Jean de Ville de Goyet

3-month and 12-month mortality after first liver transplant in adults in Europe: predictive models for outcome

BACKGROUND Mortality after liver transplantation depends on heterogeneous recipient and donor factors. Our aim was to assess risk of death and to develop models to help predict mortality after liver transplantation. METHODS We analysed data from 34,664 first adult liver transplants from the European Liver Transplant Registry to identify factors associated with mortality at 3-months (n=21,605 in training dataset) and 12-months (n=18,852 in training dataset) after transplantation. We used multivariable logistic regression models to generate mortality scores for each individual, and assessed model discrimination and calibration on an independent validation dataset (n=9489 for 3-month model and n=8313 for 12-month model). FINDINGS 2540 of 21,605 (12%) individuals in the 3-month training sample had died by 3 months. Compared with those transplanted in 2000-03, those transplanted earlier had a higher risk of death. Increased mortality at 3-months post-transplantation was associated with acute liver failure (adjusted odds ratio 1.61), donor age older than 60 years (1.16), compatible (1.22) or incompatible (2.07) donor-recipient blood group, older recipient age (1.12 per 5 years), split or reduced graft (1.96), total ischaemia time of longer than 13 h (1.38), and low United Network for Organ Sharing score (score 1: 2.43; score 2: 1.67). However, cirrhosis with hepatocellular carcinoma, alcohol cirrhosis, hepatitis C or primary biliary cirrhosis, donor age 40 years or younger, or less, hepatitis B, and larger size of transplant centre (> or = 70 transplants per year) were associated with improved early outcomes. The 3-month mortality score discriminated well between those who did and did not die in the validation sample (C statistic=0.688). We noted similar findings for 12-month mortality, although deaths were generally underestimated at this timepoint. INTERPRETATION The 3-month and 12-month mortality models can be effectively used to assess outcomes both within and between centres. Furthermore, the models provide a means of assessing the risk of post-transplantation mortality, giving clinicians important data on which to base strategic decisions about transplant policy in particular individuals or groups.

Split liver transplantation in Europe--1988 to 1993.

The shortage of liver grafts results in the fact that 8% of potential recipients die before receiving a graft. Liver graft division has therefore been proposed to maximize the current available liver graft pool. However, the question of benefit or additional risk for the recipient that this technique might carry remains unanswered. The European Split Liver Registry was opened in March 1993 and reviewed retrospectively the clinical experience obtained at nine European centers regarding the use of split liver transplants, during the five year period from March 1988 to March 1993. From 50 donor livers, 100 grafts were prepared: 2 grafts were discarded and the other 98 were transplanted in 53 children (2 times in 3 children) and 42 adults (2/42 in heterotopic position). Sixty-three grafts were implanted in an urgent recipient (half of whom had acute hepatic failure). Portal vein thrombosis, hepatic artery thrombosis, biliary complications, and retransplantation rates were 4%, 11.5%, 18.7%, and 18.7%, respectively. Most of these complications were unrelated to the technique itself. Actual 6-month graft survivals of elective and urgent orthotopic transplants were 80% and 61.3% in children, and 72.2% and 55.6% in adults; actual 6-month patient survival rates for similar groupings were 88.9% and 61.1%, and 80% and 67.7%, respectively. Similar rates are reported after conventional transplants in Europe. It is concluded that split liver transplantation is an efficient transplant technique that benefits both urgent patients who otherwise could have died before getting a graft in time and elective patients.

Pediatric liver transplantation with cadaveric or living related donors: comparative results in 90 elective recipients of primary grafts.

STUDY DESIGN Between July 1993 and March 1997, 110 children were listed for primary elective liver transplantation with cadaveric (Cad: n = 68) or living-related (LR: n = 42) donors. Pregraft mortality, post-transplant survival, and surgical and immunologic complications were retrospectively compared in both groups. RESULTS The pregraft mortality rate was 10 (15%) of 68 versus 1 (2%) of 42 in the Cad and LR groups, respectively (P =.049). Postliver transplantation 1-year patient and graft survival rates were 87% and 75% in the Cad group (n = 49) versus 92% and 90% in the LR group (n = 41), respectively (NS). The incidence of post-transplant complications was as follows: hepatic artery thrombosis (Cad: 16%; LR: 0%, P =.020), portal vein thrombosis (Cad: 8%; LR: 2%, NS), and biliary complications (Cad: 14%; LR: 34%, P =.044). The overall incidence of acute rejection was similar in both groups; however, a lower incidence of acute rejection occurred in LR graft recipients treated with tacrolimus. CONCLUSIONS The introduction of an LR donor liver transplantation program allowed a significant decrease in the pretransplant mortality rate, with a consequent overall improvement in patient survival compared with the Cad series. The incidence of biliary complications was higher in the LR series, whereas better human leukocyte antigen matching in this subgroup did not result in a lower rejection incidence.

