What is the recommended workup and treatment for hepatitis C?

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Last updated: October 7, 2025View editorial policy

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Recommended Workup and Treatment for Hepatitis C

The recommended workup for hepatitis C begins with HCV antibody testing with reflex HCV RNA PCR testing to confirm active infection, followed by evaluation of liver disease severity and viral characteristics to guide treatment with direct-acting antivirals (DAAs), which can achieve cure rates exceeding 95% in most patients. 1, 2

Initial Diagnostic Testing

  • HCV antibody testing should be performed as the initial screening test for hepatitis C infection 1, 2
  • If anti-HCV antibodies are detected, HCV RNA testing should be performed using a sensitive molecular method (lower limit of detection <15 IU/ml) to confirm active infection 2
  • In cases of suspected acute hepatitis C or in immunocompromised patients, HCV RNA testing should be included in the initial evaluation 2
  • Anti-HCV positive, HCV RNA negative individuals should be retested for HCV RNA 3 months later to confirm true clearance of infection 2
  • Regular laboratory monitoring (every 4-8 weeks for 6-12 months) is recommended in acute HCV infection until ALT normalizes and HCV RNA becomes repeatedly undetectable, suggesting spontaneous resolution 2

Pre-Treatment Assessment

  • Evaluate for liver disease severity using non-invasive methods (FibroScan, FibroTest) or liver biopsy to determine presence of advanced fibrosis or cirrhosis 2
  • Determine HCV genotype and viral load (HCV RNA quantification) to guide treatment decisions 2
  • Screen for other causes of liver disease, including HBV, HIV, alcohol use, and metabolic factors 2
  • Assess for potential drug-drug interactions before initiating treatment 2
  • Evaluate for comorbidities that may affect treatment decisions 2

Treatment Recommendations

  • The goal of HCV therapy is to cure the infection to prevent hepatic cirrhosis, decompensation, hepatocellular carcinoma, and death 2
  • Treatment is defined as successful when sustained virologic response (SVR) is achieved, defined as undetectable HCV RNA 12 weeks (SVR12) or 24 weeks (SVR24) after treatment completion 2
  • Direct-acting antiviral (DAA) regimens should be used for all patients with chronic HCV infection 1, 2
  • Treatment regimens should be selected based on:
    • HCV genotype 2
    • Prior treatment history (treatment-naïve vs. treatment-experienced) 2
    • Presence of cirrhosis and its severity (compensated vs. decompensated) 2
    • Potential drug-drug interactions 2

Special Populations

  • For patients with acute HCV infection, monitoring for spontaneous clearance for at least 12-16 weeks is recommended before initiating treatment 2
  • Patients with decompensated cirrhosis require specialized care and may need adjusted treatment regimens 2
  • For patients with HCV who actively inject drugs, access to harm reduction programs is mandatory, and treatment should not be withheld based solely on drug use 2
  • Post-liver transplant patients with recurrent HCV infection require specific treatment considerations 2
  • Patients with HIV/HCV coinfection may require adjusted treatment regimens and monitoring 2

Post-Treatment Follow-up

  • Non-cirrhotic patients who achieve SVR should be retested for HCV RNA at 48 weeks post-treatment to confirm cure 2
  • Patients with cirrhosis who achieve SVR should remain under surveillance for hepatocellular carcinoma every 6 months by ultrasound 2
  • Patients with advanced fibrosis or cirrhosis require continued surveillance for complications even after achieving SVR 2

Common Pitfalls to Avoid

  • Do not rely solely on ALT levels to determine disease severity, as patients with normal ALT may still have significant fibrosis 2
  • Avoid assuming that HCV antibody testing alone is sufficient for diagnosis; confirmation with HCV RNA testing is essential 1, 2
  • Do not overlook the importance of assessing for alcohol use and counseling patients to abstain during treatment 2
  • Do not miss screening for HBV before starting HCV treatment, as HBV reactivation can occur during or after HCV therapy 1
  • Do not assume a negative HCV antibody test excludes infection in immunocompromised patients or those with recent exposure; consider HCV RNA testing in these cases 1

References

Guideline

Hepatitis Diagnosis and Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 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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