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Reply to: Liver transplantation for cirrhosis in cystic fibrosis
EDITORIAL CORRESPONDENCE
Liver transplantation for cirrhosis in cystic fibrosis To the Editor." We wish to comment on the recent article by Mack et al (J Pediatr 1995;127:881-7) and the accompanying editorial by Sharp (J Pediatr 1995;127:944-6). The Mack report adds to the growing experience that, in children with life-threatening hepatic cirrhosis complicating cystic fibrosis, fiver transplantation alone (without simultaneous lung or heart-lung transplantation) offers a good chance of prolonged survival with a greatly improved quality of fife and improved respiratory function. The debate, therefore, should now focus on the difficult problem of judging the optimal timing for liver transplantation in these children. Mack et al. refer to the important fact that, because the deficiency of the cystic fibrosis transmembrahe regulator affects blliary epithelial cells and not hepatocytes, the initial manifestation of the liver disease is portal hypertension rather than hepatoeelhilar failure, and yet they recommend that affected children be considered for liver transplantation only when there is evidence of progressive hepatocellular failure. Sharp, in his editorial, is even more conservative, stating that liver transplantation should be considered only in children with profound and progressive evidence of hepatocyte loss, as indicated by coagulopathy, hyperbilirubinemia, and hepatic encephalopathy. For patients with recurrent variceal bleeding, a transjugular intrahepatic portal shunt or, if unsuccessful, a surgical portosystemic shunt is recommended, although both of these are only palliative procedures and the latter will greatly increase the surgical risks of any future transplantation. Our experience with liver transplantation in 12 children with hepatic cirrhosis complicating cystic fibrosis 1,2 has led us to the conclusion that transplantation should be considered when there is established portal hypertension and before signs of hepatocellular failure are prominent. The risk of premature death from respiratory complications is increased in children with hepatic cirrhosis, 3 presumably because fiver disease can compromise pulmonary function in various ways including diaphragmatic splinting, malnutrition, decreased resistance to infection, and the hepatopulmonary syndrome. Only 3 of the 12 children who received transplants in our unit had advanced signs of hepatocelhilar failure when referred, but all were malnourished and in eight there had been rapid deterioration in pulmonary function during the previous 6 to 12 months. Assessment for fiver transplantation was undertaken when significant portal hypertension and varices were present, and children were then actively listed if (1) variceal hemorrhages were life threatening or recurrent despite sclerotherapy, (2) malnutrition was progressive despite full nutritional support with adequate pancreatic enzyme supplementation, or (3) pulmonary function was deteriorating rapidly as a consequence of hepatic disease rather than irreversible lung disease. With earlier transplantation the outcome for these children can be further improved: 11 of the 12 children who received transplants are alive and well 4 to 60 (median 35) months after the operation. The improvement in their quality of life has been
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remarkable, and we share the experience of Mack et al. that nutritional status and pulmonary function are also improved. Liver transplantation is a major undertaking in these children, but if it is considered only as a last resort, it may be too late. Gabi Noble-Jamieson, MD Nick D. Barnes, FRCP Department of Paediatrics Addenbrooke's Hospital Cambridge CB2 2QQ, England 9/35/73464 REFERENCES 1. Noble-Jamieson G, Valente J, Barnes ND, Friend PJ, Jamieson NV, Rasmussen A, et al. Liver transplantation for hepatic cirrhosis in cystic fibrosis. Arch Dis Child 1994;71:349-52. 2. Noble-Jamieson G, Barnes ND, Jamieson N, Friend P, Calne R. Liver transplantation for hepatic cirrhosis in cystic fibrosis. J R Soc Med 1996;89(Supp1 27):31-7. 3. Feigelson J, Anagnostopoulos C, Poquet M, Pecan Y, Munck A, Navarro J. Liver cirrhosis in cystic fibrosis: therapeutic implications and long-term follow-up. Arch Dis Child 1993;68: 653-7.
Reply To the Editor: As indicated in our article, we concluded that fiver transplantation should be considered for patients with cystic fibrosis and fiver disease manifesting evidence of progressive hepatocelhilar decompensation. In those patients with esophageal hemorrhaging without evidence of hepatic decompensation, injection sclerotherapy may offer benefit, but fullow-np for failure of sclerotherapy and for determination of pulmonary function and general status is warranted so that fiver transplantation can be considered in these other patients. Our data showed that some patients can have rapid deterioration of lung function before transplantation, that the deterioration can rapidly reverse after transplantation, and that malnutrition is common in these patients. We are much more in agreement with the more conservative position stated for actively listing patients stated by Noble-Jamieson and Barnes in their present letter than with their earlier stated position 1 on considering liver transplantation for patients with cystic fibrosis once esophageal varices are discovered to be present. David R. Mack, MD Byers Shaw, MD Alan Langnas, DO Departments of Pediatrics and Surgery University of Nebraska Medical Center Omaha, NE 68198 9/35/73469 REFERENCE 1. Noble-Jamieson G, Valente J, Barnes ND, et al. Liver transplantation for hepatic cirrhosis in cystic fibrosis. Arch Dis Child 1994;71:349-52.
