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

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Recommended Treatment for Hepatitis C (HCV)

The first-line treatment for hepatitis C is a pangenotypic direct-acting antiviral (DAA) regimen consisting of either sofosbuvir/velpatasvir for 12 weeks or glecaprevir/pibrentasvir for 8-12 weeks, depending on cirrhosis status and treatment history. 1, 2

Treatment Selection Based on Patient Factors

Recommended First-Line Options:

  • Sofosbuvir/velpatasvir (400mg/100mg) once daily for 12 weeks is a recommended first-line option for all HCV genotypes, with SVR rates of 98% in genotype 1 infection 2
  • Glecaprevir/pibrentasvir is an alternative first-line option with treatment duration of 8 weeks for non-cirrhotic patients and 12 weeks for those with compensated cirrhosis 2, 3
  • For genotype 2 infection, sofosbuvir/velpatasvir for 12 weeks is highly effective 4, 2
  • For genotype 3 infection, sofosbuvir/velpatasvir for 12 weeks and sofosbuvir/daclatasvir for 12 weeks are recommended first-line options 4, 2

Treatment Duration Based on Patient Characteristics:

  • Non-cirrhotic patients:

    • Glecaprevir/pibrentasvir: 8 weeks 3
    • Sofosbuvir/velpatasvir: 12 weeks 5
  • Compensated cirrhosis (Child-Pugh A):

    • Glecaprevir/pibrentasvir: 8-12 weeks (depending on genotype and treatment history) 3
    • Sofosbuvir/velpatasvir: 12 weeks 5
  • Decompensated cirrhosis (Child-Pugh B or C):

    • Sofosbuvir/velpatasvir plus ribavirin for 12 weeks 5
    • Note: Glecaprevir/pibrentasvir is contraindicated in decompensated cirrhosis 3

Special Populations

Treatment-Experienced Patients:

  • For patients who failed previous pegylated interferon and ribavirin treatment, the same DAA regimens can be used as for treatment-naïve patients 4
  • For patients who failed previous DAA therapy, treatment should be guided by resistance testing when available 4

HIV Co-infection:

  • The same HCV treatment regimens can be used as in patients without HIV infection, with dose adjustments needed in case of interactions with antiretroviral drugs 4
  • The dose of daclatasvir must be adjusted to 30 mg in HIV-coinfected patients receiving ritonavir- or cobicistat-boosted atazanavir or cobicistat-boosted elvitegravir, and to 90 mg in HIV-coinfected patients receiving efavirenz 2

Pre-Treatment Assessment

  • HCV RNA quantitative assay and genotyping/subgenotyping prior to initiating antiviral treatment 1
  • Test all patients for evidence of current or prior HBV infection by measuring HBsAg and anti-HBc before initiating HCV treatment with DAAs 3, 5
  • Assessment of liver disease severity to guide therapy decisions and predict prognosis 1
  • Evaluation for potential drug-drug interactions with all concurrent medications 1

Treatment Efficacy and Monitoring

  • Modern DAA regimens achieve SVR rates exceeding 95% in most patient populations 2
  • Sustained virological response (SVR), defined as undetectable HCV RNA 12 weeks after treatment completion, represents a cure of the infection in more than 99% of patients 1
  • Monitor HCV RNA or HCV core antigen at 12 weeks post-treatment (SVR12) to assess treatment success 1

Important Caveats and Pitfalls

  • Risk of HBV reactivation: Test all patients for evidence of current or prior HBV infection before initiating treatment with DAAs. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct-acting antivirals 3, 5
  • Drug-drug interactions: Must be carefully evaluated before initiating DAA therapy, particularly with anticonvulsants, HIV medications, and other commonly prescribed drugs 2, 6
  • Post-SVR monitoring: Patients with cirrhosis who achieve SVR still require monitoring for hepatocellular carcinoma with ultrasound every 6 months, as they remain at risk for complications, though at significantly reduced rates 1
  • Treatment adherence: Despite shortened treatment durations with modern DAAs, adherence remains crucial for achieving SVR 7

The introduction of all-oral DAA regimens has revolutionized HCV treatment, allowing virtually all patients to achieve SVR regardless of HCV genotype or disease stage, replacing older interferon-based therapies that had lower efficacy and more side effects 1, 8, 9.

References

Guideline

Hepatitis C Treatment Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

First-Line Treatment for Reactive Hepatitis C

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Direct-acting antivirals for the treatment of hepatitis C virus infection: optimizing current IFN-free treatment and future perspectives.

Liver international : official journal of the International Association for the Study of the Liver, 2016

Research

Hepatitis C virus: standard-of-care treatment.

Advances in pharmacology (San Diego, Calif.), 2013

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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