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

Hepatitis C Treatment

All patients with chronic Hepatitis C should be treated with pangenotypic direct-acting antiviral (DAA) regimens, with sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks being the preferred first-line option across all genotypes, achieving cure rates of 98%. 1, 2

First-Line Treatment Regimens

Sofosbuvir/velpatasvir is the preferred pangenotypic regimen:

• Single tablet (400mg/100mg) once daily for 12 weeks 1, 2
• Achieves 98% SVR rates across all genotypes 1, 2
• Works regardless of prior treatment history or presence of compensated cirrhosis 2

Glecaprevir/pibrentasvir is an equally effective alternative:

• Three tablets (300mg/120mg total) once daily with food 2
• 8 weeks for patients without cirrhosis 2
• 12 weeks for patients with compensated cirrhosis (Child-Pugh A) 2

For genotype 1 specifically, older but still effective options include:

• Ledipasvir/sofosbuvir (90mg/400mg) daily for 12 weeks 3, 4
• Paritaprevir/ritonavir/ombitasvir plus dasabuvir for 12 weeks (genotype 1b) 3
• Sofosbuvir plus simeprevir for 12 weeks (without Q80K variant in genotype 1a) 3

Pre-Treatment Assessment Requirements

Before initiating DAA therapy, obtain:

• HCV RNA quantitative testing 2, 5
• HCV genotype and subtype determination 2, 5
• Fibrosis staging using noninvasive methods (FibroScan, APRI, FIB-4) 2, 5
• Comprehensive drug-drug interaction screening 2, 5
• Baseline liver function tests, complete blood count, and renal function 3

Treatment Modifications by Clinical Scenario

Compensated Cirrhosis (Child-Pugh A)

• Use same pangenotypic regimens as non-cirrhotic patients 2, 5
• Extend glecaprevir/pibrentasvir to 12 weeks 2, 5
• Monitor closely for side effects, which are increased compared to non-cirrhotic patients 5

Decompensated Cirrhosis (Child-Pugh B and C)

• Sofosbuvir/ledipasvir with ribavirin for 12-24 weeks 3, 2
• SVR rates of 87-89% in Child-Pugh B and C cirrhosis 3, 2
• Starting ribavirin dose: 600mg daily regardless of weight, with dose adjustments as tolerated 3, 4
• Treatment improves liver function (bilirubin, albumin, INR) and MELD/Child-Pugh scores 3

Liver Transplant Recipients

• Sofosbuvir/velpatasvir plus ribavirin for 12 weeks 5
• Applies to both pre- and post-transplant settings 5

End-Stage Renal Disease (ESRD) on Dialysis

• Ledipasvir/sofosbuvir for 8-12 weeks 4
• No dose adjustment needed for sofosbuvir in dialysis patients 4

HIV/HCV Coinfection

• Same HCV treatment regimens as HCV mono-infected patients 5
• Identical virological outcomes expected 5
• Careful attention to antiretroviral drug interactions required 5

Pediatric Patients (≥3 years old)

• Ledipasvir/sofosbuvir for 12 weeks for genotype 1 or 4 4
• Sofosbuvir plus ribavirin for genotype 2 or 3 (age ≥12 years or weight ≥35kg) 6

Treatment Prioritization

Immediate treatment priority should be given to:

• Advanced fibrosis (≥F3) or any degree of cirrhosis 1, 2, 5
• Pre- and post-liver transplant patients 2, 5
• Severe extrahepatic manifestations (symptomatic vasculitis, HCV immune complex nephropathy) 2, 5
• Hepatocellular carcinoma 2, 5
• High-risk transmission groups: people who inject drugs, men who have sex with men with high-risk practices, women of childbearing age wishing to conceive, hemodialysis patients 3, 1

Patients with minimal or no fibrosis (F0-F2) should still be scheduled for treatment without deferral, though timing may be more flexible 5

Critical Drug-Drug Interactions

Absolute contraindications for DAAs:

• P-glycoprotein (P-gp) inducers (rifampin, St. John's wort) 5
• Moderate-to-strong CYP3A4 inducers (carbamazepine, phenytoin, phenobarbital) 5
• These significantly decrease DAA concentrations and reduce efficacy 5

Important interactions requiring dose adjustment or monitoring:

• Proton pump inhibitors with ledipasvir/sofosbuvir 3
• Salmeterol and other CYP3A4 substrates with paritaprevir/ritonavir/ombitasvir plus dasabuvir 3
• Check online interaction databases before prescribing (www.hcvguidelines.org/drug-inter) 3

Monitoring Protocol

During treatment:

• HCV RNA at baseline, weeks 4 and 12, end of treatment 2, 5
• Week 2 assessment for adherence in IFN-free regimens 3
• Liver function tests and complete blood count at regular intervals 3

Post-treatment:

• HCV RNA at 12 weeks post-treatment (SVR12) - primary measure of cure 1, 2, 5
• SVR12 represents permanent viral eradication in >99% of cases 1, 5
• Optional HCV RNA at 24 weeks post-treatment 3

Retreatment Strategies for DAA Failure

For patients who failed sofosbuvir alone or sofosbuvir plus ribavirin:

• Retreat with sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, or sofosbuvir/daclatasvir with ribavirin 3, 2, 5
• Duration: 12 weeks for F0-F2, 24 weeks for F3-F4 5

For patients who failed NS5A inhibitor-containing regimen:

• Use sofosbuvir with a protease inhibitor (simeprevir) plus ribavirin 3, 5
• Duration: 12 weeks for genotype 1b or 4 without cirrhosis, 24 weeks for genotype 1a or cirrhosis 5

For patients who failed sofosbuvir/simeprevir:

• Switch to sofosbuvir with daclatasvir or ledipasvir 3

For patients who failed paritaprevir/ritonavir/ombitasvir plus dasabuvir:

• Switch to any sofosbuvir-based regimen 3

Expected Clinical Benefits

Achieving SVR provides:

• Prevention of cirrhosis complications, hepatocellular carcinoma, hepatic decompensation, and death 1, 2, 5
• Improvement in liver histology with regression of fibrosis 3, 2
• Resolution of extrahepatic manifestations 2, 5
• Improved quality of life and removal of stigma 1, 2

Post-SVR Follow-Up

For patients with advanced fibrosis or cirrhosis (F3-F4):

• Lifelong HCC surveillance with ultrasound every 6 months indefinitely 1, 2
• Patients remain at reduced but ongoing risk for hepatocellular carcinoma even after achieving SVR 1

For all patients:

• Fibrosis reassessment to document improvement 2
• Monitoring for reinfection in at-risk patients (active injection drug users, high-risk sexual practices) 2

Common Pitfalls and Caveats

Ribavirin-containing regimens:

• Women of childbearing potential and/or their male partners must use effective contraception during treatment and for 6 months after completion 3
• Mild anemia is common; monitor hemoglobin regularly 3

Simeprevir:

• Causes photosensitivity; patients require sun protection measures 3
• Higher exposures in East Asian ancestry patients may increase adverse reactions 3

Decompensated cirrhosis:

• Treatment should be performed with special care when albumin <3.5 g/dL or platelets <100,000 5
• Close monitoring for worsening liver function is essential 5

Recently acquired hepatitis C:

• Treat with sofosbuvir/velpatasvir or glecaprevir/pibrentasvir for 8 weeks 3
• SVR should be assessed at both 12 and 24 weeks post-treatment due to reported late relapses 3
• No indication for post-exposure prophylaxis without documented HCV transmission 3