Aiman Obed

Pre-existent portal vein thrombosis in liver transplantation: influence of pre-operative disease severity

Doenecke A, Tsui T‐Y, Zuelke C, Scherer MN, Schnitzbauer AA, Schlitt H‐J, Obed A. Pre‐existent portal vein thrombosis in liver transplantation: influence of pre‐operative disease severity.
Clin Transplant 2010: 24: 48–55.

Calcineurin Inhibitor Sparing With Mycophenolate Mofetil in Liver Transplantion: A Systematic Review of Randomized Controlled Trials

Liver transplant recipients are at high risk of developing acute and chronic renal failure. Moreover, introduction of the model for end‐stage liver disease (MELD) score for primary allocation of liver grafts favors patients with pretransplant kidney dysfunction, which in turn have a higher risk of posttransplant renal failure. Calcineurin inhibitors (CNI) further increase the risk of renal failure and therefore sparing CNI with the use of mycophenolate mofetil (MMF) may improve renal function. MMF may either be used de novo in the immediate posttransplant period in combination with low‐dose CNI (scenario 1) or patients that receive immunosuppression based on CNI may be converted to MMF in combination with minimization or elimination of CNI (scenario 2). Although many retrospective cohort studies and nonrandomized trials have implicated efficacy of this approach the evidence from randomized controlled studies has not been summarized. In the current review we report the results of a systematic review and meta‐analysis of randomized controlled trials.

Posterior cavoplasty: a new approach to avoid venous outflow obstruction and symptoms for small-for-size syndrome in right lobe living donor liver transplantation

PurposeA common and serious problem after living donor liver transplantation (LDLT) of small grafts is small-for-size syndrome (SFSS). Although hyperdynamic portal inflow and portal hypertension are cornerstones in the development of SFSS, inadequate outflow may aggravate SFSS. Therefore, enlargement of the portal outflow tract by incision of the anterior rim of the orifice of the right hepatic vein (RHV) has been advocated for right lobe LDLT. But backwards tilt of a small graft into a large abdominal cavity may lead to a choking of the otherwise large anastomosis and thus we propose posterior enlargement of the orifice of the RHV.MethodIn this test-of-concept study, we evaluated portal vein pressure (PVP), clinical parameters, and laboratory measurements in 22 patients that underwent right lobe LDLT and either received standard end-to-end anastomosis of the RHV or posterior cavoplasty.ResultsIn patients that underwent posterior cavoplasty, we observed significantly lower PVP and less hyperbilirubinemia. There was a non-significant trend to lower incidence of SFSS. Other laboratory measurements and clinical parameters were not significantly different.ConclusionWe recommend posterior cavoplasty for enlargement of the hepatic venous outflow tract in right lobe LDLT as a method to avoid portal hypertension, hyperbilirubinemia, and possibly SFSS, especially in patients that receive small grafts.

A therapeutic exploratory study to determine the efficacy and safety of calcineurin-inhibitor-free de-novo immunosuppression after liver transplantation: CILT

BackgroundImmunosuppression with calcineurin inhibitors (CNI) increases the risk of renal dysfunction after orthotopic liver transplantation (OLT). Controlled trials have shown improvement of renal function in patients that received delayed and/or reduced-dose CNI after OLT. Delaying immunosuppression with CNI in combination with induction therapy does not increase the risk of acute rejection but reduces the incidence of acute renal dysfunction. Based on this clinical data this study protocol was designed to assess the efficacy and safety of calcineurin-inhibitor-free de-novo immunosuppression after liver transplantation.Methods/DesignA prospective therapeutic exploratory, non-placebo controlled, two stage monocenter trial in a total of 29 liver transplant patients was designed to assess the safety and efficacy of de-novo CNI-free immunosuppression with basiliximab, mycophenolate sodium, prednisolone and everolimus. The primary endpoint is the rate of steroid resistant rejections. Secondary endpoints are the incidence of acute rejection, kidney function (assessed by incidence and duration of renal replacement therapy, incidence of chronic renal failure, and measurement glomerular filtration rate), liver allograft function (assessed by measurement of AST, ALT, total bilirubin, AP, GGT), treatment failure, (i. e., re-introduction of CNI), incidence of adverse events, and mortality up to one year after OLT.DiscussionThis prospective, two-stage, single-group pilot study represents an intermediate element of the research chain. If the data of the phase II study corroborates safety of de-novo CNI-free immunosuppressive regimen this should be confirmed in a randomized, prospective, controlled double-blinded clinical trial. The exploratory data from this trial may then also facilitate the design (e. g. sample size calculation) of this phase III trial.Trial registration numberNCT00890253 (clinicaltrials.gov)

Fourteen-year survival of a renal graft reused 2 years after initial transplantation: a case report

We report on the successful regrafting of a transplanted kidney. The donor kidney was first transplanted into a 32‐year‐old patient with renal atrophy. More than 2 years later, he suffered from severe grand mal seizure with brain edema and the patient met the criteria for brain death. The well‐functioning graft was recovered and subsequently transplanted into a 66‐year‐old woman with chronic glomerular nephritis. Neither the first nor the second recipient experienced any acute rejection. To date, more than 14 years later, she is in good health with excellent graft function. This case report implies that excellent long‐term graft function is viable in a graft reused 2 years after the initial transplantation.

