Treatment of acute cellular rejection in liver transplantation
- Scott J Cotler, MD
Scott J Cotler, MD
- Professor of Medicine
- Director, Division of Hepatology
- Loyola University Medical Center
- Section Editor
- Robert S Brown, Jr, MD, MPH
Robert S Brown, Jr, MD, MPH
- Section Editor — Liver Transplantation
- Vice Chair, Transitions of Care, Department of Medicine
- Interim Chief, Division of Gastroenterology and Hepatology
- Weill Cornell Medical College
- Professor of Clinical Medicine, Columbia University College of Physicians & Surgeons
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 post-transplantation, 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 "Liver transplantation: Diagnosis of acute cellular rejection".)
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 "Liver transplantation: Diagnosis of acute cellular rejection".)
Antibody-mediated rejection (AMR) is a rare cause of allograft injury and loss after ABO-compatible liver transplantation that can be confused with and overlap with acute cellular rejection. Proposed features of AMR in liver transplants include donor-specific HLA alloantibodies in serum, microvascular endothelial cell injury on biopsy, and linear C4d positivity in liver sinusoids, in the absence of other causes of liver injury [11,12].
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