A notable proportion of liver transplant candidates with alcohol-related cirrhosis can be delisted because of clinical improvement.

BACKGROUND & AIMS: To what extent patients with alcohol-related decompensated cirrhosis can improve until recovery from decompensation remains unclear. We aimed to investigate the probability of recovery and delisting due to improvement in patients with alcohol-related decompensated cirrhosis on the waiting list (WL) for liver transplantation (LT). METHODS: We conducted a registry-based, multicenter, retrospective study including all patients admitted to the LT WL in Catalonia (Spain) with the indication of alcohol-, HCV-, cholestasis- or non-alcoholic steatohepatitis-related decompensated cirrhosis between January 2007 and December 2018. Competing-risk analysis was used to investigate variables associated with delisting due to improvement in patients with alcohol-related decompensated cirrhosis. Criteria for delisting after improvement were not predefined. Outcomes of patients after delisting were also studied. RESULTS: One-thousand and one patients were included, 420 (37%) with alcohol-related decompensated cirrhosis. Thirty-six (8.6%) patients with alcohol-related decompensated cirrhosis were delisted after improvement at a median time of 29 months after WL admission. Lower model for end-stage liver disease (MELD) score, higher platelets and either female sex or lower height were independently associated with delisting due to improvement, while time of abstinence did not reach statistical significance in multivariate analysis (p = 0.055). Five years after delisting, the cumulative probability of remaining free from liver-related death or LT was 76%, similar to patients with HCV-related decompensated cirrhosis delisted after improvement. CONCLUSIONS: A significant proportion of LT candidates with alcohol-related cirrhosis can be delisted due to improvement, which is predicted by low MELD score and higher platelet count at WL admission. Women also have a higher probability of being delisted after improvement, partially due to reduced early access to LT for height discrepancies. Early identification of patients with potential for improvement may avoid unnecessary transplants. LAY SUMMARY: Patients with alcohol-related cirrhosis can improve until being delisted in approximately 9% of cases. Low model for end-stage liver disease score and high platelet levels at admission predict delisting after improvement, and women have higher probabilities of being delisted due to improvement. Long-term outcomes after delisting are generally favorable.

Interobserver Agreement for Classifying Post-liver Transplant Biliary Strictures in Donation After Circulatory Death Donors.

INTRODUCTION: Biliary strictures are a common complication of donation after circulatory death (DCD) liver transplantation (LT) and require multiple endoscopic retrograde cholangiopancreatography (ERCP) procedures. Three classification systems, based on cholangiograms, have been proposed for categorizing post-LT biliary strictures. We examined the interobserver agreement for each of the three classifications. METHODS: DCD LT recipients from 2012 through March 2017 undergoing ERCP for biliary strictures were included in the study. Initial cholangiograms delineating the entire biliary tree prior to endoscopic intervention were selected. One representative cholangiogram was selected from each ERCP. Five interventional endoscopists independently viewed each anonymized cholangiogram and classified the post-LT stricture according to each of the three classification systems. The Ling classification proposes four types of post-LT strictures based on their location. The Lee classification proposes four classes based on location and number of intrahepatic strictures. The binary system classifies strictures into anastomotic or non-anastomotic types. The Krippendorff's alpha reliability estimate was used to grade the strength of agreement as "poor," "fair," "moderate," "good," or "excellent" for values between 0-0.20, 0.21-0.4, 0.41-0.6, 0.61-0.08, and 0.81-1, respectively. RESULTS: One hundred DCD LT recipients (age 57.07 ± 8.8 years; 71 males) were initially evaluated. Of these, 49 patients who underwent 206 ERCP procedures for biliary strictures were included in the analysis. One hundred thirty-nine cholangiograms were selected and subsequently classified by five endoscopists. Interobserver agreement for post-LT biliary strictures was 0.354 for Ling classification (fair agreement), 0.405 for Lee classification (fair agreement), and 0.421 for the binary classification (moderate agreement). The binary classification provided the least amount of detail regarding the location and number of biliary strictures. DISCUSSION: The currently available classification systems for assessing post-LT biliary strictures have sub-optimal interobserver agreement. A better-designed classification system is needed for categorizing post-LT biliary strictures.

Case Report of Relay Liver Transplantation With Graft Infected With Hepatitis B Virus.

