Hepatitis C Treatment
First-Line Treatment Recommendation
For chronic hepatitis C infection, initiate treatment with a pangenotypic direct-acting antiviral (DAA) regimen: either sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks or glecaprevir/pibrentasvir for 8-12 weeks (8 weeks without cirrhosis, 12 weeks with compensated cirrhosis). 1, 2, 3
These pangenotypic regimens achieve sustained virologic response (SVR) rates exceeding 95-98% across all genotypes and have superseded older genotype-specific regimens. 1, 3
Treatment Algorithm by Clinical Scenario
Treatment-Naïve Patients Without Cirrhosis
- Sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks 1, 4
- Glecaprevir/pibrentasvir for 8 weeks 1, 5
- Both regimens are equally effective with SVR rates >95% 2, 3
Treatment-Naïve Patients With Compensated Cirrhosis (Child-Pugh A)
- Sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks 4
- Glecaprevir/pibrentasvir for 12 weeks (extended from 8 weeks) 3, 5
Patients With Decompensated Cirrhosis (Child-Pugh B or C)
- Sofosbuvir/velpatasvir PLUS ribavirin for 12 weeks 1, 4
- Ribavirin dosing: 1,000 mg/day if <75 kg, 1,200 mg/day if ≥75 kg, divided twice daily with food 4
- Glecaprevir/pibrentasvir is contraindicated in decompensated cirrhosis 5
Genotype-Specific Considerations (When Pangenotypic Regimens Unavailable)
While pangenotypic regimens are preferred, genotype-specific options remain valid alternatives:
Genotype 1a (Treatment-Naïve, No Cirrhosis)
- Ledipasvir 90mg/sofosbuvir 400mg once daily for 12 weeks 6
- Paritaprevir/ritonavir/ombitasvir plus dasabuvir with ribavirin for 12 weeks 6
- Sofosbuvir 400mg plus simeprevir 150mg for 12 weeks (if Q80K variant negative) 6
Genotype 1a (With Cirrhosis)
- Extend treatment to 24 weeks for ledipasvir/sofosbuvir 6
- Avoid simeprevir if Q80K polymorphism present (lower SVR rates) 6, 1
Genotype 1b
- Ledipasvir 90mg/sofosbuvir 400mg for 12 weeks 6
- Paritaprevir/ritonavir/ombitasvir plus dasabuvir for 12 weeks (no ribavirin needed) 6
Genotype 2
- Sofosbuvir/velpatasvir for 12 weeks without ribavirin 1
- Alternative: Sofosbuvir plus weight-based ribavirin for 12 weeks (16 weeks if cirrhosis) 6
Genotype 3
- Sofosbuvir/velpatasvir for 12 weeks (treatment-naïve without cirrhosis) 1
- Add ribavirin for 12 weeks if treatment-experienced or cirrhotic 1
- Genotype 3 is historically the most difficult to treat with DAAs 6
Genotypes 4,5, and 6
- Sofosbuvir/velpatasvir for 12 weeks without ribavirin 1
- Alternative for genotype 4: Ledipasvir/sofosbuvir for 12 weeks or paritaprevir/ritonavir/ombitasvir with ribavirin for 12 weeks 6
Special Populations
HIV/HCV Coinfection
- Use the same HCV treatment regimens as HCV mono-infected patients 1, 2, 3
- Screen for drug-drug interactions with antiretroviral therapy 1
- SVR rates are identical to mono-infected patients 3
Liver Transplant Recipients
- Sofosbuvir/velpatasvir plus ribavirin for 12 weeks (pre- or post-transplant) 3
- For compensated cirrhosis (Child-Pugh A): Sofosbuvir/velpatasvir for 12 weeks without ribavirin 1
Treatment-Experienced Patients
Prior NS5A Inhibitor Failure (Genotype 1):
- Glecaprevir/pibrentasvir for 16 weeks (with or without cirrhosis) 5
Prior NS3/4A Protease Inhibitor Failure (Genotype 1):
- Glecaprevir/pibrentasvir for 12 weeks 5
Prior Peginterferon/Ribavirin Failure:
- Ledipasvir/sofosbuvir for 12 weeks (no cirrhosis) or 24 weeks (cirrhosis) 6
- For genotype 1a with cirrhosis, 24-week treatment reduces relapse rates compared to 12 weeks 6
Pre-Treatment Requirements
Mandatory Testing
- HBsAg and anti-HBc to screen for hepatitis B (risk of HBV reactivation with DAA therapy) 4, 5
- HCV RNA quantitative testing 3
- HCV genotype and subtype determination 3
- Fibrosis staging (assess for cirrhosis) 3
- Comprehensive drug-drug interaction screening 3
Treatment Prioritization
Immediate treatment priority for: 3
- Advanced fibrosis (≥F3) or any cirrhosis
- Pre- and post-liver transplant patients
- Severe extrahepatic manifestations
- Hepatocellular carcinoma
- Active injection drug users (reduce transmission risk) 6
Monitoring Protocol
- HCV RNA levels: Baseline, weeks 4 and 12 during treatment, end of treatment, and 12 weeks post-treatment 3
- SVR12 (undetectable HCV RNA 12 weeks after treatment completion) is the primary measure of cure, achieved in >99% of patients 3
- For cirrhotic patients: Continue hepatocellular carcinoma surveillance with ultrasound every 6 months even after achieving SVR 1, 2
Critical Drug-Drug Interactions
Absolute Contraindications
- P-glycoprotein (P-gp) inducers (e.g., rifampin, St. John's wort) 3
- Moderate-to-strong CYP3A4 inducers (significantly decrease DAA concentrations) 3
Important Interactions
- Ledipasvir/sofosbuvir: Potential interaction with proton pump inhibitors 6
- Paritaprevir/ritonavir/ombitasvir plus dasabuvir: Substantial interaction with salmeterol and CYP3A4 substrates 6
- Carefully evaluate all concomitant medications before initiating DAA therapy 1
Common Pitfalls and Caveats
HBV Reactivation Risk
- All patients must be tested for current or prior HBV infection before starting DAAs 4, 5
- HBV reactivation has resulted in fulminant hepatitis, hepatic failure, and death 4, 5
- Monitor HCV/HBV coinfected patients during and after HCV treatment 4, 5
- Initiate HBV antiviral therapy as clinically indicated 4, 5
Q80K Polymorphism in Genotype 1a
- Test for Q80K variant if using sofosbuvir plus simeprevir in cirrhotic patients 6, 1
- Patients with Q80K polymorphism and cirrhosis have lower SVR rates with simeprevir-based regimens 6
- Use alternative regimen if Q80K positive 1
Cirrhosis Status Determines Duration
- Glecaprevir/pibrentasvir: 8 weeks without cirrhosis, 12 weeks with compensated cirrhosis 5
- Treatment-experienced genotype 1a patients with cirrhosis require 24 weeks of ledipasvir/sofosbuvir (not 12 weeks) to minimize relapse 6
Decompensated Cirrhosis
- Always add ribavirin to sofosbuvir/velpatasvir 4
- Glecaprevir/pibrentasvir is contraindicated in Child-Pugh B or C cirrhosis 5