Pediatric liver transplantation : The Indian perspective

Symposium : Pediatric Surgery Indian J Pediatr 1996; 63 : 751-760

Pediatric Liver Transplantation : The Indian Perspective

V. Bhatnagar

Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi

Abstract. Liver transplantation is now the accepted treatment for end stage liver disease, hepatic- based inborn errors of metabolism and Iocalised primary hepatic malignancies. In children the commonest indication is biliary atresia. Innovations in surgical techniques, particularly liver reductions/splits and living related transplants have not only shortened the waiting period but have improved the results of surgery as welt. The long term survival for pediatric liver transplant recipients in most large series from the Western world is more than 85%. Treatment protocols for ITU care of donors and recipients, anaesthetic care during surgery and post-operative immunosuppression are available. A country like India has a crying need for the development of facilities for liver transplantation in children but a number of factors have hampered the progress. The cost of surgery and post-operative immunosuppression and attitudes on life and death issues have been the greatest impediment. A few organisational details have also to be addressed to in order to minimise interdepartmental clashes of interest. It is hoped that a viable programme would soon be available for the children in India. (Indian J Pediatr 1996; 63 : 751-760)

Key words: Liver failure; Chronic liver disease; Liver transplantation, Children

The practice of h u m a n liver t ransplanta- tion started in the 1960s and since the 1970s it has been the accepted m o d e of t reatment for all end stage liver diseases, hepatic based inborn errors of metabol ism and malignancies restricted to the liver. Liver t ransplantat ion is a well establ ished clinical service in all deve loped countr ies and in m a n y deve lop ing countr ies as well 1-z. Liver t ransplantat ion has not ye t become a clinical service in India, al though it has shown remarkable progress in m a n y scientific fields.

The need for a pediatric l iver transplantation facility

The majori ty of children who require liver

Reprint requests : Dr. V. Bhatnagar, Associate Professor, Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi-ll0 029.

transplantation have end stage liver disease from biliary atresia or post-necrotic cirrhosis. It is est imated that there would be more than 100 new pediatr ic cases of end stage liver disease, metabolic disor- ders and malignancies requiring liver transplantation in the state of Delhi every year. Cases wou ld also be referred from not only surrounding areas but from dis- tant places as well once a programme gets going.

The need for a separate pediat r ic l iver transplant service

The pre-operative, intra-operative and post-operative care of children undergoing surgical procedures is very different from that of adults because of basic physiological differences. This has been the rationale for creating pediatric surgery as a separate

752 THE INDIAN JOURNAL OF PEDIATRICS 1996; Vol. 63, No, 6

speciality 3. Liver t ransplantat ion in children is also very different from adults because of a n u m b e r of reasons. The spec- trum of diseases is different; requirements for pre-operat ive, intra-operative and post-operative care are variable because of the unique age related physiological considerations; operat ive procedures for children demand technical innovations spe- cifically tailored for them; and the management of pos t -opera t ive complications and sequelae require specialised skills in pediatric surgery and pediatr ic gastroen- terology. Hence, pediatric liver transplantation needs special at tention ".m terms of organisational details.

Human organ donation for transplantation

Human organs can be transplanted either from brain stem dead (heait beating) donors or from living donors. H u m a n anatomy allows only one kidney and parts of the liver and bowel to be taken from a :lying donor. Ethical considerat ions had not prevented the commercial isat ion of kidney donation in India (and many other developing countries) till the formation of an organ donat ion law which prohibits commercialisation of h u m a n organs for transplantation.

Lawful cadaveric organ retrieval

India did not have a brain stem death law till recently. It was passed by Parliament in mid-1994 but was enacted only in early- 19954. Cadaveric liver transplantation was, therefore, not legally possible in India all this while. Now that it is lawful, cadaveric organs can be harves ted for transplantation.