Reuse of liver graft for transplantation is extremely uncommon. We report the 1st case of reuse of liver graft from a recipient who had hepatitis B virus (HBV) infection, 11 years after the 1st transplantation. Our relay liver transplantation challenged conventional thinking because of late reuse of graft in the presence of HBV infection. Moreover, both the 1st and the 2nd donors were of advanced age. The key questions were whether the liver graft could be reused safely, especially in the setting of HBV infection, and technical concerns during organ procurement and implantation. The absence of HBV replication was confirmed with negative hepatitis B surface antigen and undetectable serum HBV DNA in the 2nd donor. Based on our experience in managing HBV infection after liver transplantation, we were confident that the adequately suppressed HBV infection in the donor would not jeopardize graft function and that the graft would be able to withstand another ischemia-perfusion injury to continue to function well in our recipient.

Early occurrence of new-onset diabetes after transplantation is related to type of liver graft and warm ischaemic injury.

BACKGROUND & AIMS: We studied new-onset diabetes after transplantation (NODAT) in liver transplantation with grafts donated after brain death (DBD) or circulatory death (DCD), focusing on the early post-transplant period. METHODS: A total of 430 non-diabetic primary liver transplant recipients [DCD, n = 90 (21%)] were followed up for 30 months (range 5-69). NODAT was defined as the composite endpoint of one of following: (i) Two non-fasting plasma glucose levels > 11.1 mmol/L ≥ 30 days apart, (ii) oral hypoglycaemic drugs ≥ 30 days consecutively (iii) insulin therapy ≥ 30 days and (iv) HbA1c ≥ 48 mmol/L. Resolution of NODAT was defined as cessation of treatment or hyperglycaemia. RESULTS: Total of 81/430 (19%) patients developed NODAT. Incidence and resolution of NODAT over time showed significantly different patterns between DCD and DBD liver graft recipients; early occurrence, high peak incidence and early resolution were seen in DCD. In multivariate logistic regression including age, ethnicity, HCV, tacrolimus level and pulsed steroids, only DCD was independently associated with NODAT at day 15 post-transplant (OR 6.5, 95% CI 2.3-18.4, P < 0.001), whereas age and pulsed steroids were significant factors between 30-90 days. Combined in multivariate Cox regression model for NODAT-free survival, graft type, age and pulsed steroids were each independent predictor for decreased NODAT-free survival in the first 90-postoperative days. CONCLUSION: Early peak of NODAT in DCD graft recipients is a novel finding, occurring independently from known risk factors. Donor warm ischaemia and impact on insulin sensitivity should be further studied and could perhaps be associated with graft function.

10 años de trasplante hepático en el Perú / 10 years of liver transplantation in Peru

El artículo revisa la experiencia única en el Perú de 10 años de trasplantes realizada por el departamento de trasplantes del Hospital Nacional Guillermo Almenara Irigoyen (HNGAI), describiendo la historia, resultados quirúrgicos en adultos y niños, retrasplantes, trasplantes combinados hígado-riñon, las diferentes complicaciones encontradas y toda la experiencia recogida en los 72 trasplantes realizados hasta la presentación de este artículo.

The article reviews the experience in 10 years of hepatic transplants performed by The Transplant Department of the National Hospital Guillermo Almenara Irigoyen (HNGAI), describing the history, surgical outcomes in adults and children, retransplantation, combined liver-kidney transplants, complications in 72 transplants performed at the time of submission of the article.

Hepatitis autoinmune en niños: clínica y manejo / Autoimmune hepatitis in children: clinical and management

La hepatitis autoinmune (HAI), es una enfermedad inflamatoria crónica y progresiva, que se caracteriza histológicamente por un denso infiltrado de células mononucleares en vías portales, y cuya patogenia se le atribuye a una reacción inmune frente a autoantígenos hepatocelulares demostrado serológicamente por la presencia de autoanticuerpos específicos y aumento en los niveles de las aminotransferasas y de inmunoglobulina tipo IgG, en ausencia de una etiología conocida. Son reconocidos dos tipos de HAI en la infancia: HAI tipo I, que se caracteriza por la presencia de anticuerpos (anti músculo liso SMA) y/o antinucleares (ANA), y la HAI tipo II,que se caracteriza por anticuerpos antimicrosomales de riñón hígado (anti-LKM). La etiología de la HAI es desconocida, aunque tanto factores genéticos como ambientales están implicados en su expresión. El fenotipo clínico de la HAI en niños varía en gran medida, va desde una evolución leve a un curso fulminante. La HAI es sensible a la terapia inmunosupresora. El trasplante hepático está indicado en pacientes que presentan insuficiencia hepática fulminante (encefalopatía) y los que desarrollan enfermedad hepática terminal.

