Pediatric Liver Transplantation: small recipient < 10 Kg

Transcription

1 Pediatric Liver Transplantation: small recipient < 10 Kg Introduction The pediatric liver transplant evolved in the 1980s and became established in the 1990s. First successful pediatric liver transplant was performed in 1967 by Prof. Startz. There were rapid advances in adult transplantation throughout the 1970s. 1986, when most adult units claimed a 1 year survival rate of 80%, average 1 year survival rates in children were only 60% 1. Since then, there have been considerable advances in both medical and surgical management, with international 1 year survival rates from pediatric liver transplant in excess of 90% and 5-10 year survival rates of more than 80% 2. The success of this complex procedure has led to a significant increase in the number of children undergoing liver transplant world wide and has radically changed the prognosis of many babies and children dying of end-stage liver failure. In India, the liver transplant programme picked up only in 2000 s and gradually gained momentum. The growth has been very slow initially, as is expected in any new programme. However, over the last 4-5 years there has been a rapid growth in liver transplantation programme in India. More than a dozen liver transplant centers are now developed in our country but more than 50% of the liver transplants are carried out in a single center, Sir Ganga Ram Hospital, Delhi. Liver Transplant programme has really picked up in India and it is expected to have more new liver transplant centers in the country in the near future. However, unfortunately the pace in Government hospitals has been slow till now. Economic burden is a major set back in public sector hospitals. Indications for liver transplantation in children 1. Chronic Liver Failure 2. Acute liver failure 3. Certain Inborn Errors of Metabolism 4. Certain Hepatic Tumors Chronic Liver Failure Table 1 : Common causes of Chronic Liver failure requiring liver transplantation in children - Cholestatic liver disease Chronic hepatitis Biliary atresia Autoimmune Idiopathic neonatal hepatitis Idiopathic Alagille syndrome Postviral (hepatitis B, C, other) Progressive familial intrahepatic Cryptogenic cirrhosis cholestasis Fibropolycystic liver disease ± Caroli disease Nonsyndromic biliary hypoplasia Primary immunodeficiency Sclerosing cholangitis Metabolic liver disease α1-antitrypsin deficiency Tyrosinemia type I Cystic fibrosis Glycogen storage disease type IV 1

2 Acute Liver Failure Table - 2 : Acute Liver Failure requiring liver transplantation in children Fulminant hepatitis Autoimmune hepatitis Acetaminophen poisoning Viral hepatitis (A, B, C, or NA-G) Metabolic liver disease Fatty acid oxidation defects Neonatal hemochromatosis Tyrosinemia type I Wilson disease Halothane anesthesia Inborn Errors of metabolism A number of inborn errors of metabolism are secondary to hepatic enzyme deficiencies that do not lead to liver disease. Liver function is normal, but the enzyme deficiency leads to severe extrahepatic disease. The purpose of liver transplant in this group of diseases is to replace the missing hepatic enzyme to prevent or reverse extrahepatic disease. Table 3 Common causes of Inborn errors of Metabolism requiring liver transplantation Crigler-Najjar syndrome type I Familial hypercholesterolemia Organicacidemia Urea cycle defects Primary oxalosis Maple syrup urine disease Hepatic Tumors Table 4 Common cause of Hepatic tumors requiring liver transplantation Benign tumors : hemangiomas, hemangioendotheliomas, adenomas, focal nodular hyperplasia Unresectable malignant tumors : unresectable hepatoblastoma or hepatocellular carcinoma In this chapter we restrict our discussion to children with weight less than 10 Kg. Common causes in children less than 10 kg body weight which require liver transplantation are : A) Cholestatic liver disease: Biliary atresia Cholestatic liver disease is the commonest indication of liver transplantation in children. Of the Cholestatic liver disease, biliary atresia remains the main indication worldwide. Neonatal Cholestasis contributes to nearly 30% of the chronic liver disease in children in India and ~ 30% of neonatal cholestasis cases are due 2

