"Current state and prospects in managing liver transplanted children".

Pediatric liver transplantation (LTx) has revolutionized life chances and perspectives of children with liver disease. Following rapid establishment of the therapeutic concept in the early years of pediatric transplant medicine, more aspects beyond plain survival become increasingly important. In addition to improving the short to medium-term survival rates, researchers are focusing on themes such as rehabilitation, adherence and quality of life, long-term graft fibrosis and dysfunction, as well as the consequences of long-term immunosuppression. Also, more protocol biopsy data are available to evaluate increasing graft fibrosis. To manage their conditions, patients will need access to highly experienced pediatric liver transplant centers where clinical research will examine modulators of renal disease, endocrine and cardiovascular comorbidity and the development of graft fibrosis and malignancies. Assessment and evaluation of health-related quality of life and factors which influence clinical tolerance, adherence and transition from child to adult care will also be investigated. The analysis of multi-national registry data and more than 40years of experience with large patient cohorts will provide important clues to treatment and will thus get increasing attention. In the future, longitudinal assessment of the outcome for pediatric LTx patients should include more functional aspects than plain survival rates or laboratory parameters.

Liver transplantation in children with cystic fibrosis: experience in our centre and preliminary results with a combined en bloc liver-pancreas graft.

AIM OF THE STUDY: Cystic fibrosis (CF) is a multisystemic disease, with some patients developing end-stage liver disease (ESLD), requiring liver transplantation (LT). These children usually present with severe mutations of the CFTR gene. Almost 100% of patients with severe mutations develop exocrine pancreatic insufficiency, leading later to endocrine insufficiency. Immunosuppression accelerates the development of insulin-dependent diabetes (IDD) in transplanted children with CF. Our aims were: (1) to analyze our experience with CF-related ESLD children who received LT, and the relationship to the development of IDD; (2) to report our preliminary results with en bloc liver-pancreas transplantation (CLPT). METHODS: 9 children (6M/3F) with CF and ESLD underwent LT between 1993 and 2010; median age and weight were 12.3 years (range: 5.4-17.0) and 36.7 kg (range: 14.2-58.5), respectively. 4 patients received a whole graft, 4 had reduced grafts (1 split) and 1 underwent CLPT. Immunosuppression followed the protocols at the time of transplantation. RESULTS: Liver function was restored in all patients and none of them needed re-transplantation. Median follow-up was 105 months (range: 4-206). 1 child died of respiratory failure at 23 months after transplantation while awaiting pulmonary transplantation. Survival (Kaplan-Meier) at 105 months was 87.5%. 4 children already had IDD before transplantation and 3 developed diabetes immediately after transplantation. 2 had not developed IDD at the end of the study: the youngest at the time of LT (5.4 years, follow-up 7.1 years) and the girl who had had CLPT and who recovered normal exocrine and endocrine pancreatic function after transplantation. CONCLUSIONS: LT is a realistic option to treat CF-related ESLD children. IDD is common in these patients. En bloc liver-pancreas transplantation is an appealing option, since it simultaneously restores exocrine function and prevents IDD. This procedure has clear technical advantages over simultaneous isolated liver and pancreas transplantation.

[Infant mortality in a third level paediatric hospital. therapeutic effort limitation, clinical-pathological agreement and diagnostic accuracy]. / Mortalidad infantil en un hospital de nivel terciario. Limitación de esfuerzo terapéutico, correspondencia clínico-patológica y precisión diagnóstica.