Autoimmune hepatitis (HAI) is a chronic and progressive inflammatory disease, characterizedhistologically by a dense infiltrate of mononuclear cells in the process portals, and whose pathogenesis is attributed to an immune response against hepatocellular autoantigens demonstratedserologically by the presence of specific autoant ibodies and increased levels of aminotransferases and immunoglobulin IgG, in the absence of known etiology. Recognized two types of HAI in childhood: type I, characterized by the presence of antibodies (smooth muscle anti SMA) and / or antinuclear (ANA) and type II, characterized by anti-microsomal antibodies liver kidney (anti-LKM). The etiology of HAI is unknown, a l though both gene t i c and environmental factors are involved in its expression. The clinical phenotype of the HAI in children varies greatly, ranging from a slight evolution to a fulminant course. The HAI is sensitive to immunosuppressive therapy. Liver transplantation is indicated in patients with fulminant hepatic failure (encephalopathy) andthose who develop end-stage liver disease.

Inmunosupresíón en niños con trasplante hepático / Immunosuppression in children with liver transplantation

La inmunosupresión en niños con trasplante hepático, ha evolucionado con dos momentos clave: la disponibilidad de los inhibidores de calcineurina ciclosporina y tacrolimus. La inmunosupresión primaria se diseña sobre la base de un inhibidor de calcineurina como fármaco principal. Los esteroides se incluyen en la pauta de inmunosupresión primaria en la mayoría de los centros. Las pautas habituales a largo plazo consisten en ciclosporina o tacrolimus, en monoterapia a niveles inferiores a los deseados en el periodo precoz postrasplante, o en combinación con dosis bajas de esteroide. Los inhibidor e s de c a l c ineur ina induc en vasoconstricción arterial aguda y crónica que causa nefrotoxicidad, con disminución del filtrado glomerular y tubulopatía. Los niveles ensangre de ciclosporina o de tacrolimus se determinan para evaluar el estado de inmunosupresión. La edad de adolescente y adulto joven es una etapa de riesgo para el injerto por ser frecuente la omisión accidental de dosis de medicación inmunosupresora, una irregularidad que es difícil de evaluar en su extensión a pesar de una buena relación médicopaciente y frecuentes chequeos. El rechazo tiene una incidencia entre el 30 y 50% de los pacientes, entre los días 5 y 30 postrasplante.

Immunosuppression in children with liver transplantation has evolved with two key moments: the availability of calcineurin inhibitors, cyclosporine and tacrolimus. The primary immunosuppression is designed on the basis of a calcineurin inhibitor as primary drug. Steroids are included in the pr imary immunosuppression regimen in most schools. The long-term normal patterns consist of cyclosporine or tacrolimus as monotherapy to lower than desired levels in the early period aftertransplantation, or in combination with low dose steroid. Calcineurin inhibitors induce arterial vasoconstriction causing acute and chronic nephrotoxicity, with reduced glomerular filtration and tubular. Blood levels of cyclosporine or tacrolimus are determined to assess the state of immunosuppression. The age of adolescence and young adulthood is a time of risk to the graft by the accidental omission to be frequent doses ofimmunosuppressive medication, an irregularitywhich is difficult to assess its extent in spite of a good doctor-patient relationship and frequentcheckups. The rejection has an incidence between 30 and 50% of patients, between 5 and 30 aftertransplantation.

Is Roux-en-Y choledochojejunostomy an independent risk factor for nonanastomotic biliary strictures after liver transplantation?

Biliary reconstruction using Roux-en-Y choledochojejunostomy has been suggested as a risk factor for the development of nonanastomotic biliary strictures (NAS) after liver transplantation. Roux-en-Y reconstruction, however, is preferentially used in patients transplanted for primary sclerosing cholangitis (PSC), and the disease itself is also associated with a higher incidence of NAS. The aim of this study was to determine whether Roux-en-Y reconstruction is really an independent risk factor for NAS. A series of 486 consecutive adult liver transplants were studied. Biliary reconstruction in patients transplanted for PSC was either by Roux-en-Y choledochojejunostomy or by duct-to-duct anastomosis, depending on the quality of the recipient's extrahepatic bile duct. Univariate and multivariate statistical analyses were used to identify risk factors for the development of NAS. The overall incidence of NAS was 16.5% (80/486). In univariate analyses, the following variables were significantly associated with NAS: PSC as the indication for transplantation, type of biliary reconstruction (Roux-en-Y versus duct-to-duct), and postoperative cytomegalovirus infection. After multivariate logistic regression analysis, PSC as the indication for transplantation (odds ratio, 2.813; 95% confidence interval, 1.624-4.875; P < 0.001) and postoperative cytomegalovirus infection (odds ratio, 2.098; 95% confidence interval, 1.266-3.477; P = 0.004) remained as independent risk factors for NAS. Biliary reconstruction using Roux-en-Y choledochojejunostomy was not identified as an independent risk factor for NAS. In conclusion, the association between Roux-en-Y choledochojejunostomy and NAS observed in previous studies can be explained by the more frequent use of Roux-en-Y reconstruction in patients with PSC. Roux-en-Y reconstruction itself is not an independent risk factor for NAS. Liver Transpl 15:924-930, 2009. (c) 2009 AASLD.

