Infectious Disease Advisor: How has the introduction of DAAs affected the use of HCV-positive grafts? When is it acceptable to use an HCV-positive liver for transplant?

Dr Lilly: HCV-positive (HCV-RNA-positive) livers are not routinely used in non-HCV-infected recipients, although there are cases when this has been done. With the availability of highly effective agents to eradicate HCV, however, one could make the case that a very ill recipient without HCV would benefit from transplantation with an infected graft and very likely be cured of HCV afterward. There are, of course, issues of consent, as well as medicolegal aspects that need to be resolved. It is also unclear whether drugs will be as available posttransplant for newly infected patients, as they have become available for patients with disease recurrence, and there are no data on the efficacy of these drugs if they are used in this setting.


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Infectious Disease Advisor: When would you start DAA for someone who received an HCV-positive liver?

Dr Lilly: I would endorse the use of DAAs in newly infected recipients as soon as is practically possible, perhaps within a month of transplant, assuming drug availability. The timing would be influenced by the patient’s clinical status, comorbidities, medications, and other factors.

Infectious Disease Advisor: How common is HCV recurrence in the posttransplant setting, and what are some of the risks?

Dr Lilly: Patients who are RNA positive before their liver transplant will develop recurrence in the graft in more than 99% of cases.

Infectious Disease Advisor: What steps should be taken to prevent HCV recurrence after transplant?

Dr Lilly: The most effective method to prevent recurrence is to eradicate the virus in the recipient before transplantation. There are no established methods for preventing recurrence, which likely occurs immediately on perfusion of the new liver in the operating room.

Infectious Disease Advisor: How has the introduction of DAAs changed outcomes for patients with HCV who undergo a liver transplant?

Dr Lilly: It has long been established that patients who develop recurrent HCV after liver transplantation have a markedly improved long-term survival if the virus can be eradicated, whether that was by interferon- or DAA-based regimens. The ease with which cure can now be achieved allows more patients to enjoy that benefit.

Infectious Disease Advisor: What are the risks of delaying DAA after transplant?

Dr Lilly: Most antiviral regimens become less effective as liver disease progresses, although this is becoming less of an issue with the DAAs that are now available. Early treatment would reduce or eliminate the risk for a particularly deadly form of recurrence: fibrosing cholestasis. The virus can also cause renal damage and complicates the interpretation of liver biochemistry in liver transplant recipients, resulting in more imaging, blood tests, and even liver biopsies, which carry a small but real risk in these patients.

Infectious Disease Advisor: Are there any interactions between immunosuppressant drugs and DAAs that clinicians should watch for?

Dr Lilly: Protease inhibitors have a profound effect on the levels of calcineurin inhibitors, and regimens that do not include them are preferred in transplant recipients.

Infectious Disease Advisor: When is retransplant preferred over antiviral therapy?

Dr Lilly: I cannot imagine a situation where retransplant would be preferable; ideally, the need for retransplantation for recurrent HCV will continue to diminish, and those few patients who require it can be treated before surgery to protect the next graft.

Infectious Disease Advisor: Can DAAs be used in patients with hepatitis who are coinfected with HIV?

Dr Lilly: Yes, both in the nontransplant and posttransplant setting. 

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References

  1. Hepatitis C FAQs for health professionals. Centers for Disease Control and Prevention. https://www.cdc.gov/hepatitis/hcv/hcvfaq.htm Updated January 27, 2017. Accessed June 1, 2017.
  2. Viral hepatitis. Centers for Disease Control and Prevention. https://www.cdc.gov/hepatitis/featuredtopics/youngpwid.htm Updated April 17, 2017. Accessed June 1, 2017.
  3. Belli LS, Duvoux C, Berenguer M, et al; ELITA board members. ELITA consensus statements on the use of DAAs in liver transplant candidates and recipients [published online March 18, 2017]. J Hepatol. doi: 10.1016/j.jhep.2017.03.006
  4. Terrault NA, Berenguer M, Strasser SI, et al. International Liver Transplantation Society Consensus Statement on hepatitis C management in liver transplant recipients. Transplantation. 2017;101:956-967. doi: 10.1097/TP.0000000000001704
  5. Terrault N, McCaughan G, Curry M, et al. International Liver Transplantation Society Consensus Statement on hepatitis C management in liver transplant candidates. Transplantation. 2017;101:945-955. doi: 10.1097/TP.0000000000001704