Effects of mycophenolate mofetil introduction in liver transplant patients: results from an observational, non-interventional, multicenter study (LOBSTER)

The benefits of calcineurin inhibitor (CNI)‐sparing regimens on renal function following liver transplantation (LT) have been demonstrated in clinical studies. This observational study assessed the real‐life effects of mycophenolate mofetil (MMF) introduction in LT patients. Four hundred and ninety‐seven patients in whom MMF was introduced according to local standards or clinical considerations were entered. Patients were grouped by time between transplantation and start of MMF (start of study): Group A (n = 263): ≤6 d; Group B (n = 64): >6 d to ≤1 month; Group C (n = 74): >1 month to ≤1 yr; and Group D (n = 96): >1 yr. CNI sparing occurred in all groups, particularly in Groups C and D. Mean MMF doses at 12 months were 1202.7, 1363.5, 1504.7, and 1578.1 mg/d, respectively, in Groups A–D. At introduction of MMF, median glomerular filtration rate was 73.3, 81.7, 62.7, and 53.7 mL/min/1.73 m2 in Groups A–D. At 12 months, this decreased to 66 mL/min/1.73 m2 in Groups A and B, remained stable in Group C, and increased in Group D (64.8 mL/min/1.73 m2). Serious adverse drug reactions were lowest in Group D. In conclusion, MMF with a subsequent decrease in CNI was well tolerated and improved renal function even years after transplantation. A more forceful MMF dosing strategy with greater CNI sparing may further improve renal function.

“Rescue allocation offers” in liver transplantation: Is there any reason to reject “unwanted” organs?

Abstract To increase the number of transplanted organs, the Eurotransplant foundation uses a so-called “rescue-organ-allocation” procedure for organs that had been rejected by at least three consecutive transplant centers for medical reasons. The transplant center that finally accepts such an organ can then freely choose a patient from its own waiting list, without being bound to regular allocation criteria. Almost 30% of deceased donor livers are now allocated through this process in the Eurotransplant region. We report our results of 38 “rescue-allocation” livers (RA livers) transplanted at our institution (2003–2007), compared to a group of 115 regularly allocated organs within the same period. From our data, RA livers have the same results as regularly allocated livers. Type and frequency of postoperative morbidity did not differ between both groups, though the analysis of subgroups showed a tendency toward reduced survival of RA livers in patients with viral hepatitis. Interestingly, the Donor Risk Index (DRI) showed no difference between RA livers and regularly allocated livers. Although preliminary due to small numbers, we conclude that RA livers can be safely transplanted without increased mortality or morbidity. However, no donor specific criteria which would justify rejecting a RA liver were found. This highly challenges the applicability of the RA procedure in its current form.

Liver transplantation as curative approach for advanced hepatocellular carcinoma: is it justified?

BackgroundsLiver transplantation is considered as one of therapeutic approaches to hepatocellular carcinoma (HCC). The present study aims to evaluate the efficacy of various therapeutic options for HCC.Materials and methodsOne hundred twenty patients with known HCC in various tumour stages were evaluated in the present study. Patients were treated either with primary tumour resection, transarterial chemoembolisation (TACE) or liver transplantation (LTx) by an interdisciplinary team.ResultsThe overall 1-year and 5-year survivals of patients in LTx group were 95 and 57%, respectively, which were significantly higher than those in primary tumour resection group (65 and 33%, P < 0.01) and those in TACE group (44 and 4%, P < 0.01). In parallel, 1-year and 5-year tumour-free survivals of patients in LTx group (75 and 62%) were significantly higher than those in primary tumour resection group (50 and 11%, P < 0.01). There were no significant differences in 1- and 5-year survivals of patients with early tumour stage received LTx or primary tumour resection, whereas patients in advanced tumour stage based on pathological findings of explanted liver significantly benefited from LTx as compared to primary resection.ConclusionsLTx can be a curative approach for patients with advanced HCC without extrahepatic metastasis. However, organ shortage is a major limiting factor in the selection of HCC patients for LTx.

Liver transplantation in patients with liver cirrhosis and active pneumonia: an observational study

Patients with chronic liver disease are at high risk for severe infection because of increased bacterial translocation and immune suppression associated with liver dysfunction. Patients presenting with severe pneumonia and acute decompensation of cirrhosis are generally not considered for liver transplantation because it is unknown if these patients can recover from infection while under immunosuppression. We performed an observational study where patients with cirrhosis of the liver remained on the waiting list, although suffering from active pneumonia. Nine patients were included, but only six patients improved under goal‐directed therapy and subsequently underwent liver transplantation. All six patients recovered quickly from infection; five patients recovered without sequelae and one patient died because of late complications. We propose that in patients with chronic liver disease and active pneumonia transplantation is a treatment option that should not hastily be abandoned.

Acute paranoid psychosis as sole clinical presentation of hepatic artery thrombosis after living donor liver transplantation

BackgroundHepatic artery thrombosis is a devastating complication after orthotopic liver transplantation often requiring revascularization or re-transplantation. It is associated with considerably increased morbidity and mortality. Acute cognitive dysfunction such as delirium or acute psychosis may occur after major surgery and may be associated with the advent of surgical complications.Case presentationHere we describe a case of hepatic artery thrombosis after living-donor liver transplantation which was not preceded by signs of liver failure but rather by an episode of acute psychosis. After re-transplantation the patient recovered without sequelae.ConclusionThis case highlights the need to remain cautious when psychiatric disorders occur in patients after liver transplantation. The diagnostic procedures should not be restricted to medical or neurological causes of psychosis alone but should also focus vascular complications related to orthotopic liver transplantation.