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 (400mg/100mg once daily for 12 weeks) or glecaprevir/pibrentasvir (8-12 weeks depending on cirrhosis status). 1, 2, 3, 4

Preferred Pangenotypic Options

• Sofosbuvir/velpatasvir is the preferred first-line regimen, administered as a single tablet (400mg/100mg) once daily for 12 weeks, achieving 98-100% SVR rates across all genotypes 1, 2, 3, 4

• Glecaprevir/pibrentasvir is an equally effective alternative, dosed as 3 tablets (300mg/120mg total) once daily with food for 8 weeks in patients without cirrhosis or 12 weeks in those with compensated cirrhosis (Child-Pugh A) 1, 3, 4

• These regimens are effective regardless of HCV genotype (1-6), prior treatment history, or HIV coinfection status 1, 2, 4

Treatment Duration by Clinical Scenario

Patients Without Cirrhosis

• Sofosbuvir/velpatasvir: 12 weeks for all genotypes 2, 3
• Glecaprevir/pibrentasvir: 8 weeks for treatment-naïve patients 1, 3, 4

Patients With Compensated Cirrhosis (Child-Pugh A)

• Sofosbuvir/velpatasvir: 12 weeks for all genotypes 1, 3
• Glecaprevir/pibrentasvir: 12 weeks (extended from 8 weeks) 1, 3, 4

Patients With Decompensated Cirrhosis

• Sofosbuvir/velpatasvir plus ribavirin for 12 weeks 3

Alternative Genotype-Specific Regimens

While pangenotypic regimens are preferred, genotype-specific options remain acceptable when pangenotypic DAAs are unavailable or unaffordable 1:

For Genotype 1b

• Grazoprevir/elbasvir for 12 weeks achieves 97-100% SVR in treatment-naïve patients 1
• Ledipasvir/sofosbuvir for 12 weeks (can be shortened to 8 weeks in non-cirrhotic patients with baseline HCV RNA <6 million IU/mL) 1

For Genotype 3

• Sofosbuvir/velpatasvir/voxilaprevir for 8 weeks achieves 96-99% SVR rates 1
• Sofosbuvir plus ribavirin for 24 weeks in treatment-experienced patients 5

Pre-Treatment Assessment Requirements

Before initiating DAA therapy, the following assessments are mandatory 2, 3, 4:

• HCV RNA quantitative testing to confirm active infection 2, 4
• HCV genotype and subtype determination (though less critical with pangenotypic regimens) 3, 4
• Hepatitis B testing (HBsAg and anti-HBc) due to risk of HBV reactivation 5
• Fibrosis staging using non-invasive methods (FibroScan, APRI, FIB-4) or liver biopsy if uncertainty exists 3, 4
• Comprehensive drug-drug interaction screening with all concurrent medications 2, 3

Treatment Prioritization

Immediate treatment should be prioritized for 4:

• Patients with advanced fibrosis (≥F3) or any degree of cirrhosis 2, 4
• Pre- and post-liver transplant patients 4
• Patients with severe extrahepatic manifestations (symptomatic vasculitis, HCV immune complex nephropathy) 4
• Patients with hepatocellular carcinoma 4

Treatment Monitoring Protocol

• Baseline HCV RNA before treatment initiation 4
• On-treatment monitoring at weeks 4 and 12 (optional with high SVR regimens) 4
• End-of-treatment HCV RNA 4
• SVR12 assessment (undetectable HCV RNA 12 weeks post-treatment) is the primary measure of cure 2, 3, 4

SVR12 represents virologic cure in more than 99% of patients, with fewer than 1% experiencing late relapse 2, 4

Critical Drug-Drug Interactions

Absolute contraindications include coadministration with 4:

• P-glycoprotein (P-gp) inducers (rifampin, St. John's wort, carbamazepine) 5
• Moderate-to-strong CYP inducers that significantly decrease DAA concentrations 4

Amiodarone coadministration with sofosbuvir-containing regimens may cause serious symptomatic bradycardia and is not recommended; if no alternative exists, cardiac monitoring is required 5

Special Populations

HIV/HCV Coinfection

• Use the same HCV treatment regimens as HCV mono-infected patients with identical expected outcomes 1, 4
• Dose adjustments may be needed due to antiretroviral drug-drug interactions 1

Liver Transplant Recipients

• Sofosbuvir/velpatasvir plus ribavirin for 12 weeks in both pre- and post-transplant settings 4

Patients Awaiting Liver Transplantation

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

Treatment Outcomes and Expected Benefits

Modern DAA regimens achieve 3, 4, 6:

• SVR rates exceeding 95-97% in most patient populations 1, 2, 3, 6
• Improvement in liver histology and decreased risk of cirrhotic complications 3, 4
• Reduced occurrence of hepatocellular carcinoma (though not eliminated in cirrhotic patients) 2, 3
• Improved survival rates and resolution of extrahepatic manifestations 3, 4
• Excellent tolerability with adverse events occurring in only 8% of patients, most commonly itching, fatigue, and dizziness 6

Post-Treatment Surveillance

Patients Without Advanced Fibrosis

• Generally have excellent outcomes with resolution of liver disease after achieving SVR 2
• Routine HCV RNA testing beyond 48 weeks post-treatment is not supported by evidence 2

Patients With Cirrhosis

• Require indefinite monitoring despite achieving SVR due to residual risk of complications 2, 3
• Annual HCC surveillance with ultrasound every 6 months is mandatory 2
• Residual HCC risk remains 0.3-2.4% annually even after SVR 2

Common Pitfalls and Caveats

• Baseline resistance-associated substitutions (RASs) may affect treatment response with certain regimens (particularly NS5A inhibitors), though pangenotypic regimens largely overcome this issue 3
• Renal function monitoring is important as serum creatinine may increase during treatment (mean 8.5%), with acute kidney injury criteria met in 7.3% of patients 7
• Patients with albumin <3.5 g/dL or platelets <100,000 require special care during treatment 4
• Generic DAAs produced under Medicines Patent Pool licenses and WHO-prequalified have shown similar efficacy to original compounds, providing affordable options in resource-limited settings 1