OBJECTIVE: To study infant and child mortality in a third level children's hospital treating highly complex patients. PATIENTS AND METHODS: All children dying in the period 2007- 2009 at La Paz Children's Hospital were evaluated. Epidemiological data, autopsy rate, clinical and autopsy diagnoses and their correspondence and the number of, patients with precise final diagnoses were analysed. Therapeutic effort limitation and palliative care were also evaluated as well as if the final result was expected according to the initial disease or clinical condition of the patients. All the variables were prospectively defined at the start of the study period. RESULTS: A total of 253 cases (6.08‰ admissions) were analysed. The two leading causes of death were disorders related to prematurity and low birth weight, and haematology oncology malignant diseases. Most patients (87%) died in an intensive care unit (neonatal or paediatric). During the study period 134 autopsies (53%) were performed, and new clinically significant findings were observed in 12 of these (7.8%) but in only one case the treatment could have possibly modified the prognosis (class I discrepancy). Therapeutic effort limitation and palliative care were implemented in 41.9%. Death was initially expected in 83.9% of cases. An accurate final diagnosis was defined in 92%, and the aetiology of the disease was considered to be identified in 86.4% of all deaths. CONCLUSIONS: Hospital mortality analysis is useful to evaluate the quality of the paediatric care and to detect adverse results that could be corrected. Paediatric autopsy continues to provide clinically significant data for paediatricians and families. Therapeutic effort limitation and palliative care is increasingly applied in paediatric end of life care. The number of infants and children dying without a final aetiological diagnosis is still considerably high.

[Orthotopic liver transplantation in children younger than one year]. / Trasplante hepático en menores de un año.

BACKGROUND: Orthotopic liver transplantation (OLT) in children younger than one year is associated to higher waiting list mortality and alternative graft sources are required. We present our experience with this particular group of age. METHODS: Infants younger than one year who received an OLT between 1986 and 2005 were reviewed focused on graft and children survival depending on period and type of graft. Periods were 1:1986-1995; 2:1996-2000 and 3:2001-2005. We also evaluate cold ischemia time (CIT), graft lost causes and differences between CIT and anhepatic time (AT) depending on graft type. RESULTS: Eighty-three children received 103 OLT. Liver transplant indications were 59 (72%) biliary atresia, 8 (10%) metabolic causes, 6 (8%) liver failure, 3 (4%) cirrhosis and 7 (6%) miscelaneous. Patient and graft survival after 5 years was increased depending on period: 45% and 65% on period 1, 70% and 80% on period 2, 94% y 97% on period 3 (p < 0.0198). Thirty-seven grafts were reduced lobes (42%); 8 (21%), 17 (45%) and 12 (35%) during periods 1, 2 and 3 respectively and their 5 years survival rate was 68%. Twenty-four were whole grafts (31%); 11 (45%), 10 (45%) and 3 (14%) during periods 1, 2 and 3 and their 5 years survival rate was 63%. Fourteen grafts were living-related donor (16%); 1 (7%), 2 (14%) and 11 (79%) during periods 1, 2 and 3 and their 5 years survival rate was 93%. Eight (11%) were split; 0, 1 (12%) and 7 (90%) during periods 1, 2 and 3 and their 5 years survival rate was 100%. Average CIT depending on graft was: living donor 5,5 hours (IQR: 4-7), split 6,1 hours (IQR: 5-8), whole 9.2 hours (IQR: 6-11) and reduced 8.5 hours (IQR: 6-11) (p < 0.05). Average AT depending on graft was: living donor 1 hour (IQR: 0.5-1.5), split 1 hour (IQR: 0.5-1.4), whole 1,1 hours (IQR: 0.5-1.5) (p > 0.1). Twenty-four grafts were lost (28%): 10 (41%) were surgical related causes and 6/10 (60%) of them were whole grafts. CONCLUSIONS: Survival rates in children younger than one year are similar to another groups of age. There was a significant increase on graft survival according to transplantation group experience. A higher rate of graft lost is associated to whole grafts. Most frequent reasons of graft lose were related to sepsis and immunosuppresion. A significant shortening of CIT is observed in related living donor and split grafts.

Cyclosporine monitoring in the early post-transplant period in pediatric liver transplant recipients.

