Saudi Journal of Gastroenterology
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SPECIAL ARTICLE Table of Contents   
Year : 2001  |  Volume : 7  |  Issue : 1  |  Page : 1-5
Life after liver transplantation


From the Liver Unit, Birmingham Children's Hospital, Birmingham, United Kingdom

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How to cite this article:
Kelly DA. Life after liver transplantation. Saudi J Gastroenterol 2001;7:1-5

How to cite this URL:
Kelly DA. Life after liver transplantation. Saudi J Gastroenterol [serial online] 2001 [cited 2019 Jul 15];7:1-5. Available from: http://www.saudijgastro.com/text.asp?2001/7/1/1/33408


As survival has improved in children post liver transplantation, most survivors will achieve a normal lifestyle. Although long-term results in children are limited to 10-15 years, follow up these children will have a normal life expectancy [1] .

We know that children transplanted for end-stage liver failure secondary to biliary atresia or fulminant liver failure will have complete recovery from their liver failure [2],[3] following a successful transplant while children transplanted for metabolic liver diseases such as alpha- I-antitrypsin deficiency [4] , tyrosinemia type I [5],[6] and Wilson disease [7] should have both phenotypic and functional recovery.

Children with inborn errors of metabolism such as Crigler-Najjar type I will have functional recovery of hepatic enzyme activity following either orthotopic or auxiliary liver transplantation and will achieve normal levels unconjugated bilirubin and be free of danger from Kernicterus. Children transplanted for primary oxaloses will achieve a functional recovery of the missing hepatic enzyme, but the pretransplant load of oxalate takes some considerable time to reduce leading to recurrent renal oxaloses and consequent morbidity[9] . Those children transplanted for organic acidemia have a good outcome, as the enzyme defect is not restricted to the liver (proprionic acidemia or methylmalonic acidemia) and thus there is palliation of the enzyme defect. These children need to have dietary restriction and remain at risk for metabolic crises during inter-current illnesses. In the same way, children transplanted for urea cycle defects have partial functional recovery and may require protein restriction during acute illness [10] .


   Nutritional Rehabilitation Posttransplant Top


The most important aspect in achieving normal quality of life is the return to normal nutritional status. Approximately 60% of children undergoing assessment for liver transplantation are malnourished (weight and/or height less than 2 standard deviations below the mean) [11],[12],[13].

Early studies of growth in children following liver transplantation showed that most children did not achieve normal growth [14] , but more recent data demonstrated the effectiveness of good nutrition in achieving normal growth patterns in 80% of survivors [11],[15],[16] .

Normal nutrition starts immediately posttransplant with an increase in muscle and fat stores [11],[16],[17] . In the first few months posttransplant weight gain may be excessive due to the effects of steroids on appetite and salt and water retention, but most children regain normal weight within 12 months.

Catch up linear growth is delayed as a result of steroid therapy but returns to normal within 6-24 months [18] . Children who were particularly stunted pre-transplant (<-1 height standard deviation score) may have rapid catch up immediately posttransplant but rarely achieve normal height (19) . Factors which affect growth posttransplant and include pre­operative nutritional status, intensity of steroid administration, nutrition posttransplant. The effect of gluco-corticoids posttransplant is well known and considerable data are available to demonstrate this [13],[20],[21] .

