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Liver transplantation in children with metabolic and genetic disorders: Experience of one centre
Abstracts / Digestive and Liver Disease 39 (2007) A49–A87 PP 33 ANTIMITOCHONDRIAL ANTIBODIES: TWO PAEDIATRIC CASE REPORT G. Torre a , V. Casotti a , M. Candusso a , M.L. Melzi a , P. Stroppa a , M. Bravi a , L. Cavalleri a , M. Bosisio a , M.G. Alessio b , A. Sonzogni c , P. Invernizzi d a
Pediatric Liver Transplantation Centre, Ospedali Riuniti, Bergamo, Italy Biochemistry Laboratory Ospedali Riuniti, Bergamo, Italy c Clinical Pathology, Ospedali Riuniti, Bergamo, Italy d Division of internal medicine and liver unit, S. Paolo Hospital, School of Medicine, Milan, Italy b
Antimitochondrial antibodies (AMA) are the classic serologic marker in primary biliary cirrhosis (PBC). Unlike other autoimmune liver diseases, PBC has not been reported in childhood. We report here two cases of AMA detection in paediatric patients. Case 1: A 4-year-old girl developed acute cholestatic disease (bilirubin 24 mg/dl; liver enzymes × 100) with rapid progression to acute liver failure. Her laboratory tests showed a hypergammaglobulinaemia (>2 g/l) and the positivity of both AMA and liver–kidney microsomial (LKM)-type 1 antibodies, as determined by conventional indirect immunofluorescence on rodent-triple tissues and confirmed by two different liver-blot and immunoblot and a dot-blot. The presence of LKM 1 autoantibody leads to diagnosis of AIH type 2. She was treated by steroid and i.v. cyclosporine. Liver biopsy was not performed at admission, because of coagulation disorder. Two days after starting the therapy, she improved with a rapid recovery of neurological damage and progressive decrease in bilirubin level and liver enzymes. One month after, her liver function tests were within normal range. Liver biopsy showed both inflammatory lobular/interface and intrahepatic biliary tree lesions with ductular proliferation and biliary metaplasia as demonstrated by specific staining techniques (citokeratine) similar to adult PBC. Case 2: A 4-year-old child was investigated in our centre for persistent temperature. We determined occasionally the positivity of AMA autoantibodies on HEP 2 in occasion of ANA investigation. Liver index were completely normal. AMA positivity was determined also by conventional indirect immunofluorescence on rodent-triple tissues and confirmed by two different liver-blot and immunoblot and a dot-blot. These are first two reports of AMA detection under age 10. In first child typical lesions of adult PBC were associated with cholestatic AIH type 2. In the second girl at moment there is no biochemical evidence of liver involvement (further investigations are in progress). doi:10.1016/j.dld.2007.07.096 PP 34 LIVER TRANSPLANTATION IN CHILDREN WITH METABOLIC AND GENETIC DISORDERS: EXPERIENCE OF ONE CENTRE P. Stroppa a,b,c , M. Candusso a,b,c , M.L. Melzi a,b,c , M. Bravi a,b,c , L. Cavalleri a,b,c , M. Bosisio a,b,c , F. Bruni a,b,c , G. Torre a,b,c a
Pediatric Liver Transplantation Centre, Italy Biochemistry Laboratory, Italy c Clinical Pathology, Ospedali Riuniti, Bergamo, Italy b
Metabolic and genetic diseases are a heterogeneous group of disorders, often with liver involvement. Transplant could be a feasible therapy both for irreversible, acute or chronic, liver failure and for enzyme replacement. In our centre metabolic diseases are the second largest indication for orthotopic liver transplantation (OLTx) in children after extrahepatic biliary atresia (EHBA). We retrospectively reviewed the 350 OLTX performed in 312 children between October 1997 and April 2007; out of these, 67 children (40 M, 27 F) with metabolic/genetic disease (21.5%) underwent 75 OLTX for: Alagille’s syndrome (26 cases), Byler disease (14), Crigljer Najjar 1 (4), glicogenosis IV (3), familiar haemolytic uremic syndrome (SEU) (2), neonatal haemochromatosis (2), Wilson’s disease (2), congenital hep-
A67
