What are the considerations and management plan for transplanting Hepatitis C (HCV) positive donor lungs into a Hepatitis C (HCV) negative patient?

From the Guidelines

Transplanting hepatitis C virus (HCV) positive donor lungs into an HCV negative recipient requires a proactive management approach, with the current standard of care involving initiating direct-acting antiviral (DAV) therapy immediately post-transplant, typically within 24-48 hours, using a pangenotypic DAA regimen such as glecaprevir/pibrentasvir (Mavyret) 300mg/120mg daily for 8-12 weeks, or sofosbuvir/velpatasvir (Epclusa) 400mg/100mg daily for 12 weeks 1. The goal of this approach is to undertake DAA therapy as early as clinically possible to avoid the development of acute hepatitis and other complications of HCV infection, with emerging data suggesting that initiating prophylactic/preemptive DAA therapy before viremia occurs reduces the likelihood of complications, such as fibrosing cholestatic hepatitis 1. Some key considerations in the management of these patients include:

• Close monitoring, including baseline HCV RNA testing pre-transplant, followed by weekly viral load measurements for the first month, then monthly until treatment completion 1
• Liver function tests should be monitored regularly 1
• The transplant team should coordinate with hepatology specialists before transplantation to ensure immediate availability of DAV therapy 1
• Patients should be counseled about the excellent cure rates (>95%) with modern antivirals and the minimal impact on long-term outcomes when HCV is promptly treated 1
• The risk of HCV transmission is essentially eliminated with this protocol, making these transplants as safe as HCV-negative donor organs when managed appropriately 1
• Informed consent should include the risk of transmission from an HCV-viremic donor, the risk of liver disease if HCV treatment is not available or treatment is unsuccessful, and the benefits of reduced waiting time and possibly lower waiting list mortality 1

From the Research

Key Considerations

• Hepatitis C positive (HCV+) donor lungs can be transplanted into HCV negative patients using direct-acting antiviral (DAA) therapy to prevent HCV infection 2, 3.
• The use of DAA therapy has been shown to be safe and effective in preventing HCV infection in lung transplant recipients 2, 4.
• The primary outcome of interest is sustained virologic response (SVR) at 12 weeks after completion of DAA therapy (SVR12) 5, 6.

Plan of Management

• Recipients should be treated with a pangenotypic DAA regimen for 4 weeks, initiated within a few hours after transplantation 2.
• The treatment regimen and duration may be at the discretion of the hepatologist 6.
• Close monitoring of HCV viral load and liver function is necessary to assess the effectiveness of DAA therapy 2, 4.
• Patients should be educated and consented on the transplantation of HCV-viremic organs and the use of DAA therapy 6.

Outcomes

• Short-term outcomes of lung transplantation from HCV viremic donors are promising, with no difference in early complications or survival 4.
• SVR12 rates have been reported to be high, ranging from 95% to 99.6% in different studies 2, 5, 6.
• Long-term outcomes, including chronic rejection and infection, need to be further explored 5, 4.

Special Considerations

• Acute cellular rejection may occur more frequently in HCV-infected lung-transplant recipients than in those who receive lung transplants from donors who do not have HCV infection 2.
• The effects of seroconversion and long-term outcomes, including chronic rejection and infection, need to be further explored 4.