There is little catch up growth in the first 6 months posttransplant when steroid dosage is high. Multiple regression analysis in patients surviving at least one year posttransplant demonstrated that in the first year posttransplant the combined incidence of bilirubin concentration and steroid dosage correlated with the standard deviation score for growth velocity (R = 0.63, P = 0.001) [14] . In the second year posttransplant only accumulative steroid dosage was significant (R = 0.47, P = 0.003) [15] . Many studies confirm the positive effect on growth by successful withdrawal of steroids either by reducing to alternate steroid [22] or by withdrawing steroids between 12 and 24 months [14],[22],[23],[24]. It is also possible that gluco-corticoids may inhibit growth hormone secretion and prevent normal growth posttransplant. Sarna et al [25] evaluated the effect of cortico-steroids on GH secretion and IGF-1 and IGFBP3 concentration. GH secretion was abnormal in only 2 out of 18 patients, serum IGF-1 concentration was normal but serum IGFBP3 was elevated in 62% of this group. Endogenous cortisol production was reduced in most patients receiving steroid therapy. Growth velocity posttransplant only correlated with serum basal or stimulated concentration suggesting that endogenous cortisol production was the best indicator of growth inhibition [25] . Another possibility for the inhibition of normal growth posttransplant may be the pre-transplant diagnosis. Failure to thrive is an intrinsic part of Alagille Syndrome. 50% of children who were transplanted for this disease and who were stunted pre-transplant did not achieve normal height [26] . Recent reports have suggested that children transplanted for acute liver failure, who had normal growth pre-transplant did not maintain normal height posttransplant [22],[26],[27] although the reasons for this are not clear, and are not universal [17] . As chronic illness leads to failure to thrive and delayed development, those children who have high postoperative morbidity will have slow nutritional rehabilitation. This is common in children with chronic rejection as they have the combined effect of hepatic dysfunction with cholestasis and increased steroid therapy [18],[27]. Approximately 30% of children may develop feeding problems posttransplant and will require persistent nutritional support with nocturnal enteral feeding [18] .


   Endocrine Rehabilitation Top


A recent study has demonstrated that both genders have normal puberty and will develop secondary sexual characteristics [22] , although puberty may be delayed. Chronic liver disease causes amenorrhea and delayed menarche in up to 50% of female patients [28] . Normal menstrual function and fertility are restored in both adolescents and adults following liver transplantation [29] and accordingly contraceptive advice should be given to transplant recipients of child bearing age. Pregnancy should be avoided in the first 6-12 months posttransplant because of the intensity of immunosuppression [28] and the development of opportunistic infection such as cytomegalovirus [30] . Intrauterine devices are not recommended because of the increased risk of infection [31] . Barrier contraception is the safest method of contraception. Combined oral contraceptives may be used cautiously inpatients with hypertension or active hepatic disease and can decrease cyclosporin metabolism. Progestogen only methods or the continuous use of oral contraceptives may be more effective [30] . Although pregnancy in women following liver transplantation carries a high risk of pre-eclampsia, worsening hypertension, pre­term or premature rupture of membranes, anaemia, small pre-gestational age or pre-term delivery successful pregnancies have been documented and are dependent on careful management. Pregnancies have been documented in women taking both cyclosporin and tacrolimus [30] . Male transplant recipients have also successfully fathered infants.


   Psycho-social Development Top


There are now considerable data that neurodevelopmental outcome following liver transplantation is normal.

We know that chronic liver disease has a detrimental effect on both mental development and growth in children due to the effect of protein energy malnutrition on brain development. Stewart et al [32] demonstrated that liver disease in early life had a bad effect on intellectual function and linear growth and documented that recovery of intellectual and motor function was related to the age at transplantation [33] . Subsequent studies have demonstrated that there is an initial deterioration in psychosocial development in the first year posttransplant as indicated by loss of social skills, language development and eye/hand coordination which may be related to the stress of the operation, the intensity of immunosuppressibn and prolonged hospitalization both before and after transplantation [34] . Even so, there is a marked improvement in mental development within one year of transplantation in up to 70% of children studied pre and posttransplant [35] . Longer-term studies have demonstrated that the majority of children will achieve normal psychosocial development for all modalities of development within 2-4 years of transplantation [34] . Risk factors for persistent developmental delay include malnutrition pre­transplant, length of hospital stay and age at transplantation with younger children at particular risk of developmental delay [35] . A 5-year study of 20 patients demonstrated that 80% achieved normal height and weight and that all the children attended school with only 30% requiring special education support. Psychological testing of this group of children indicated that 75% were functioning normally [36] . Many parents have improved psychological symptoms following liver transplantation, but a recent study has indicated that 20% of marriages dissolved and 30% of families were functioning outside the normal range [36] .