Organisation of a cadaver based transplant programme

Liver transplantation demands a very high level of infrastructure for diagnostic facilities, patient monitoring and intensive care and interdisciplinary co-ordination. The organisational set-up in the Western world revolves a round the Transplant Co- ordinator (TC) who is usual ly a t rained nurse bu t has opted to specialise in this field. In India there is immense scope for this kind of work and even medical ad- ministrators could deve lop the base for this. There is a Regional (RTC) and a Local (LTC) co-ordinator and the entire multi-organ t ransplant service depends on them. The RTC liases with the donor 's family for organ donat ion and co-ordinates the mult i -organ retrieval by the heart, liver and kidney teams in the hospital where the donor is s i tuated and after the organ har- vest the RTC is responsible for the final preparat ion of the body before handing it over to the family for the final rites. The LTC co-ordinates the activities for the recipient procedure. The RTC and LTC have to work in tandem s .

In India, k idney t ransplantat ion has been practised for three decades and heart t ransplantat ion for the past two years bu t all these have been done without a special- ist TC - RTC or LTC. This work has been handled b y the doctors themselves and this is possibly one of the reasons for the absence of a cohesive organ transplantation p rogramme in this country. For a viable nation-wide programme or even a regional programme the co-ordination has to be done by a full-time TC and not part- time by a doctor who in any case has h is / her hands full with other responsibilities. Personali ty clashes, which are all too fre-

1996; Vol. 63. No. 6 THE INDIAN JOURNAL OF PEDIATRICS 753

quent in our country and often prove to be counter -product ive , will also be avoided by the services of the TC.

T h e d o n o r

The d o n o r for pediatric liver t ransplant may be either cadaveric (fulfilling criteria for bra in stem death) or living related (parentage should be genetically proven). The b lood g roup of the donor and recipient should ideally be identical but compat- ible blood groups may also be acceptable 6.

The cadaveric donor briefly should have normal liver function, not have any malignancy, be free from sepsis and have-a normal viral profile, and above all should have been haemodynamicaUy stable before and after brain death 7.

The living related donor briefly should also be healthy and have vascular anatomy which w o u l d allow left lateral segment- ectomy without technical difficulty so that the donor is not placed unden risk 8.

L I V E R R E T R I E V A L

The prerequis i tes for the donor operat ion are summar ised in Table 1. The surgery of liver retrieval is technically demanding because the entire success of the t ransplant d e p e n d s on the quali ty of the graft ob- tained and the integrity of the afferent and efferent vasculatureL Organisation of port- able sets for the operation has been done in our Depar tment /Hospi ta l . It is possible to go to another hospital for the liver re- t r ieval bu t non-uniform theatre facilities and s t andards are the biggest deterrants. The other opt ion is to t ransport a brain dead donor to the recipient hospital.

Liver retrieval dur ing a mult i -organ ha rves t also has its problems. Some car-

TaBL~ 1. Check list for donor surgery.

1. Declaration of brain stem death by competent authority.

2. Consent for organ donation by a responsibe family memebr.

3. History of alcoholism, drug abuse or past illness in donor,

4, Intensive care unit charts for donor management before and after brain death

5. Drug charts for dose and duration of vasoactive drugs.

6. Virology screening for HBV, HCV, CMV, EBV and HIV.

7. Liver function tests. 8. Septic screening.

diac surgeons prefer the use of a cardio- pulmonary bypass machine. This often in- terferes with adequate liver perfusion and may result in a sub-optimal graft.

Core cooling is a very important aspect of the surgery and is done by perfusion of preservative solutions via the portal vein and the aorta. The currently popular solutions for infusion dur ing the retrieval are the University of Wisconsin (UW) and Marshal's solutions. These solutions allow storage of the liver for engraftment up to 18 hours after the retrievaP ~ However , these solutions are very expensive - a one litre vac of the UW solution can cost Rs. 5,000-6,000 and Marshal 's can cost up to Rs. 1,000-2,000. Approximately 4 litres each may be required in one donor operation (Rs. 24,000-32,000). These solutions are also not a lways stocked by the chem- ists due to a very short shelf life and may have to be procured by direct purchase from abroad. Another preservative solution - the Euro-Collin's (EC) is available in India and costs approximately Rs. 2,500 per I litre vac, but affords a cold

