What is the recommended treatment for acute hepatitis C?

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Last updated: December 12, 2025View editorial policy

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Treatment for Acute Hepatitis C

Patients with acute hepatitis C should be treated with sofosbuvir/velpatasvir (or sofosbuvir/ledipasvir or sofosbuvir/daclatasvir) for 8 weeks without ribavirin, after considering a watchful waiting period of 8-12 weeks to allow for potential spontaneous clearance. 1

Initial Management Strategy

Delay treatment for 8-12 weeks after diagnosis to allow for spontaneous viral clearance, which occurs in 20-50% of cases. 1, 2 This approach is supported by randomized controlled trials showing that delayed treatment is non-inferior to immediate treatment when accounting for spontaneous recovery rates. 1

During the Observation Period:

  • Monitor HCV RNA levels every 4 weeks to assess for spontaneous clearance 2
  • Initiate treatment if HCV RNA remains positive at 12 weeks after initial presentation 2
  • Recognize that spontaneous clearance is more likely in symptomatic patients with jaundice, females, younger individuals, and those with favorable IL28B (IFNL3) genetic polymorphisms 1, 2

Diagnostic Considerations:

  • Test for HCV RNA directly when acute hepatitis C is suspected, as anti-HCV antibodies may be negative early in infection (appearing 8-12 weeks post-infection) 1, 2
  • Most patients with acute hepatitis C are asymptomatic, making diagnosis challenging 1, 2

Current First-Line Treatment Regimens

Standard Therapy (All Genotypes):

Treat for 8 weeks with one of the following direct-acting antiviral (DAA) combinations without ribavirin: 1, 2

  • Sofosbuvir/velpatasvir (400 mg/100 mg) - covers all genotypes 1, 2, 3
  • Sofosbuvir/ledipasvir - for genotypes 1,4,5, and 6 1, 2
  • Sofosbuvir/daclatasvir - for all genotypes 1, 2

These regimens achieve sustained virologic response (SVR) rates exceeding 90% in acute hepatitis C. 1, 2 A recent 2023 study confirmed 100% SVR12 in all adherent patients with acute HCV monoinfection treated with 8 weeks of sofosbuvir/velpatasvir. 4

Extended Duration for High-Risk Patients:

Extend treatment to 12 weeks (using the same DAA combinations) for patients with: 1, 2

  • HIV coinfection
  • Baseline HCV RNA level >1 million IU/ml (6.0 log IU/ml)

Post-Treatment Monitoring

  • Assess SVR at both 12 and 24 weeks post-treatment, as late relapses have been reported in acute hepatitis C 1, 2
  • This differs from chronic hepatitis C where SVR12 alone is typically sufficient 1

Important Clinical Pitfalls

What NOT to Do:

  • Do not use antiviral therapy as post-exposure prophylaxis in the absence of documented HCV transmission 1, 2
  • Do not add ribavirin to DAA regimens for acute hepatitis C in most patients, as it provides no additional benefit and increases adverse effects 1, 2

Historical Context:

Prior to the DAA era, peginterferon alpha monotherapy for 24 weeks was standard treatment, achieving SVR rates of 80-90%. 1, 2 However, this interferon-based approach has been completely replaced by the superior efficacy, shorter duration, and better tolerability of DAA regimens. 1, 2

Strength of Evidence

The EASL 2017 guidelines provide the most comprehensive and recent recommendations for acute hepatitis C treatment, based on three small trials with sofosbuvir/ledipasvir showing SVR rates of 77-100% after 4-6 weeks of treatment. 1 The recommendation for 8 weeks of therapy is extrapolated from chronic hepatitis C data requiring at least 8 weeks to maximize SVR rates, given the limited sample sizes in acute hepatitis C studies. 1 The 2023 HepNet study further validates this 8-week approach with sofosbuvir/velpatasvir. 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Treatment of Acute Hepatitis C

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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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