Chronic rejection (CR) is the leading indication for long term graft loss. We discuss our centers' experience with CR diagnosis and management. Method: Electronic medical records searched for histologically confirmed CR (ductopenia, aberrant cytokeratin-7 and minimal portal inflammation) between 2000-16. Clinical data was compared to patients without CR. Standard induction with tacrolimus and steroids. Results: Of 435 patients, 17 (3.9%) had CR over an average follow up of 7.4y: 5 had biliary atresia, 2 each: Alagille, other cholestasis, autoimmune hepatitis, indeterminate acute liver failure and 1 each: OTC deficiency, CF, A1AT deficiency, and hepatoblastoma. Median age at LT was 1.8y (4m–17y) same as control. Median age of CR was 5y(2-21y) with range of 3m–14y post LT. Demographics in CR vs control included male (59% vs 51% NS), Hispanic (41% vs 46%), African Americans (35% vs 12%), Caucasians (12% vs 36%) p<0.0001 and public insurance (71% vs 64% NS). Whole graft (76% vs 85%) and ABO incompatible (6% vs 5%) (NS). On average, patients had 2.8 episodes of acute cellular rejection (ACR) prior to CR and 13 had acute on CR. In 5 cases tacrolimus (TAC) was reduced; 3 PTLD and 2 PRES. At CR Presentation: 41% asymptomatic; 42% icterus, 42% splenomegaly, 24% ascites, 12% had pruritus, ALT 242 IU/L, AST 190 IU/L, GGT 603 IU/L, total/direct bilirubin 4.6/3.7 mg/dL, platelet 192K, INR 1.3. ANA>1; 160 in 8, IgG was elevated in 2, LKM was transiently positive in 2 cases; all treated with steroids. Prior to CR the TAC medication level variability index (MLVI) was 4.2. Therapy included monotherapy; Rapamune (Rapa) 2, combination Rapa+Mycophenolate (MMF) 4 or prednisone 2, TAC+MMF 1 or Pred 1 and 7 on triple therapy. Outcomes included mortality in 4 patients (3 multi-organ failure 1 unknown) at average 9.3y, 1 re-transplanted after 1.5y, 2 sustained normalization of liver enzymes and remainder 10 had fluctuating lab values. 9 had sequential Bx in which 4 showed improved number of bile ducts, 3 sustained and 2 worsening. Conclusion: CR was infrequent in our population. Risk factors included non-adherence (high MLVI), ACR, ANA, ethnicity and intentional TAC dose reduction. Most patients were treated with additional immunosuppressants and only minority normalized graft function. Further research is required to identify risk factors, effective therapy and prevention of chronic rejection.

CITATION INFORMATION: Miloh T., Cheng A., Schady D., Himes R., Mysore K., Hosek K., Goss J. Chronic Rejection: Risk Factors, Clinical Presentation and Outcome in Pediatric Liver Transplant Recipients: A Single Center Experience Am J Transplant. 2017;17 (suppl 3).

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