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Chapter category: Transplant

Chronic Allograft Dysfunction—Liver

Chapter authors:
Susan Lerner, Pauline Chen and Paul Martin

In the United States, more than six thousand patients undergo liver transplantation (LT) annually with generally excellent outcomes reflected in patient survival of 88% at one year and 80% at three years and graft survival of 83% and 74%. Advances in immunosuppression have made acute cellular rejection a negligible threat to hepatic graft survival in compliant patients and generally long‑term threats to graft survival reflect recurrent disease rather than rejection. Chronic rejection although relatively infrequent in LT recipients remains an important cause of graft loss and may reflect noncompliance. However, other threats to graft viability have been recognized as the practice of liver transplant has evolved. Use of nonheart beating donors results in frequent non‑anastomotic stricturing and higher graft failure (relative risk 1.85) with the need for retransplantation. Older donor grafts are a factor in more severe recurrence of HCV. Interferon therapy to treat HCV recurrence has been implicated in profound graft dysfunction reminiscent of chronic rejection. With longer term follow‑up recurrence of nonviral disease has become more obvious. Recurrent cholestatic liver disease, most notably primary sclerosing cholangitis, can lead to graft loss. As the significance of non‑alcoholic fatty liver disease as a cause of decompensated cirrhosis and hepatocellular carcinoma has become more fully appreciated, recurrent hepatic steatosis has now entered into the differential of graft dysfunction as has de novo hepatic steatosis. As time from LT increases, the differential evolves with early (i.e., first three postoperative months) graft dysfunction due to impaired graft function due to a suboptimal donor, technical issues such as hepatic artery thrombosis or anastomotic biliary stricture, acute cellular rejection or opportunistic infection such as cytomegalovirus infection. Beyond the initial three months, the differential of graft dysfunction increasingly reflects recurrent disease, although technical problems most notably unrecognized hepatic artery thrombosis as well as anastomotic strictures can present with cholangitis or cholestatic liver biochemistries. Acute rejection beyond three to six months postLT often reflects inadequate immunosuppression. Hepatic allograft dysfunction can occur early or late and the definitions can vary as to the time point that separates those two categories. Monitoring hepatic allograft dysfunction is an intergral part of the longterm management of the liver transplant recipient. As time from transplant increases, the frequency and intensity of follow‑up diminishes although late graft dysfunction may be the first clue to important processes such as chronic rejection.or hepatic artery thrombosis. For both of these processes retransplantation may be required. Retransplants now account for approximately 8% to 10% of all transplants performed in the United States per year. Hepatic allograft dysfunction is indicated by increasing or persistent elevation of serum levels of alanine aminotransferase, alkaline phosphatase, or bilirubin. Depending on the biochemical pattern, the initial evaluation may be with one of the three key diagnostic studies: ultrasonography with Doppler assessment of the hepatic vasculature, cholangiography, or liver biopsy. Of the three, liver biopsy usually plays the most important role in elucidating the cause of late allograft dysfunction. Important causes of late graft dysfunction often are impossible to distinguish from each other in the absence of a biopsy. Decisions regarding the treatment of late allograft dysfunction can be particularly challenging since elevations in hepatic enzymes are nonspecific. The choice of major alterations in a patient’s immunosuppressive regimen or even retransplantation thus often rests on histologic findings.

Susan Lerner
The Mount Sinai Medical Center

Pauline Chen
The Mount Sinai Medical Center

Paul Martin
The Mount Sinai Medical Center

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