3 plus cirrhosis is the toughest cure scenario.
Global distribution
GT1 and GT3 dominate; GT4–6 cluster regionally.
Fibrosis Stage Assessment
Liver scarring stage F0–F4 predicts baseline cure difficulty.
- F0–F4: Fibrosis stages (METAVIR scoring system)
- Cirrhosis: F4 definition (advanced, irreversible scarring)
- Elastography: Primary tool (non-invasive liver stiffness scan)
- ~20%: Cirrhosis prevalence (of untreated chronic HCV)
Staging method
Transient elastography replaces most liver biopsies today.
Why fibrosis lowers cure odds
Scarred tissue alters drug metabolism and clearance.
F3–F4 fibrosis modestly reduces SVR12 across genotypes.
Reversibility
Cure often allows measurable fibrosis regression over years.
DAA Regimen Selection
Sofosbuvir/velpatasvir treats all six genotypes with one pill.
- SOF/VEL: Regimen (sofosbuvir 400mg + velpatasvir 100mg)
- Pan-genotypic: Genotype coverage (GT1 through GT6)
- Once daily: Dosing (single fixed-dose tablet)
- Selected cases: Ribavirin add-on (decompensated cirrhosis)
Mechanism
NS5B and NS5A inhibitors block viral replication together.
Genotype-adjusted decisions
GT3 with cirrhosis may add ribavirin or extend therapy.
Regimen choice always follows genotype and fibrosis stage.
Baseline testing
Resistance-associated substitution testing is rarely required now.
12-Week Treatment Course
Daily DAA dosing drives viral load toward undetectable levels.
- 12 weeks: Standard duration (most genotype/fibrosis combinations)
- 24 weeks: Extended duration (select decompensated cirrhosis cases)
- >95%: On-treatment adherence (needed for reliable cure)
- Undetectable: Viral load at week 4 (typical response pattern)
Viral kinetics
HCV RNA drops sharply within the first two weeks.
Adherence matters
Missed doses raise relapse risk, especially in GT3.
Full 12-week completion is required before SVR12 testing.
Side effect profile
DAAs are far better tolerated than older interferon regimens.
SVR12 Cure Rate Result
Undetectable RNA at 12 weeks post-treatment confirms cure.
- Undetectable RNA: SVR12 definition (12 weeks after last dose)
- ~99%: Best-case SVR12 (GT1/GT5/GT6, no cirrhosis)
- ~89%: Toughest-case SVR12 (GT3 with F4 cirrhosis)
- <1%: Relapse after SVR12 (considered a durable cure)
Reading the matrix
Each cell is one genotype-fibrosis SVR12 prediction.
Clinical use
Predicted SVR12 informs counseling and regimen adjustments.
Genotype and fibrosis stage together set realistic cure odds.
After cure
Cured patients still need cirrhosis and HCC surveillance.