UNLABELLED: Monitoring of CsA blood levels two h post-dose (C2) has shown a higher correlation to drug exposure than monitoring of trough levels (C0) at least in adults, but initial doses and target blood levels of CsA have yet to be established in pediatric transplant patients. The objectives of the study were to describe the pharmacokinetics of CsA administered by NGT in the first days after transplantation and the dose of Sandimmun Neoral required to achieve minimum therapeutic range blood levels. This study included 20 pediatric liver transplant recipients (mean age of 3.2 yr) treated with CsA administered by NGT from day one post-transplant until they were able to ingest oral medication. The study was continued until one yr of post-transplant follow-up. Eight h pharmacokinetic profiles were performed on days one, three, and five post-transplant to determine the minimum dose required to achieve the therapeutic range. All children received an initial dose of 15 mg/kg/day of CsA by NGT. Mean CsA doses administered on days one, three, and five were 16.8, 29.5, and 36.5 mg/kg/day, respectively. Mean C0 levels of 119, 310, and 337 ng/mL and mean C2 levels of 213, 753, and 888 ng/mL were obtained. No correlation was found between C0 and C2 levels and the AUC(0-8 h). Intravenous administration of CsA was required in 55% of patients. The biopsy-confirmed acute rejection rate was 45%, with graft and patient survival rates of 95 and 100%, respectively. CONCLUSIONS: Poor absorption of CsA in small children requires a considerable increase in dose. CsA exposure cannot be estimated by single C0 or C2 determinations in the early post-transplant period.

[Congenital portosystemic shunt. The Abernethy malformation]. / Shunt porto cava congénito. Malformación de Abernethy.

BACKGROUND: Congenital portosystemic shunt (CEPS) is a rare condition that was first reported by John Abernethy in 1793. Two types of CEPS are described: type I (side to end anastomosis) or congenital absence of the portal vein, and type II (side to side anastomosis) with portal vein supply partially conserved. Type I CEPS is usually seen in girls and associates multiple malformations as polysplenia, malrotation, and cardiac anomalies. Type II is even rarer with no sex preference and no malformations associated. Hepatic encephalopathy is a common complication of both types in adulthood. Liver transplantation is the only effective treatment for symptomatic type I CEPS. A therapeutic approach for type II could be surgical closure of the shunt. OBJECTIVE: To analyse our experience in diagnosis and management of portosystemic shunts. METHODS: We report 4 cases of CEPS (3 type I and 1 type II) diagnosed between January-1997 and March-2005 in our department. RESULTS: We present 4 patients with ages at diagnosis ranging from 0 to 28 months, 3 type I CEPS (2 boys and 1 girl) and 1 boy type II. The type I girl was prenatally diagnosed at 12 weeks of gestation. Initial clinical signs in type 1 boys were splenomegaly and hypersplenism, both with normal pondo-statural growth. No polysplenia or cardiac anomalies were assessed. One of them presented mild developmental delay, dismorphic features and facial telangiectasias. He had normal coagulation tests with chronic hepatic dysfunction (high transaminases) and regenerative nodular lesions were seen by imaging techniques. The other type I patient had hypoprothrombinemia, tendency to capillary bleeding (haematomas and epistaxis) with preserved liver function. Both patients have developed mild portal hypertension and present steatosis signs at liver biopsy. The type I girl presents a 21 trisomy and associates a cardiac anomaly (interauricular communication). Her hepatic function test are normal but liver calcifications can be seen by ultrasound. Type II child associates hypospadias but he has no clinical sigh or symptom related to the shunt. In our three cases diagnosis was suggested by conventional and Doppler ultrasound and confirmed by angio-resonance imaging. All our patients are included in a meticulous clinical and radiological follow-up with no need of surgical treatment for the shunt until now. CONCLUSIONS: Although diagnosis of these malformations could be casual we have to think about CEPS in children presenting unspecific liver disease. Magnetic angio-resonance imaging is actually the best diagnosis methods for CEPS. These patients have a high risk for developing hepatic encephalopathy and portal hypertension, so a careful follow-up is required although surgery is not usually needed until adulthood.