754 THE INDIAN JOURNAL OFPEDIATRICS 1996; Vol. 63. No. 6

ischaemia t ime of abou t 8 hours only n. In addi t ion to these so lu t ions a lot of o ther disposable i tems and d rugs are n e e d e d in or after the operat ion, the total cost of which would be approximately Rs. 40,000- 50,000. The cost could b e significantly lower in living related donor operation because of the lower requ i rements of these preserva t ive solut ions - on an average only one litre of U W solu t ion w o u l d be needed per operation.

Liver preservat ion

The aim of l iver preserva t ion is to con- serve its myr iad synthetic, catabolic, storage and excretory fundtions which are es- sential for successful ou tcome after l iver transplantat ion. This complexi ty of l iver function d e m a n d s high energy consump- tion, even dur ing hypothermic storage. It also leads to p roduc t ion of potent ia l ly toxic intermediates as electron transport in mi tochondr ia and the endoplasmic e t i cu lum cont inues dur ing s torage without molecular oxygen. Consequently, suc- tessful p reserva t ion of livers is more demanding than for other grafts. Graft injury may occur at four stages dur ing liver transplantation : before hepatec tomy (pre- preservation), dur ing organ s torage (cold preservation), dur ing implanta t ion (rewarming) and upon restorat ion of b lood /oxygen supply (reperfusion) 9.

T h e rec ip ient

The majori ty of children requir ing liver t ransplanta t ion have biliary atresia and they have usually undergone previous surgery. Other major indications include cirrhosis secondary to hepatit is, a-1- ant i t rypsin deficiency, Alagille's syn- d rome etc., metabolic d isorders like Crigler-Najjar syndrome, glycogen storage disease etc. and hepatoblastoma x2 (Table 2). Preliminary evaluation should be detailed and pains taking (Table 3). Pre-operat ive care will be required for pat ients with fu lminant hepat ic failure and those with acute decompensat ion. Children in fulminant hepatic failure may require pre- opera t ive d ia lys i s /p lasma exchange to correct renal failure and coagulopathy, and insert ion of intracranial pressure probe for intra-operative monitoring.

A n a e s t h e t i c preparat ion and intraoperat ive m a n a g e m e n t

The pre -opera t ive assessment should be a longwi th the physicians and surgeons and special evaluat ion is requi red for renal, respiratory, cardiovascular and neuro- logical functions.

Minimum requirements in the operation theatre include arterial, central and pe- r ipheral venous lines, endotracheal tube, nasogastr ic tube, urethral catheter and

T^BL~. 2. Indications for Liver Transplantion

Cholestatic diseases - Biliary atresia - Scl. cholangitis - Alagille's syndrom~ - Fam. cholestasis

Metabolic diseases - Byler disease - Wilson's disease - a-l-AT deficiency - Crigler-Najjar - Glycogenosis I - Tyrosinemia

Miscellaneous -- Chr. act. hep. -- Ac. hep. fail. - Neonat. hep. -- Tumours - Budd-Ch. syndr. -Cong. hep. fib.

1996; VoL 63. No . 6

TABL~ 3. The Preoperative Evaluation for Liver Transplant R e c i p i e n t s

1. Assessment of growth, size and nutri- tional status

2. Haematological studies and coagulation profile

3. Urinalysis 4. Renal biochemistry 5. Liver function tests 6. Biochemical work-up-glucose, electro-

lytes, inorganic phosphates, calcium 7. Acid base and blood gas assessment 8. imaging studies depending on the patho-

logical diagnosis. The following may be required - chest X-ray, abdominal ultra- sound with doppler, abdominal CT

9. Virological screening - CMV, EBC, VZ, Adenovirus, HBV, HCV

10. Bacteriological screening- throat, nasal, skin swabs etc.

temperature probe. The anaesthetic drugs include fen tanyl , pancuronium, suxa- methonium, atropine, atracurium, dopamine, adrenaline, CaCI 2, KC1, NaHCO3, mannitol, dextrose, methyl prednisolone and antibiotics.

