Is acute rejection deleterious to long-term liver allograft function?

Background/Aims: The decreasing incidence of chronic rejection after liver transplantation emphasizes the need for an alternative end-point to assess the long-term consequences of acute rejection. The purpose of this study was to determine the effects of resolved episodes of acute rejection on late liver allograft function. Methods: Parameters of hepatic function (liver biochemistry, indocyanine green and sulfobromophthalein clearances, histology) were analyzed in 170 consecutive adult recipients, who were followed prospectively on the basis of repeat annual work-up. Mean follow-up was 3.7+/-0.2 years. Results: The rates of acute and chronic rejection were 51% and 4.1%, respectively. At the last follow-up, there was no significant difference in graft function between patients with a single episode of acute rejection (n=56) and those without rejection (n=84). Among patients treated for a single episode of acute rejection, late hepatic function was not influenced by the severity of acute rejection and the response to corticosteroids, In contrast, patients with recurrent acute rejection (n=30) had significant impairment of liver function tests (aspartate aminotransferase, p<0.05; alanine aminotransferase, p<0.01; alkaline phosphatase, p<0.01; gamma-glutamyl transpeptidase, p<0.001), lower dye clearances (indocyanine green, p<0.01; sulfohromophthalein, p<0.01) and more severe histologic damage (p<0.001). Conclusions: Single episodes of acute rejection do not impair the long-term hepatic function, whereas recurrent episodes leave sequellar damage to the liver allograft. These results provide a rationale for converting patients with rejection to a heavier immunosuppressive regimen, while leaving nearly half the recipients on a lifelong light immunosuppressive regimen.