Direct‐acting antiviral regimens are safe and effective in the treatment of hepatitis C in simultaneous liver–kidney transplant recipients

Abstract

Hepatitis C (HCV) remains the single most common etiology of end-stage liver disease leading to simultaneous liver/kidney transplant (SLKT) and has worse post-transplant survival compared to non-HCV patients. We aim to assess the effectiveness and tolerance of the all-oral direct-acting antiviral (DAA) agents with or without ribavirin (RBV) in the treatment of HCV recurrence post-SLKT. Thirty-four patients were studied retrospectively, composed predominantly of treatment-naïve (73.5%) non-Caucasian (61.8%) males (82.4%) infected with genotype 1a (64.7%). 94.1% reached a sustained virologic response (SVR) after 24 weeks (32/34 patients), without difference between 12 and 24 weeks of therapy. 64.7% had no clinical side effects. Three deaths occurred, all unrelated to treatment. One patient had liver rejection; tacrolimus was increased and prednisone was initiated while HCV treatment was continued and the patient ultimately achieved SVR. No liver graft losses. No kidney rejection or losses. We demonstrated that DAA combinations with or without RBV result in a remarkable SVR rate and tolerated in the majority of the studied SLKT patients. It is safe to wait to treat until post-kidney transplant and therefore increase the donor pool for these patients. Our cohort is ethnically diverse, making our results generalizable.

Impact of direct‐acting antivirals for hepatitis C virus therapy on tacrolimus dosing in liver transplant recipients

“…In a study examining the impact of DAAs on the enzymatic liver function of 21 LT recipients, TAC concentration‐to‐dose ratio significantly decreased stepwise from the start of treatment until week 12 of therapy, indicating increased TAC metabolism during and after treatment . Similarly, in a retrospective review of 34 simultaneous liver/kidney transplant recipients with HCV, immunosuppression dosage increases were required in seven patients during DAA treatment and five patients following treatment . A recent retrospective study examining DAA use in all types of organ transplants (n = 108), found no difference in TAC doses (3.1 vs 3.2 mg/d, P = 0.06) or concentrations (6.0 vs 6.9 ng/mL, P = 0.46) from baseline to week 4 of DAA treatment, but 45% of patients had a change in their immunosuppression regimen during this time .…”

“…21 Similarly, in a retrospective review of 34 simultaneous liver/kidney transplant recipients with HCV, immunosuppression dosage increases were required in seven patients during DAA treatment and five patients following treatment. 22 A recent retrospective study examining DAA use in all types of organ transplants (n = 108), found no difference in TAC doses (3.1 vs 3.2 mg/d, P = 0.06) or concentrations (6.0 vs 6.9 ng/mL, P = 0.46) from baseline to week 4 of DAA treatment, but 45% of patients had a change in their immunosuppression regimen during this time. 27 Although we found a substantial decline in TAC concentrations from baseline to week 4, changes occurred 12 weeks post-DAA and it is possible that Mansour et al 27 did not follow patients long enough to detect a difference in TAC concentrations.…”

“…The majority of large randomized controlled trials evaluating HCV DAA therapy post‐LT do not specifically report on immunosuppression management during and following HCV DAA therapy . However, there are a small number of retrospective reports that observed a decline in TAC whole blood concentrations in LT recipients during treatment with DAAs …”

“…[14][15][16][17][18] However, there are a small number of retrospective reports that observed a decline in TAC whole blood concentrations in LT recipients during treatment with DAAs. [19][20][21][22] The hypothesis for this decline in whole blood trough concentrations is that there is repression of drug-metabolizing enzymes from inflammatory and infectious stimuli while patients are actively infected with HCV. 19 As the HCV virus is cleared and there is an increase in liver cell function, CYP3A4/5 activity normalizes and larger TAC doses are necessary to achieve adequate troughs.…”

Liver, simultaneous liver‐kidney, and kidney transplantation from hepatitis C‐positive donors in hepatitis C‐negative recipients: A single‐center study

“…However, the advent of highly effective direct‐acting antiviral therapy (DAAs) has led to post‐transplantation HCV cure rates exceeding 95%, and with it, a negation of the ill effects of HCV previously seen in both LT and KT recipients . A number of clinical trials, along with data from the HCV‐TARGET cohort, have demonstrated the efficacy and safety of the use of these agents in the post‐transplant setting . In the HCV‐TARGET cohort, adverse events leading to treatment discontinuation were uncommon, affecting only 1.6% .…”