Cryopreserved liver cell transplantation controls ornithine transcarbamylase deficient patient while awaiting liver transplantation.

Liver cell transplantation was performed in a child with urea cycle disorder poorly equilibrated by conventional therapy as a bridge to transplantation. A 14‐month‐old boy with ornithine transcarbamylase (OTC) deficiency received 0.24 billion viable cryopreserved cells/kg over 16 weeks. Tacrolimus and steroids were given as immunosuppressive treatment while the patient was kept on the pre‐cell transplant therapy. Mean blood ammonia level decreased significantly following the seven first infusions, while urea levels started to increase from undetectable values. After those seven infusions, an ammonium peak up to 263 μg/dL, clinically well tolerated, was observed. Interestingly, blood urea levels increased continuously to reach 25 mg/dL, after the last three infusions. Eventually, he benefited from elective orthotopic liver transplantation (OLT) and the post‐surgical course was uneventful. We conclude that use of cryopreserved cells allowed short‐ to medium‐term metabolic control and urea synthesis in this male OTC‐deficient patient while waiting for OLT.

Surgical guidelines for the management of extra-hepatic portal vein obstruction

Abstract:  The recent introduction of the meso Rex bypass raises a possible paradigm shift in the therapeutic approach to extra‐hepatic portal vein obstruction (EHPVO). Long‐term follow‐up of patients with EHPVO has revealed a variety of complications including variceal hemorrhage, hypersplenism, biliopathy, growth/development retardation and neuropsychiatric disease. The meso Rex bypass restores physiologic blood flow to the liver. Thus, when feasible, the meso Rex bypass should be considered in patients with clinically significant manifestations of EHPVO. The opinions of a panel of experts regarding the surgical approach to the management of EHPVO are presented.

Liver transplantation for hepatoblastoma: Indications and contraindications in the modern era

Abstract:  In the past 20 yr, a dramatic improvement has been achieved in the outcome of children with hepatoblastoma by combining cisplatin based chemotherapy and surgery. Treatment of patients in the USA is an exception to the rule that all patients should receive neoadjuvant chemotherapy. It is paramount that surgical resection be complete, both macro‐ and microscopically. Complete tumor resection can be achieved after chemotherapy with a partial hepatectomy when the intrahepatic extent is limited to 1–3 sectors. In multifocal (and solitary) hepatoblastomas invading all four liver sectors, and in centrally located tumors with close proximity to the major veins, the SIOPEL‐1 study and an extensive review of the world experience have shown that primary transplantation provides high, long term, disease‐free survival rate in the range of 80%. In contrast, the results of rescue transplants for incomplete tumor resection or disease recurrence after partial hepatectomy are disappointing (in the range of 30%). Hazardous attempts at partial hepatectomy in children with extensive hepatoblastoma should be discouraged. Guidelines are provided for early referral of children with extended hepatoblastoma to a transplant surgeon. There is a trend for a better patient survival after living related liver transplantation. Patients who will become candidates to liver transplantation should be treated with chemotherapy following the same protocols as for children undergoing a partial hepatectomy. There is a concern about cumulative nephrotoxicity of calcineurin inhibitors and chemotherapeutic drugs. Recent data suggest that these patients tolerate lower Tacrolimus trough blood levels than those transplanted for non‐malignant conditions, without increasing the risk of acute rejection. Due to the rarity of the disease, these children should be treated in specialized centers.