   Side Effects of Immunosuppression Top


The long-term outcome following liver transplantation is also related to the long-term effects of immunosuppression. Acute hypertension posttransplant is related to therapy with steroids, cyclosporin and tacrolimus. In 75% of children this tends to be short term and related to the degree of immunosuppression. As indicated above, growth failure and stunting secondary to steroid therapy has a significant effect on the ability to regain normal height and nutritional rehabilitation. Both hirsutism and gingival hyperplasia, which are recognized side effects of cyclosporin, are dose related. Although not life threatening these cosmetic side effects have an important effect on quality of life particularly in adolescence.

The development of nephrotoxicity with both cyclosporinand tacrolimus is inevitable and may be exacerbated by pretransplant renal dysfunction or hepatorenal syndrome. Adult experience in liver transplant recipients has shown that chronic renal failure posttransplant may develop in approximately 5% of patients some of whom required renal transplantation [37] . In a large study of 221 children [38] the incidence of acute renal failure posttransplant was 6.2% but increased the mortality rate in this group to 85%. Early postoperative hypertension was seen in 65% of children but persisted in only 28%. Long-term renal dysfunction developed in approximately 30% of children at some time posttransplant but was not completely related to cyclosporin dosage, increased intensity of immunosuppression for rejection or the association of other nephrotoxic drugs such as antibiotics. The incidence of renal failure may be higher in children with diseases such as tyrosinemia type I who not only have renal dysfunction pretransplant but has continued production of the toxic metabolites, succinyl acetone, by the kidney posttransplant [39] .


   Assessment of Quality of Life Top


There is increasing demand for outcome analysis, which includes quality of life, and financial analysis following liver transplantation. Although no data are available for pediatric survivors of liver transplantation, a number of recent studies have documented an improvement in the health related quality of life (QOL) after liver transplantation in adults demonstrating an improvement in social functioning and mental health [40] , an improvement in sexual relationships and domestic environment [41] . Although most adult recipients indicated an improved quality of life compared to pretransplant factors, the health related QOL scores were less than the general population [42] . The cost effectiveness of liver transplantation remains to be proven in either adults or children.


   Conclusion Top


Liver transplantation for acute or chronic liver failure is effective treatment, which should restore good quality of life to over 80% of pediatric recipients. Technical advances in both medical and surgical expertise have improved both survival and quality of life for children undergoing liver transplantation in the 1990's. Following the liver transplant procedure, it is important to emphasize the return to normal life for both child and family while recognizing the necessity for continued counseling and support. The long-term outlook for children receiving liver transplantation in the 21 st century may be limited by organ donor shortages, the side effects of immunosuppressive drugs and the potential development of posttransplant lymphoproliferative disease or other tumors. Further research and development are required to answer the above problems and in particular to develop new more specific immunosuppressive drugs for the treatment of rejection.

