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Q&A: Guideline updates for HCV infection in patients with chronic kidney disease

Craig E. Gordon

The introduction and success of direct-acting antivirals drove the Kidney Disease: Improving Global Outcomes work group to make major updates to its clinical practice guidelines regarding hepatitis C virus infection in chronic kidney disease, or CKD.

A synopsis of 32 guideline updates was published in the Annals of Internal Medicine to give physicians the most up-to-date information on the prevention, diagnosis, treatment and management of HCV infection in patients with CKD.

The updates included recommendations for HCV screening and testing in patients with CKD, the use and timing of direct-acting antiviral (DAA) therapy in kidney transplant candidates, and how to manage HCV-infected patients before and after kidney transplantation.

Lead author Craig E. Gordon, MD, MS, a nephrologist at Tufts Medical Center, discussed the guideline updates with Healio Primary Care. – by Erin Michael

Q: Why is it important for physicians to screen for HCV infection in all patients with CKD and in patients starting in-center hemodialysis?

A: For patients starting in-center hemodialysis, the recommendation for HCV testing is to identify HCV-infected patients for infection control reasons as well as for the management of potential HCV-related complications. The CDC and other guideline groups make the same recommendation, which is generally the practice followed by the dialysis organizations.

The recommendation to screen once for HCV infection in all patients with CKD derives from several factors, including the CDC recommendation for one-time testing of the 1945 to 1965 birth cohort (which has the highest prevalence of HCV), and the generally accepted recommendation to screen those with risk factors for the acquisition of HCV (injection and intranasal drug use, patients who have ever been incarcerated, ever been on chronic dialysis, or prior recipients of solid organ transplantation or transfusions, among others). The prevalence of HCV is higher among CKD patients, even not on dialysis, so the yield of screening is higher and there is also provocative early evidence that HCV treatment in the CKD population may be associated with slower CKD progression to end-stage kidney disease (ESKD).

Q: The guidelines favor the use of DAAs over interferon-based treatment for patients with CKD infected with HCV. What does the literature tell us about DAAs in patients with CKD and HCV?

A: At this point, DAAs have replaced interferon-based treatment as the HCV treatment of choice in all patient populations. There are now several moderate-sized randomized control trials and cohort studies showing excellent efficacy of DAAs in patients with CKD stages 4 to 5, ESKD, and among kidney transplant recipients. Little direct data exists to support DAAs in patients with CKD stages G1 to 3; these patients were very likely included among the numerous large randomized controlled trials published on DAAs, but the results of the subset with CKD were not specifically reported. At this point, cure of HCV (sustained viral response, or SVR) occurs in essentially all studied patient populations, including the majority of CKD patients.

Q: How should physicians determine whether to give HCV-infected patients DAA treatment before or after a kidney transplant?

A: DAA treatment should be considered early in the course of CKD when HCV is identified. The timing of treatment gets more nuanced as ESKD approaches, and an individualized approach is likely the most prudent. Patients with advanced liver disease should be treated without specific consideration of kidney transplant candidacy. The remainder of HCV-infected patients with CKD stages G4 to G5 and ESKD would probably benefit from accepting an HCV-infected deceased donor kidney (often with a dramatically shorter time on the waiting list) followed by DAA treatment after transplant. However, this is more complicated and should be individualized in patients who have a potential living donor. Finally, several published small studies have shown excellent outcomes among HCV-uninfected patients who accept HCV-infected deceased donor kidneys with DAA treatment immediately following transplantation. A recent study highlights that this practice is rapidly becoming widely adopted in the U.S., and it wouldn’t be surprising if this accelerates, which would impact the strategic benefit of delaying DAA treatment until after transplant as the shorter waiting list time might no longer exist in the future.

Q: What is the importance of DAA treatment timing in HCV-infected patients receiving a kidney transplant from a noninfected patient?

A: It is probably advisable to treat fairly soon after transplant to avoid HCV-related complications such as post-transplant diabetes mellitus and/or glomerulonephritis. This needs to be balanced with the fact that the GFR is dynamically changing following transplant and careful attention is needed, particularly when regimens that are renally excreted are under consideration. Finally, physicians need to attend to the possibility of drug-drug interactions between DAA and immunosuppressive agents that can result in fluctuating calcineurin inhibitors. These patients should be managed by physicians with a high level of experience with HCV treatment in solid organ transplant patients, the drug-drug interactions and resultant need to monitor the patients more carefully.

Reference:

Gordon C, et al. Ann Intern Med. 2019;doi:10.7326/M19-1539.

Disclosures: Gordon served as a consultant for AbbVie. Please see study for all other authors’ relevant financial disclosures.