atic fibrosis (4), methylmalonic acidaemia (2), tyrosinaemia (2) and 1 case for each propionic acidaemia, ornithine transcarbamylase deficiency (OTC), cystic fibrosis, oxalosyis oxaluria, citrullinemia and cranio ectodermic dysplasia. At OLTX the median age was 2.63 years (range 29 days–16.7 years); the median weight 11 kg (range 2.3–55 kg); the median waiting time 37 days (range 1–367 days). Split liver technique was performed in 45 cases, whole liver in 19 and reduced liver in 3, all from cadaveric donors. Indication for combined kidney and liver transplantation included oxaluria (1), familiar SEU (2), congenital hepatic fibrosis (2), methylmalonic acidaemia, cranio ectodermal dysplasia. Retransplant was required in 8 cases (13.4%), for chronic rejection in the OTC patient, acute rejection in 1 case (SEU), PNF in 3 Alagille’s syndrome, in 2 Byler diseases and in one haemochromatosis. The overall survival rate (OSR) is 87% at 1 year (OSR of EHBA is 92%). The main complications were acute (11 cases, 16.4%) and chronic (10 cases, 14.9%) rejection, de novo autoimmune hepatitis (4), and PTLD (1). Biliary complications were reported in 13 pts (19.4%), vascular complications in 3 pts. Neurological complication in one case of SEU. OLTx represents an effective therapy for replacing failing liver, and corrects underlying defects. Clinical phenotype of all our patients was corrected and metabolic decompensation did not occur after OLTX. Transplantation should be considered as a promising treatment currently available to improve quality of life. Mortality rates of this group of patient are mostly comparable to that of the other group of transplanted children. doi:10.1016/j.dld.2007.07.097 PP 35 FULMINANT HEPATIC FAILURE IN CHILDREN: MORTALITY AND THE ROLE OF ORTHOTOPIC LIVER TRANSPLANTATION F. Bruni, M. Bravi, M. Candusso, L. Cavalleri, M. Bosisio, M.L. Melzi, P. Stroppa, D. Pinelli, M. Colledan, Giuliano Torre Paediatric Liver Transplantation Centre, Ospedali Riuniti, Bergamo, Italy To evaluate the role of orthotopic liver transplantation (OLTx) in fulminant hepatic failure (FHF), defined by coagulopathy (INR > 2) with or without encephalopathy in a patient with no identified chronic liver disease. Retrospective analysis of all children with FHF referred to our centre from October 1997 to August 2006. FHF was diagnosed in 41 patients (23 male, 18 female; mean age 41 months; range 1 day–163 months): metabolic disorder in 10, toxic hepatitis in 7, autoimmune hepatitis in 6, multi-systemic disease in 4 patients; in 14 patients there was a cryptogenic hepatic failure. In 56% of cases, waiting list for OLTx was activated; in the others, there was no indication for it because of underlying disease (multi-systemic disorder) or improvement after appropriate medical therapy. The overall mortality rate was 20%. OLTx was performed in 19 out of 23 listed children; 4 were not transplanted for spontaneous recovery (2), for parents’ refusal (1), for death on waiting list (1). Indications for OLTx in the 19 patients were: cryptogenic hepatic failure (nine), metabolic diseases (five cases: three neonatal hemocromatosis, two Wilson’s disease), autoimmune hepatitis (four) and mushroom poisoning (one). Survival rate was 74% (14/19) in OLTx for FHF and 87% in OLTx with elective indication; the difference between FHF OLTx and elective OLTx cases is not significant (Fischer test). Primary non-function, re-transplantation for chronic reject, multi-organ failure and neurological complications were the cause of death. At a mean of 36.5 months follow-up time, in the transplanted children, we reported four biliary complications: two chronic rejections, one neurological delay as major long-term complications. According to intention-to-treat analysis, the survival rate was 74% (17/23) among listed children and 89% (16/18) among children not assessed for OLTx (2 children died for the underlying disease (respiratory-chain disorder)). The difference in mortality rate in the two groups was not statistically significant (Fischer test). Children with FHF should be referred to a specialized transplantation centre to receive all needed treatments. In our experience, mortality in FHF patients is low, as compared with other series, even in transplanted cases.