[Childhood cholestasis and bile transporters]. / Colestasis infantil y transportadores biliares.

Identification of the transport systems involved in bile secretion and of the genes codifying these systems has allowed the etiology of familial intrahepatic cholestasis to be determined in most affected children. Mutations in ATP8B1 cause a defect in FIC1, an aminophospholipid flipase, and give rise to a variable spectrum of disease, ranging from progressive intrahepatic cholestasis to benign recurrent cholestasis, due to alterations in the lipid composition of the membranes and decreased expression of the nuclear factor FXR. Mutations in ABCB11 cause a defect of the canalicular bile salt export pump (BSEP), with early clinical manifestations and progression to hepatocellular failure in childhood. Mutations in ABCB4 cause an alteration in the MDR3 phospholipid transporter, and a variable spectrum of disease from progressive ductal injury to cirrhosis in children, and gallstones, cholestasis of pregnancy, or late cirrhosis in adults.

[Pediatric liver transplantation]. / Trasplante hepático pediátrico.

There are no differences in results between pediatric liver transplantation and liver transplantation in adults. The reverts of the liver disease prior to transplantation (particularly the need of intensive care is the best predictor of perspective mortality. Therefore, liver transplantation in children should be indicated prior a severe decompensation of the disease.

Comparative study between living and cadaveric donors in pediatric liver transplantation.

UNLABELLED: We examined whether the results in living-related hepatic transplantation (LRLT) are better than those from a cadaveric donor (CDLT). MATERIAL AND METHODS: The last 27 consecutive LRLT, performed from 1998 to 2005, were compared with 27 CDLT matched for age, weight, date, and diagnosis. Grafts in LRLT group were left lateral segment (n = 22), left lobe (n = 3), and right lobe (n = 2). In the CDLT group, the grafts were split in situ (n = 10), hepatic reduction (n = 9) and whole liver (n = 8). We analyzed the actuarial survivals (grafts and children), retransplantation, primary nonfunction, initial graft malfunction (liver enzymes >2000 U/L), surgical complications, rejection, and resource consumption. RESULTS: Patient survivals at 6 months, 1 year, and 5 years were 100%, 96%, and 96% in LRLT and 100%, 100%, and 100% in CDLT (P = NS). Graft survivals were 93%, 89%, and 89% versus 96%, 96%, and 96%, respectively (P = NS). Complications were biliary complications (LRLT, 25% vs CDLT, 3%; P = .021); portal vein thrombosis (LRLT, 7% vs CDLT, 3%; NS), and hepatic artery thrombosis (LRLT, 0% vs CDLT, 3%; NS). The overall incidence of acute rejection was slightly higher (NS) in LRLT (LRLT, 18% vs CDLT, 11%; NS). Liver enzyme levels were higher in the CDLT group, but initial malfunction rate was not statistically different. Regarding resource consumption: blood product needs were higher in LRLT (P < .05) and hospital stay and ICU stay were longer, although not significantly, among LRLT. CONCLUSIONS: The results in LRLT among children are similar to those obtained in CDLT. We found a trend towards less initial graft malfunction in LRLT. Blood product needs were higher in LRLT. Hospital and ICU stay were longer, but not significantly different in LRLT. The benefits of LRLT are saving a scarce resource: a cadaveric donor liver graft.

Intestinal transplantation in children: differences between isolated intestinal and composite grafts.

