+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

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

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.

(PDF emailed within 1 workday: $29.90)

Accession: 035980750

Download citation: RISBibTeXText

Related references

Marked Differences in acute cellular rejection rates between living-donor and deceased-donor liver transplant recipients. Transplantation 80(8): 1072-1080, 2005

Incidence and severity of acute cellular rejection in recipients undergoing adult living donor or deceased donor liver transplantation. American Journal of Transplantation 9(2): 301-308, 2009

Acute cellular rejection rates in living-donor and deceased-donor liver transplantation. Liver Transplantation 12(5): 886-887, 2006

Comparison between two high-dose methylprednisolone schedules in the treatment of acute hepatic cellular rejection in liver transplant recipients: a controlled clinical trial. Liver Transplantation 8(6): 527-534, 2002

Comparison of pharmacokinetics of mycophenolic acid and its metabolites between living donor liver transplant recipients and deceased donor liver transplant recipients. Liver Transplantation 15(11): 1473-1480, 2010

Delay of hepatitis C recurrence in liver transplant recipients: impact of mycophenolate mofetil on transplant recipients with severe acute rejection or with renal dysfunction. Transplantation Proceedings 34(5): 1561-1562, 2002

Differences in cellular rejection rates between living donor and cadaveric liver transplant recipients. Hepatology 34(4 Pt 2): 234A, 2001

Pharmacokinetics of tacrolimus in living donor liver transplant and deceased donor liver transplant recipients. Transplantation 85(4): 554-560, 2008

High dose vs low dose steroids for acute rejection episodes in renal transplant recipients. Drug Intelligence & Clinical Pharmacy: 482-483, 1981

Liver Stiffness Measurements Using Acoustic Radiation Force Impulse in Recipients of Living-Donor and Deceased-Donor Orthotopic Liver Transplant. Experimental and Clinical Transplantation 2017, 2017

Perioperative bacterial infections in deceased donor and living donor liver transplant recipients. Journal of Clinical and Experimental Hepatology 2(1): 35-41, 2012

Donor-Specific HLA Antibodies in Living Versus Deceased Donor Liver Transplant Recipients. American Journal of Transplantation 16(8): 2437-2444, 2017

Acute cellular rejection in liver transplant recipients under cyclosporine immunosuppression: predictive factors of response to antirejection therapy. Transplantation 73(12): 1936-1943, 2002

Cytokine concentrations and regulatory T cells in living donor and deceased donor liver transplant recipients. Pediatric Transplantation 17(2): 185-190, 2013

Correlation between risk of hepatitis B virus recurrence and tissue expression of covalently closed circular DNA in living donor liver transplant recipients treated with high-dose hepatitis B immunoglobulin. Transplantation Proceedings 46(10): 3548-3553, 2015