Pediatric Liver Transplantation Centre, Ospedali Riuniti, Bergamo, Italy Biochemistry Laboratory Ospedali Riuniti, Bergamo, Italy c Clinical Pathology, Ospedali Riuniti, Bergamo, Italy d Division of internal medicine and liver unit, S. Paolo Hospital, School of Medicine, Milan, Italy b
Antimitochondrial antibodies (AMA) are the classic serologic marker in primary biliary cirrhosis (PBC). Unlike other autoimmune liver diseases, PBC has not been reported in childhood. We report here two cases of AMA detection in paediatric patients. Case 1: A 4-year-old girl developed acute cholestatic disease (bilirubin 24 mg/dl; liver enzymes × 100) with rapid progression to acute liver failure. Her laboratory tests showed a hypergammaglobulinaemia (>2 g/l) and the positivity of both AMA and liver–kidney microsomial (LKM)-type 1 antibodies, as determined by conventional indirect immunofluorescence on rodent-triple tissues and confirmed by two different liver-blot and immunoblot and a dot-blot. The presence of LKM 1 autoantibody leads to diagnosis of AIH type 2. She was treated by steroid and i.v. cyclosporine. Liver biopsy was not performed at admission, because of coagulation disorder. Two days after starting the therapy, she improved with a rapid recovery of neurological damage and progressive decrease in bilirubin level and liver enzymes. One month after, her liver function tests were within normal range. Liver biopsy showed both inflammatory lobular/interface and intrahepatic biliary tree lesions with ductular proliferation and biliary metaplasia as demonstrated by specific staining techniques (citokeratine) similar to adult PBC. Case 2: A 4-year-old child was investigated in our centre for persistent temperature. We determined occasionally the positivity of AMA autoantibodies on HEP 2 in occasion of ANA investigation. Liver index were completely normal. AMA positivity was determined also by conventional indirect immunofluorescence on rodent-triple tissues and confirmed by two different liver-blot and immunoblot and a dot-blot. These are first two reports of AMA detection under age 10. In first child typical lesions of adult PBC were associated with cholestatic AIH type 2. In the second girl at moment there is no biochemical evidence of liver involvement (further investigations are in progress). doi:10.1016/j.dld.2007.07.096 PP 34 LIVER TRANSPLANTATION IN CHILDREN WITH METABOLIC AND GENETIC DISORDERS: EXPERIENCE OF ONE CENTRE P. Stroppa a,b,c , M. Candusso a,b,c , M.L. Melzi a,b,c , M. Bravi a,b,c , L. Cavalleri a,b,c , M. Bosisio a,b,c , F. Bruni a,b,c , G. Torre a,b,c a
Pediatric Liver Transplantation Centre, Italy Biochemistry Laboratory, Italy c Clinical Pathology, Ospedali Riuniti, Bergamo, Italy b
Metabolic and genetic diseases are a heterogeneous group of disorders, often with liver involvement. Transplant could be a feasible therapy both for irreversible, acute or chronic, liver failure and for enzyme replacement. In our centre metabolic diseases are the second largest indication for orthotopic liver transplantation (OLTx) in children after extrahepatic biliary atresia (EHBA). We retrospectively reviewed the 350 OLTX performed in 312 children between October 1997 and April 2007; out of these, 67 children (40 M, 27 F) with metabolic/genetic disease (21.5%) underwent 75 OLTX for: Alagille’s syndrome (26 cases), Byler disease (14), Crigljer Najjar 1 (4), glicogenosis IV (3), familiar haemolytic uremic syndrome (SEU) (2), neonatal haemochromatosis (2), Wilson’s disease (2), congenital hep-
A67