The results of the isolated intestinal grafts were compared with those of composite grafts (intestinal graft + liver) in a series of 18 transplantations performed in 17 children; 5 isolated intestinal grafts, 12 hepatointestinal grafts, and 1 multivisceral graft. Causes of intestinal failure were short bowel syndrome (n = 13), motility disorders (n = 2) and congenital epithelial disorders (n = 2). Transplantation was indicated due to end-stage liver disease (n = 14), loss of venous access (n = 2), untreatable diarrhea (n = 1) and high morbidity associated with a poor quality of life (n = 1). Six children, all with a composite graft, died after transplantation due to lymphoma (n = 2), sepsis (n = 1); intraabdominal bleeding (n = 1); pneumonia (n = 1); and overwhelming adenoviral infection (n = 1). Digestive autonomy was achieved in 16 of 18 grafts, the 11 surviving children are free of parenteral nutrition with a reasonably good quality of life. In conclusion, intestinal transplantation is a viable therapeutic alternative for children with permanent intestinal failure. The results of transplantation with an isolated intestine are clearly better that those with a composite graft.

[The multifocal hepatic hemangioendothelioma. Is always a benign tumor?]. / Hemangioendotelioma multifocal hepático infantil. Es siempre un tumor benigno?

UNLABELLED: The hepatic multicentric haemangioma is defined by its extension, affecting all the mass of the liver. The high mortality associated with it is mostly related with the complications produced by its enormous size (haemodynamic, platelet trapping, spontaneous rupture and bleeding). There is a general belief that is a benign tumor with possibility of spontaneous regression and cure. AIM: Retrospective analysis of our recent cases of MHH with the purpose of: 1 degrees) To show the evolution and results. 2 degrees) To realize if the "benign character" of the tumor is real or if some cases may be considered as malignant tumors. MATERIAL AND METHODS: 10 cases of MHH treated in the last 10 years. In 9 the age of presentation was less than 6 months and one patient was diagnosed at 3 and half years. The diagnosis was confirmed by image techniques in 7 cases and by biopsy in 3. In 7 patients extrahepatic vascular lesions were associated prior to the treatment. Methylprednisolone was given to all the cases and alpha-2-interferon was administered to the patients that not responded to the steroids. Vincristine was added to 2 patients. In two cases the hepatic artery embolization was tried and one patient had a liver transplant. RESULTS: Four children had at least one episode of congestive cardiac insufficiency, two patients suffered a consumption coagulopathy (Kasabach Merrit syndrome), and one presented acute hepatic failure. In six children it has been complete regression of the tumor, one more is still under treatment and three died. The dead were produced by the malignant behavior of the tumor in one case (tumoral rupture of a MHH recurrence in the transplanted liver), and possibly in other (intracranial haemorrhage and hepatic failure in a liver transplantation candidate without demonstrated extrahepatic extension in the previous studies, but with multiorgan dissemination at autopsy. In both cases it was impossible to discover signs of histologic or biologic malignancy neither in the primitive lesion nor in the metastasis. CONCLUSIONS: 1a) The regression of the MHH, spontaneous or induced by the treatment is frequent. 2a) Some cases of MHH are aggressive and develop local recurrences and distant metastasis. 3a) The discrimination between MHH of "benign" or "malignant" behaviour is not possible. 4a) Despite of the unpredictable biological conduct of the tumor, the liver transplantation must be considered as an option in the symptomatic cases that not respond to the conventional treatment.

[Prognostic factors in pediatric liver transplantation. Multivariate analysis]. / Factores pronósticos del trasplante hepático pediátrico. Análisis multivariante.

