What is the treatment for Hepatitis C (Hep C)?

Treatment for Hepatitis C

For chronic Hepatitis C, use pangenotypic direct-acting antiviral (DAA) regimens as first-line therapy, with sofosbuvir/velpatasvir for 12 weeks being the preferred option for most patients regardless of genotype, treatment history, or presence of compensated cirrhosis. 1

First-Line Treatment Regimens

The following pangenotypic DAA combinations are recommended based on the most recent guidelines:

Preferred Regimens (All Genotypes)

• Sofosbuvir/velpatasvir: 12 weeks for all genotypes (1-6), treatment-naïve or treatment-experienced patients, with or without compensated cirrhosis, no ribavirin needed 2, 1

• Glecaprevir/pibrentasvir: 8 weeks for non-cirrhotic patients; 12 weeks for compensated cirrhosis 2, 1, 3

• Ledipasvir/sofosbuvir: 12 weeks for genotype 1,4,5, or 6 (can be shortened to 8 weeks in treatment-naïve, non-cirrhotic patients with baseline HCV RNA <6 million IU/mL) 2, 1, 4

• Elbasvir/grazoprevir: 12 weeks for genotype 1 or 4 (requires absence of NS5A resistance-associated substitutions for genotype 1a) 2, 1

Genotype-Specific Considerations

Genotype 1

• All pangenotypic regimens listed above are highly effective 2
• Real-world data confirms 95-98% SVR rates with ledipasvir/sofosbuvir 5, 6, 7
• Eight-week ledipasvir/sofosbuvir is appropriate for treatment-naïve, non-cirrhotic patients with HCV RNA <6 million IU/mL 1, 5, 6

Genotype 2

• Sofosbuvir/velpatasvir for 12 weeks 2
• Sofosbuvir plus ribavirin for 12 weeks (alternative) 4

Genotype 3

• Sofosbuvir/velpatasvir for 12 weeks (treatment-naïve without cirrhosis) 2
• Add ribavirin or extend to 24 weeks for treatment-experienced or cirrhotic patients 2
• Glecaprevir/pibrentasvir: 8 weeks (non-cirrhotic), 12 weeks (cirrhotic), or 16 weeks (treatment-experienced) 2

Genotype 4

• Ledipasvir/sofosbuvir, elbasvir/grazoprevir, glecaprevir/pibrentasvir, or sofosbuvir/velpatasvir all for 12 weeks 2

Genotypes 5 and 6

• Ledipasvir/sofosbuvir or sofosbuvir/velpatasvir for 12 weeks 2

Special Populations

Compensated Cirrhosis (Child-Pugh A)

• Most regimens require 12-week duration 2, 1
• Glecaprevir/pibrentasvir: 12 weeks 2, 1
• Sofosbuvir/velpatasvir: 12 weeks 2
• Consider adding ribavirin for genotype 3 2

Decompensated Cirrhosis

• Ledipasvir/sofosbuvir plus ribavirin for 12 weeks 1
• Sofosbuvir/velpatasvir plus ribavirin for 12 weeks 1
• Avoid glecaprevir/pibrentasvir in decompensated cirrhosis 3

HIV/HCV Coinfection

• Use same regimens and durations as HCV monoinfection 2
• Sofosbuvir/velpatasvir achieves 92-95% SVR in coinfected patients 2

Patients on Rifampicin (TB Treatment)

• Glecaprevir/pibrentasvir is preferred due to lack of significant drug interactions 3
• Daclatasvir plus sofosbuvir is an alternative 3
• Monitor liver function weekly if AST/ALT ≥2× normal; consider stopping both medications if AST/ALT ≥5× normal or bilirubin rises 3

Monitoring During Treatment

• Measure HCV RNA at baseline, week 4, week 12, end of treatment, and 12-24 weeks post-treatment 1
• Sustained virologic response (SVR12) is defined as undetectable HCV RNA 12 weeks after treatment completion and represents virological cure 1

Critical Warnings and Contraindications

Hepatitis B Reactivation

• Test all patients for HBsAg and anti-HBc before starting HCV treatment 4
• HBV reactivation can cause fulminant hepatitis, hepatic failure, and death 4
• Monitor HCV/HBV coinfected patients during and after treatment 4

Drug Interactions

• Avoid amiodarone with sofosbuvir-containing regimens due to risk of serious symptomatic bradycardia, particularly with concurrent beta-blockers or in patients with cardiac comorbidities 4
• Avoid P-glycoprotein inducers (rifampin, St. John's wort, carbamazepine) with most DAA regimens 4
• Proton pump inhibitors reduce efficacy of ledipasvir/sofosbuvir; consider modification or discontinuation 5

Common Pitfalls to Avoid

• Do not use 8-week ledipasvir/sofosbuvir in cirrhotic patients, treatment-experienced patients, or those with baseline HCV RNA ≥6 million IU/mL 1, 4
• Do not delay treatment waiting for genotype results when pangenotypic regimens are available 1
• Real-world data shows only 44% of eligible patients received appropriate 8-week therapy, suggesting underutilization of shorter regimens 5
• Baseline NS5A resistance testing is generally not required, as modern regimens achieve high SVR even with resistance-associated substitutions 8