atic fibrosis (4), methylmalonic acidaemia (2), tyrosinaemia (2) and 1 case for each propionic acidaemia, ornithine transcarbamylase deficiency (OTC), cystic fibrosis, oxalosyis oxaluria, citrullinemia and cranio ectodermic dysplasia. At OLTX the median age was 2.63 years (range 29 days–16.7 years); the median weight 11 kg (range 2.3–55 kg); the median waiting time 37 days (range 1–367 days). Split liver technique was performed in 45 cases, whole liver in 19 and reduced liver in 3, all from cadaveric donors. Indication for combined kidney and liver transplantation included oxaluria (1), familiar SEU (2), congenital hepatic fibrosis (2), methylmalonic acidaemia, cranio ectodermal dysplasia. Retransplant was required in 8 cases (13.4%), for chronic rejection in the OTC patient, acute rejection in 1 case (SEU), PNF in 3 Alagille’s syndrome, in 2 Byler diseases and in one haemochromatosis. The overall survival rate (OSR) is 87% at 1 year (OSR of EHBA is 92%). The main complications were acute (11 cases, 16.4%) and chronic (10 cases, 14.9%) rejection, de novo autoimmune hepatitis (4), and PTLD (1). Biliary complications were reported in 13 pts (19.4%), vascular complications in 3 pts. Neurological complication in one case of SEU. OLTx represents an effective therapy for replacing failing liver, and corrects underlying defects. Clinical phenotype of all our patients was corrected and metabolic decompensation did not occur after OLTX. Transplantation should be considered as a promising treatment currently available to improve quality of life. Mortality rates of this group of patient are mostly comparable to that of the other group of transplanted children. doi:10.1016/j.dld.2007.07.097 PP 35 FULMINANT HEPATIC FAILURE IN CHILDREN: MORTALITY AND THE ROLE OF ORTHOTOPIC LIVER TRANSPLANTATION F. Bruni, M. Bravi, M. Candusso, L. Cavalleri, M. Bosisio, M.L. Melzi, P. Stroppa, D. Pinelli, M. Colledan, Giuliano Torre Paediatric Liver Transplantation Centre, Ospedali Riuniti, Bergamo, Italy To evaluate the role of orthotopic liver transplantation (OLTx) in fulminant hepatic failure (FHF), defined by coagulopathy (INR > 2) with or without encephalopathy in a patient with no identified chronic liver disease. Retrospective analysis of all children with FHF referred to our centre from October 1997 to August 2006. FHF was diagnosed in 41 patients (23 male, 18 female; mean age 41 months; range 1 day–163 months): metabolic disorder in 10, toxic hepatitis in 7, autoimmune hepatitis in 6, multi-systemic disease in 4 patients; in 14 patients there was a cryptogenic hepatic failure. In 56% of cases, waiting list for OLTx was activated; in the others, there was no indication for it because of underlying disease (multi-systemic disorder) or improvement after appropriate medical therapy. The overall mortality rate was 20%. OLTx was performed in 19 out of 23 listed children; 4 were not transplanted for spontaneous recovery (2), for parents’ refusal (1), for death on waiting list (1). Indications for OLTx in the 19 patients were: cryptogenic hepatic failure (nine), metabolic diseases (five cases: three neonatal hemocromatosis, two Wilson’s disease), autoimmune hepatitis (four) and mushroom poisoning (one). Survival rate was 74% (14/19) in OLTx for FHF and 87% in OLTx with elective indication; the difference between FHF OLTx and elective OLTx cases is not significant (Fischer test). Primary non-function, re-transplantation for chronic reject, multi-organ failure and neurological complications were the cause of death. At a mean of 36.5 months follow-up time, in the transplanted children, we reported four biliary complications: two chronic rejections, one neurological delay as major long-term complications. According to intention-to-treat analysis, the survival rate was 74% (17/23) among listed children and 89% (16/18) among children not assessed for OLTx (2 children died for the underlying disease (respiratory-chain disorder)). The difference in mortality rate in the two groups was not statistically significant (Fischer test). Children with FHF should be referred to a specialized transplantation centre to receive all needed treatments. In our experience, mortality in FHF patients is low, as compared with other series, even in transplanted cases.