AIM: To analyze independent risk factors associated with poor graft and patient survival in a series of 292 pediatric liver transplants (PLT) performed in 234 children during a 15 years period. MATERIAL AND METHODS. 1. Univariate graft and patient survival analysis in 45 variables related to pretransplant patient status, surgical technique and donor conditions. 2. Variables found with univariate analysis to be associated with outcome were entered into a stepwise backward proportional hazard model (Cox), to determine independent prediction of outcome. RESULTS: 11 variables influence the graft survival: recipient age, z-score recipient height, UNOS status, recipient and donor weight, transplant for immune hepatitis, platelet transfusion during the transplant, blood index > 4 during the surgery, type of arterial reconstruction, retransplantation and era of the transplant (first er: 1986-1990; 2nd. era: 1991-1995; 3rd. era: 1996-2000). Four of those variables are independent in the multivariate analysis: UNOS 1 status (Odds Ratio, OR = 2.82, 95% confidence interval = 1.36-5.85), recipient < 3 years (OR = 3.76, 95% CI = 2.13-6.63), transplants for autoimmune hepatitis and era (OR of first and second versus third era respectively 3.93 and 2.81). The independent variables influencing the patient survival were: children receiving more than one graft children less than 3 years old and transplant era. CONCLUSIONS: Liver transplant in small children is associated with an increased risk of graft loss and patient dead. The experience of the hospital in pediatric liver transplantation improves the results, particularly in small children.

Pediatric living donor liver transplantation.

AIM: The aim of this study was to analyze the results of living donor in a pediatric liver transplantation program. PATIENTS: Twenty-six living donor liver transplantations were performed in children from 0.5 to 14.8 years of age. The main indication was biliary atresia (72%) followed by tumors (2 hepatoblastomas and 1 hepatocarcinoma). Left lateral segments were used in 23 (1 transformed into a monosegment), 1 left lobe was used in 1, and right lobes were used in 2. Arterial reconstruction employed saphenous venous grafts in the first 3 cases and end-to-end anastomoses with a microsurgical technique in the following 22 cases. RESULTS: There has been no major morbidity in the donors, with a median hospitalization of 6 days. Four grafts have been lost; 2 in the first 3 cases. In only 1 case, the graft loss was related to the procedure saphenous venous graft thrombosis). Early biliary complications were frequent (23%). Six month, 1 year, and 5 year graft and patient survival rates were 91%, 85%, and 85% and 100%, 96%, and 96%, respectively. CONCLUSIONS: Living donor liver transplantation is an excellent option for transplantation in children.

[Liver transplantation in infants younger than one year of age]. / Trasplante hepático en niños menores de un año.

BACKGROUND: The development of the surgical techniques of hepatic division has maken that the young age (less than one year old) is no longer considered a risk factor in the pediatric liver transplant (TH). AIM: To show our experience with the TH in children younger than one year, comparing these results with the rest of the series and in second place to analyze if a bigger experience improves the results of the TH in this group of patients. METHODS: 44 patients that received a TH with less than a year of age are reviewed. Among them, 27 were in the last five years. The survival indexes of the graft and the patient are determined at 1, 5 and 10 years comparing them with three rest of the series. RESULTS: The grafts and patients survival was slightly inferior in the less than one year old, although in the last five years it improved 71.4% vs 82.1% at one year follow-up, and 61.9 in front of 74.5% at five years. The clinical situation of the patients that were transplanted before the year of life was worse: 43% (UNOS III, IV) in front of 13.1% in the same stadiums in the rest of the serie. In the younger patients, 54% of the grafts were reduced, versus 21% in the older. There were not a higher rate of complications in the young group. CONCLUSIONS: In spite of the difficulties of the TH in children younger than one year of age, the results are not very different from those obtained in the rest of the patients. In these results the experience of the transplant center have a great influence.

[Prognosis in children with biliary atresia successfully treated with Kasai's operation]. / Pronóstico de los niños con atresia biliar tratados con éxito con la operación de Kasai.

