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D Houssin

Publications and source records attributed to D Houssin.

At least 91 records · Page 5Linked to original sources
PubMed1995

Liver transplantation in children with Alagille syndrome--a study of twelve cases.

Cholestasis associated with Alagille syndrome may, in a few cases, be extremely severe and result in major impairment in the quality of life during early childhood and end up in cirrhosis eventually. We report the results of liver transplantation in 12 children with a severe hepatic form of Alagille syndrome. All children presented with cholestatic jaundice from birth, peculiar facies, stenosis of the peripheral pulmonary artery, and posterior embryotoxon; butterfly-like vertebrae were present in 9 children. At the time of transplantation (mean age 7 years 10 months) refractory pruritus was present in 9 children, xanthoma in 11, and height and weight retardation in 11. Total serum bilirubin ranged from 116 to 322 mumol/L and total serum cholesterol from 3.5 to 29 mmol/L. Systolic right ventricular pressure was moderately raised (36 to 48 mmHg) in 5 children; mean creatinine clearance was 99 ml/min/1.73 m2. Histologic examination of the removed livers showed cirrhosis, severe annular fibrosis, and moderate portal fibrosis in 4 children each. Follow-up in the 11 survivors has ranged from 14 months to 5 1/2 years. All lead normal lives. Pruritus and xanthomas disappeared. Increase in height was observed in 8 of the 10 survivors who had growth retardation prior to transplantation. School level is normal in 4 (median age at LT: 5 yr 9 mo) and below normal in 6 (median age at OLT: 9 yr 9 mo). Liver function tests are normal in 10 children. Mean creatinine clearance is 101 ml/min/1.73 m2. These results indicate that the quality of life can be considerably improved after liver transplantation in children with a severe hepatic form of Alagille syndrome and suggest that it could be carried out before these children attend elementary school.

Alagille Syndrome↗
PubMed1995

Risk and prognostic factors of gut perforation after orthotopic liver transplantation for biliary atresia.

The aim of this study was to assess the risk and prognostic factors of gut perforation after orthotopic liver transplantation in children with biliary, atresia using univariate and stepwise regression analysis. Among 51 pediatric recipients who underwent transplantation because of biliary atresia after failure of portoenterostomy, 10 patients (20%) had 19 episodes of gut perforations after 14 transplantations. The median delay between transplantation and perforation was 13 days. These perforations were treated either by suture (n = 21) or ostomy (n = 11). The study of preoperative and perioperative variables showed that children with gut perforation were in surgery for a significantly longer period of time including a longer period of receiving hepatectomy and undergoing portal venous clamp. These children also needed large amounts of blood transfused during hepatectomy. After transplantation there was no difference regarding total steroid doses and early occurrence of cytomegalovirus disease between the two groups. Stepwise regression analysis identified three factors associated with the occurrence of gut perforation: duration of transplant operation, posttransplant intra-abdominal bleeding requiring reoperation, and early portal vein thrombosis. During the postoperative course, severe fungal infections were significantly more frequent in the gut perforation group. The 3-year patient survival rate was 70% in the group with gut perforation and was not different from the group without perforation (80%). This study shows that children with previous portoenterostomy carry a high risk of developing gut perforation after liver transplantation. This is especially true for those patients with the most difficult hepatectomies, which are responsible for the iatrogenic injury of the bowel. Other risk factors pointed out in this study were splanchnic congestion in case of prolonged portal venous clamp time or early portal vein thrombosis and repeated trauma of the bowel caused by reoperations. On the other hand, other well known risk factors, such as steroid therapy and viral diseases, were not involved in the occurrence of gut perforations in this study. Besides emergent surgical treatment, this type of complication requires aggressive therapy against fungal infections.

Biliary Atresia↗
PubMed1995

Metastatic endocrine tumors: is there a place for liver transplantation?

The authors describe their experience with liver transplantation (OLT) for metastatic endocrine tumors (MET) in order to determine reasonable indications for OLT in patients with this disease. Removal of the primary lesion and subsequent liver transplantation were performed in two separate procedures in all patients except one. Only those patients suffering from objective tumor progression and symptoms with no evidence of extrahepatic spread after complete work-up (including endoscopic ultrasonography (US) and 123I-labeled Tyr3-octreotide body scanning) underwent liver transplantation. Fifteen patients were referred for liver transplantation. Seven patients were excluded either because of stability of liver metastases (n = 3), extrahepatic spread, general contraindication (n = 2), or feasibility of aggressive surgical resection (n = 2). Liver transplantation was undertaken in eight patients with carcinoid tumor (n = 4), gastrinoma (n = 3) and glucagonoma (n = 1). Three patients did not survive the surgical procedure itself, whereas two additional patients died from chronic rejection or from recurrent disease. Three patients who received transplants for metastatic carcinoid tumor are alive without biochemical or imaging evidence of disease recurrence at 6, 15, and 52 months. The best indication for transplantation seems to be patients with metastases restricted to the liver and unresponsive to adjuvant therapy after aggressive surgical resection including excision of the primary lesion and reduction of hepatic metastases. In such highly-selected patients, liver transplantation remains a high-risk operation, but it can yield long-term survival.