The Journal of Pediatrics
Liver transplantation for cirrhosis in cystic fibrosis To the Editor." We wish to comment on the recent article by Mack et al (J Pediatr 1995;127:881-7) and the accompanying editorial by Sharp (J Pediatr 1995;127:944-6). The Mack report adds to the growing experience that, in children with life-threatening hepatic cirrhosis complicating cystic fibrosis, fiver transplantation alone (without simultaneous lung or heart-lung transplantation) offers a good chance of prolonged survival with a greatly improved quality of fife and improved respiratory function. The debate, therefore, should now focus on the difficult problem of judging the optimal timing for liver transplantation in these children. Mack et al. refer to the important fact that, because the deficiency of the cystic fibrosis transmembrahe regulator affects blliary epithelial cells and not hepatocytes, the initial manifestation of the liver disease is portal hypertension rather than hepatoeelhilar failure, and yet they recommend that affected children be considered for liver transplantation only when there is evidence of progressive hepatocellular failure. Sharp, in his editorial, is even more conservative, stating that liver transplantation should be considered only in children with profound and progressive evidence of hepatocyte loss, as indicated by coagulopathy, hyperbilirubinemia, and hepatic encephalopathy. For patients with recurrent variceal bleeding, a transjugular intrahepatic portal shunt or, if unsuccessful, a surgical portosystemic shunt is recommended, although both of these are only palliative procedures and the latter will greatly increase the surgical risks of any future transplantation. Our experience with liver transplantation in 12 children with hepatic cirrhosis complicating cystic fibrosis 1,2 has led us to the conclusion that transplantation should be considered when there is established portal hypertension and before signs of hepatocellular failure are prominent. The risk of premature death from respiratory complications is increased in children with hepatic cirrhosis, 3 presumably because fiver disease can compromise pulmonary function in various ways including diaphragmatic splinting, malnutrition, decreased resistance to infection, and the hepatopulmonary syndrome. Only 3 of the 12 children who received transplants in our unit had advanced signs of hepatocelhilar failure when referred, but all were malnourished and in eight there had been rapid deterioration in pulmonary function during the previous 6 to 12 months. Assessment for fiver transplantation was undertaken when significant portal hypertension and varices were present, and children were then actively listed if (1) variceal hemorrhages were life threatening or recurrent despite sclerotherapy, (2) malnutrition was progressive despite full nutritional support with adequate pancreatic enzyme supplementation, or (3) pulmonary function was deteriorating rapidly as a consequence of hepatic disease rather than irreversible lung disease. With earlier transplantation the outcome for these children can be further improved: 11 of the 12 children who received transplants are alive and well 4 to 60 (median 35) months after the operation. The improvement in their quality of life has been
314
August 1996
remarkable, and we share the experience of Mack et al. that nutritional status and pulmonary function are also improved. Liver transplantation is a major undertaking in these children, but if it is considered only as a last resort, it may be too late. Gabi Noble-Jamieson, MD Nick D. Barnes, FRCP Department of Paediatrics Addenbrooke's Hospital Cambridge CB2 2QQ, England 9/35/73464 REFERENCES 1. Noble-Jamieson G, Valente J, Barnes ND, Friend PJ, Jamieson NV, Rasmussen A, et al. Liver transplantation for hepatic cirrhosis in cystic fibrosis. Arch Dis Child 1994;71:349-52. 2. Noble-Jamieson G, Barnes ND, Jamieson N, Friend P, Calne R. Liver transplantation for hepatic cirrhosis in cystic fibrosis. J R Soc Med 1996;89(Supp1 27):31-7. 3. Feigelson J, Anagnostopoulos C, Poquet M, Pecan Y, Munck A, Navarro J. Liver cirrhosis in cystic fibrosis: therapeutic implications and long-term follow-up. Arch Dis Child 1993;68: 653-7.
Reply To the Editor: As indicated in our article, we concluded that fiver transplantation should be considered for patients with cystic fibrosis and fiver disease manifesting evidence of progressive hepatocelhilar decompensation. In those patients with esophageal hemorrhaging without evidence of hepatic decompensation, injection sclerotherapy may offer benefit, but fullow-np for failure of sclerotherapy and for determination of pulmonary function and general status is warranted so that fiver transplantation can be considered in these other patients. Our data showed that some patients can have rapid deterioration of lung function before transplantation, that the deterioration can rapidly reverse after transplantation, and that malnutrition is common in these patients. We are much more in agreement with the more conservative position stated for actively listing patients stated by Noble-Jamieson and Barnes in their present letter than with their earlier stated position 1 on considering liver transplantation for patients with cystic fibrosis once esophageal varices are discovered to be present. David R. Mack, MD Byers Shaw, MD Alan Langnas, DO Departments of Pediatrics and Surgery University of Nebraska Medical Center Omaha, NE 68198 9/35/73469 REFERENCE 1. Noble-Jamieson G, Valente J, Barnes ND, et al. Liver transplantation for hepatic cirrhosis in cystic fibrosis. Arch Dis Child 1994;71:349-52.
The Journal of Pediatrics