Andrea Brunati

Early occurrence of hepatocellular carcinoma in biliary atresia treated by liver transplantation

Abstract:u2002 A case of liver transplantation for HCC complicating BA in an eight‐month old infant is reported. HCC in BA is extremely rare. Screening of AFP and ultrasonographic examination should be performed regularly in patients with secondary biliary cirrhosis for early detection of HCC.

The first one thousand liver transplants in Turin: a single-center experience in Italy

The first Italian liver transplant center to reach the goal of 1000 procedures was Turin. The paper reports this single‐center experience, highlighting the main changes that have occurred over time. From 1990 to 2002, 1000 consecutive liver transplants were performed in 910 patients, mainly cirrhotics. Surgical technique was based on the preservation of the retrohepatic vena cava of the recipient. The veno‐venous bypass was used in 30 cases only and abandoned since 1997. Operating time, warm ischemia time and length of hospital stay significantly decreased over the years, while operating room extubation became routine. Immunosuppression pivoted on cyclosporine A. Management of retransplantations, marginal grafts, and of HCV‐positive, HBV‐positive and hepatocellular carcinoma recipients were optimized. Median follow‐up of the patients was 41u2003months. Overall survival rates at 1, 5 and 10u2003years were 87%, 78% and 72% respectively. Survival rates obtained in the second half of the cases (1999–2002 period) were significantly better than those obtained in the first half (1990–1998 period) (90% vs. 83% at 1u2003year and 81% vs. 76% at 5u2003years respectively). Increasing experience in liver transplant surgery and postoperative care allowed standardization of the procedure and expansion of the activity, with parallel improvement of the results.

Liver retransplantation in children. A 21-year single-center experience*

In this study, the epidemiology and outcome of graft loss following primary pediatric liver transplantation (LT) were analysed, with the hypothesis that early retransplantation (reLT) might be associated with lower immunologic risks when compared with late reLT. Between March 1984 and December 2005, 745 liver grafts were transplanted to 638 children at Saint‐Luc University Hospital, Brussels. Among them, a total of 90 children (14%) underwent 107 reLT, and were categorized into two groups (early reLT, nu2003=u200358; late reLT, nu2003=u200332), according to the interval between either transplant procedures (< or >30u2003days). Ten‐year patient survival rate was 85% in recipients with a single LT, vs. 61% in recipients requiring reLT (Pu2003<u20030.001). Ten‐year patient survival rates were 59% and 66% for early and late reLT, respectively (Pu2003=u20030.423), the corresponding graft survival rates being 51% and 63% (Pu2003=u20030.231). Along the successive eras, the rate of reLT decreased from 17% to 10%, whereas progressive improvement of outcome post‐reLT was observed. No recurrence of chronic rejection (CR) was observed after reLT for CR (0 of 19). Two children developed a positive cross‐match at reLT (two of 10, 20%), both retransplanted lately for CR secondary to immunosuppression withdrawal following a post‐transplant lymphoproliferative disease. In summary, the results presented could not evidence better results for late reLT when compared with early reLT. The former did not seem to be associated with higher immunologic risk, except for children having withdrawal of immunosuppression following the first graft.

Liver transplantation for aHUS: still needed in the eculizumab era?

BackgroundThe risk of disease recurrence after a kidney transplant is high in patients with atypical hemolytic uremic syndrome (aHUS) and mutations in the complement factor H (FH) gene (CFH). Since FH is mostly produced by the liver, a kidney transplant does not correct the genetic defect. The anti-C5 antibody eculizumab prevents post-transplant aHUS recurrence, but it does not cure the disease. Combined liver–kidney transplantation has been performed in few patients with CFH mutations based on the rationale that liver replacement provides a source of normal FH.MethodsWe report the 9-year follow-up of a child with aHUS and a CFH mutation, including clinical data, extensive genetic characterization, and complement profile in the circulation and at endothelial level. The outcome of kidney and liver transplants performed separately 3xa0years apart are reported.ResultsThe patient showed incomplete response to plasma, with relapsing episodes, progression to end-stage renal disease, and endothelial-restricted complement dysregulation. Eculizumab prophylaxis post-kidney transplant did not achieve sustained remission, leaving the child at risk of disease recurrence. A liver graft given 3xa0years after the kidney transplant completely abrogated endothelial complement activation and allowed eculizumab withdrawal.ConclusionsLiver transplant may definitely cure aHUS and represents an option for patients with suboptimal response to eculizumab.

Early Liver Transplantation for Neonatal-Onset Methylmalonic Acidemia.

With conventional dietary treatment, the clinical course of methylmalonic acidemia due to cobalamin-unresponsive methylmalonyl-CoA mutase (MCM) deficiency is characterized by the persistent risk of recurrent life-threatening decompensation episodes with metabolic acidosis, hyperammonemia, and coma. Liver transplant has been proposed as an alternative treatment and anecdotally attempted in the last 2 decades with inconsistent results. Most criticisms of this approach have been directed at the continuing risk of neurologic and renal damage after transplant. Here, we report the perioperative and postoperative clinical and biochemical outcomes of 2 patients with severe MCM deficiency who underwent early liver transplant. In both cases, liver transplant allowed prevention of decompensation episodes, normalization of dietary protein intake, and a marked improvement of quality of life. No serious complications have been observed at 12 years’ and 2 years’ follow-up, respectively, except for mild kidney function impairment in the older patient. On the basis of our experience, we strongly suggest that liver transplant should be offered as a therapeutic option for children with cobalamin-unresponsive MCM deficiency at an early stage of the disease.

