Olga Ciccarelli

Pediatric liver transplantation using left hepatic segments from living related donors: Surgical experience in 100 recipients at Saint-Luc University Clinics

Abstract: Living‐related liver transplantation was developed in the context of deceased donor organ shortage, which is particularly acute for pediatric recipients. This retrospective study analyzes the surgical technique and complications in the first 100 pediatric liver transplantation using left segmental liver grafts from living donors, performed at Saint‐Luc University Clinics between July 1993 and April 2002. Pre‐operative evaluation in donors and recipients, analysis of the surgical technique, and postoperative complications were reviewed. After a median follow‐up period of 2526 days, no donor mortality was encountered, with a minimal morbidity and no long‐term sequelae. At one and five yr post‐transplantation, the actuarial patient survival rates were 94% and 92%, the corresponding figures being 92% and 89% for graft survival. The incidences of portal vein and hepatic artery thromboses, and of biliary complications were 14%, 1%, and 27%, respectively. Living‐related liver transplantation in children constitutes an efficient therapy for liver failure to face the increased demand for liver grafts. Donor morbidity was kept to acceptable incidence, and surgical technique in the recipient needs to be tailored to minimize postoperative complications.

Liver transplantation from donation after cardiac death donors: initial Belgian experience 2003–2007

The Belgian experience with donation after cardiac death (DCD) liver transplantation (LT) was retrospectively reviewed, particularly evaluating patient and graft survivals, and biliary complications. From 2003 to 2007, 58 DCD‐LT were performed in Belgium. Mean procurement total warm ischemia time was 25 ± 2 min (mean ± SEM). Mean cold ischemia time was 451 ± 18 min. Mean follow‐up was 23 ± 2.2 months. Post‐transplant peak aspartate aminotransminases was 2241 ± 338 UI/l. Patient survivals at 1 month, 1 and 3 years, were 91.3%, 83.3% and 66.9% respectively. Graft survivals at 1 month, 1 and 3 years, were 84.4%, 72.4% and 48.8% respectively. Two patients (3.4%) developed primary nonfunction. Regarding the biliary complications, seven grafts (12%) were lost because of intrahepatic cholangiopathy, and 12 other patients (20.6%) developed bile duct stenoses requiring endoscopic and/or surgical management. The rate of symptomatic ischemic biliary lesions for grafts surviving more than 3 months was 38% (19/50). Although DCD organ donors may be a source of viable liver grafts, results were inferior to those obtained with donation after brain death LT in this series. Prognostic criteria have to be developed to improve results of DCD‐LT.

Liver transplantation and neuroendocrine tumors: lessons from a single centre experience and from the literature review.

Neuroendocrine tumor (NET) metastases represent at this moment the only accepted indication of liver transplantation (LT) for liver secondaries. Between 1984–2007, nine (1.1%) of 824 adult LTs were performed because of NET. There were five well differentiated functioning NETs (four carcinoids and one gastrinoma), three well differentiated non functioning NETs and one poorly differentiated NET. Indications for LT were an invalidating unresectable tumor (4×), and/or a diffuse tumor localization (3×) and/or a refractory hormonal syndrome (5×). Median post‐LT patient survival is 60.9 months (range 4.8–119). One‐, 3‐ and 5‐year actuarial survival rates are 88%, 77% and 33%; 1, 3 and 5 years disease free survival rates are 67%, 33% and 11%. Due to a more rigorous selection procedure, results improved since 2000; three out of five patients are alive disease‐free at 78, 84 and 96 months. Review of these series together with a review of the literature reveals that results of LT for this oncological condition can be improved using better selection criteria, adapted immunosuppression and neo‐ and adjuvant surgical as well as medical tretament. LT should be considered earlier in the therapeutic algorithm of selected NET patients as it is the only therapy that can offer a cure.

Liver transplantation and HBsAg-positive postnecrotic cirrhosis : adequate immunoprophylaxis and delta virus co-infection as the significant determinants of long-term prognosis

