Charles M. A. Bijleveld

Selection criteria for liver donation: a review

An overview of the criteria that are currently being used for the selection of liver donors is presented. The validity of the different criteria is discussed. The potential benefits of introducing other modalities is dealt with.

Graft Loss After Pediatric Liver Transplantation

ObjectiveTo describe the epidemiology and causes of graft loss after pediatric liver transplantation and to identify risk factors. Summary Background DataGraft failure after transplantation remains an important problem. It results in patient death or retransplantation, resulting in lower survival rates. MethodsA series of 157 transplantations in 120 children was analyzed. Graft loss was categorized as early (within 1 month) and late (after 1 month). Risk factors were identified by analyzing recipient, donor, and transplantation variables. ResultsKaplan-Meier 1-month and 1-, 3-, and 5-year patient survival rates were 85%, 82%, 77%, and 71%, respectively. Graft survival rates were 71%, 64%, 59%, and 53%, respectively. Seventy-one of 157 grafts (45%) were lost: 18 (25%) by death of patients with functioning grafts and 53 (75%) by graft-related complications. Forty-five grafts (63%) were lost early after transplantation. Main causes of early loss were vascular complications, primary nonfunction, and patient death. Main cause of late graft loss was fibrosis/cirrhosis, mainly as a result of biliary complications or unknown causes. Child-Pugh score, anhepatic phase, and urgent transplantation were risk factors for early loss. Donor age, donor/recipient weight ratio, blood loss, and technical-variant liver grafts were risk factors for late loss. ConclusionsTo prevent graft loss after pediatric liver transplantation, potential recipients should be referred early so they can be transplanted in an earlier phase of their disease. Technical-variant liver grafts are risk factors for graft survival. The logistics of the operation need to be optimized to minimize the length of the anhepatic phase.

Retransplantation of the liver in children

Background. Because of the poor outcome of hepatic retransplantation, it is still debated whether this procedure should be performed in an era of donor organ scarcity. The aim of this study was to analyze outcome of hepatic retransplantation in children, to identify risk factors influencing this outcome, and to assess morbidity and causes of death. Methods. A series of 97 children after a single transplantation and 34 children with one retransplantation was analyzed. Results. The 1-, 3-, and 5-year survival of children with a retransplantation was 70, 63, and 52%, respectively, compared with 85, 82, and 78%, respectively, for children after a single transplantation (P =0.009). Survival of children with a retransplantation within 1 month after primary transplantation was worse (P =0.007) and survival of children with a late retransplantation was comparable (P =0.66) with single transplantation. In early retransplantations, the Child-Pugh score was higher, donors were older and weighed more, and more technical variant liver grafts were used compared with single transplantations. Biliary atresia and a high Child-Pugh score were associated with decreased patient survival after retransplantation. Sepsis was the most important complication and cause of death after retransplantation. Conclusions. Retransplantation is a significant event after pediatric liver transplantation. Outcome after hepatic retransplantation in children is inferior compared with single transplantation. This difference is explained by low survival after early retransplantation and can be explained by the poor clinical condition of the children at time of retransplantation, especially in children with biliary atresia, and by the predominant use of technical variant liver grafts in retransplantations.

Cyclosporine A-induced reduction of bile salt synthesis associated with increased plasma lipids in children after liver transplantation.