Combination of tissue expansion and porcine mesh for secondary abdominal wall closure after pediatric liver transplantation.

Lafosse A, de Magnee C, Brunati A, Bayet B, Vanwijck R, Manzanares J, Reding R. Combination of tissue expansion and porcine mesh for secondary abdominal wall closure after pediatric liver transplantation.

Liver transplantation after severe hepatic trauma: a sustainable practice. A single-center experience and review of the literature

Severe hepatic trauma is a rare indication for liver transplantation (LT). We report our single‐center experience of LT for hepatic trauma. Four new cases are discussed in light of a literature review in order to depict the pathways leading from hepatic trauma to LT and to assess the outcomes of this practice. LT is generally indicated in case of uncontrollable hemorrhage, acute liver failure, or post‐traumatic late sequelae. Hepatic vessels thrombosis, sepsis, major hepatic resections, and a late referral are factors associated with the progression toward irreversible liver failure. Considering all reported cases, early patient and graft survival reached 68% and 62%, respectively, but in the last decade both have improved to 84%. LT after severe hepatic trauma is a sustainable practice considering the current good outcomes and the ineluctable death of these patients without LT.

Liver transplantation in severe methylmalonic acidemia: The sooner, the better

new arguments for answering those questions. 3 First, given the dismal natural course of the disease in spite of rigorous medical management, we are persuaded that the organ transplant approach should be considered in all patients with neonatal-onset, cobalamin-unresponsive MMA. In our patients, timely liver transplantation allowed an excellent clinical course both perioperatively and in the long-term, consistent with the results by Niemi et al. Second, we are convinced that transplantation should be performed early, ideally within the first year of life, thereby avoiding repeated metabolic decompensations and the consequent neurologic deterioration. Third, we believe that isolated liver transplantationshould bethe preferred option,asit providesthe greatest mutase enzyme activity (5-fold greater than kidney transplantation), sufficient for preserving renal function and avoiding, or at least delaying, the need for kidney transplantation. In light of these independent reports, early liver transplantation currently appears to be the best therapeutic option in patients with severe MMA. Although not fully curative, this approach will ensure healthier clinical outcome with respect to traditional medical management.

An UPLC MS/MS method coupled with automated on-line SPE for quantification of tacrolimus in Peripheral Blood Mononuclear Cells

BACKGROUNDnTacrolimus is an immunosuppressor used to treat patients undergoing liver transplantation. TDM of hematic tacrolimus by liquid chromatography became standard practice, but it does not necessarily reflect its concentration at its active site. Our aim was to validate a new method for tacrolimus quantification into target cells (peripheral blood mononuclear cells, PBMCs) and testing it on 100 real samples from 37 pediatric patients.nnnMETHODSnPBMCs were collected using cell-preparation-tubes; cells number and MCV were evaluated. Tacrolimus was quantified using UPLC-MS/MS coupled with a new automated on-line SPE platform. Chromatographic run was performed on an Acquity UPLC(®) BEH C18 1.7 μm (2.1 mm × 50 mm) column for 5 min, with a gradient of water and methanol (both with 2 mM/L ammonium acetate and 1 mL/L formic acid). XBridge(®) C8 10 μm (1 mm × 10 mm) SPE cartridges were used. The internal standard was 6,7-dimethyl-2,3-di(2-pyridyl)quinoxaline.nnnRESULTSnFull validation following FDA guidelines was performed: the method showed high sensitivity and specificity (LLOQ of 0.010 ng; LLOD of 0.005 ng). Intra- and inter-day imprecision and inaccuracy were <15%. A positive and stable matrix effect was observed, with a good recovery for tacrolimus. All drug amounts in real samples resulted within the calibration range and calibration curves were linear (r(2)=0.998). Concentrations from each patient were standardized using their evaluated MCV: intra-PBMCs concentration was meanly 12.7 times higher than the hematic one.nnnCONCLUSIONnThis method might be eligible and useful for a clinical routine use, giving more reliable data on drug concentration at the active site.

The role of interventional radiology in the treatment of biliary strictures after paediatric liver transplantation.

PurposeThe aim of this study is to evaluate the safety and efficacy of percutaneous treatment of biliary strictures after paediatric liver transplantation.Materials and methodsIn the period between October 1999 and October 2010, a total of 92 transplants in 86 children were performed at our Liver Transplant Centre. Eighteen patients had anastomotic biliary strictures (in four cases associated with intrahepatic bile duct stenosis). Percutaneous treatment (transhepatic biliary drainage and conventional/cutting balloon dilatation) was proposed as a first approach in 13/18 patients. Strict radiation protection precautions were taken in accordance with the ALARA (as low as reasonably achievable) principle. Mean follow-up time was 2,364xa0days.ResultsSurgical correction was required in 3/13 patients; in 8/13 cases, there was complete disappearance of clinical symptoms without bile duct dilatation; in one case, an asymptomatic persistent bile duct dilatation was detected while in the other case, the liver is currently in cirrhotic degeneration (69xa0% clinical success including the asymptomatic patient with biliary dilatation). Two of the five patients who were initially treated with surgery required percutaneous revision (clinical success of 100xa0%). There were two cases of long-term restenosis and two cases of transient haemobilia.ConclusionsPercutaneous procedures are safe and effective therapeutic options for the treatment of biliary strictures after paediatric liver transplantation.