BACKGROUND/AIMS The place of liver transplantation in hepatitis B viral (HBV)-related diseases remains controversial because of the high rate of reinfection. The aim of this study was to define the determinants of long-term prognosis after transplantation. METHODS Fifty-eight patients were transplanted during the period February 1984-September 1996. Six patients died during the early (< 3 months) posttransplant period from causes unrelated to HBV infection. All 52 long-term (> 3 months) survivors were evaluated in relation to the mode of presentation, viral replication at time of transplantation, absence of hepatocellular cancer at time of transplantation and use of adequate immunoprophylaxis (IP). Adequate immunoprophylaxis, defined as maintenance of anti-HBs levels over 100 mUI/ml, was introduced in December 1989. Intention-to-treat IP analysis compared patients transplanted before and after this date. The median follow-up was 74 months (range 4 to 131). Forty-seven patients (90%) had a minimal follow-up of 3 years. RESULTS Five-year actuarial survival rates of 58 patients and of 52 long-term survivors were 72 +/- 6% and 80 +/- 6%, respectively. Univariate analysis showed that delta co-infection (n = 25) significantly improved survival (p < 0.001) [96 +/- 4% vs 63 +/- 10% in HBV patients (n = 27) at 5 years] as did absence of hepatocellular cancer (n = 36) (p = 0.020) [89 +/- 5% vs 61 +/- 12% in 16 non-cancer patients]. IP, however, significantly influenced 5-year survival in the HBV-patient group (n = 17) (p = 0.001) [85 +/- 10% vs 30 +/- 14% in 10 patients without IP). Multivariate analysis selected delta co-infection (p = 0.002) and IP (p = 0.01) as the significant determinants of prognosis independently influencing survival. Uni- and multivariate analyses showed that survival without reinfection was significantly influenced by IP (p = 0.002) [73 +/- 8% (n = 31) versus 33 +/- 12% in 15 non-treated patients). CONCLUSIONS Delta virus co-infection and immunoprophylaxis are the most important prognostic factors after transplantation for postnecrotic HBsAg-positive cirrhosis. Transplantation can be proposed as a therapeutic tool only if life-long adequate adjuvant therapy can be achieved. Under this condition good results can even be obtained if there is viral replication at the time of transplantation.

Non‐adherence in adolescent transplant recipients: The role of uncertainty in health care providers

Aujoulat I, Deccache A, Charles A‐S, Janssen M, Struyf C, Pélicand J, Ciccarelli O, Dobbels F, Reding R. Non‐adherence in adolescent transplant recipients: The role of uncertainty in health care providers.
Pediatr Transplantation 2011: 15:148–156.

Transjugular intrahepatic portosystemic shunt approach and local thrombolysis for treatment of early posttransplant portal vein thrombosis.

Early portal vein thrombosis is a rare but severe posttransplant complication that may lead to graft and/or patient loss. Transjugular intrahepatic portosystemic shunting and local thrombolysis may represent an easy solution to this major complication of liver transplantation.

Tacrolimus monotherapy in liver transplantation: one-year results of a prospective, randomized, double-blind, placebo-controlled study.

Background:Minimal immunosuppression (IS) is desirable in organ transplantation to reduce side effects and to promote the process of tolerance induction. Material and Methods:Between February 2000 and September 2004, 156 adults (>15 years old) receiving a primary liver graft were enrolled in a prospective, randomized, double-blind, placebo-controlled, investigator-driven single-center study comparing tacrolimus (TAC)-placebo (PL) and TAC-low-dose, short-term (64 days) steroid (ST) IS. There were no exclusion criteria at moment of randomization. All patients had a 12-month follow-up (range, 12–84). Results:Three- and 12-month patient survival rates were 93.6% and 87.2% in the TAC-PL group and 98.7% and 94.7% in TAC-ST group (P = 0.096 and P = 0.093, respectively). Three- and 12-month graft survival rates were 92.3% and 85.9% versus 97.4% and 92.3% (P = 0.14 and 0.13, respectively). By 3 and 12 months, rejection treatment had been given in 20.5% (16 pts) and 23% (18 pts) of TAC-PL patients and in 12.7% (10 pts) and 20.5% (16 pts) of TAC-ST patients (P = 0.20 and 0.54). Corticosteroid-resistant rejection (CRR) at 3 and 12 months was recorded in 12.8% (10 pts) of TAC-PL patients and 3.8% (3 pts) of TAC-ST patients (P = 0.04). When considering the 145 patients transplanted without artificial organ support (n = 145), CRR at 3 and 12 months was recorded in 8.8% (6/68 pts) of TAC-PL patients and in 3.9% (3/77 pts) of TAC-ST patients (P = 0.22). Vanishing bile duct syndrome was diagnosed in 1 (1.2%) TAC-PL patient and 4 (5.1%) TAC-ST patients (P = 0.17). By 1 year, 78.2% (61/78) of TAC-PL patients and 82% (64/78) of TAC-ST patients were on TAC monotherapy (P = 0.54). When considering 67 TAC-PL and 74 TAC-ST survivors, rates of monotherapy were 91% (61 pts) and 86.5% (64 pts) (P = 0.39). At 1 year, 62.5% (42 pts) of TAC-PL survivors and 64.9% (48 pts) of TAC-ST survivors were on low-dosage (<6 ng/mL) TAC monotherapy (P 0.79). Conclusion:TAC monotherapy can be achieved safely without compromising graft nor patient survival in a primary, even unselected, adult liver transplant population. The higher incidence of early CRR in the TAC-PL group related to the significantly higher number of patients transplanted while being on artificial organ support. In such condition, this monodrug immunosuppressive strategy needs to be adapted. TAC monotherapy strategy should lay the basis for further large scale minimization studies in liver transplantation.

