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

Abstract

Biliary cirrhosis complicates some adults with cystic fibrosis (CF) and may require transplantation. Cardiorespiratory disease severity varies such that patients may require liver transplantation, heart/lung/liver (triple) grafts or may be too ill for any procedure. A 15-year experience of adults with CF-related liver disease referred for liver transplantation is presented with patient survival as outcome. Twelve patients were listed for triple grafting. Four died of respiratory disease after prolonged waits (4-171 weeks). Eight underwent transplantation (median wait 62 weeks); 5-year actuarial survival was 37.5%. Four died perioperatively; only one is alive at 8-years. Eighteen patients underwent liver transplant alone (median wait 7 weeks); 1-and 5-year actuarial survival rates were 100% and 69%. Three long-term survivors required further organ replacement (two heart/lung and one renal). Two others were turned down for heart/lung transplantation and four have significant renal impairment. Results for triple grafting were poor with unacceptable waiting times. Results for liver transplant alone were satisfactory, with acceptable waiting times and survival. However, further grafts were required and renal impairment was frequent. The policy of early liver transplantation for adults with CF with a view to subsequent heart/lung or renal transplantation needs assessment in the context of long-term outcome. Key words: Clinical liver transplantation, cystic fibrosisAbbreviations: ATG, anti-thymocyte globulin; BMI, body mass index; CF, cystic fibrosis; CNI, calcineurin inhibitor; FEV 1 , forced expiratory volume in 1 second; HIV, human immunodeficiency virus; IVC, inferior vena cava; MELD, model for end-stage liver disease; TIPS, transjugular intrahepatic porto-systemic shunt; UK, United Kingdom.

A single centre experience of liver disease in adults with cystic fibrosis 1995–2006

“…In addition, adults with CF and chronic liver failure are more likely to have cardio-respiratory disease precluding liver transplantation alone and are more likely to need multi-organ transplantation. An audit at this centre indicated that patients with CF undergoing simultaneous heart, lung and liver transplantation had a poor outcome [25] as reported by others [26].…”

“…The poor outcome of simultaneous heart, lung and liver transplantation for adults with CF in the combined Addenbrooke's/Papworth series [25] was the major stimulus to establish the joint CF/liver clinic. The purpose was to identify patients with early progressive liver disease before respiratory failure deteriorated to a level that would preclude multi-organ or liver transplantation.…”

The proteasomal system

“…The symptoms of CF, a result of premature UPS-mediated degradation of the functional FTR protein, respectively, the expression of a non-functional CFTR-mutant protein, are pancreatic failure and lung disease the main reason of patient mortality (Strong et al, 2005;Nash et al, 2008;Vender, 2008;Dodge et al, 2007;Bellis et al, 2007;Della et al, 2008;Banjar, 2003). CFTR is a chloride ion channel protein that is found on the surface of epithelial cells in lungs and gut working in an ATP-consuming manner, regulating Cl À -transport (Ciechanover and Brundin, 2003;Lu et al, 2006;.…”

Lungentransplantation bei Mukoviszidose – ein Positionspapier

“…Patienten mit dekompensierter portaler Hypertension und reduzierter Syntheseleistung sollten einer isolierten Lungentransplantation nicht zugeführt werden [12]. Der MELD-Score, in den Kreatinin, Bilirubin und INR eingehen, korreliert eng mit der 3-Monats-Sterblichkeit bei Leberzirrhose.…”