Hyperlipidemia is a common side effect of cyclosporine A (CsA) after solid organ transplantation. CsA also markedly reduces the synthesis rate of bile salts in rats and can inhibit biliary bile salt secretion. It is not known, however, whether CsA inhibits the synthesis of bile salts in humans, and whether the hyperlipidemic effects of CsA are related to bile salt metabolism. Our objective was to assess the effects of CsA on the synthesis rate of bile salts and on plasma triglycerides and cholesterol levels in pediatric liver transplant patients. Before and after discontinuation of CsA treatment after liver transplantation, synthesis rate and pool size of the primary bile salts cholate and chenodeoxycholate were determined using a stable isotope dilution technique and related to plasma lipids. In 6 children (age: 3–16 years) CsA treatment was discontinued at 2 years (median 2.3 years) after liver transplantation. Discontinuation of CsA increased synthesis rate of chenodeoxycholate (+38%, P < .001) and cholate (+21%, P < .05) and the pool size of chenodeoxycholate (+54%, P < .001). Discontinuation of CsA decreased plasma levels of cholesterol (–18%, P < .05) and triglycerides (–23%, P < .05). Bile salt synthesis rate appeared to be inversely correlated with plasma cholesterol (Spearman rank correlation coefficient [rs] = −0.82, P < .01) and plasma triglyceride levels (rs = −0.62, P < .05). In conclusion, CsA inhibits bile salt synthesis and increases plasma concentration of cholesterol and triglycerides in pediatric liver transplant patients. Suppression of bile salt synthesis by long‐term CsA treatment may contribute to hyperlipidemia and thus to increased risk for cardiovascular disease. (Liver Transpl 2004;10:872–880.)

Doppler ultrasound of the hepatic artery and vein performed daily in the first two weeks after orthotopic liver transplantation - Useful for the diagnosis of acute rejection?

RATIONALE AND OBJECTIVES To analyze changes in Doppler ultrasound variables in relation to liver biopsy findings for the diagnosis of acute rejection after orthotopic liver transplantation (OLT), the authors performed in a prospective study 316 Doppler ultrasound examinations in the first 2 weeks after OLT on 23 patients. METHODS Recordings were obtained daily from the hepatic artery (resistive index [RI]) and hepatic vein (damping index [DI]). Correlations were explored between the Doppler ultrasound findings and histologic data. The chi-square test was used to analyze differences in Doppler ultrasound variables in patients with and without acute rejection. RESULTS Serial Doppler ultrasound examinations showed a significant increase in the RI in 11 of 22 patients (50%); the 23rd patient was excluded because of hepatic artery thrombosis. Despite an agreement in 15 of 22 patients (68%) no statistically significant correlation could be found (positive predictive value 6/11 = 55%; negative predictive value 9/11 = 82%; chi-square = 3.14; P > 0.05). A significant increase in the DI was observed in 14 of 23 patients (61%). However, no statistically significant correlation could be found as well with this parameter (positive predictive value 6/14 = 43%; negative predictive value 6/9 = 67%; chi-square = 0.00; P > 0.05). CONCLUSION Serial Doppler ultrasound examinations were not helpful in predicting acute rejection.

Predictive factors for portal fibrosis in pediatric liver transplant recipients

Background. Recent histopathological studies showed an unexpected high incidence of pathological changes in asymptomatic survivors after pediatric liver transplantation. The aim of this study was to analyze the occurrence of histological abnormalities, to assess the clinical significance, and to identify predictive factors for these pathological changes. Methods. The first annual protocol graft biopsies of 84 consecutive liver transplants were analyzed and correlated with concomitant liver function tests. Identification of predictive factors for the histological abnormalities in the biopsies was performed by a multivariate logistic regression analysis. Results. The incidence of portal fibrosis (PF) was 31%. Liver function tests showed except for the albumin level, an increase in the PF group compared with the group without PF. Mean values of alkaline phosphatase and direct bilirubin were 264 U/liter and 3 &mgr;mol/liter, respectively, in the normal group, and 435 U/liter and 23 &mgr;mol/liter, respectively, in the PF group (P =0.043 and 0.037). Eight of 19 univariantly tested variables were entered into a logistic regression model: cold ischemia time, preservation solution, type of allograft, cytomegalovirus recipient status, type of biliary reconstruction, biliary complications, graft complications, and rejection. A significant positive correlation with PF was found for cold ischemia time, biliary complications, and cytomegalovirus status. Acute rejection showed a negative correlation. Conclusions. The incidence of PF within 1 year post liver transplantation was 31%. This finding was accompanied by cholestatic liver function test abnormalities. Factors predisposing to PF were a prolonged cold ischemia time, biliary complications, and a positive cytomegalovirus recipient status. Acute rejection seemed to prevent for PF.