3 to biliary atresia. Children who have biliary atresia constitute at least 50% of the pediatric liver transplant population. Kasai portoenterostomy should be the primary surgical intervention for all infants who have biliary atresia unless the initial presentation is at age greater than 120 days and the liver biopsy shows advanced cirrhosis. One of the major problems in our country is that there is a significant delay in the referral of these patients to tertiary referral centre and therefore, patients rarely benefit from a palliative Kasai s portoenterostomy. Patients who have progressive disease after a Kasai procedure should be offered early liver transplantation [1,2].Failure of the Kasai portoenterostomy can be manifest by various combinations of complications such as progressive jaundice, recurrent bacterial cholangitis, ascites, rapidly progressive portal hypertension, malnutrition, or progressive hepatic synthetic failure. Most require liver transplantation within the first 2 years of life. Children in whom biliary drainage has been established successfully or who have normal postoperative serum bilirubin levels may still develop progressive cirrhosis with eventual portal hypertension, hypersplenism, variceal hemorrhage, and ascites formation. The development of hepatopulmonary syndrome is increasingly recognized in long-term survivors and can occur with stable liver function. These children have undergone liver transplantation to avoid progressive hypoxia or fixed pulmonary hypertension. Approximately 20% of all patients who have biliary atresia may not require liver transplantation [3,4]. The sequential use of the Kasai procedure and liver transplantation optimizes overall survival and organ use [2,5]. On occasion, other cholestatic conditions, such as intrahepatic cholestasis syndromes like PFIC and Alagille syndrome may cause cirrhosis and require liver transplantation [6 8].Neonatal sclerosing cholangitis and Caroli disease may also present with decompensated cirrhosis in early infancy necessating liver transplantation. (B) Metabolic liver disease The common metabolic liver diseases in small children less than 10 Kg for which liver transplant is indicated are α1-antitrypsin deficiency, tyrosinemia type I, neonatal haemochromatosis, galactosemia and rarely organic acidemia, urea cycle defects and MSUD. Tyrosinemia type 1 is an autosomal recessive disorder of tyrosine metabolism, with a clinical presentation that includes both acute and chronic liver disease and multiorgan failure with cardiac, renal, and neurologic involvement. The management of this disorder has changed dramatically since the introduction of 2(2-nitro- 4- trifluoromethylbenzoyl)-1,3-cyclohexenedione (NTBC), which prevents the formation of toxic metabolites and produces rapid clinical and biochemical improvement. Liver transplant is now indicated only for those children who have a poor quality of life and do not respond to NTBC or in whom hepatic malignancy is thought to have developed 3. However in India because of the high cost of NTBC which needs to be imported and costs and >Rs. 50,000 a month,it is more practical to offer one time expense of liver transplantation. Neonatal haemochromatosis : It is the result of chronic in utero liver disease and present with decompensated cirrhosis but lesser elevation of aminotransferase levels. Timely administration of antioxidant cocktails containing desferroxamine, N-acetylcysteine, selenium, vitamin E, and prostaglandin E-1, even while awaiting confirmatory diagnosis, has salvaged selected infants. Failure to respond within 48 to 72 hours mandates transplantation. Galactosemia : Hereditary galactosemia is among the most common carbohydrate metabolism disorders and can be a life-threatening illness during the newborn period. 1,2,3 First described in a variant patient in 1935 by Mason and Turner, galactose-1-phosphate uridyltransferase (GALT) deficiency is the most common enzyme deficiency that causes hypergalactosemia. Untreated infants with severely deficient galactose-1-phosphate uridyltransferase (GALT) activity typically present with poor growth within the first 3