BACKGROUND: The Kasai procedure, portoenteroanastomosis (PEA) didn't reach international spreading until the seventy's decade, making difficult to find long-term results from children with ABE successfully treated with this technique. At our institution in the last fifteen years all the therapeutics procedures for these patients can be offered, including the liver transplant. AIM: To show the evolution of our patients with ABE treated with the PEA and that survive long-term without being transplanted. METHODS: The clinical course of 22 patients that survive more than 10 years after the PEA with their own liver is reviewed. The hepatic survival indexes of (success, death or transplant) are beyond the tenth year. The problems raised during the follow-up are analysed. RESULTS: From 99 patients with ABE treated primarily in our center, 22 reached the 10 year-old age after the PEA without a liver transplant. In the follow-up, seven if the these finally needed the transplant. Their median age was 12.2 year-old (range: 10.5-13.8) for a progressive hepatocellular damage in 5 cases associated to syndrome hepatopulmonar in two cases. The other fifteen patients have a compensated hepatopathy. Five of them do not have hyperesplenisme and the serum bilirrubine levels are lower than 1.3 mg/dL. The medium age of these patients at the end of the follow-up was 14.8 years. CONCLUSIONS: In spite of the reestablishment of the biliary flow with the PEA, few are the patients with ABE that preserve their hepatic function lapsed long periods of time. Nevertheless the prognosis of these patients is excellent.

[Pre-hepatic portal hypertension as a late complication of liver transplantation in children]. / Hipertensión portal prehepática como complicación tardía del trasplante hepático pediátrico.

UNLABELLED: In the long-term after liver transplantation (LT), some children develop prehepatic portal hypertension (PPH) and raise problems not very well known yet; many of the lessons learned with the management of these patients may be useful outside the LT. AIM: 1. To analyze the incidence and risk factors of PPH after LT. 2. To evaluate the results with the different treatments used. METHODS: Retrospective study over 164 children surviving more than 1 year after LT. Univariant analysis of possible risk factors associated and multivariant (logistic regression), for those that had significance in the univariant analysis. Other factors associated are analyzed as well as the indications and results of two types of treatment: percutaneous pneumatic dilatation and surgical shunt (splenorenal and Rex shunt). RESULTS: 9 children developed symptomatic PPH (hemorrhage in 8, ascites in 1), associated to lymphoproliferative post-LT disease in 2, and to anastomotic biliary stricture in 1. The age at first LT (children under 1 year old), weight (below 10 kg), and need of retransplantation (reLT) were in the univariant analysis the associated variables with increased risk of PPH. The diagnosis (biliary atresia) and the emergency status of the LT were almost significative. In the multivariant analysis, the need of reLT is the only independent variable that increases the risk (relative risk: 4.5, confidence interval 95%: 1.29-18.87). At diagnosis 3 cases showed portal estenosis, and 5 showed absence of permeability with cavernomatous transformation. The PPH was caused in one case because of the esplenic vein disconnection (treatment not required at the moment); the three cases of portal estenosis were dilated percutaneously with success, and 2 of the 5 cases with portal thrombosis have been surgically shunted: one by an splenorenal shunt and the other by a Rex shunt (first case done in Spain); the other 3 cases are stable waiting for a surgical solution. The hepatic function is normal in the 9 cases. CONCLUSIONS: The PPH can complicate the prognostic of the pediatric LT in the long term. The treatment depends on the permeability of the portal trunk. Whenever possible, percutaneous dilatation should be attempted; should surgery be required, the Rex shunt is the best option.

Liver transplantation in patients with homozygotic familial hypercholesterolemia previously treated by end-to-side portocaval shunt and ileal bypass.

Familial hypercholesterolemia is the result of mutations in the gene that encodes the synthesis of the cellular receptor for low density lipoprotein (LDL). In the homozygous form of the disease (HFHC), cellular LDL receptors either do not form, or, when present, cannot bond LDL and mediate its cellular uptake LDL, and the cholesterol that it transports accumulate in plasma, producing severe premature atherosclerosis and death from coronary artery disease usually before the age of 20. Currently, the only effective treatment is liver transplantation, which, alone or in association with medications, normalizes plasma cholesterol levels. The authors report the cases of 2 siblings with HFHC who underwent portocaval shunt at the ages of 2.5 and 1.5 years, respectively. Portocaval shunt produced an immediate, but insufficient decrease in cholesterol (by 40% and 35%, respectively), leaving them with cholesterol concentrations of about 500 mg/dL. One year later they each underwent ileal bypass without obtaining any significant response. Liver transplantation at the ages of 18 and 16 years, respectively, reduced plasma cholesterol concentrations to 129 and 225 mg/dL, respectively. The earlier operations seriously increased the technical difficulty of liver transplantation and did not produce a favorable effect on the natural course of the disease, so portocaval shunt and ileal bypass are not indicated in HFHC, not even for the purpose of delaying liver transplantation.

