Acute cellular rejection in hepatitis C recipients following liver transplantation in the era of direct‐acting antivirals: chronological analysis of the United Network for Organ Sharing database

Abstract

IntroductionInterferon (IFN) treatment for liver transplant (LT) recipients with hepatitis C virus (HCV) increases acute cellular rejection (ACR) and worsens graft and patient survival. It is unknown if direct‐acting antivirals (DAAs) affect rejection rates or post‐transplant survival.MethodThe United Network for Organ Sharing STAR files of December 2017 (n = 25,916) were analyzed.ResultsCompared with non‐HCV‐LT, HCV‐LT survival was worse in the IFN‐era (2007–2008) and IFN+DAA‐era (2011), but not in the DAA‐era (2014–2015). ACR6m rate has been less frequent in newer eras and was lower in HCV‐LT than in non‐HCV‐LT in both the DAA‐era (6.9% vs. 9.3%, P < 0.001) and in the IFN+DAA‐era (8.8% vs. 11.8%, P = 0.001), but not in the IFN‐era (10.8% vs. 11.0%, P = 0.39). HCV‐LT recipients who had ACR6m had worse 2‐year survival than those without ACR6m, in the IFN‐era (80.0% vs. 88.4%, P < 0.0001) and in the IFN+DAA‐era (81.4% vs. 89.2%, P < 0.01) but not in the DAA‐era (90.4% vs. 93.2%, P = 0.085). Cox proportional hazard model identified ACR6m as independent risk factor for mortality in HCV‐LT in the IFN‐era (HR = 1.88, P ≤ 0.001) and in the IFN+DAA‐era (HR = 1.84, P = 0.005), but not in the DAA‐era (P = n.s.).ConclusionsTwo‐year survival of HCV‐LT recipients were significantly better in the DAA‐era; these were associated with reduced rate and impact of ACR6m.

Recipient risk factors for acute cellular rejection after orthotopic liver transplant ‐ a single‐center, retrospective study

“…This is in opposite with the findings of Levitsky et al, who found that HCV was associated with a higher rate of acute cellular rejection in the UNOS database with patients transplanted before the wide use of the direct antiviral agents era [11]. However, outcome of our analysis in our center is similar to Tanaka et al and Dogan et al, both of whom found that HCV was not associated with an increased risk of rejection [13,30]. The first study was done also on the UNOS database using time spans marked by type of HCV treatment available: interferon based, interferon + direct antiviral, and direct antiviral agents and probable what is clinically relevant for our time that the risk of ACR in HCV patients in the setting of new treatment should not be major clinical problem.…”

The Continued Impact of Acute Rejection in the Last Decade of Liver Transplantation

“…In this study, we corroborate our prior study 1 that AR continues to be a predictor for graft failure and patient death in the non-HCV patient cohort, independent of DAA era. This has also been substantiated in a study by Tanaka et al 2 As in our prior study, 1 this is contrary to data prior to 2000 which suggested that AR had no effect on outcomes. 3,4 Ultimately, AR continues to be a significant adverse event, mainly because treatment with highdose immunosuppression contributes to complications (malignancy, cardiovascular disease, infection, renal dysfunction), likely more so than the impact of AR on the graft itself.…”

The fundamentals of sex‐based disparity in liver transplantation: Understanding can lead to change

“…Increased risk of rejection may be explained by hormonal differences, as lower estrogen levels in postmenopausal women result in increased proinflammatory levels, [ 5 ] reinfection of the graft (may stimulate the immune system), and viral clearance in the interferon era (altered the immune response). [ 45 ] The obvious effect of pre‐LT eradication of HCV and posttransplantation HCV recurrence cure in the direct‐acting antiviral era will have significantly reduced this concern in the current era of LT. [ 45 ] These differences in rejection rates appear to be more related to underlying liver disease etiology. Studies that included all etiologies of liver disease have shown no differences in either acute or chronic rejection based on sex.…”