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Treatment of acute cellular rejection with high-dose steroids, but not modulation of baseline immunosuppression, is associated with severe HCV recurrence in both living and deceased donor liver transplant recipients



Treatment of acute cellular rejection with high-dose steroids, but not modulation of baseline immunosuppression, is associated with severe HCV recurrence in both living and deceased donor liver transplant recipients



Hepatology 38(4 Suppl 1): 651A, October



Introduction: Histologic injury due to recurrent HCV occurs in up to 90% of HCV infected patients after liver transplantation, while the incidence of acute cellular rejection (ACR) following transplantation is 60-70%. Bolus steroids to treat ACR is associated with decreased graft and patient survival in HCV infected recipients of deceased donor grafts (DD). However, the natural history of HCV recurrence following living donor liver transplant (LDLT) remains incompletely described. Similarly the avoidance of steroid boluses in the treatment of rejection in HCV patients has not been studied. Aim: To explore the impact of rejection treatment with bolus steroids or modulation of baseline immunosuppression on the severity of HCV recurrence in LDLT and DD recipients. Methods: We performed a retrospective analysis of 93 patients with HCV-associated cirrhosis who underwent LDLT and DDLT, comparing the incidence of histologic HCV recurrence following episodes of treated ACR. 65 DD (49 m, 16 w) were compared to 28 LDLT (18 m, 10 w). Mean time of patient follow up was 25 months (range 6 to 39 months). All patients were HCV antibody positive by ELISA or RIBA and 98% were HCV viremic prior to transplant. Following transplant, elevated serum transaminases, positive HCV RNA, and liver biopsy consistent with histologic evidence of HCV defined recurrence. Severe HCV recurrence was defined as either Stage III-IV fibrosis or cholestatic hepatitis C. ACR was defined by Banff criteria. All biopsies were read by a single experienced hepatopathologist (JL). Results: 72 of 93 pts (77.4%) developed histologic recurrence of HCV; 47 (72.3%) DD and 25 (89.0%) LDLT (p=0.003). Of these 72 patients, 37 experienced ACR prior to the diagnosis of HCV (51.4%). 31 (83.8%) had received IV steroids or recycled oral steroids in response to ACR, while 6 (16.2%) had modulation of baseline immunosuppressive therapy without high dose steroids, defined as increased doses of calcineurin inhibitor, CellCept, or ltoreq10 mg/day increase in steroids. Of 37 patients with recurrent HCV following ACR, 12 (32.4%) experienced severe recurrence of HCV: 8 (17%) CAD and 4 (16%) LDLT p=NS. 11 (91.7%) cases of severe recurrent HCV had received IV steroids or recycled oral steroids in response to ACR (4 of 4 LDLT and 7 of 8 CAD), while 1 (8.3%) had modulation of immunosuppressive therapy (p=0.001). 7 of 12 patients (58%) with severe recurrent HCV developed graft failure resulting in retransplantation or death (4 of 8 CAD and 3 of 4 LDLT). Only 1 of 6 patients treated with modulation of immunosuppression had severe HCV recurrence (16%, p=0.003 c/w steroid group) and none had worsening of rejection, requirement for OKT3 or Thymoglobulin, or graft loss. Conclusions: (1) In LDLT and DD patients, bolus steroid use in the management of ACR is associated with a significant incidence of severe HCV recurrence in LDLT. (2) Severe recurrence of HCV was associated with a significant rate of graft failure. (3) Immunosuppression strategies which modulate baseline immunosuppression without bolus corticosteroids appears to have lower rates of severe HCV without worsening rejection and deserve further study.

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