Long term effect of alpha interferon in children with chronic hepatitis B.

BACKGROUND/AIMS: The purpose of this study was to better define the long term prognosis of infection and disease in children with chronic hepatitis B treated with interferon (IFN) alpha. PATIENTS: A total of 107 children with chronic hepatitis B who received IFN alpha for three or six months in two clinical trials were followed for a mean period of 69 (17) months. Response to treatment was defined as loss of hepatitis B e antigen (HBeAg) within 12 months after stopping treatment. A control group of 59 patients was also followed for a shorter mean time (46 (19) months). RESULTS: Sixteen (15%) treated children responded during therapy and 18 (17%) during post-treatment follow up; 31 (29%) non-responders lost HBeAg during subsequent years. High pretreatment levels of transaminases and a greater histological activity index were predictors of response. Kaplan-Meier estimates of cumulative HBeAg clearance rates at five years were similar between treated patients (60%) and controls (65%). After HBeAg clearance, all cases lost hepatitis B virus DNA and 94% had normal transaminase levels. Loss of hepatitis B surface antigen (HBsAg) occurred in four (25%) patients who responded during treatment but in none of the other treated or untreated patients. CONCLUSIONS: After five years' observation, the proportion of treated children with sustained HBeAg clearance comprised an equal number of responders and non-responders and did not differ from that observed in untreated controls, suggesting that IFN simply accelerated a spontaneous event. However, IFN significantly improved the rate of HBsAg loss in cases with more prominent disease activity who were early responders, and may be particularly useful in this type of patient.

Long-term survival expectancy after liver transplantation in children.

PURPOSE: The aim of this study was to assess the long-term survival rate in children who have undergone orthotopic liver transplantation (OLT) in the last 13 years. METHODS: The records of 198 consecutive patients under 18 years of age who underwent 249 OLTs between 1986 and 1998 were reviewed. Actuarial patient survival rates were assessed at 1, 3, 5, and 10 years in the whole series, in the last 5 years, and in patients surviving more than 1 year. Age, weight, and indications were analyzed, as well as type and incidence of posttransplant complications. The median follow-up period was 41 months (0 to 154 months). RESULTS: Biliary atresia was the most common indication (41.9%) followed by alpha-1 antitrypsin deficiency (8.1%), Alagille syndrome (7.6%), and fulminant hepatic failure (6.6%). One hundred forty-six patients (58.6%) were below 5 years, and 46 patients were (18.5%) younger than 1 year at operation. Sixty-eight patients (27.3%) weighed less than 10 kg. One hundred seventy whole organs and 70 reduced, 5 living-related donor, and 4 split-liver allografts were used. Hepatic artery thrombosis (n = 18), primary nonfunction (n = 15), and chronic rejection (n = 14) were the most common causes for allograft failure. Fourteen patients (7%) had posttransplant lymphoproliferative disorders (PTLD) at a median time of 28 months (4 to 124 months) postoperation (3 died). The 1-, 3-, 5-, and 10-year actuarial patient survival rates are 80%, 76%, 74%, and 74%, respectively; over the last 5 years it is 88% at 1 year and 82% at 3 and 5 years. For patients surviving more than 1 year, 3-, 5-, and 10-year actuarial survival rates are 95%, 93%, and 93%, respectively. CONCLUSIONS: (1) Overall results of OLT improve with increasing experience. (2) Children who survive more than 1 year after OLT have an excellent prognosis, although long-term complications of immunosuppression can be expected.