Resource utilization of living donor versus deceased donor liver transplantation is similar at an experienced transplant center.

Although living donor liver transplantation (LDLT) has been shown to decrease waiting-list mortality, little is known of its financial impact relative to deceased donor liver transplantation (DDLT). We performed a retrospective cohort study of the comprehensive resource utilization, using financial charges as a surrogate measure-from the pretransplant through the posttransplant periods-of 489 adult liver transplants (LDLT n = 86; DDLT n = 403) between January 1, 2000, through December 31, 2006, at a single center with substantial experience in LDLT. Baseline characteristics differed between LDLT versus DDLT with regards to age at transplantation (p = 0.02), male gender (p < 0.01), percentage Caucasians (p < 0.01) and transplant model for end-stage liver disease (MELD) score (p < 0.01). In univariate analysis, there was a trend toward decreased total transplant charges with LDLT (p = 0.06), despite increased surgical charges associated with LDLT (p < 0.01). After adjustment for the covariates that were associated with financial charges, there was no significant difference in total transplant charges (p = 0.82). MELD score at transplant was the strongest driver of resource utilization. We conclude that at an experienced transplant center, LDLT imposes a similar overall financial burden than DDLT, despite the increased complexity of living donor surgery and the addition of the costs of the living donor. We speculate that LDLT optimizes transplantation by transplanting healthier and younger recipients.

Adult orthotopic liver transplantation in the United Kingdom and Ireland between 1994 and 2005.

BACKGROUND: The UK and Ireland Liver Transplant Audit collects information on all liver transplantations that are carried out in both countries. In this paper, we describe these transplantations and their outcomes in adult patients according to primary liver disease diagnosis, type of transplantation and period. METHODS: A prospective cohort study of 7906 orthotopic liver transplantations carried out between April 1994 and June 2005 in the United Kingdom and Ireland. Multivariable logistic regression was used to investigate improvements in mortality according to period of transplantation adjusted for recipient and donor characteristics. RESULTS: A total of 6,850 transplantations were done in adults (patients 16 years or older). Of these, 836 (12.2%) were first super-urgent procedures (33.7% men; median age 36 years), and 5,072 (74.0%) first elective procedures (60.0% men; median age 52 years). The percentage of patients who received a donor organ with abnormal appearance gradually increased, especially in patients receiving an elective transplant. Mortality at 90 days after first super-urgent transplant decreased from 29.6% (95% confidence interval: 23.5% to 36.9%) before October 1, 1996 to 16.0% (11.7% to 21.7%) after October 1, 2002. Considering the same time periods, mortality at 90 days after first elective transplant decreased from 10.6% (8.9% to 12.7%) to 7.7% (6.3% to 9.3%). Multivariable analysis demonstrated that these improvements cannot be explained by changes in the risk profile of recipients and donors. CONCLUSIONS: Patients undergoing a liver transplantation in the most recent years had a better survival than patients with similar characteristics transplanted 10 years earlier. Posttransplant survival has improved despite a deteriorating quality of donor organs.

Classification of human liver transplant recipients by their preoperative CD8+ T cell subpopulation and its relation to outcome.

The primed status of T cells is markedly different among liver transplant recipients, due to a lifetime of antigen exposure and reduced thymopoiesis by aging, and diseases. This study aims to characterize the preoperative immunological status of CD8+ T cell subpopulations and relate it to the outcome for liver transplant recipients. We classified 112 liver transplant recipients into 5 groups, based on hierarchical clustering of the CD8+CD45 isoform proportion of T cells. In Groups I and II (pediatric), the naive T cell proportion was more than 50%. In adult recipients, Group III was characterized by a naive T cell proportion of 50%, Group IV had the greatest effector/memory T cells (EM), and Group V had the greatest proportion of effector T cells. In Groups IV and V, the effector T cell proportion was considerably higher, and was accompanied by marked downregulation of the CD27+CD28+ subsets and upregulation of interferon gamma (IFN)-gamma, tumor necrosis factor-alpha, and perforin expression. Group V recipients tended to be complicated postoperatively, with a significantly reduced survival rate (1 yr, 66.8%) and markedly reduced Eastern Cooperative Oncology Group performance status.