Adult↗
PubMed1995

Evidence for the detrimental role of proteolysis during liver preservation in humans.

BACKGROUND/AIMS: Proteolysis may persist in the liver allograft during cold storage. The aim of this study was to determine the significance of proteolysis within liver allografts stored at 4 degrees C in University of Wisconsin preservation fluid. METHODS: Thirty recipients of 32 liver allografts were studied prospectively. Amino acid content of the preservation fluid was analyzed at the end of cold storage and was correlated to graft and patient outcome after transplantation. RESULTS: Analysis of the preservation fluid showed the presence of free amino acids, the profile of which was different from that of stored liver parenchyma. Concentrations of amino acids (alanine, cysteine, leucine, isoleucine, methionine, lysine, ornithine, and threonine) and transaminases (alanine aminotransferase and aspartate aminotransferase) in the preservation fluid correlated with the duration of cold ischemia. Indexes of graft dysfunction (serum alanine aminotransferase and aspartate aminotransferase peaks and prothrombin rate) correlated with concentrations of cysteine, alanine, isoleucine, leucine, methionine, lysine, ornithine, and threonine, whereas enzyme concentrations in the fluid were not predictive of graft dysfunction. CONCLUSIONS: These data suggest that liver proteolysis occurs during cold storage and may have a detrimental effect on the outcome after transplantation. The measurement of the amino acids in the preservation fluid at the end of the cold storage period could help to identify the most severely damaged organs.

Adenosine↗
PubMed1995

Pulmonary arteriovenous shunting in children with liver disease.

Pulmonary arteriovenous shunting (PAVS) with hypoxemia is a severe complication of cirrhosis that may regress after liver transplantation. We report PAVS in 25 children with cirrhosis and in 1 with portal vein obstruction; proof of shunting was obtained by technetium Tc 99m microaggregated albumin pulmonary scanning or a high alveoloarterial O2 gradient or both. Cyanosis or dyspnea or both occurred at ages ranging from 6 months to 14 years, earlier in children with biliary atresia and polysplenia syndrome (p < 0.01). Mean arterial oxygen tension (PaO2) was 57 mm Hg (range, 42 to 81 mm Hg) during breathing of 21% O2 and 367 mm Hg (range, 179 to 535 mm Hg) in 100% O2. Cardiac index was always raised, significantly more in children with biliary atresia and polysplenia syndrome (p < 0.01). Seven untreated children died 3 months to 8 years after the diagnosis of PAVS. Eleven underwent liver transplantation: seven are alive (follow-up, 1 to 4 years) and have no signs of PAVS. The PaO2 value during breathing of 100% O2 was > 300 mm Hg in the survivors and < 200 mm Hg in the four nonsurvivors (p < 0.01). These results indicate (1) that PAVS can occur at any age in children with portal hypertension, and that the risk is highest and earliest in children with biliary atresia and polysplenia syndrome, (2) that early liver transplantation allows regression of PAVS, and (3) that the prognosis may in part be related to the level of PaO2 while the patient is breathing 100% O2. The results indicate that systematic screening for PAVS should be part of the examination of these children.

Adolescent↗
PubMed1995

Efficient retroviral-mediated gene transfer into primary culture of murine and human hepatocytes: expression of the LDL receptor.

The ex vivo approach to hepatic gene therapy involves several steps, which include the isolation and culture of hepatocytes, followed by their transduction with a retrovirus. Subsequently, autologous hepatocytes are transplanted. The number of hepatocytes that can be transduced by retroviruses bearing the therapeutic gene is one of the limiting steps that can impair the success of this strategy. We presently describe an experimental approach that leads to improved transduction efficiency in mouse and human hepatocytes in vitro. By using a recombinant retrovirus bearing the Escherichia coli beta-galactosidase gene, we show that addition of growth factors to the cells, namely human hepatocyte growth factor (HGF), allows marked increase in the transduction efficiency in mouse (up to 80%) and human (40%) hepatocytes. Familial hypercholesterolemia (FH) is due to mutation in the low-density lipoprotein (LDL) receptor gene and results in a deficiency in LDL receptors. Transduction of the human LDL receptor cDNA under the transcriptional control of the L-type pyruvate kinase promoter-activator into mouse hepatocytes led to an elevated tissue-specific expression of the human protein. These results suggest that the ex vivo approach remains a promising alternative for hepatic gene therapy.

Animals↗
PubMed1995

Intraoperative blood loss in pediatric liver transplantation: analysis of preoperative risk factors.

