Acute cellular rejection following liver transplantation has decreased in incidence with the use of potent immunosuppressive agents, but it still affects 15 to 25 percent of liver transplantation recipients [1,2]. Most episodes occur within one month posttransplantation, although acute cellular rejection may present later . A retrospective analysis of 970 liver transplantations found an 11 percent incidence of late acute cellular rejection (>90 days post-transplantation) that was associated with recent changes in and lower levels of immunosuppression . In addition to the type and level of immunosuppression, certain transplantation related characteristics may influence the risk of rejection. As an example, patients who receive an organ from a living related donor may have a lower rate of acute cellular rejection compared with deceased donor liver transplantation recipients [1,5].
The consequences of acute cellular rejection are variable. While it can predispose to steroid-resistant rejection and graft loss, most episodes do not have long-term adverse effects except in hepatitis C virus (HCV)-positive patients . (See 'Hepatitis C' below.) Furthermore, acute cellular rejection identified by protocol liver biopsy in the absence of biochemical dysfunction often resolves without increasing immunosuppression . There is even a suggestion that such subclinical immune activation might be beneficial in inducing a degree of tolerance . The timing of rejection might affect outcomes. In a large retrospective study, compared with patients without an episode of rejection, early acute rejection was associated with better graft survival and late acute rejection was associated with reduced graft survival . Patients who developed late acute cellular rejection had a 28 percent rate of chronic rejection and a 6 percent risk of graft failure.
This topic will review the treatment of acute cellular rejection following liver transplantation. The diagnosis of acute cellular rejection following liver transplantation is discussed separately. (See "Diagnosis of acute cellular rejection in liver transplantation".)
The diagnosis of acute cellular rejection is usually suspected by elevations in serum aminotransferase and alkaline phosphatase levels, which typically precede clinical symptoms of jaundice and fever. However, biochemical parameters are not sensitive or specific for detecting acute cellular rejection and do not correlate with its severity . Thus, the diagnosis should be confirmed by liver biopsy before initiating treatment for rejection. Histologic features include endothelitis, nonsuppurative cholangitis, and mixed mononuclear cell portal inflammation . (See "Diagnosis of acute cellular rejection in liver transplantation".)
High dose corticosteroids are usually first line therapy for acute cellular rejection. Methylprednisolone doses vary among centers, ranging from 500 mg to 1000 mg boluses given daily for one to three days. A gradual corticosteroid taper is provided at some centers following bolus methylprednisolone. In a randomized trial, 1000 mg of methylprednisolone followed by a six day taper from 200 mg/day to 20 mg/day was more effective for the treatment of acute cellular rejection and associated with less infectious complications than giving 1000 mg of methylprednisolone on three consecutive days .