Liver transplantation for cholestasis associated with cystic fibrosis in the pediatric population

Abstract

The most common hepatic complications of cystic fibrosis (CF) are steatosis, fibrosis, biliary cirrhosis, atretic gallbladder, cholelithiasis, and sclerosing cholangitis. Cholestatic liver disease is a slow progressive disorder, but will stabilize for many patients. CF patients may suffer from the consequences of their liver disease and without liver transplantation, variceal hemorrhage, malnutrition, or end-stage liver disease can lead to death. Prospective data were collected and reviewed on 311 liver transplants performed in 283 patients at the Children's Medical Center of Dallas between October 1984 and November 2000. Ten children received an orthotopic liver transplant (OTLX) for end-stage liver disease associated with cystic fibrosis. Pulmonary function tests were obtained preoperatively in all cases. There were nine boys and one girl. Six are currently alive, and four are dead. Both patient and graft survival was 5.75 yr. Among those currently alive, mean patient and graft survival is 7.71 yr (range 0.10-12.62 yr). Mean patient and graft survival of those who died was 2.35 yr (range 0.78-5.33 yr). No survivor required re-transplantation and currently, all have normal serum aminotransferase values. Chronic sinusitis was not a significant pre- or post-transplant morbidity, although systematic radiographic evaluation of the sinuses did not occur. Pulmonary deaths occurred in three patients from pulmonary hemorrhage, pulmonary infection with Aspergillus and Candida glabrata, and acute bronchopneumonia associated with polymicrobial sepsis because of Pseudomonas, Klebsiella, and Candida albicans 1.44, 0.78, and 1.83 yr, respectively, after transplantation. The fourth death was associated with chronic rejection, and occurred 5.33 yr after transplantation. All non-survivors were below the 5th percentile for height and weight at the time of liver transplantation. Mean age at transplantation was 9.72 yr (range 1.23-19.09, median 9.61). Survivors were transplanted at a younger age than non-survivors (mean of 9.21 yr vs. 10.66 yr), and had shorter waiting times from diagnosis of end-stage liver disease to transplantation (6.87 months vs. 13.83 months). Eighty percentage (n = 8) of patients had pretransplant variceal bleeds (83% of survivors, 75% of non-survivors). While all non-survivors had a history of meconium ileus and preoperative need of pancreatic enzymes, only 67% of those alive experienced these complications. Preoperative forced vital capacity FVC was 103% for survivors and 95% for non-survivors. The corresponding numbers for forced expiratory flow (FEF) 25-75 were 74-84% respectively. Preoperative Aspergillus was identified in 30% of patients (n = 3). Two of these patients are alive. Cystic fibrosis constitutes an indication for 3.5% of pediatric liver transplants. Evaluation and transplantation for end-stage liver disease associated with cystic fibrosis should be undertaken at an early age. Most deaths were associated with pulmonary/septic events, and occurred less than 2 yr after OLTX. Those children who ...

Cystic Fibrosis Liver Disease: To Transplant or Not to Transplant?

“…There is evidence that end-stage CF-related liver disease has an adverse effect on nutritional status and that nutritional depletion in turn affects both liver and pulmonary prognosis adversely. Furthermore, poor nutritional status has been found to be associated with a higher mortality rate following liver transplantation (36). It has been suggested that patients with liver disease and evidence of nutritional depletion be considered for early and elective liver transplantation (34) to preserve long-term pulmonary function.…”

Liver Transplantation for Cystic Fibrosis in Adults

“…However, little is known regarding liver transplantation for endstage liver disease associated with cystic fi brosis in adults. [1][2][3][4][5] We herein discuss liver transplantation for cystic fi brosis in the adult population.…”

“…[1][2][3][4][5][6][7][8][9] Its pathogenesis is an abnormality in the chloride channel in epithelial cells, making exocrine secretions thick and viscous. [5][6][7][8][9] This process results in recurrent plugging mucus in exocrine glands and it causes ductal obstruction in many organs, particularly the lungs, pancreas and liver.…”

“…8,9 A pulmonary manifestation of this disease, especially in childhood, demonstrates a high morbidity and mortality and previously most such cases were usually fatal. [1][2][3][4][5][6][7][8][9] Owing to advances in the management of pulmonary complications, the life expectancy of cystic fi brosis patients has been steadily improving in recent decades. 8,9 As a result, the adult cystic fi brosis population has increased.…”

Reply

“…In addition, in the series by Molmenti et al, frequency of a history of meconium ileus was as high as 80%. 1 Besides the effects of genetic or environmental factors that may condition different susceptibility for liver involvement in CF patients, heterogeneity of study design is another source of substantial disagreement in the ascertainment of risk factors for CFLD. For example, inconsistent identification of male sex as a risk factor, which Slieker et al cited in their letter, may well result from biases inherent in retrospective designs that prevent any meaningful comparison between the available studies.…”