The relative contribution of 14 preoperative risk factors to a high intraoperative blood loss was studied in 95 consecutive first pediatric orthotopic liver transplantations (OLT). Patients were distributed in two groups according to red blood cell (RBC) requirements. Wide interindividual RBC requirements were observed (median, 79 mL/kg; range, 4-586). The upper quartile of the population was defined as the high blood loss group and required 123 mL/kg or more (median, 161). On univariate analysis, the high blood loss group had a significantly higher proportion of patients with portal vein hypoplasia, intraabdominal malformations, signs of severe liver failure (encephalopathy, ascites, prolonged prothrombin time), and requiring inpatient support. Age, previous abdominal surgery, and platelet count had no prognostic value. All variables used in the univariate analysis were included in a stepwise logistic regression analysis. Only presence of portal vein hypoplasia, inpatient support, and use of a reduced-size liver graft were independently associated with a high blood loss. Adjusted odds ratios were 40.4 (95% confidence interval; 5.9-278), 5.4 (1.6-17.9), and 3.8 (0.9-15.2), respectively, highlighting the importance of portal vein hypoplasia as a risk factor for high blood loss.

Abdomen↗
PubMed1995

Pediatric liver transplantation for Langerhans' cell histiocytosis.

Langerhans' cell histiocytosis (LCH) represents 15% to 20% of sclerosing cholangitis (SC) in children. In LCH-associated SC, a very poor response to chemotherapy has been reported, and spontaneous prognosis is very bad. Few cases of orthotopic liver transplantation (OLT) for LCH have been reported and little is known about the risk of recurrence and the effect of immunosuppression after OLT. Since 1986, five children (mean age +/- SD, 12.6 +/- 3.6 years) underwent OLT for SC complicating LCH. All patients presented with growth retardation, and severe liver disease including repeated episodes of variceal bleeding (n = 5), liver insufficiency (n = 4), jaundice (n = 5), and ascitis (n = 4). Four patients presented with previous abdominal surgery (mesocaval shunt in two and explorative laparotomy in two). OLT was performed using a whole (n = 2) or a reduced liver graft (n = 3). Pathological examination of the recipient liver showed biliary cirrhosis in all cases. Three patients are alive and well 9 to 88 months after OLT. None presented with recurrence of LCH or SC within the liver graft or in other organs. General condition (including growth and puberty) improved dramatically in the three surviving patients. Absence of recurrence after up to 7 years of follow-up after liver transplantation in our patients, as well as in all other reported cases, is encouraging and shows that OLT may be indicated in end-stage liver disease complicating LCH. Furthermore, cyclosporine may be beneficial for preventing recurrence of LCH, in which autoimmunologic mechanisms have been advocated.

Adolescent↗
PubMed1994

A randomized trial of OKT3-based versus cyclosporine-based immunoprophylaxis after liver transplantation. Long-term results of a European and Australian multicenter study.

A multicenter randomized trial was performed to compare two immunosuppressive protocols after first ABO-compatible liver transplantation. Forty six patients were randomized to a 14-day treatment with Orthoclone (OKT3) in association with steroids and azathioprine, cyclosporine being progressively introduced on day 11 posttransplant. Fifty patients were randomized to a standard protocol of cyclosporine with steroids and azathioprine. Minimum follow-up was 1 year and graft and patient survivals were updated for the purpose of the study. The cumulative 1-year incidence of acute rejection tended to be greater in the cyclosporine group (75%) than in the OKT3 group (67%), especially when patients who did not receive full-course treatment with OKT3 were excluded (59%). Renal function was better preserved during the first two postoperative weeks in the OKT3 group than in the control group but plasma creatinine levels were comparable in both groups thereafter. The incidence of severe infections was lower in the OKT3 group (13.6%) than in the cyclosporine group (32%). The 4-year incidences of patient and graft survival in the OKT3 group (69% and 61%, respectively) were not different from those in the cyclosporine group (62% versus 54%, respectively). Thus this prospective trial shows that OKT3 immunoprophylaxis is a safe alternative to cyclosporine immunoprophylaxis in unselected recipients of a first liver graft.

Adolescent↗
PubMed1994

[Liver transplantation in children].

Liver transplantation has become the treatment of many chronic liver diseases, acute hepatic failure and several metabolic diseases in children. Early referral to a transplantation center represents the major condition for its favourable outcome, in order to undertake this complex surgical procedure under the best conditions and to allow a rapid and complete recovery. The increasing shortage of organs leading to graft reduction, graft splitting and living related donation, the feasibility of multiple organ transplantation, the progress of gene therapy, the development of new extra-corporeal liver assist devices and the introduction of the auxiliary partial orthotopic liver transplantation have all contributed to significative changes in the perspectives of pediatric liver transplantation. Furthermore, new immunosuppressors as well as encouraging experimental results on graft tolerance may help in the near future to improve the long-term quality of life of pediatric recipients.

Child↗