Analysis of growth in children after orthotopic liver transplantation.

Growth after pediatric liver transplantation is an important factor in determining the quality of life. We collected data on height, skeletal age, and liver function of 45 consecutive pediatric transplant recipients and assessed the influence of primary diagnosis, liver function, and immunosuppressive regimen on their growth. Height and skeletal age were plotted as median standard deviation scores versus years post-transplantation. Growth, in terms of both height and skeletal age, were continuous without catch-up growth. Primary diagnosis was found to have no influence on height and poor liver function had a negative effect on both height and skeletal growth. A higher alternate day prednisolone maintenance dose also had a negative effect on skeletal growth. Thus, it can be concluded that a pretransplant lack of growth will not be restored and is an indication for early transplantation in endstage liver disease, especially in younger children.

The effect of HLA mismatches, shared cross-reactive antigen groups, and shared HLA-DR antigens on the outcome after pediatric liver transplantation

The aim of this study was to analyze the effect of human leukocyte antigen (HLA) class I and HLA‐DR mismatching, sharing cross‐reactive antigen groups (CREGs), and sharing HLA‐DR antigens on the outcome after pediatric liver transplantation. Outcome parameters were graft survival, acute rejection, and portal fibrosis. A distinction was made between full‐size (FSLTx) and technical‐variant liver transplantation (TVLTx). A total of 136 primary transplants were analyzed. The effect of HLA on the outcome parameters was analyzed by adjusted multivariate logistic and Cox regression analysis. HLA mismatches, shared CREGs, and shared HLA‐DR antigens affected neither overall graft survival nor survival after FSLTx. Survival after TVLTx was superior in case of 2 mismatches at the HLA‐DR locus compared to 0 or 1 mismatch (P = 0.01) and in case of no shared HLA‐DR antigen compared to 1 shared HLA‐DR antigen (P = 0.004). The incidence of acute rejection was not influenced by HLA. The incidence of portal fibrosis could be analyzed in 62 1‐yr biopsies and was higher after TVLTx than FSLTx (P = 0.04). The incidence of portal fibrosis after TVLTx with 0 or 1 mismatch at the HLA‐DR locus was 100% compared to 43% with 2 mismatches (P = 0.004). After multivariate analysis, matching for HLA‐DR and matching for TVLTx were independent risk factors for portal fibrosis. In conclusion, an overall beneficial effect of HLA matching, sharing CREGs, or sharing HLA‐DR antigens was not observed. A negative effect was present for HLA‐DR matching and sharing HLA‐DR antigens on survival after TVLTx. HLA‐DR matching might be associated with portal fibrosis in these grafts. (Liver Transpl 2005;11:1541–1549.)

THE INFLUENCE OF INTRAOPERATIVE BLOOD-LOSS ON GRAFT-SURVIVAL AND MORBIDITY AFTER ORTHOTOPIC LIVER-TRANSPLANTATION IN CHILDREN

The aim of this study was to analyze the influence of intraoperative blood loss, expressed as an index of the circulating blood volume (BL), on patient and graft survival and on morbidity after primary orthotopic liver transplantation (OLT) in a series of 40 consequetive children (Mann-Whitney test, Pearson test). The influence on patient survival could not be assessed due to the low mortality. Graft survival and overall morbidity were not affected. Increased BL led only to a higher incidence of postoperative bleeding, with a subsequent higher intervention rate. In the group of children aged 3.75 years or less, significantly higher BL was found compared to the older children. In addition, prolonged intensive care unit stays and ventilator times were observed in this younger age group. The BL thus has limited repercussions on graft survival and morbidity after primary pediatric OLT.

The outcome of primary liver transplantation from deceased donors in children with body weight ≤ 10 kg

Abstract:  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%, 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 (3.0–7.0), 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.