The anaesthesia is based on opiate anal- gesia supp lemen ted with isoflurane sup- pl ied in an oxygen air mixture. Atracurium is used for muscle relaxation. Ni t rous oxide is avoided because of the potential for bowel distension. Nasal intubation is preferred. The following are very important :

- invasive hemodynamic monitoring; - vascular access for rapid infusion; - nasopharyngeal and rectal tempera-

ture probes; and - oximetry, capnography, frequent

THE INDI~I JOURNAL OF PEDIATRICS 755

hematocrit, coagulation profile fPT) and electrolyte monitoring.

Fluid replacement should be rapidly ad- justed. Temperature homeostasis should be done by use of radiant heaters dur ing induction, warming mattress, warming and humidification of anaesthetic gases and warming of all intravenous fluids. Veno-venous bypass is seldom required 13.

T h e surgery of liver transplantation

The operative techniques d e p e n d on whether the donor was size matched or not and whether liver reduction would be required. This would also determine the durat ion of bench surgery and cold ischaemia time. Liver transplant is done is the following phases : hepatec tomy, anhepatic period, grafting, reperfusion, haemostatis. Magnification may be required during arterial and biliary recon- struction. In general, facilities like rapid in- fusions, veno-venous bypass and cell sav- ers are not required during pediatric liver transplant. Specific requirements include ultrasonic dissector and argon beam co- agulator in addit ion to some ~pecial ised operative instruments and suture material.

The recipient operation calls for a high degree of precision in very quick t ime on the par t of the surgeon and a constant competent vigil and homeostatic measures on the part of the anaesthetist. Hepa - tectomy is per formed through a bilateral sub-costal incision. The donor's IVC above and be low the liver and portal vein are anastomosed to the recipient 's corre- sponding vessels and the donor ' s hepat ic ar tery/coel iac axis is anastomosed to the donor 's hepatic artery or the aorta via a vascular conduit. Bile duct anastomosis is

756 THE INDIAN JOURNAL OF PEDIATRICS 1996; Vol. 63. No. 6

ei ther duct to duct or via a Roux-en-Y anastomosis. Haemostasis at the end of the operation is time consuming because there is a significant coagulopathy which takes some time to settle. The competence of In- d ian surgeons, anaesthetists, operat ing room personnel , pediatr icians etc. have never been in doubt, although there is general shortage of first hand experience. The support ive services e.g. laboratories, blood banks, facilities for monitoring blood levels of drugs etc. need to be developed fur- ther so that they are easily available and affordable.

Improvements in operative techniques have al lowed major innovations 14.1s. These are (i) reduced liver t ransplantat ion (part of the liver is used as a graft) - this is particularly useful in children where an adult liver can be reduced and transplanted; (ii) split liver transplantation (the liver can

e split into the right and left lobes and oth can be used in different recipients) -

this is particularly useful when organs are not freely available and one donor organ can be used for two recipients, ideally one child wi th the left lobe or the left lateral segment and one adult with the right lobe; (iii) auxiliary orthotopic liver transplantation (the recipient's left lobe can be excised and a size matched left lobe can be transplanted) - this is particularly useful in cer- tain non-cirrhotic hepatic based inborn errors of metabol ism e.g. the Crigler-Najjar syndrome; and (iv) living related liver t ransplanta t ion (a relative donates a part of the liver, usually the left lobe, for the recipient) -- this is ideal for a country like ours where donor management may not be either uni form or adequate. Living related liver transplantation will at least en- sure a proper graft a l though donor mor- bidi ty and mortal i ty are the main ethical

considerations. For children in India, living related liver transplantation seems to be the ideal choice 16. However; the experience in the past two years of offering this mode of treatment has been something of a disappointing revelation on the prevailing atti tudes in our society -- the average In- dian family seems to find it cheaper/more cost effective to produce another child rather than risk so much money on a child who needs a liver transplant.

