Treating hepatitis C viral infection in patients with chronic kidney disease: When and how

The Patient With Acute Glomerulonephritis With or Without Cryoglobulinemia

HCV has a tropism for B cells and is associated with both lymphoproliferative disorders and several histological forms of immune-complex glomerular disease and cryoblobulinemia.18, 19 In this setting, treatment for eradication of virus would be appropriate because clearance of the virus would be expected to be accompanied by decrease in the ongoing immune-complex injury to the kidney. The recently published article “Sofosbuvir Plus Ribavirin for Hepatitis C Virus-Associated Cryoglobulinaemia Vasculitis: VASCUVALDIC Study”20 reported that patients with a HCV vasculitis syndrome and cryoglobulinemia who received sofosbuvir (400 mg/day) and ribavirin (200-1400 mg/day) had a high rate of a complete clinical response, SVR12 of about 75%, and a low rate of adverse events. Some patients may present with a more aggressive vasculitic syndrome accompanied by cryoglobulinemia. In these cases, antiviral therapy should be preceded by interventions designed to reduce the inflammatory activity involving the endothelium, including corticosteroids, rituximab, and possibly therapeutic plasma exchange.21-23

The HCV-Infected Patient With Stage 1 to 3a CKD

HCV-infected patients with CKD and GFR greater than 45 mL/min should be considered for DAA therapy. From a strictly renal perspective, the major indication for treatment in this group would be slowing the progression of the CKD. HCV infection has been associated with an accelerated rate of CKD progression, as demonstrated in several recently published reports.3, 5 If this finding is confirmed in additional studies, this would represent a compelling indication for treatment.

The Patient With Advanced Stage 3 and 4/5 CKD

This group of patients must be viewed differently because they are clearly progressing into later stages of CKD and the issue of renal replacement therapy begins to enter into the decision tree. In this situation, the nephrologist and hepatologist must work closely and consider whether treatment before or after kidney transplant is advisable. For the patient with a living kidney donor it would be reasonable to treat for a cure before transplant. However, if the patient is going to be placed on the deceased donor waiting list, then other options might be available. For example, delaying antiviral treatment and transplanting with a kidney from an anti-HCV-positive donor is an option at some centers. Programs using this approach have reported dramatically shortened waiting times for a deceased donor kidney.11, 24, 25 In this setting, treatment with DAA can be introduced early after transplantation. Sawinski et al.26 recently reported the outcomes of 20 kidney recipients who received DAAs posttransplant; the DAA therapy achieved an SVR of 100% and was well tolerated without affecting allograft function. Kidney transplant candidates with compensated METAVIR stage 4 liver disease without portal hypertension require close collaboration between the hepatologist and transplant team to determine whether the patient is a candidate for a kidney-alone transplant and/or should receive DAA therapy pretransplant or posttransplant in the context of receiving a kidney from an anti-HCV-positive donor.

The Patient With ESRD Who Is on Dialysis

It has been reported that 5% to 10% of the US dialysis population is infected with HCV, many of whom still remain undiagnosed.27 It is well established that the anti-HCV-positive patient with ESRD has increased mortality when compared with the negative cohort.1 No prospective data, however, have demonstrated that clearance of the virus from these patients translates into improved outcomes. Because this is a population with multiple comorbidities, it would be difficult to demonstrate a change in hard outcomes, such as mortality. The decision to treat must be individualized, taking into account future transplant candidacy, magnitude of ongoing comorbidities, and expected survival.

The Kidney Transplant Recipient

There are large numbers of post-kidney-transplant patients with HCV infection that predates their transplantation. HCV has been clearly associated with an adverse impact on posttransplant patient and graft survival including immune-complex injury to the allograft and a higher incidence of posttransplant diabetes mellitus.28 In contrast with the poorly tolerated interferons, the DAAs offer the opportunity of treatment for kidney recipients because early reports are demonstrating excellent safety and efficacy.29 Importantly, there are several drug–drug interactions (Table 2) with some of the immunosuppressive agents commonly used, and early reports suggest that there may be changes in tacrolimus metabolism as the virus is cleared that would require doing adjustments to maintain therapeutic immunosuppression.26, 30 In this context, post-kidney-transplant patients being considered for DAA treatment should be under the care of a team familiar with these issues so that adequate immunosuppression is maintained.

In conclusion, the availability of DAA agents has dramatically altered the landscape of treatment for the HCV-infected patient with CKD/ESRD. A group of patients who had been largely left on the sidelines of antiviral therapy is now being studied more carefully, resulting in evolving strategies for treatment that take into account the unique needs of this patient population.