What is the current treatment for hepatitis C?

Current Treatment for Hepatitis C

The standard treatment for hepatitis C is direct-acting antiviral (DAA) therapy, with sofosbuvir/velpatasvir for 12 weeks recommended as first-line treatment for all HCV genotypes, with high efficacy across all genotypes and suitable for both treatment-naïve and treatment-experienced patients, with or without compensated cirrhosis. 1

Treatment Regimens by Genotype

Treatment selection is based on viral genotype, presence of cirrhosis, and prior treatment history:

Genotype 1

• First-line options:
  • Sofosbuvir/velpatasvir for 12 weeks
  • Sofosbuvir/ledipasvir for 12 weeks (8 weeks may be sufficient for treatment-naïve non-cirrhotic patients with low viral load) 1, 2
  • Elbasvir/grazoprevir for 12 weeks (add ribavirin if protease inhibitor + PEG-interferon/ribavirin failure) 3

Genotype 2

• First-line option: Sofosbuvir/velpatasvir for 12 weeks 1, 4

Genotype 3

• First-line option: Sofosbuvir/velpatasvir for 12 weeks (add ribavirin if NS5A Y93H mutation is present) 1

Genotypes 4,5, and 6

• First-line option: Sofosbuvir/velpatasvir for 12 weeks 1

Pan-genotypic Regimens

Two regimens are particularly valuable as they work across all genotypes:

• Sofosbuvir/velpatasvir for 12 weeks
• Glecaprevir/pibrentasvir for 8 weeks 3, 1

Treatment Duration

• Standard duration: 8-12 weeks for most patients without cirrhosis
• Extended duration (12-24 weeks) may be needed for:
  • Patients with compensated cirrhosis
  • Prior treatment failure
  • Presence of resistance-associated substitutions (RASs) 3, 1

Special Patient Populations

Patients with Cirrhosis

• Compensated cirrhosis: Standard DAA regimens with possible extension of treatment duration
• Decompensated cirrhosis: Sofosbuvir-based regimens (avoid protease inhibitors) with ribavirin 1

HIV/HCV Coinfection

• Same regimens as HCV monoinfection
• Careful attention to potential drug interactions with antiretroviral therapy 1

Renal Impairment

• Severe renal impairment/dialysis: Glecaprevir/pibrentasvir preferred 1
• Sofosbuvir-based regimens may be used with caution in moderate renal impairment 2, 4

Recently Acquired Hepatitis C

• Treat with sofosbuvir/velpatasvir or glecaprevir/pibrentasvir for 8 weeks 3

Monitoring During and After Treatment

• HCV RNA or HCV core antigen should be assessed at week 12 (SVR12) or 24 (SVR24) post-treatment to confirm cure 3
• Patients with cirrhosis require continued HCC surveillance every 6 months even after achieving SVR 1
• Medication adherence is crucial to achieve cure and prevent resistance 1

Treatment Challenges and Considerations

Hard-to-Cure Populations

Some patients remain challenging to treat with standard regimens:

• Severe liver decompensation
• Active hepatocellular carcinoma
• HCV genotype 3 infection
• Multiple DAA treatment failures 5

Resistance Considerations

• NS5A inhibitor resistance can persist for years and affect retreatment options
• NS3-4A protease inhibitor resistance typically resolves within months 6
• Resistance testing may guide retreatment options for patients who fail initial DAA therapy 1

Drug Interactions

Many DAAs interact with common medications, making it essential to check for interactions before starting therapy 1

Evolution of Treatment

The treatment landscape for hepatitis C has evolved dramatically:

• Pre-2014: Interferon-based regimens with low efficacy (40-50% for genotype 1) and significant side effects 3
• Current era: All-oral DAA combinations with >95% cure rates and minimal side effects 1, 7

This revolution in treatment has transformed HCV from a difficult-to-treat chronic disease to one that can be cured in the vast majority of patients with a short course of well-tolerated oral therapy.

3, 1

[Note: The goal of therapy is to achieve sustained virological response (SVR), which is associated with resolution of liver disease in non-cirrhotic patients and reduced risk of complications in cirrhotic patients.]