The immediate catastrophic complications are due to thrombosis of the hepatic artery or the portal vein and outflow ob- struction at the caval anastomosis. Biliary complications are usually not fatal but add to the morbidity.

The inputs required for pediatric liver transplantation are much less than those for adults - veno-venous bypass is not es- sential; other equipment like rapid infusion pumps can possibly be done without; blood and blood product requirement is less; the cost of suture material is less; lesser quantities of preservative solutions are required; immunosuppressive drugs are also used in smaller doses (the total reduction of cost may be as much as Rs. 50,000-75,000 per transplant). Yet the total cost of liver transplant in a child may be Rs. 75,000-1,00,000.

Post-operative intens ive care

This is as crucial as the surgery itself. It can be arranged under the premises of the anaesthetists, the hepatologists or the pediatric surgeons but it should be a team approach with the patient's welfare being the foremost consideration.

Facilities for the following are manda- tory : ventilatory support with monitoring of acid-base and gases, monitoring of heart

1996; Vol. 63. No. 6 THE INDIAN JOURNAL OF PEDIATRICS 757

rate, respiratory rate, arterial, central venous and pulmonary wedge pressures, core and peripheral temperatures, oxygen saturation, intake-output balance, management of drains and catheters and monitoring of haematological and b~iochemical pa- rameters and coagulation vrofile (Table 4).

Immunosuppression and follow-up

Since the introduction of cyclosporin-A most of the post-operat ive immunosuppressive regimens now are cyclosporin based and use methyl prednisolone and azathioprine in combination but FK506 is now being increasingly used~L Cy- closporin-A and methyl prednisolone are being freely marketed in India bu't are expensive. The cost of treatment is likely to reduce once the drugs are manufactured locally. Immunosuppress ion has to be life long as per current knowledge but some research is now being directed towards discontinuing it 10 years after the transplantation TM. At today 's prices the immunosuppression for a 10-15 kg child would cost approximately Rs. 2,000-3,000 per month. FK506, which has been shown to be more effective than cyclosporin is not available in India and has to be imported from Japan if necessary. OKT3, another second line immunosuppress ive drug is being marketed in India but one course is likely to cost approximately Rs. 10,000.

Ideally the dosage of these drugs should be monitored with blood level estimations bu t it can be done with renal functions also. Episodes of rejection should be con- firmed by histopathologic examination of liver biopsy specimen and treated by high dose prednisolone or increasing cyclosporin-A. If FK506 and OKT3 are available then treatment of rejection will become

more effective. Constant monitoring for bacteriological, viral and fungal infections should be done and treatment inst i tuted accordingly. In the immediate post-operative per iod Doppler ul t rasound will be necessary for assessment of vascular anastomosis potency.

The follow-up should be carried out jointly by the pediatric surgeons and pediatric hepatologists.

Detailed protocols a l ready in use at Khag's College Hospital, London, for management of liver transplantation pat ients during surgery and post-operat ively are available and have been used by the au- thor while there. It is p roposed to follow the protocols for patient management , as far as possible, making changes to suit our conditions.

Post transplant quality of life

The first year after the transplant is a diffi- cult period in the patient 's life because of frequent rejection episodes, infective complications and repeated hospital visits. Later, the patients lead a near normal life and most survivors are able to re turn to their pre- transplant vocations. In estab- lished centres the immediate survival following liver transplant is about 90% and 5 year survival for children is bet ter than that for adults.