 
   References Top

1.Kelly DA. Current results and evolving indications for liver transplantation in children. J Paed Gastroenterol Nutriti1998; 27: 214-21.  Back to cited text no. 1    
2.Beath SV, Brook GD, Kelly DA et al. Successful liver transplantation in babies under 1 year. BMJ 1993a; 307: 825-8.  Back to cited text no. 2    
3.Goss JA et al. Liver transplantation for fulminant hepatic failure in the pediatric patient. Arch Surg 1998; 839-44.  Back to cited text no. 3    
4.Hood JM, Kope LJ, Peters RC et al. Liver transplantation for advanced liver disease with alpha- l-antitrypsin deficiency. N Engl J Med 1980; 302: 272-5.  Back to cited text no. 4    
5.Mohan N et al. Inidcations and outcome of liver transplantation in tyrosinaemia type I. Eur J Pediatri, 1999 (in press).  Back to cited text no. 5    
6.Paradis K, Weber A, Scidman EG et al. Liver transplantation for hereditary tyrosinaemia: the Quebec experience. Am J Hum Genet1990; 47: 338-42.  Back to cited text no. 6    
7.Rela M, Heaton ND, Vougas V et al. Orthotopic liver transplantation for hepatic complications of Wilson's disease. Br J Surg 1993; 80: 909-11.  Back to cited text no. 7    
8.Kelly DA. Organ transplantation for inherited metabolic disease. Arch Dis Child 1994; 71: 181-3.  Back to cited text no. 8    
9.Jamieson NV. The results of combined liver/kidney transplantation for primary hyperoxaluria type 1: timing and preliminary results. Journal of Nephrology 1998; 11: 46-8.  Back to cited text no. 9    
10.Whitington PF, Alonso EM, Boyle JT et al. Liver transplantation for the treatment of urea cycle disorders. J of Inherited Metabolic Disease 1998; 21 Suppl 1: 112-8.  Back to cited text no. 10    
11.Beath S, Kelly DA, Booth I. Nutritional support in children with liver disease. Arch Dis Childhood 1993b; 307: 825-8.  Back to cited text no. 11    
12.Moukarzel AA, Najm I, Vargas J, McDiarmid Sv, Busuttil RW, Ament ME. Effect of nutritional status on outcome of orthotopic liver transplantation in pediatric patients. Transplant Proc 1990; 22: 1560-3.  Back to cited text no. 12  [PUBMED]  
13.Chin SE, Shepherd RW, Cleghorn GJ. Survival, growth and quality of life in children after orthotopic liver transplantation: A 5 year experience. J Paediatr Child Health 1991; 27: 380-5.  Back to cited text no. 13    
14.Andrews W, Sommerauer J, Roden J, Andersen J, Conlin C, Moore P. 10 years of pediatric liver transplantation. J Ped Surg 1996; 31: 619-24.  Back to cited text no. 14    
15.Rodeck B, Melter M, Hoyer PF, Ringe B, Brodehi J. Growth in long term survivors after orthotopic liver transplantation in childhood. Transplant Proc 1994; 26: 165­6.  Back to cited text no. 15    
16.Holt RI et al. Orthotopic liver transplantation reverses the adverse nutritional changes of end stage liver disease in children. Am Journ of Clin Nut, 1997; 65: 534-42.  Back to cited text no. 16    
17.Kelly DA. Nutritional factors affecting growth before and after liver transplantation. Pediatric Transplantation 1997; 1: 80-4.  Back to cited text no. 17  [PUBMED]  
18.Kelly DA. Posttransplant growth failure in children. Liver Transplantation and Surgery 1997; 3: 1-9.  Back to cited text no. 18    
19.Sama S, Sipila I, Jalanko H, Lame J, Holmberg C. Factors affecting growth afted pediatric liver transplantation. Transplant Proc 1994; 26: 161-4.  Back to cited text no. 19    
20.Robinson I, Gabrielsson B, Klaus G, Mauras N, Holmberg C, Mehis O. Glucocorticoids and growth problems. Acta Paediatr Suppl 1995; 411: 81-6.  Back to cited text no. 20    
21.McKieman PJ, Thomson JM, Dodge JA, McCraken KJ, Guiney EJ, Glasgow JFT. Increased energy expenditure in extra hepatic biliary atresia. J Pediatr Gastroenterol Nutr 1991; 13: 318.  Back to cited text no. 21    
22.Codoner-Franch P, Bernard O, Alvarez F. Long-term follow up of growth in height after successful liver transplantation. J of Pediatrics 1994; 124: 368-73.  Back to cited text no. 22    
23.Dunn SP, Falkenstein K, Lawrence JP et al. Monotherapy with cyclosporine for chronic immunosuppression in pediatric liver transplant recipients. Transplantation 1994; 57: 544-7.  Back to cited text no. 23    