4 few weeks of life, jaundice, bleeding from coagulopathy,liver dysfunction and/or hepatomegaly,cataracts (sometimes as early as the first few days of life), lethargy,hypotonia,sepsis (E coli) etc. Treatment is elimination of galactose from the diet, diets without lactose or galactose, (Nutramigen, Pregestimil) continued for years, possibly for life. Mothers should be on a galactose-free diet during the subsequent pregnancy (symptoms present at birth might be modified). With early therapy, any liver damage which occurred in the first few days of life will nearly completely heal. C) Tumours: In a small child, hemangioendothelioma and giant cavernous hemangioma of liver can lead to haemodynamic instability and are an indication of liver transplantation. Occasionally, hepatoblastoma may present in early infancy and if both lobes are involved then transplantation is required instead of hepatectomy. Fig 1 : Primary Indications of Liver Transplantation in children in West n= 3, 998 pediatric patients, adapted from the European Liver Transplantation Registry, 2002 Criteria for listing for liver transplantation in chronic liver disease The major functions of the liver are: synthetic functions formation and excretion of bile metabolic functions like glucose homeostasis and metabolism of nitrogenous wastes and drugs immunological functions hemodynamic functions. Any patient with chronic liver disease who has clinically significant abnormalities in 2 or more areas will likely to be benefited from liver transplantation. The selection process 4

5 The primary aim of the evaluation process is to identify appropriate candidates for liver transplantation and to establish a pretransplantation plan. The timing of liver transplantation for children with chronic liver failure may be difficult. It must be remembered that a patient of chronic liver disease must be referred early to a liver transplant centre so that optimum timing for transplant can be decided before the complications of liver disease adversely impair the quality of child s life and before growth & development are irreversibly retarded. The primary evaluation identifies areas for intervention before transplantation to optimize success, such as nutritional improvement, immunizations and preventive dental care. In children who have acute liver failure or rapidly progressive deterioration, aggressive critical care intervention is essential to maintain other physiologic systems until a suitable donor organ can be found. There are certain parameters which are taken as a guide for listing for liver transplantation Lab Parameters : The most useful guide to the timing of liver transplant is provided by a variety of parameters that include A persistent rise in total bilirubin > 150 µmol/l (> 9 mg/dl), Prolongation of the prothrombin ratio international normalized ratio [INR] > 1.4), and A persistent fall in serum albumin to < 35 g/l. 7 Clinical Parameters : (A) Nutritional Assessment : Among the clinical parameters, one of the most important indicator for liver transplantation is nutritional assessment Serial evaluation of nutritional parameters is a useful guide to early hepatic decompensation. Progressive reduction of fat stores (measured by triceps skinfold or subscapular skinfold) or protein stores (measured by midarm circumference or midarm muscle area) despite intensive nutritional support is a good guide to hepatic decompensation. 8 Recently, the development of the PELD Score (PELD = pediatric end-stage liver disease) has confirmed these observations. 9 (B) Psychosocial development : Children with chronic liver disease may have both social and motor 10,11, 12 developmental delays that increase with time unless reversed following early liver transplant (C) Hepatic complications : Children with severe hepatic complications such as chronic hepatic encephalopathy, refractory ascites, intractable pruritus and recurrent variceal bleeding despite medical management should be referred immediately for transplant. In some patients hepatopulmonary syndrome develops secondary to pulmonary shunting and this is an important indication for liver transplantation. The clinical score used in chronic liver disease are child Pugh score and PELD score. PELD: Pediatric End-Stage Liver Disease. A disease severity scoring system for children under 18 years of age, designed to improve the organ allocation in transplantation based on the severity of liver disease rather than time on the waiting list. The PELD score is based on both laboratory data and growth data. The laboratory values are a patient's albumin, bilirubin, and international normalized ratio or INR (a measure of blood-clotting time). These values are used together with the patient's degree of growth failure to determine the PELD score Contraindications For Liver Transplant 1. Severe systemic sepsis (in particular, fungal sepsis) at the time of operation. 2. Malignant hepatic tumors with confirmed extrahepatic metastases Severe extrahepatic disease that is not considered reversible following liver transplant. This includes severe cardiopulmonary disease for which there is no possibility of corrective surgery or severe structural brain damage with a poor prognosis. 5