THE INDIAN REALITY

The present situation in India and the vari- ous problems have been highlighted where ever relevant. The Indian perspect ive can be summarised as follows :

. It is est imated that approximate ly 2 lacs patients with end stage liver disease die every year in India 19,2~


TAB~ 4. Outline of Post-operative Managment

1. Ventilatory support (24-26 hrs) 2. Arterial line 3. Multilumen CVP line

4. Peripheral line for blood and blood product transfusion

5. Core and peripheral temperature 6. ECG, pulse oximetry

7. Urinary catheter and drain output

8. Hourly input, output and fluid balance 9. Baseline haemogram, PT, urea, Na § K ~, Ca +, albumin, CXR

10. Medications - - Antibiotics - Cefotaxime + Amikacin + Metronidazole - - Nystatin 50,000 u TDS NG if weight < 10 kg; 1,00,000 u TDS NG if weight > 10 kg - - Ranitidine 1 mg/kg /dose - T D S - - Methyl prednisolone 2 mg/kg/dose - O D

- - Azathioprine 1.5 mg/kg /dose - O D - - Vitamin K 1-5 mg - OD

Folic acid 1-5 mg - OD - - Cyclosporin I mg/kg /dose - BD W (start after 24 hrs)

Morphine 20-60 p~g/kg/hour Midazolam 50-300 ~g /kg /hour Atracurium 300-800 ~g /kg /hour

- - Dopamine 2-3 ~g /kg /min Heparin or Aspirin Fluconazole IV at the earliest indication of sepsis

11. Monitoring 1 h o u r l y - BP, HR, ECG, CVP, Temp, 02 sat, fluid balance 4 h o u r l y - ABG, Hb, PT, Na*, K § Ca*, blood sugar, albumin

- - 6 hourly - gastric pH - - Daily - CXR, LFT, weight, c /s ET aspirate and wound drain

12. Fluid infusion maintenance fluids as 10% dextrose 4.5% albumin if CVP < 6 mmHg replace wound and drain losses with albumin

- - rep}ace NG losses with normal saline - - whole blood if PCV < 0.35

Na, K depending on serum levels Ca I mmol /kg/day, Mg 0.5 mmol /kg/day

13. Monitoring graft function - indicators of poor function - - plasma bicarbonate < 24 mmol/L - - high or rising serum K, low blood sugar

deranged PT (at 4 hrs > immediate post-op) high OT/PT, rising bilirubin

- - U/S scan and doppler for vascular patency

1996; VoL 63. No. 6 THE INDIAN JOURNAL OF PEDIATRICS 759

2. N o ins t i tu t ion in India p r o v i d e s l iver t r ansp l an t as a clinical se rv ice although the AIIMS, N e w Delhi and two centres in Madras have unsuccessful ly p e r f o r m e d l iver t ransplant . It is no t clear as to h o w many institutions in In- dia h a v e e i the r the in f r a s t ruc tu re or t rained m a n p o w e r to start such a pro- g ramme.

3. There is a genera l lack of a w a r e n e s s among the publ ic as well as the medi - cal f r a t e rn i t y abou t l iver t r ansp lan ta - tion as possible mode of t reatment.

4. Parenta l a t t i tudes towards chi ldren as l iver t r a n s p l a n t rec ip ients h a v e b e e n ra the r ind i f fe rent . For the b r ead win- ner of the fami ly even the most expensive a n d complex t r ea tmen t w o u l d be u n d e r t a k e n even if it means selling off the ent ire family assets. The same does not ho ld t rue for the child. A la rge n u m b e r of famil ies w o u l d op t for a cheaper a l ternat ive - p roduce ano the r child.

5. The l aw for cadaver ic o rgan h a rv e s t - ing has o n l y recent ly been e n a c t e d which has m a d e this legal. But at t i- tudes take m u c h longer to change a n d p e r m i s s i o n b y the re la t ives for o r g a n d o n a t i o n f r o m hear t bea t ing b r a i n d e a d d o n o r s will take m a n y yea r s to b e c o m e the ' done thing ' . The m e d i a has n o t ye t t aken up this issue for a publ ic i ty bl i tz or for mass educat ion.

6. The cos t of l iver t ansp lan ta t ion in In- dia has b e e n e s t ima ted to be Rs. 1,00,000-2,00,000 for an adu l t a n d about half of that for a child. This is far less t han w h a t it costs in the USA (ap- p r o x i m a t e l y $ 2,00,000) or UK (ap- p r o x i m a t e l y s 75,000) bu t it is still too m u c h for an average pat ient . Unless i n su rance companies , g o v e r n m e n t

agenc ies a n d socia l s e rv ice o rgan i sa - t ion p lay a v e ry ma jo r role it is doub t - ful that l iver t r ansp l an t a t i on will eve r become a viable p r o g r a m m e in India.

