Aplastic Anemia Complicating Orthotopic Liver Transplantation for Non-A, Non-B Hepatitis

Abstract

Aplastic anemia developed in 9 of 32 patients (28 percent) undergoing orthotopic liver transplantation for acute non-A, non-B hepatitis, at one to seven weeks after the procedure. No patient previously had evidence of hematologic dysfunction or conditions known to be associated with aplastic anemia. No other cases of aplastic anemia were identified among 1463 patients undergoing liver transplantation for all other indications at the four centers participating in the study (chi-square = 415, P<0.001; 95 percent confidence interval for the incidence of aplastic anemia after transplantation for non-A, non-B hepatitis, 13 to 44 percent, vs. 0.00 to 0.13 percent for all other indications).The operative and postoperative treatment of these patients was not otherwise different, indicating that the aplastic anemia was a complication of the hepatitis, not of the transplantation procedure. Four of the nine patients died of complications due to infections. Three of the surviving patients have been followed for less than six months, one for one year, and one for two years. The two patients followed the longest have recovered marrow function to an appreciable degree, and two of the others have evidence of early recovery.We conclude that patients undergoing orthotopic liver transplantation for non-A, non-B hepatitis are at a high risk for the development of aplastic anemia.Liver failure after severe acute or subacute hepatitis is an accepted indication for orthotopic liver transplantation. A recent analysis of 29 patients with acute liver failure demonstrated that the odds in favor of survival were greatly increased by transplantation, and the causes of treatment failure did not appear to be different from those in patients who underwent transplantation for other reasons. [1][2][3] We present clinical data on nine patients who had aplastic anemia after transplantation, a complication that may be unique to patients with acute non-A, non-B viral hepatitis.

Hematopoietic stem-cell transplantation following solid-organ transplantation in children

“…SAA is a well-reported and common complication of liver transplantation for non-A, non-B, non-C hepatitis with reports of mortality rates as high as 40-50% during courses of immunosuppressive therapy, primarily due to infectious complications. 27,28 HSCT for SAA has been reported following liver and kidney transplantation. 29 However, successful allogeneic HSCT in pediatric patients developing SAA following orthotopic liver transplantation has been previously described only in case reports.…”

Should we be performing more combined hematopoietic stem cell plus solid organ transplants?

“…45 Aplastic anemia, however, can also develop in patients after liver transplant performed for viral hepatitis. 46 Aplastic anemia arising in this situation has been attributed to the underlying viral process, since it has not been reported to occur after liver transplantation for other indications. 47 Seven patients (five children and two adults) have been reported in the literature who received BMT between 2 and 44 months after their liver transplant.…”

Successful bone marrow transplantation for severe aplastic anemia following orthotopic liver transplantation: long-term follow-up and outcome

“…1,2 This complication has been noted to be significantly more frequent among children than adults, and mortality is high. Clinical experience suggests that aplastic anemia is a complication of the underlying disease which led to hepatic failure, rather than due to the process of transplantation, as SAA does not generally occur following liver transplantation for other reasons.…”

“…3 Outcomes for patients whose aplastic anemia was treated with immunosuppressive agents have varied. 1,2 Full hematologic recovery following immunosuppression has been reported, however time to recovery is often on the order of several months to years. 1,2 Sato et al 4 recently described a child successfully treated with growth factors and immunosuppression for SAA which developed following living-related orthotopic liver transplantation for FHF.…”

“…However, others have reported mortality rates of 40-50% during courses of immunosuppressive therapy, due primarily to infectious complications. 1,2 In this report, we describe the 8-year follow-up of an 11-year-old boy who underwent orthotopic cadaveric liver transplantation at the age of 3.5 years for fulminant hepatic failure secondary to non-A, non-B, non-C hepatitis, followed by sibling donor BMT for SAA.…”