6 4. Multiorgan failure, especially owing to mitochondrial cytopathy In the respiratory chain defects like Alper s disease. 6. Autoimmune and hemolytic anemia in association with giant cell hepatitis is a rare and fatal disease in which there is a 100% recurrence rate post-transplant, and transplant is not recommended. 7. Brain dead Pre Transplant Evaluation The pre transplantation evaluation of the patient is particularly important and should include the following Assessment of the severity of the liver disease and the possibility for medical management Assessment of the technical feasibility of the operation Consideration of any contraindications Psychological preparation of the family and child The assessment has been tabulated in Table no.7 Table - 7 Pretransplant assessment Nutritional status Height, weight, triceps skinfold, midarm muscle area, midarm circumference Identification of hepatic complications Ascites, varices Cardiac assessment Electrocardiography, echocardiography, chest radiography, cardiac catheterization Respiratory function Oxygen saturation, ventilation-perfusion scan, lung function tests Neurologic and developmental assessment Electroencephalography, Bailey developmental scales, Stanford-Binet intelligence scales Renal function Urea, creatinine, electrolytes, urinary protein-to-creatinine ratio, chromium EDTA Serology Cytomegalovirus; Epstein-Barr virus; varicella-zoster virus; herpes simplex virus; hepatitis A, B, and C; HIV; measles Hematology Full blood count, platelets, blood group Radiology Ultrasonography of liver and spleen for vascular patency, wrist radiography for bone age and rickets, CT Scan angiography for vascular anatomy Dental assessment Preparations for liver transplantation Nutritional support It has been demonstrated with several studies that nutritional status at liver transplant is an important prognostic factor in survival. 17,18 In a child with weight less than 10 Kg, nutritional rehabilitation is the most important thing which should be taken care of. A high calorie feed (150 to 200% estimated average 6

7 requirement) is required with supplements. Additional calories are needed for catch-up growth if a significant deficit in weight is present. The infant formula can be mixed with less water to provide 24 or 27 kcal/oz. Alternatively, glucose polymers (8 cal/teaspoon ) or MCT (medium-chain triglyceride) oil (7.7 cal/ml) can be added to the standard 20 cal/oz dilution of the formula. Whenever possible, oral feeding is preferred, but with increasing anorexia and debilitation secondary to progressive liver disease, supplemental nocturnal nasogastric infusions may be required to meet caloric and fluid requirements and prevent or reverse inadequate weight gain, particularly in children awaiting liver transplantation. Protein is given at 1-2 gm/kg / day. The restriction of proteins is not recommended now. Table:8 Recommended medical management Vitamin A 10,000-15,000 IU/day Vitamin E IU/day Vitamin D IU/day of D2 or 3-5 µg/kg/day of 25 OH cholecalciferol Vitamin K mg Micronutrient Calcium, phosphate, or zinc supplementation deficiency Water soluble vitamins Twice the recommended daily allowance Retention of biliary Ursodeoxycholic acid, 15-20mg/Kg/day constituents Immunizations Most units consider live vaccines to be contraindicated after liver transplant because of the risk of dissemination secondary to immunosuppression. It is therefore better to complete normal immunizations before transplant. Varicella zoster, MMR vaccine can be given even at 9 months of age for the purpose of completion. Management of hepatic complications It is important to ensure that specific hepatic complications are appropriately managed while the patient waits for transplant. Recurrent variceal bleeding should be managed preferably with esophageal varix ligation than sclerotherapy. Intractable variceal bleeding may require the insertion of a transjugular intrahepatic portal systemic shunt. 15 Sepsis that includes ascending cholangitis and spontaneous bacterial peritonitis should be treated with broad-spectrum antibiotics, whereas in children awaiting transplant for acute liver failure, prophylactic antifungal therapy is essential. Ascites should be managed with diuretics and restriction of salt. Intervention with hemodialysis and hemofiltration should be considered if acute renal failure or hepatorenal failure develops. 16 Psychological Preparation Liver transplant is a major undertaking for the child and family; thus, psychological counselling, information giving, and preparation of the child and family are paramount using a skilled multidisciplinary team with play therapists, psychologists, and schoolteachers. 7

