What is the treatment for hepatitis C?

Treatment of Hepatitis C

Recommended First-Line Treatment Regimens

All patients with chronic hepatitis C should be treated with interferon-free, ribavirin-free, pangenotypic direct-acting antiviral (DAA) regimens, specifically sofosbuvir/velpatasvir for 12 weeks or glecaprevir/pibrentasvir for 8-12 weeks depending on cirrhosis status. 1, 2, 3

Pangenotypic Regimens (Preferred)

These regimens work across all HCV genotypes and represent the current standard of care:

• Sofosbuvir/velpatasvir (400 mg/100 mg): One tablet once daily for 12 weeks, effective for all genotypes including treatment-naïve and treatment-experienced patients with or without compensated cirrhosis 1, 3, 4

• Glecaprevir/pibrentasvir (300 mg/120 mg): Three tablets once daily with food for 8 weeks in patients without cirrhosis, or 12 weeks in those with compensated cirrhosis 1, 3, 4

• These regimens achieve sustained virological response (SVR) rates exceeding 95-97% in most patient populations 1, 3

Genotype-Specific Considerations

While pangenotypic regimens are preferred, genotype-specific options remain available:

For Genotype 1a:

• Sofosbuvir/velpatasvir for 12 weeks achieves 98-100% SVR 1, 3
• Ledipasvir/sofosbuvir for 12 weeks (can be shortened to 8 weeks in non-cirrhotic patients with baseline HCV RNA <6,000 IU/mL) 1
• Elbasvir/grazoprevir for 12 weeks in patients without NS5A resistance-associated substitutions (RASs) 1

For Genotype 1b:

• Grazoprevir/elbasvir for 12 weeks achieves 97-100% SVR in treatment-naïve patients 1
• Sofosbuvir/velpatasvir for 12 weeks 1, 3

For Genotype 3:

• Sofosbuvir/velpatasvir/voxilaprevir for 8 weeks achieves 96-99% SVR in both treatment-naïve and treatment-experienced patients 1
• For patients with compensated cirrhosis, consider sofosbuvir/velpatasvir with ribavirin for 12 weeks or sofosbuvir/velpatasvir/voxilaprevir for 12 weeks 4

Pre-Treatment Assessment

Before initiating therapy, the following evaluations are mandatory:

• HCV RNA quantitative testing and genotyping/subtyping to confirm active infection and guide regimen selection 2, 3

• Hepatitis B screening by measuring HBsAg and anti-HBc, as HBV reactivation can occur during HCV treatment and may result in fulminant hepatitis, hepatic failure, and death 2, 5

• Assessment of liver disease severity through non-invasive methods (FibroScan, APRI, FIB-4) or biopsy to determine presence and stage of cirrhosis 2, 3

• Comprehensive drug-drug interaction screening with all concurrent medications, particularly important for patients on antiretroviral therapy, cardiovascular medications, or immunosuppressants 2, 3

Special Populations

Patients with Compensated Cirrhosis (Child-Pugh A)

• Use the same pangenotypic regimens as non-cirrhotic patients, with duration adjusted to 12 weeks for glecaprevir/pibrentasvir 1, 3, 4
• These patients achieve similar SVR rates (>95%) to those without cirrhosis 1

Patients with Decompensated Cirrhosis

• Sofosbuvir/velpatasvir plus ribavirin for 12 weeks is the preferred regimen 3, 4
• Avoid protease inhibitor-containing regimens (glecaprevir/pibrentasvir, grazoprevir/elbasvir) as they are contraindicated in decompensated cirrhosis 4

Patients with Severe Renal Impairment (eGFR <30 mL/min/1.73 m²)

• Glecaprevir/pibrentasvir is the treatment of choice as it does not require dose adjustment 4, 5
• Sofosbuvir-based regimens should be avoided or used with extreme caution, as no dosage recommendation can be made for severe renal impairment 5
• Monitor serum creatinine during treatment, as increases averaging 8.5% have been observed with DAA therapy 6

HIV-HCV Coinfected Patients

• Use the same HCV treatment regimens as HCV-monoinfected patients 1, 4
• Carefully evaluate antiretroviral drug interactions before initiating DAA therapy 4
• Grazoprevir/elbasvir for 12 weeks achieved 95% SVR in genotype 1b-infected patients coinfected with HIV 1

Patients Awaiting Liver Transplantation

• Sofosbuvir in combination with ribavirin for up to 48 weeks or until liver transplantation, whichever occurs first 5

Treatment Monitoring and Confirmation of Cure

• On-treatment viral load monitoring is no longer required due to high efficacy and low viral breakthrough rates of current DAA regimens 4

• SVR12 (sustained virological response at 12 weeks post-treatment) represents virologic cure in more than 99% of patients and should be confirmed by undetectable HCV RNA 2, 3

• Fewer than 1% of patients relapse after achieving SVR12, making this endpoint tantamount to permanent viral eradication 2

• For most patients on DAA regimens with expected high SVR rates, checking SVR is optional except in patients at risk of reinfection 2

Critical Drug Interactions and Safety Considerations

Amiodarone Coadministration

• Coadministration of amiodarone with sofosbuvir-containing regimens is NOT recommended due to risk of serious symptomatic bradycardia, particularly in patients also receiving beta blockers or those with underlying cardiac comorbidities 5

• If no alternative viable treatment options exist, cardiac monitoring is mandatory 5

P-glycoprotein Inducers

• Intestinal P-gp inducers (e.g., rifampin, St. John's wort) may significantly decrease sofosbuvir levels and should be avoided 5

Post-Treatment Surveillance

Patients Without Cirrhosis

• After achieving SVR, patients without advanced fibrosis generally have excellent outcomes with resolution of liver disease 2
• No ongoing HCV-specific monitoring is required 2

Patients With Cirrhosis

• Indefinite hepatocellular carcinoma (HCC) surveillance with ultrasound every 6 months is required even after achieving SVR 2, 4
• The risk of HCC is significantly reduced but not eliminated, with residual annual risk of 0.3-2.4% 2
• Continued monitoring for cirrhotic complications is necessary, though at significantly reduced rates compared to untreated patients 2, 3

Resource-Limited Settings

In settings where pangenotypic DAA combinations are not available or affordable:

• Generic sofosbuvir and daclatasvir combination is safe, well-tolerated, and provides high SVR rates at very low cost 1
• Generic drugs produced under Medicines Patent Pool licenses and pre-qualified by WHO generate similar results to original compounds 1

Common Pitfalls to Avoid

• Do not use 8-week sofosbuvir/velpatasvir/voxilaprevir in genotype 1a patients, as this yields inferior results (89-92% SVR) compared to 12-week sofosbuvir/velpatasvir (99% SVR) 1

• Do not overlook baseline NS5A RASs when using elbasvir/grazoprevir, as patients with RASs require ribavirin addition and 16-week duration 1

• Do not use protease inhibitors in decompensated cirrhosis, as they can worsen hepatic function 4

• Do not assume cure eliminates all risks - patients with cirrhosis remain at risk for HCC and require lifelong surveillance 2