REFERENCES

1. Starzl TE, Demetrius AJ. Liver transplantation. A 31-year perspective. Chicago : Year Book Medical Publishers. Inc., 1990.

2. Williams R, Tan KC. Requirements of staff and facilities. In : Williams R, Heaton ND, Tan KC, eds. The Practice of Liver Transplantation. London : Churchill Livingstone, 1995 : 3-6.

3. Ports WJ. The Surgeon and the Child. Philadelphia : WB Saunders, 1959.

4. Ministry of Health and Family Welfare Notification. The Gazette of India. Part II, Section 3 (i), NO. 1995; 39 : 11-19.

5. Boyd F, Jackson M, Heaton ND. The role of the transplant co-ordinator. In : Williams R, Heaton ND, Tan KC, eds. The Practice of Liver Transplantation. London : Churchill Livingston, 1995 : 7- 10.

6. Tanaka K, Uemoto S, Tokunaga Yet al. Living related liver transplantation. Transplant Proc, 1992; 24 : 2252-2253.

7. Heaton ND, Tan KC. Retrieval team and national organisation. In : Williams R, Heaton ND, Tan KC, eds. The Practice of Liver Transplantation. London, Churchill Livingstone, 1995 : 11-16.

8. Broelsch CE, Lloyd DM. Living related donors for liver transplants. Adv Surg 1993; 26 : 209-231.

9. Rela M, Dunne JB, Tredger JM. Donor operation and organ preservation. In : Williams R, Heaton ND, Tan KC, eds. The Practice of Liver Transplantation. Lon- don, Churchill Livingstone, 1995 :-125- 134.

10. Todo S, Nery J, Yanaga K et al. Extended preservation of human liver grafts with UW solution. JAMA 1989; 261 : 711-714.


11. Badger IL, Buckels JAC. Hepatic allograft preservation. Br J Intensive Care 1991; 143-149.

12. Tan KC. Liver transplantation. In : Howard ER, ed. Surgery of Liver Disease in Children. Oxford Butterworth-Heine- mann, 1991 : 224-238.

13. Potter DR, Cottam S. Anaesthesia and intraoperative managment. In : Williams RM, Heaton ND, Tan KC, eds. The Prac- tice of Liver Transplantation. London : Churchill Livingstone, 1995 : 107-116.

14. Bismuth H, Houssain D. Reduced size orthotopic liver graft in hepatic transplantion in children. Surgery 1984; 95 : 367- 372.

15. Broelsch CE, Emond JC, Whitington PF, et al. Application of reduced size liver transplants as split grafts, auxiliary orthotopic grafts and living related seg- mental transplants. Ann Surg 1990; 212 : 368-377.

16. Bhatnagar V, Rela M, Heaton ND, Tan KC. Liver. transplantion from living related donors. Indian J Pediatr 1994; 61 : 387-392.

17. Batnagar V, Dhawan A, Rela Met aL Ex- perience with FK506 conversion therapy for liver allograft rejection in children. Gut 1994; 35 (12) : 21.

18. Starzl TE. The basis of graft acceptance. The David vervat lecture, XXXX1 Annual International Congress, The Brit- ish Association of Pediatric Surgeons, Rotterdam, The Netherlands, 29 June-1 July, 1994.

19. Naik SR, Bhandari M. Cadaver organ transplantat ion p rog ramme in India : Needs and difficulties. Indian J Gastroen- terol 1991; 10 : 1-3.

20. Mathur SK, Shah SR. Liver t ransplanta- tion. In : Chattopadhyaya TK, ed. GI Sur- gery Annual. Indian Association of Surgical Gstroenterology, 1995; 2 : 149-165.

Documents

Pediatric liver transplantation : The Indian perspective