What is the recommended treatment for Hepatitis C (HCV)?

Hepatitis C Treatment Overview

For chronic hepatitis C infection, treat with pangenotypic direct-acting antiviral (DAA) regimens: either sofosbuvir/velpatasvir for 12 weeks or glecaprevir/pibrentasvir for 8-12 weeks depending on cirrhosis status, achieving cure rates exceeding 95% across all genotypes. 1, 2

First-Line Treatment Regimens

The preferred approach uses pangenotypic regimens that work across all HCV genotypes (1-6), eliminating the need for genotype testing in resource-limited settings:

• Sofosbuvir/velpatasvir (400 mg/100 mg): Single tablet once daily for 12 weeks, effective for all genotypes regardless of cirrhosis status or treatment history 1, 2, 3

• Glecaprevir/pibrentasvir (300 mg/120 mg): Three tablets once daily with food for 8 weeks in non-cirrhotic patients or 12 weeks in compensated cirrhosis 1, 2, 3, 4

Both regimens achieve SVR rates of 95-99% across all patient populations. 3, 5 The choice between them depends primarily on treatment duration preference, drug interactions, and cirrhosis status.

Treatment Duration by Patient Category

Treatment-Naïve Patients Without Cirrhosis

• 8 weeks of glecaprevir/pibrentasvir for all genotypes 1, 2, 4
• 12 weeks of sofosbuvir/velpatasvir for all genotypes 1, 2

Treatment-Naïve Patients With Compensated Cirrhosis (Child-Pugh A)

• 8 weeks of glecaprevir/pibrentasvir for genotypes 1,2,4,5,6 6, 4
• 12 weeks of glecaprevir/pibrentasvir for genotype 3 2
• 12 weeks of sofosbuvir/velpatasvir for all genotypes 1, 2

Treatment-Experienced Patients

• Prior NS5A inhibitor failure (genotype 1): 16 weeks of glecaprevir/pibrentasvir regardless of cirrhosis 4
• Prior NS3/4A protease inhibitor failure (genotype 1): 12 weeks of glecaprevir/pibrentasvir 4
• Prior peginterferon/ribavirin/sofosbuvir only: 8 weeks (no cirrhosis) or 12 weeks (compensated cirrhosis) of glecaprevir/pibrentasvir for genotypes 1,2,4,5,6 4
• Genotype 3 with prior treatment: 16 weeks of glecaprevir/pibrentasvir or sofosbuvir/velpatasvir, consider adding ribavirin 2, 4

Special Populations

Decompensated Cirrhosis (Child-Pugh B or C)

• Sofosbuvir/velpatasvir plus weight-based ribavirin (1,000-1,200 mg) for 12 weeks 6, 2
• Avoid glecaprevir/pibrentasvir - contraindicated in decompensated cirrhosis 6, 2, 4
• If ribavirin contraindicated or poorly tolerated: sofosbuvir/velpatasvir for 24 weeks without ribavirin 6

HIV/HCV Coinfection

• Use the same regimens and durations as HCV monoinfection 1, 2
• Critical caveat: Screen for drug-drug interactions with antiretroviral therapy, particularly with protease inhibitors and integrase inhibitors 7
• Dose adjustments of antiretrovirals may be needed 1

Acute Hepatitis C

• Sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, or sofosbuvir/daclatasvir for 8 weeks without ribavirin 6
• Extend to 12 weeks if HIV coinfected or baseline HCV RNA >6 million IU/mL 6
• Treat early after diagnosis to prevent chronicity (50-90% risk without treatment) 6

Post-Liver Transplant Recurrence

• Without cirrhosis or compensated cirrhosis: Sofosbuvir/velpatasvir for 12 weeks (no immunosuppressant adjustment needed) OR glecaprevir/pibrentasvir for 12 weeks (requires monitoring of immunosuppressant levels) 6
• Decompensated cirrhosis: Sofosbuvir/velpatasvir plus ribavirin for 12 weeks 6
• Initiate treatment early post-transplant (after first 3 months when stable) as SVR rates decrease with advanced disease 6

Renal Impairment

• Glecaprevir/pibrentasvir: Safe in all stages of renal disease including dialysis 4
• Sofosbuvir-based regimens: Use with caution in severe renal impairment (eGFR <30 mL/min); glecaprevir/pibrentasvir preferred in this population 4

Pre-Treatment Assessment

Mandatory testing before initiating therapy:

• Hepatitis B screening: Measure HBsAg and anti-HBc in all patients - HBV reactivation can occur during HCV treatment and may cause fulminant hepatitis or death 4
• HCV RNA quantitative testing (baseline viral load) 3
• HCV genotype and subtype (if available and affordable, helps optimize therapy) 1, 3
• Liver disease severity assessment (imaging, labs, or non-invasive fibrosis testing) 3
• Complete medication review for drug-drug interactions 3, 7
• Renal function (creatinine clearance) 4

Treatment Monitoring

• HCV RNA testing schedule: Baseline, week 4 (optional), end of treatment, and 12 weeks post-treatment 2
• SVR12 (sustained virologic response at 12 weeks): Undetectable HCV RNA 12 weeks after treatment completion defines cure in >99% of patients 3
• Also check SVR24 (24 weeks post-treatment) as late relapses have been reported, particularly in acute hepatitis C 6

Post-Treatment Surveillance

Patients with cirrhosis who achieve SVR still require ongoing monitoring:

• Hepatocellular carcinoma surveillance: Ultrasound every 6 months indefinitely, as HCC risk persists despite cure (though significantly reduced) 1, 3
• Monitor for signs of hepatic decompensation 3
• Assess for improvement in liver function and portal hypertension 3

Critical Pitfalls and Caveats

Drug-Drug Interactions

• Glecaprevir/pibrentasvir: Requires immunosuppressant monitoring in transplant recipients; dose adjustments needed during and after treatment 6, 4
• Proton pump inhibitors: May reduce absorption of some DAAs; specific timing requirements exist 7
• Statins: Some combinations contraindicated or require dose reduction 7
• Always check comprehensive interaction databases before prescribing 3, 7

Hepatitis B Reactivation

• This is a black box warning - HBV reactivation during HCV treatment has caused fulminant hepatitis and death 4
• If HBsAg positive or anti-HBc positive with detectable HBV DNA: initiate HBV antiviral therapy before or concurrent with HCV treatment 4
• Monitor HBV DNA and liver enzymes during and after HCV treatment 4

Resistance-Associated Substitutions (RAS)

• Baseline RAS testing generally not required for first-line pangenotypic regimens 3
• May affect treatment response in specific scenarios (particularly NS5A inhibitor failures); consider extended duration or ribavirin addition 3

Administration Requirements

• Glecaprevir/pibrentasvir must be taken with food to ensure adequate absorption 4, 8
• Sofosbuvir/velpatasvir can be taken without regard to food 2

Treatment Failure Management

• Virologic failure occurs in <1-5% of patients 8, 5
• Refer to hepatology specialist for resistance testing and salvage therapy selection 9
• Do not retreat with the same regimen 9