What is the current standard of care for chronic hepatitis C, including preferred direct‑acting antiviral regimens, treatment duration, and considerations for genotype, cirrhosis status, prior therapy, and viral load?

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Last updated: February 27, 2026 • View editorial policy

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Hepatitis C Treatment

First-Line Treatment Recommendation

All patients with chronic hepatitis C should be treated with pangenotypic direct-acting antiviral (DAA) regimens: sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks or glecaprevir/pibrentasvir for 8 weeks (without cirrhosis) or 12 weeks (with compensated cirrhosis). 1, 2, 3

Treatment Selection Algorithm

Step 1: Assess Cirrhosis Status and Treatment History

Non-cirrhotic, treatment-naïve patients:

  • Glecaprevir/pibrentasvir for 8 weeks (preferred for shorter duration) 1, 2, 4
  • Sofosbuvir/velpatasvir for 12 weeks (alternative) 1, 2

Compensated cirrhosis (Child-Pugh A), treatment-naïve:

  • Glecaprevir/pibrentasvir for 8 weeks (can be used in most cases) 1
  • Sofosbuvir/velpatasvir for 12 weeks 1, 3

Treatment-experienced without cirrhosis:

  • Sofosbuvir/velpatasvir for 12 weeks 1
  • Glecaprevir/pibrentasvir for 12 weeks (genotypes 1a, 1b, 2,4,5,6) 1

Treatment-experienced with compensated cirrhosis:

  • Sofosbuvir/velpatasvir for 12 weeks 1
  • Glecaprevir/pibrentasvir for 12 weeks 1

Genotype-Specific Modifications

Genotype 3 Requires Special Attention

Genotype 3 without cirrhosis (treatment-naïve):

  • Sofosbuvir/velpatasvir for 12 weeks 1
  • Glecaprevir/pibrentasvir for 8 weeks 1

Genotype 3 without cirrhosis (treatment-experienced):

  • Sofosbuvir/velpatasvir for 12 weeks 1
  • Glecaprevir/pibrentasvir for 12 weeks 1

Genotype 3 with compensated cirrhosis (treatment-naïve):

  • Sofosbuvir/velpatasvir + weight-based ribavirin (1,000mg if <75kg, 1,200mg if ≥75kg) for 12 weeks 1
  • Sofosbuvir/velpatasvir/voxilaprevir for 12 weeks 1
  • Glecaprevir/pibrentasvir for 12 weeks 1

Genotype 3 with compensated cirrhosis (treatment-experienced):

  • Sofosbuvir/velpatasvir + weight-based ribavirin for 12 weeks 1
  • Sofosbuvir/velpatasvir/voxilaprevir for 12 weeks 1
  • Glecaprevir/pibrentasvir for 16 weeks 1

Other Genotypes (1,2,4,5,6)

These genotypes respond excellently to standard pangenotypic regimens without modification. 1, 2

Mandatory Pre-Treatment Assessment

Before initiating any DAA regimen, obtain:

  • HCV RNA quantitative testing (confirm active viremia with assay lower limit ≤25 IU/mL) 2
  • HCV genotype and subtype determination (especially distinguish 1a from 1b) 1, 2
  • Fibrosis staging: Calculate FIB-4 score; if >3.25, obtain transient elastography (>12.5 kPa indicates cirrhosis) 2
  • Hepatitis B testing: HBsAg and anti-HBc (risk of HBV reactivation) 4
  • HIV testing 2
  • Comprehensive medication reconciliation including over-the-counter, herbal, and dietary supplements 2
  • Renal function (eGFR) to guide regimen selection 2
  • Baseline liver function tests and complete blood count 2
  • Pregnancy test in women of childbearing potential 2

Special Populations

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

Preferred regimen: Glecaprevir/pibrentasvir (achieves 97-98% SVR in CKD stage 4-5, including dialysis) 2

Contraindication: Avoid all sofosbuvir-based regimens when eGFR <30 mL/min/1.73 m² due to renal excretion concerns and lack of FDA approval. 2

Decompensated Cirrhosis (Child-Pugh B or C)

