From the Guidelines
The treatment of hepatitis C infection in dialysis patients primarily involves direct-acting antiviral (DAA) therapy, with regimens specifically adjusted for renal impairment, and the recommended first-line treatment is glecaprevir/pibrentasvir (Mavyret) at a standard dose of 300mg/120mg (three tablets) once daily for 8-12 weeks, regardless of viral genotype, as supported by the most recent and highest quality study 1.
Key Considerations for Treatment
- The choice of specific regimen should be based on HCV genotype, viral load, prior treatment history, drug–drug interactions, glomerular filtration rate (GFR), stage of hepatic fibrosis, kidney and liver transplant candidacy, and comorbidities, as recommended by the kidney disease: improving global outcomes 2018 clinical practice guideline 1.
- Patients with GFR ≥30 mL/min/1.73 m2 (CKD G1–G3b) can be treated with any licensed direct-acting antiviral (DAA)-based regimen, while those with GFR <30 mL/min/1.73 m2 (CKD G4–G5D) should be treated with a ribavirin-free DAA-based regimen 1.
- The fixed-dose combination of glecaprevir and pibrentasvir has shown high efficacy and safety in patients with stage 4 or 5 CKD, including those on haemodialysis, with an SVR12 rate of 98% (102/104) in the EXPEDITION-4 trial 1.
Alternative Options and Considerations
- Alternative options include elbasvir/grazoprevir (Zepatier) at 50mg/100mg once daily for 12 weeks for genotypes 1 and 4, which also doesn't require dose adjustment in renal failure 1.
- Sofosbuvir-based regimens should generally be avoided in patients with severe renal impairment (eGFR <30 mL/min) due to potential toxicity from drug accumulation, although they can be used in these patients with no dose adjustment when no other relevant treatment options are available 1.
- The optimal timing of treatment is an important consideration for patients on dialysis, and decisions regarding timing of HCV treatment in relation to kidney transplantation should consider the type of donor, waiting list times, centre-specific policies, HCV genotype, and severity of liver fibrosis 1.
Monitoring and Coordination of Care
- Before initiating treatment, patients should undergo baseline testing including HCV viral load, genotype determination, assessment of liver fibrosis, and screening for potential drug interactions, particularly with medications commonly used in dialysis patients.
- Treatment should be coordinated between hepatology and nephrology teams to ensure optimal care and management of potential complications.
- Regular monitoring during treatment includes checking for adverse effects and drug interactions, with post-treatment viral load testing to confirm sustained virologic response (SVR).
From the FDA Drug Label
The pharmacokinetics of sofosbuvir, GS-331007, and velpatasvir were studied in HCV-infected subjects with ESRD requiring dialysis treated with sofosbuvir and velpatasvir tablets (400 mg/100 mg) for 12 weeks. Trial 4062 was an open-label clinical trial that evaluated 12 weeks of treatment with sofosbuvir and velpatasvir tablets (400 mg/100 mg) in 59 HCV-infected adults with ESRD requiring dialysis The overall SVR rate was 95% (56/59) Of the subjects completing 12 weeks of sofosbuvir and velpatasvir, 1 subject experienced virologic relapse.
Treatment of Hepatitis C Infection in Dialysis Patients:
- Sofosbuvir and Velpatasvir can be used to treat hepatitis C infection in dialysis patients.
- The recommended dosage regimen is sofosbuvir and velpatasvir tablets (400 mg/100 mg) for 12 weeks.
- The overall SVR rate was 95% (56/59) in a clinical trial of 59 HCV-infected adults with ESRD requiring dialysis 2.
From the Research
Treatment Options for Hepatitis C Infection in Dialysis Patients
- Historically, Hepatitis C virus (HCV) infection has been difficult to cure in dialysis patients, but the introduction of interferon-free direct-acting antiviral therapies has improved treatment options 3.
- The combination of glecaprevir and pibrentasvir is a pan-genotypic, direct-acting antiviral regimen that can simplify prescribing and has been shown to be effective in treating HCV infection in dialysis patients 4.
- Other direct-acting antiviral regimens, such as daclatasvir + asunaprevir, ledipasvir/sofosbuvir, ombitasvir/paritaprevir/ritonavir, elbasvir + grazoprevir, have also been approved for the treatment of HCV infection, but some may not be suitable for dialysis patients due to contraindications or reduced efficacy 5.
Benefits and Barriers to Treatment
- The new direct-acting antiviral therapies have fewer side effects and are more effective than traditional interferon-based therapies, making them a better option for dialysis patients 3, 5.
- However, the indication for antiviral treatment in HCV-positive patients on dialysis should be individualized, and patients who are candidates for kidney transplantation should be prioritized for treatment 6.
- The safety of direct-acting antiviral therapy in elderly patients has also been confirmed, and there is basically no age limit for the use of these therapies 5.
Importance of Nephrologist Involvement
- Nephrologist involvement in the treatment of HCV infection in dialysis patients can improve access to treatment and ensure that appropriate patients are referred for HCV treatment 3.
- Nephrologists should identify which patients need referral to a hepatologist or HCV specialist prior to treatment and which can be managed by their nephrologist 3.
Previous Treatment Options
- Interferon (IFN) therapy was previously used to treat HCV infection in dialysis patients, but it has been shown to have limited efficacy and significant side effects 6, 7.
- The combination of low-dose ribavirin and conventional or pegylated IFN has been used to treat chronic hepatitis C in dialysis patients, but it is not as effective as the new direct-acting antiviral therapies 7.