Liver transplant in siblings--a single center experience.

Abstract

Experience of liver transplantation (LT) in siblings is disseminated mainly through case reports (1–7). We performed a chart review using the electronic Finnish Liver Transplant Registry database, which contains clinical information on every LT recipient in Finland; 886 individuals from 1982 to April 10, 2013. These 886 LT recipients were treated for the following conditions: cholestatic liver disease (29.3%), other cirrhosis (25.6%), acute liver failure (17.5%), cancer (9.9%), congenital biliary atresia (7.3%), and metabolic disease (5.4%). Every LT patient in Finland is transplanted at Helsinki University Central Hospital, to which they return regularly for follow-up visits. We identified 14 individual deceased donor LT recipients, who had at least one sibling with LT, creating a prevalence of 1.6%. The study group comprised six pairs of siblings, mean age of 38 years and mean follow-up 8.8 years (Table 1). We recorded three deaths, attributed to severe noncompliance problems, sepsis, and hepatocellular carcinoma (HCC) recurrence.TABLE 1: Detailed demographic and liver transplantation-related data of 14 liver transplant recipients with at least one sibling a liver transplant recipient tooEtiology that led to end-stage liver disease in all except one set of siblings was recognized as complex hereditary genetic disease. The two brothers with cryptogenic cirrhosis and HCC were not diagnosed with a specific underlying liver disease. Their family history revealed that the paternal side of the family suffered from undefined liver problems. A third brother from the same family was diagnosed with liver cirrhosis and HCC. A colorectal malignancy was found, and he was deemed unsuitable for LT. “Familial biliary cirrhosis” patient data are shown in Table 1, 4A-D: all suffered from a cholestatic fibrotic liver disease that could not be classified as any known cholestatic liver disease. The disease could not be histologically differentiated from congenital liver fibrosis. Patients’ parents were healthy, and the patients did not have any associated abnormalities or kidney disease. All had shown first signs of the liver disease in their infancy or early childhood. The indication for LT was identical within the sibling group. The course of the disease that led to liver cirrhosis, end-stage liver disease, and ultimately to LT was similar within the sibling set, and the age at transplant were close to each other in most of the cases within the set. It seems that the presence or absence of rejection was shared between the siblings. However, we feel that our cohort is too small to make statistically reliable conclusions, given that the liver donors were so heterogeneous. During the early post-LT course, two brothers with alpha-1-antitrypsin deficiency experienced severe neurologic complications. Each brother was subjected to calcineurin inhibitors immediately after LT, as a part of our routine immunosuppressive protocol. Both experienced severe paresthesias, motor weaknesses, and altered mental status that was defined retrospectively as posterior reversible encephalopathy syndrome (PRES). The PRES is a well known but rare complication of calcineurin inhibitors that are used for immunosuppressive medication. The incidence of PRES in nonsibling population varies between 0.4% and 6% (8); however, its incidence in siblings is not known. We expected to find that LT was caused by alcohol use disorders; however, we did not find any evidence for this phenomenon in our group. Currently, 10% of LTs in Finland are caused by alcohol liver disease (ALD). Although there is a strong hereditary component for heavy drinking behavior (9), the development of ALD does not have a genetic predisposition (10). It seems plausible that ALD was not found in this study because it differs significantly from other chronic diseases recorded in this group, in which the disease prevalence in relatives is increased. We recorded that primary sclerosing cholangitis was the reason for LT in a sibling pair in this current study. According to a Scandinavian study, PSC is more frequent in first-degree relatives than that in the general population (11). Seven previously published articles reported LT in siblings, and these totaled 25 individuals. The indications for LT in pediatric cases have been type IV glycogen storage disease (3), Crigler-Najjar syndrome (2) and familial hypercholesterolemia (4). Most adult sibling LT recipients are diagnosed with amyloid metabolic disturbances (1, 6, 7). Other indications are related to altered cholesterol metabolism (5). We conclude that the prevalence of sibling LT recipients in Finland is low. This study revealed several unique features within sibling pairs; the etiologies that led to liver cirrhosis were mostly because of complex genetic abnormalities. The course of the disease leading to liver cirrhosis and tolerance to calcineurin inhibitors within a sibling set is analogous. Based on the results of this survey, we recommend a thorough review of the posttransplant course of the first LT sibling when the second sibling is opted for LT. Virve S. Koljonen Heikki H. Mäkisalo Transplantation and Liver Surgery Clinic Institute of Clinical Medicine Helsinki University Hospital Helsinki, Finland