Glecaprevir/pibrentasvir is contraindicated in Child-Pugh B or C cirrhosis. 4

Use sofosbuvir/velpatasvir + ribavirin for 12 weeks (94% SVR12 in ASTRAL-4 trial). 3

HIV/HCV Coinfection

Treat with the same DAA regimens as HCV monoinfection; virologic outcomes are comparable. 2

Critical drug-drug interaction: Avoid sofosbuvir/ledipasvir with tenofovir disoproxil fumarate plus ritonavir-boosted protease inhibitors (markedly increases tenofovir nephrotoxicity). 2

Liver or Kidney Transplant Recipients

Treat for 12 weeks with standard regimens; extend to 16 weeks for genotype 1 NS5A-experienced or genotype 3 treatment-experienced patients. 4

Treatment Duration Summary Table

Patient Population Regimen Duration
No cirrhosis, treatment-naïve (all genotypes) Glecaprevir/pibrentasvir 8 weeks [1,4]
No cirrhosis, treatment-naïve (all genotypes) Sofosbuvir/velpatasvir 12 weeks [1,3]
Compensated cirrhosis, treatment-naïve (genotypes 1,2,4,5,6) Glecaprevir/pibrentasvir 8 weeks [1]
Compensated cirrhosis, treatment-naïve (genotypes 1,2,4,5,6) Sofosbuvir/velpatasvir 12 weeks [1,3]
Compensated cirrhosis, treatment-naïve (genotype 3) Sofosbuvir/velpatasvir + ribavirin 12 weeks [1]
Treatment-experienced, no cirrhosis (genotypes 1,2,4,5,6) Glecaprevir/pibrentasvir 8 weeks [1]
Treatment-experienced, compensated cirrhosis (genotypes 1,2,4,5,6) Glecaprevir/pibrentasvir 12 weeks [1]
Treatment-experienced, compensated cirrhosis (genotype 3) Glecaprevir/pibrentasvir 16 weeks [1]
Decompensated cirrhosis (all genotypes) Sofosbuvir/velpatasvir + ribavirin 12 weeks [3]

Monitoring Protocol

During treatment:

  • Routine laboratory monitoring is not required for most patients 2
  • Monitor glucose closely in diabetic patients (DAAs may cause symptomatic hypoglycemia) 2
  • Monitor INR in patients on warfarin (risk of sub-therapeutic anticoagulation) 2

Post-treatment:

  • Measure HCV RNA at 12 weeks post-treatment (SVR12) to confirm cure 2, 3, 5
  • Undetectable HCV RNA at SVR12 represents viral eradication in >99% of patients 2

Expected Outcomes

Modern DAA regimens achieve:

  • SVR rates >95% in most patient populations 1, 2
  • 70-90% reduction in liver-related mortality 2
  • 70-90% reduction in overall mortality 2
  • 75-90% reduction in hepatocellular carcinoma incidence 2
  • Improvement in liver histology and fibrosis regression 2

Critical Pitfalls to Avoid

Do not prescribe sofosbuvir-based regimens when eGFR <30 mL/min/1.73 m² – always calculate eGFR before initiating therapy; use glecaprevir/pibrentasvir instead. 2

Do not use glecaprevir/pibrentasvir in Child-Pugh B or C cirrhosis – it is contraindicated; use sofosbuvir/velpatasvir + ribavirin. 4

Do not shorten treatment duration below recommended weeks – the POLARIS-2 trial showed inferior results with 8-week sofosbuvir/velpatasvir compared to 12 weeks, particularly in genotype 1a. 3

Do not skip comprehensive drug-drug interaction screening – use AASLD/IDSA guidance or University of Liverpool checker for all medications, including over-the-counter and herbal products. 2

Do not forget to test for hepatitis B before starting DAAs – HBV reactivation has been reported, sometimes resulting in fulminant hepatitis, hepatic failure, and death. 4

Do not treat genotype 3 with compensated cirrhosis without ribavirin or extended duration – these patients have historically lower SVR rates and require intensified regimens. 1

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

2
Guideline

Hepatitis C Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

3
Guideline

Management of Chronic Hepatitis C

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

5
Guideline

First-Line Treatment for Chronic Viral Hepatitis C

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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