8 Liver transplant surgery The issues during liver transplantation are regarding the size of duct and the portal vein in such a small child as the size is very small and the anastomosis is difficult. The graft is a either cadaveric liver or a living related. In Cadaveric liver transplantation the liver of a brain dead person is used for transplantation. Cadaveric transplants could be: Whole graft : The entire graft is transplanted in the recipient. Reduced graft : When only a part of the cadaveric liver (i.e. right/ left/left lateral part) is used for the recipient Split graft : The shortage of suitable organs for young children led to development of split livers. The liver of the cadaveric donor is divided and used for two patients usually the right lobe for adults and left lobe for children. Table : 8 : Types of liver transplantation Cadaveric Whole graft Reduced graft Split graft Liver transplantation Living related Living related liver transplantation : This has been a further step to answer the shortage of organs for children. In living related liver transplantation, a part of the liver from a living related donor is used in the child. This procedure is more popular in India and Eastern countries like Japan and Korea where cadaveric liver transplantation has not been possible until recently. To carry out living related liver transplants, 2 transplant surgeons team is required as simultaneously surgery is being carried out on the donor and recipient. Fig : 2: Liver Transplant surgery Recepient New liver is inserted with anastomosis of vein, duct and artery of the recepient with graft Diseased liver is removed from the body 8

9 Auxiliary liver transplant : The term auxiliary liver transplant is referred when a part of the donor liver (usually segments 2+3) is implanted beside or in continuity with the native liver. The main purpose of this form of liver transplant is to ensure that the native liver is retained in the event of graft failure or for the future development of gene therapy. Auxiliary transplant is now accepted therapy for Crigler-Najjar syndrome type I 19 and also for propionic acidemia and ornithine transcarbamalase deficiency. 20 The role of auxiliary liver transplant in the management of fulminant hepatic failure is more controversial. The rationale for using this technique in this condition is that, with time, the native liver may regenerate. Two recent studies in adults demonstrated that the native liver regenerates in approximately half of the 21, 22 patients. In India cadaveric organ donation is next to negligible. Of all the liver transplants carried out in the country <5% have been cadaver liver transplants and similarly our centre experience has been <5%. Immunosuppression Following liver transplantation the patient requires immunosuppression usually life long according to the present consensus. The various immunosuppresive drugs used following liver transplantation are cyclosporine, tacrolimus, mycophenolate mofetil and steroids. Newer drugs like OKT3, sirolimus and basiliximab are used in occasional patients. Scenario in India It's heartening to see that liver transplantation programme in India has eventually picked up well. It has been slow to start with but the pace in the last couple of years has been good. There are several ( more than a dozen) centres in the country which are now doing liver transplantation. The adult numbers are far more than the pediatric numbers. Internationally the pediatric liver transplant constitute around 20% of the total transplants. However, in India they are still <10% of the total transplants. There are multiple reasons for this but the most common reason is that the family finds it hard to spend a lot of money on a child. In the author s centre experience, people are more willing to spend money on elderly people than infants and young children. Besides that bias of a girl child, cannot be less emphasized. One of the major problems that we are facing in the country is lack of cadaveric donation - therefore, most of the transplants whether renal or liver carried out are living related. The human organ donation act was passed in 1984 in India. The donor has to be spouse or first degree relative or emotionally related to the patient. The importance and safety of cadaveric liver transplantation cannot be undermined and I think we must all work in the direction of promoting cadaveric organ donation in our country to benefit several people from various organs. In fact following the promotion of cadaveric organ donation there will be significant impetus in the liver transplant programme in the country. Another issue is lack of central registry and availability of little published data on liver transplantation in India. Author s Centre Experience Sir Ganga Ram Hospital, Delhi is one of major centre of liver transplantation in India where presently more than 12 liver transplants are carried out monthly. They are mostly living related liver transplants due to the shortage of cadaveric organs. In fact it is among the top 3 living related liver transplant centres in the world having performed >130 liver transplant annually and it has completed 450 living related liver transplants uptil Oct