Validation of a liquid chromatography-mass spectrometric assay for tacrolimus in liver biopsies after hepatic transplantation: correlation with histopathologic staging of rejection.

The aims of this work were both to validate a sensitive and specific method to quantify tacrolimus (TAC) in liver biopsies after hepatic transplantation and to evaluate the predictive value of either tissue or blood TAC concentrations for rejection in 146 adult patients under a TAC-based immunosuppression. Trough blood levels were monitored daily during the hospital stay by immunoassay. Liver biopsies were routinely performed at day 7 posttransplantation. The tissue assay was developed by liquid chromatography-mass spectrometry. The limit of quantification was 5 pg/mg, with intra- and interassay precision ranging from 3.9% to 14.3% and 4.7% to 15.9%, respectively. The extraction efficiency was approximately 80%. TAC found in liver biopsies ranged from less than 5 up to 387 pg/mg. Blood TAC levels ranged from 2.7 to 19.3 ng/mL. Tissue levels displayed excellent correlation with liver histopathologic BANFF rejection score, whereas blood levels did not. Clinically significant rejections (BANFF scores ≥6) were characterized by mean TAC tissue and blood concentration of 13.1 pg/mg and 7.6 ng/mL, respectively, whereas these mean values became, respectively, 74.9 pg/mg (P < 0.05) and 7.1 ng/mL (not significant) for nonclinically significant rejection episodes (BANFF <6). In this study, hepatic tissue TAC concentrations were distributed in a wider range and displayed a significantly better correlation with the severity of the organ rejection than predose blood levels. A tissue TAC concentration less than 30 pg/mg is 89% sensitive and 98% specific to discriminate clinically significant cellular rejection. Further studies are required to better understand the factors affecting TAC distribution within liver tissue (such as carrier proteins and cytochrome genetic polymorphism, liver function, age, hepatic blood flow, type of organ transplanted, time posttransplantation) and to define its value in the treatment of liver allograft rejection.

Liver transplantation for hepatocellular cancer : UCL experience in 137 adult cirrhotic patients. Alpha-foetoprotein level and locoregional treatment as refined selection criteria.

Liver transplantation (LT) is a validated treatment for selected cirrhotics with hepatocellular cancer (HCC). A retrospective single center study including 137 recipients having proven HCC was done to refine inclusion criteria for LT as well as to look at impact of locoregional treatment (LRT) on outcome. At pre‐LT imaging, 42 (30.6%) patients were Milan criteria (MC)‐OUT; 28 (20.4%) were University of California San Francisco criteria (UCSFC)‐OUT. Pre‐LT LRT was performed in 109 (79.6%) patients. Multivariate analysis identified four factors to be independently predictive of recurrence: tumour number >3, AFP level ≥400 ng/ml, microvascular invasion and rejection needing anti‐lymphocytic antibodies. When considering pre‐transplant variables only, AFP level ≥400 ng/ml (HR = 5.13; P < 0.0001) was the unique risk factor for recurrence; conversely, application of LRT was protective (HR = 0.42; P = 0.04). MC‐IN patients having LRT (n = 79) had the best 5‐year tumour‐free survival (TFS) (91.6%). MC‐IN patients without LRT (n = 16) and MC‐OUT patients with LRT (n = 30) had similar good TFS (72.7% vs.77.5%); finally MC‐OUT patients without LRT (n = 12) had the worst results (45.0%; vs. 1st group: P < 0.0001). Immediate pre‐LT AFP and aggressive pre‐transplant LRT strategy, especially in MC‐OUT patients, are both important elements to further expand inclusion criteria without compromising long‐term results of HCC liver recipients.

Favorable outcome of orthotopic liver transplantation in a patient with subacute liver failure due to the emergence of a hepatitis B YMDD escape mutant virus.

BACKGROUND/AIMS Patients with end-stage liver disease due to chronic hepatitis B infection in whom a YMDD escape hepatitis B virus (HBV) mutant has emerged under lamivudine treatment are generally denied liver transplantation (OLT). METHODS We report the case of a male patient who was started on prophylactic treatment with lamivudine in the context of recurrent episodes of HBV reactivation during high dose immunosuppressive therapy for relapsing severe pulmonary sarcoidosis. RESULTS Following the emergence of a YMDD escape mutant virus under lamivudine treatment, he developed subacute liver failure requiring liver transplantation. The patient was treated with a combination of intravenous hepatitis B immune globulin (HBIG) which was started perioperatively and also continued lamivudine after OLT. Twelve months after OLT, there was no evidence of HBV reinfection of the liver graft with the use of HBIG and lamivudine. CONCLUSIONS This observation suggests that emergence of the YMDD mutation is not a contra-indication to OLT, providing adequate immunoprophylaxis using HBIG and lamivudine combination therapy.