24.Superina R, Acal L, Bilik R, Zaki A. Growth in children after liver transplantation on cyclosporin alone or in combination with a low dose Azathioprine. Transplant Proc 1993;25:2580.  Back to cited text no. 24  [PUBMED]  
25.Sama S, Siplia I, Vihervuori E, Koistinen R Holmberg C. Growth delay after liver transplantation in childhood: studies of underlying mechanisms. Pediatric Research 1995; 38: 366-72.  Back to cited text no. 25    
26.Cardona A, Houssin D, Gauthier F et al. Liver transplantation in children with Alagille syndrome - a study of 12 cases. Transplantation 1995; 60: 339-42.  Back to cited text no. 26    
27.McDiarmid SV, Gombein JA, Previn J et al. Factors affecting growth after pediatric liver transplantation. Transplantation 1999; 67: 404-11.  Back to cited text no. 27    
28.Laifer SA, Guido RS. Reproductive function and outcome of pregnancy after liver transplantation in women. Mayo Clin Proc 1995; 70: 388-94.  Back to cited text no. 28  [PUBMED]  
29.Cundy TF, O'Grady JG, Williams R. Recovery of menstruation and pregnancy after liver transplantation. Gut 1990; 31: 337-8.  Back to cited text no. 29  [PUBMED]  [FULLTEXT]
30.Casele HL, Laifer SA. Pregnancy after liver transplantation. Seminars in Perinatology 1998; 22: 149-55.  Back to cited text no. 30  [PUBMED]  
31.Zerner J, Doil KL, Drewry J et al. Intrauterine contraceptive device failures in renal transplant patients. J Reprod Med 1981; 26: 99-102.  Back to cited text no. 31    
32.Stewart S, Hiltebeitel C, Nici J, Waller D, Uauy R, Andrews W. Neuropsychological outcome of pediatric liver transplantation. Pediatrics 1987; 87: 367.  Back to cited text no. 32    
33.Stewart SM, Uauy R, Waller D, Kennard B, Benser M, Andrews W. Mental and motor development, social competence and growth one year after successful pediatric liver transplantation. J Pediatrics 1989; 114: 574.  Back to cited text no. 33    
34.Van Mourik IDM. Long term nutrition and neuro developmental outcome of liver transplantation in infants aged less than 12 months. J Paed Gastroenterol & Nutrition 1999 in press.  Back to cited text no. 34    
35.Wayman KL, Cox KL, Esquivel CO. Neurodevelopmental outcome of young children with extrahepatic biliary atresia I year after liver transplantation. Joum of Peds 1997; 131(6): 894-8.  Back to cited text no. 35    
36.Stone RD, Beasley PJ, Treacy SJ, Twente AW, Vacanti JP. Children and families can achieve normal psychological adjustment and a good quality of life following pediatric liver transplantation: a long-term study. Transplantation Proceedings 1997;29:1571-2.  Back to cited text no. 36    
37.Fisher NC, Nightingale PG, Gunson BK, Lipkin GW, Neuberger JM. Chronic renal failure following liver transplantation. Transplantation 1998; 66: 59-66.  Back to cited text no. 37    
38.Bartosh SM, Alonso EM, Whitington PF. Renal outcomes in pediatric liver transplantation. Clin Transplantation 1997; 11(5 Pt 1): 354-60.  Back to cited text no. 38    
39.Tuchman M, Freese DK, Sharp HL et al. Contribution of extrahepatic tissues to biochemical abnormalities in hereditary tyrosinaemia type 1: study of three patients after liver transplantation. J Paediatr 1987; 10: 339-403.  Back to cited text no. 39    
40.Hellgren A, Berglund B, Gunnarsson U, Hansson K, Norberg U, Backman L. Health-related quality of life after liver transplantation. Liver Transplantation and Surgery 1998; 4(3): 215-21.  Back to cited text no. 40    
41.Geevarghese SK, Bradley AE, Wright JK et al. Outcomes analysis in 100 liver transplantation patients. American Journal of Surgery 1998; 175(5): 348-53.  Back to cited text no. 41    
42.Bryan S, Ratcliffe J, Neuberger JM, Burroughs AK, Gunson BK, Buxton MJ. Health-related quality of life following liver transplantation. Quality of Life Research 1998; 7(2): 115-20.  Back to cited text no. 42    

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Correspondence Address:
Deirdre A Kelly
Consultant and Reader in Pediatric Hepatology, Birmingham Children's Hospital NHS Trust, Diana, Princess of Wales, Streethouse Lane, Birmingham, B, 6NH
United Kingdom
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Source of Support: None, Conflict of Interest: None


PMID: 19861759

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