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

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.

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.

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; sulfobromophthalein, p<0.01) and more severe histologic damage (p<0.001).

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.