10 Table 8 : Author experience Total no of transplantation 502 Pediatric liver transplantation Adult Pediatric - 47 N - 47 Cadaveric - 6 Mean age yrs (8 months 16 years) Living related Median age - 8 yrs Over success rate 90% Sex - M30:17F Follow up - Median - 16 months - Range months Outcome - 87% Table 11 : The Indications of Pediatric liver transplants in < 10 kg small recipient at Sir Ganga Ram Hospital are as follows (uptill Dec 09) n=11 Total liver transplant = 47 Paitent <10 kg = 12 ( 25.%) N = 12 Biliary atresia : 9 Tyrosinemia : 1 Caroli s Disease : 2 (* One patient had associated with Choledochal Cyst type IV a ) Outcome : 4/12 ( 66%) Mortality 4 recipients died after OLT At 1 week : Due to Hepatic artery & portal vein thrombosis with Sepsis At 2 weeks : Due to sepsis and hepatic artery thrombosis. This patient had portal vein thrombosis pre transplant and had undergone SMV LPV shunt At 1 yr 10 month - due to ductopenic rejection At 2.5 years due to ectopic variceal bleed. The patient had hemiportocaval anastomosis had undergoneembolization of 3 etopic varices arising from main portal vein. Outcome in less than 10 Kg weight Between November 1982 and March 2006, 67 children with body weight < 10 kg had a primary liver transplantation from deceased donors in our unit. The aim of this study was to analyze the outcome in terms of patient and graft survival and to search for factors affecting this outcome. Overall, one-, three-, five-, and 10-yr primary patient and graft survival rates were 73%, 71%, 66%, 63% and 59%, 56%, 53%, 48%, 10

11 respectively. Twenty-four of 67 (36%) children died and in the remaining 22 (33%), the first grafts failed and they were retransplanted. Cox regression analysis revealed that a need for retransplantation and urgent transplantation were important predictors for patient survival (p = 0.04 and p = 0.001, respectively). To assess whether the need for retransplantation can be influenced, all study variables were compared between surviving grafts and failed grafts. Cox regression analysis showed that only donor/recipient (D/ R) weight ratio proved to be independent predictor for graft survival (p = 0.004). After comparison of graft survival with the long rank test according to different D/R weight ratios ( ), the cut-off point for significantly different graft survival approached 4.0. The one-, three-, five-, and 10-yr graft survival for technical variant grafts with a D/R weight ratio <4.0 was 85%, 68%, 68%, and 68% compared with a D/R weight ratio > 4.0 was 44%, 38%, 38%, and 30%, respectively (p = 0.02). In summary, patient survival in children with body weight < 10 kg is determined by urgent transplantation and the need for retransplantation. Graft loss and retransplantation in small children can be prevented by adequate size matching of donor and recipient whereby a D/R weight ratio < 4.0 seems to offer the favorable outcome. Outcome of Pediatric liver transplantation has shown incremental improvements from the 1980s to late 1990s. Studies of pediatric liver transplantation (SPLIT) registry, which was initiated in 1995, gives an overview of the results of pediatric liver transplantation achievable in the last 7 years. Of 1092 pediatric liver transplanted children, the Kaplan Meier probability of patient survival at 1 and 3 years was 86.3% and 83.3%, respectively, with corresponding graft survival rates of 80.2% and 75.3% respectively The Kyoto series, the largest in the world, is driven by virtually nonexistent cadaveric supply ie based on living related transplantation. The Kyoto series shows excellent and comparable patient and graft survival rates, 81% and 79% at 5 years, to the overall results of cadaveric pediatric liver transplantation. In another large series, Reding et al reported a 7 year experience with living donor transplants in children, which showed 1 and 5 years survival rates of 92% and 89% for patient and 90% and 86% for graft, respectively. Although biliary complications may be more common in living donor compared with whole organ transplants, these usually do not impact on patient or graft survival. Summary Liver transplant for acute or chronic liver failure or for metabolic liver disease is an effective therapy that restores good quality of life to over 80% of recipients. Considerable advances in medical and surgical expertise and immunosuppression have improved not only survival but also quality of life for the majority of liver transplant recipients. It is hoped that advances in molecular genetics will lead to effective gene therapy 29, 30 or hepatocyte transplant In India, both the infrastructure and expertise for liver transplantation is available and it has at last picked up, but the growth of transplant programme is still far from desirable. In the West the rate of liver transplants is / million while in India its much less than 1/ million presently. Pediatric liver transplant :Acute liver failure In 1989, ALF was defined as the onset of encephalopathy or coagulopathy within 26 weeks of diagnosis of liver disease. Based on temporal progression of disease to development of encephalopathy, hepatic failure was classified as acute (<4 weeks), hyperacute (<10 days), fulminant (10-30 days) and subacute ( days) based on classification by International Association of Study in Liver disease (IASL). Although the commonest cause of acute liver failure in children is acute viral hepatitis followed by metabolic causes (Wilsons disease ), in children less than 10 Kg weight the commonest causes are metabolic 11