Hirschsprung's disease: A 20-year experience

During the period from 1972 to 1992, 59 children received surgical treatment at the University of Louvain Medical School for biopsy-proven Hirschsprungs disease (HD). The extent of aganglionosis was as follows: short segment restricted to the rectosigmoid or descending colon (n = 44, 75%); long segment (n = 9,15%); ultra-short segment (n = 3, 5%); unknown length because of death without autopsy (n = 3, 5%). The median age at operation was 7 months for short-segment disease compared with 14 months for those with long-segment disease. Surgical procedures used for short-segment disease were Swenson with colostomy (n = 16), Swenson-Pellerin without colostomy (n = 27), Duhamel (n = 1), and for long-segment disease were Martin (n = 3), Swenson-Deloyers (n = 2), Swenson-Boley (n = 2) and ileostomy only in = 2). Lynns sphincteromyotomy was performed in the three ultra-short cases. There were six deaths (10%) at a median age of 86 days (range, 28 to 1545 days), three had long-segment disease, and the others were not classified because of death before curative surgery. Enterocolitis (EC) was the most common cause of death (five cases) and was also the major source of morbidity after curative surgery (12 of 44, 27%) in short-segment patients, three of seven (43%) in long-segment patients. The functional success of the procedure was evaluated in 70% of the surviving patients (37 of 53; mean follow-up, 8.7 years; range, 1.2 to 21.5), using a novel semiquantitative scoring system, specifically designed for children who have HD. This system assesses normal stool evacuation, abdominal distention, soiling, and severe incontinence. The results were compared with those from a population of 39 healthy children and adolescents and demonstrated progressive improvement in function during childhood and adolescence (P = .04) for patients treated for short-segment disease. However, function was found to be consistently poorer in all age groups when compared with healthy controls (5 to 10 years, P < .01; 10 to 15 years, P < .05; > 15 years, P < .01).

Laparoscopic splenectomy in adults and children: experience with 31 patients.

BACKGROUND Open surgery is the standard approach for splenectomy in hematologic disorders, but a few cases of successful laparoscopic splenectomy have been reported. METHODS Thirty-one patients (18 adults, group 1; and 13 children, group 2) underwent laparoscopic splenectomy. Indications for surgery included idiopathic thrombocytopenic purpura (25 patients), congenital spherocytosis (4 patients), and hemolytic anemia (2 patients). In 97% of the patients the diameter of the spleen was less than 15 cm. RESULTS Laparoscopic splenectomy was successful in 94% of the patients; conversion to open surgery was mainly related to hemorrhage. Accessory spleen was found in 39% in group 1 and 8% in group 2. Two adults received intraoperative autotransfusion. Postoperative morbidity was minimal. The median postoperative stay was 3 days (range, 2 to 12 days) in group 1 and 2 days (range, 2 to 5 days) in group 2. CONCLUSIONS Laparoscopic splenectomy is safe in both adults and children. Adequate selection of patients (small-size spleen, splenic destruction on preoperative scanning of platelets), appropriate preparation in patients with idiopathic thrombocytopenic purpura (immunoglobulin G), and meticulous surgical technique (with routine opening of the gastrocolic ligament to search for accessory spleen) are key factors in obtaining the same long-term results as with open surgery.

Expert pediatric opinion on the Report of the Baveno IV Consensus Workshop on Methodology of Diagnosis and Therapy in Portal Hypertension

Abstract:  Portal hypertension leads to a wide variety of complications, which lead to significant morbidity and mortality and are some of the leading reasons for liver transplantation in children with chronic liver disease. Evidence‐based approaches to the management of adults with portal hypertension exist and have been comprehensively reviewed in a series of international meetings, including the Baveno meetings. Similar evidence‐based approaches for the management of portal hypertension in children do not exist and as such international meetings on portal hypertension have not focused on this problem in children. On October 7, 2005 at The Mount Sinai School of Medicine, a panel of pediatric experts reviewed the most recent Baveno statement and crafted a statement modified with their opinions vis a vis approaches to the management of portal hypertension in children.

Permanent access to the portal system for cellular transplantation using an implantable port device.

A novel application of the implantable Port‐a‐Cath (PAC) system is described in the context of cellular transplantation. A silicone catheter was inserted in a collateral branch of the portal vein and connected to a port device positioned subcutaneously on the left thoracic cage. This permanent vascular access allowed iterative intraportal infusions of allogenic hepatocytes without the need of repeated transhepatic catheterization of the portal vein. Using this technique, repeated infusions of cryopreserved and / or fresh hepatocytes were successfully carried out in 3 children with inborn errors of liver metabolism, with the aim of progressively providing a sufficient mass of transplanted liver cells to stabilize the metabolic condition of the patients. We suggest that this technique might also be valuable in pancreatic islet cell transplantation. (Liver Transpl 2004;10:1213–1215.)