Late liver allograft dysfunction: definition, risk factors and outcomes

Introduction. Impaired liver transplant function in the long term often leads to graft loss and the recipient death. There are many causes for the development of a late liver allograft dysfunction and different types of its clinical presentation, but there is no generally accepted definition. This hinders its timely diagnosis, analysis of its prevalence, and also makes it difficult to compare the performance of transplantation programs.

Objective. To determine the clinical and prognostic value of late liver allograft dysfunction.

Material and methods. The study included 103 cases of cadaveric liver transplantation from donors diagnosed with brain death to 100 recipients, of whom 36% were men, aged 48 years old (40;56) (18–68) at the time of transplant, having MELD score 17 (14;21) (7–41). The follow-up period was 52 months (20;77) (8–180). The cases where the graft loss occurred earlier than 3 months were excluded.

The late liver allograft dysfunction was defined as a dysfunction of the transplanted liver, which was manifested by at least one of three following signs and occurred at more than 3 months after transplantation: 1) increased aspartate aminotransferase, alanine aminotransferase and/or gamma glutamyl transferase, alkaline phosphatase, bilirubin; 2) impaired synthetic function (increased international normalized ratio, decreased antithrombin III, cholinesterase); 3) liver cirrhosis complications (signs of portal hypertension, ascites, encephalopathy). The following limits were chosen as a diagnostic threshold for laboratory parameter abnormalities: more than 2 upper limits of normal for total bilirubin, more than 1.5 upper limits of normal for the levels of alanine or aspartic aminotransferases, more than 1.5 upper limits of normal for gamma-glutamyltransferase or alkaline phosphatase, more than 1.6 of normal for international normalized ratio.

Results. Late liver allograft dysfunction was diagnosed at least once in 64% of recipients. Through the postoperative course, the proportion of patients with late dysfunction varied from 22% to 40%.  The etiology of late liver allograft dysfunction was viral (38%), unknown (25%), biliary (19%), immune (17%), and vascular (1%). Late liver allograft dysfunction was reversible in 75% of cases, persistent in 17%, progressive in 8% of cases. Progressive late liver allograft dysfunction led to a graft loss in all cases observed.

Recipients with late liver allograft dysfunction were found to have had a 33% higher incidence of early allograft dysfunction (OR 4.7, 95% CI [1.8–12.3]); the incidence of biliary dysfunction was 3.1 times higher with distant choledochojejunostomy (OR 3.9, 95% CI [1.1–13.9]); in patients with autoimmune and cholestatic disease, the incidence of immune dysfunction was 4.8 times higher (OR 5.8, 95% CI [1.7–20.3]).

Conclusion. The progressive nature of late liver allograft dysfunction negatively affects the results of transplantation and therefore should be considered as an indication for retransplantation. Reversible and persistent variants of late liver allograft dysfunction have favorable) prognosis. If the etiology of late dysfunction is not established, the regular surveillance with monitoring for fibrosis and repeated attempts to clarify the diagnosis should be continued.

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