12 mostly neonatal haemochromatosis, tyrosinemia, galactosemia etc. In these cases,usually child presents with fulminant hepatic failure and we have to go for an urgent liver transplantation without any delay. Indications for liver transplantation in children with acute liver failure are mentioned in Table number 2. Making decision for liver transplantation for ALF is more difficult than for patients with chronic liver disease. One has to cautious in doing the transplant before irreversible damage has occurred to the brain. Living related transplant is alternate to cadaveric transplants even in Western countires in patient with ALF Criteria for listing for liver transplantation in acute liver failure: King s college (London) have provided certain criteria in acute liver failure which are suggestive of poor prognosis and when present indicate the need for liver transplantation. Table -6 :- Kings College criteria for Liver Transplantation (A) For acetoaminophen poisoning Arterial ph < 7.3 Or the following 3 factors - PT >100 sec - Creatinine > 3.5 mg% - Grade III or IV encephalopathy (B) For other causes PT > 100 sec Or any 3 of the following - PT >50 sec - Bil>17.5 mg% - Age<10years - Cryptogenic or drug induced - Jaundice for more than 7 days before onset of encephalopathy We did a retrospective analysis of our patients (n=102) with acute liver failure to evaluate etiology, outcome and to assess the utility of KCC as prognostic criteria in different categories of ALF in Indian pediatric patients. Application of KCC in following categories: N Sensitivity Specificity PPV* NPV** Acute % 92% 90.9% 92% Hyperacute % 100% 100% 90% Fulminant %% 94.44% 94.73% 85% Subacute % 40% 76.92% 100% *PPV Positive Predictive Value, **NPV Negative Predictive Value Sensitivity and specificity of KCC exceeded 90% and is therefore recommended as a prognostic marker in ascertaining the need for liver transplant in Indian pediatric patients with ALF. Unlike fulminant and hyperacute liver failure, KCC was not found to be specific in sub-acute liver failure ( days). 12

13 Wilson s disease results from defect in copper metabolism and it may have varied presentations such as a symptomatic raised enzymes, chronic liver disease; portal hypertension, hepatomegaly or as acute liver failure. Wilson s disease presenting as acute liver failure as a very high mortality. Wilson s index is used for assessing such patients and a score of >11 suggest the need for liver transplantation. Score Bilirubin (micromol/l) > 301 INR > 2.5 AST >401 WCC (10 9 /L) >15.4 Albumin (g/l) > <20 Wilson Index Author s experience Table 9 : Our experience on acute lifer failure in pediatric as follow Total no of transplantation 502 Pediatric liver transplantation Adult Pediatric - 47 n - 13 Cadaveric - 6 Mean age yrs (4 years 11 years) Living related Sex - M8:5F Over success rate 90% Follow up - Median - 20 months - Range months Outcome -100% Indications of Pediatric liver transplantation for ALF at SGRH are follows (n=13) Wilson s disease - 5 Acute on chronic liver disease - 2 Hepatitis A - 2 Cryptogenic - 2 Autoimmune hepatitis - 1 Hepatitis E with Wilson disease

14 Summary Liver transplant is an established modality of treatment for patient with ALF. Decision for liver transplantation is more difficult in ALF patients than in chronic liver disease case. Irreversible brain damage is obviously an contraindication to liver transplant. King s college criteria are universally used for listing such cases. Our experience on ~ patients with ALF sensitivity and specificity of King s college criteria was >90%. Our experience on liver transplant in ALF pediatric patients showed excellent result with 100% survival in 12 patients over a mean follow up 24.6 months. 14