The liver. Part 6: Liver transplantation.

Advanced surgical techniques and the development of effective immunosuppressive therapies have enabled liver transplantation to be performed in any age group with a high graft and patient survival rate.

A method to use microarray and clinical data in sequential classification.

We investigate the problem of constructing a sequential classification procedure allowing for a classification into two (risk) groups at an average minimum cost or at the earliest possible time. The quality of the procedure is maintained by specified upper bounds for the conditional errors of the entire procedure.

Banff schema for grading liver allograft rejection: utility in clinical practice.

An accurate and functional system for grading acute liver allograft rejection is important for patient management, research, and communication. The Banff schema is a consensus document designed to provide an internationally accepted standard for this purpose. The aim of this study is to determine if application of the Banff schema would significantly alter the grading of acute liver allograft rejection compared with the Birmingham system. One hundred twenty-four post-liver transplantation biopsies performed by the Western Australian Liver Transplantation Service between 1992 and 1997 were retrospectively analyzed by a pathologist and a hepatologist. Each was supplied with a brief clinical history before applying the Banff and Birmingham criteria. Results were compared with each other and to the diagnosis made at the time of the biopsy, which was based on the European grading system. Rejection was diagnosed by the reviewers in 61 of 124 biopsy specimens according to the criteria of Snover. The Banff schema and Birmingham system agreed on the grade of rejection in 22 of the 61 biopsy specimens. The Banff schema elevated the grade of rejection in 39 specimens by an increment of one. In no instance did the Banff schema reduce the grade. Comparison between the Banff schema and diagnosis made at the time of biopsy showed agreement in 39 specimens, whereas the Banff schema elevated the grade in 15 specimens and reduced the grade in 23 specimens. In comparison to the Birmingham system, the Banff schema elevated the grade of liver allograft rejection in the majority of biopsy specimens, and this has the potential to alter clinical management with the adoption of the Banff schema or if the systems are used interchangeably.

Evoluçäo dos pacientes pediátricos avaliados para transplante hépatico / Follow-up of pediatric patients evaluated for liver transplantation

Objetivo: analisar a evoluçäo de pacientes pediátricos avaliados para Transplante Hepático. Métodos: Foram revisados os prontuários das primeiras 65 crianças e adolescentes portadores de hepatopatias crônicas, com idades de 5 meses a 19 anos (x=6,8 anos), que foram avaliados, de agosto de 1994 a março de 1996, para realizar transplante de fígado. Os dados colhidos foram referenes às características demográficas dos pacientes, causa da hepatopatia, avaliaçäo psicossocial dos pacientes e de seus responsáveis e avaliaçäo clínico-laboratorial. De acordo com a gravidade da doença, os pacientes foram classificados como ativos (aguardando doaçäo), em avaliaçäo, inativos (hepatopatia compensada) e excluídos por motivos psicossociais, médicos ou por má indicaçäo...

Orthotopic liver transplantation in fulminant and subfulminant hepatitis. The Paul Brousse experience.

OBJECTIVE: The authors report on the experience of orthotopic liver transplantation in fulminant hepatitis at Paul Brousse Hospital. SUMMARY BACKGROUND DATA: Liver transplantation is a breakthrough in the treatment of patients with fulminant hepatitis. However, the indications, the timing for transplantation, the type of transplantation, and the use of ABO incompatible grafts in this setting still are debated. METHODS: Transplantation was indicated in patients with confusion or coma and factor V less than 20%, younger than 30 years of age, and confusion or coma and factor V less than 30% older than 30 years of age. RESULTS: Among 139 patients who met the aforementioned criteria for transplantation, 1 recovered, 22 died before transplantation, and 116 underwent transplants with a 1-year survival of 68%. Survival was 83% in patients with grade 1 and 2 comas at transplantation versus 56% (p < 0.001) in those with grade 3 comas; it was 51% versus 81% (p < 0.001) in those transplanted with high risk (ABO-incompatible, split, or steatotic) and low-risk grafts, respectively. In a multivariate analysis, steatotic and partial grafts were predictive of poorer patient survival, and ABO incompatibility was predictive of poorer graft survival. CONCLUSIONS: Orthotopic liver transplantation is an effective treatment in fulminant hepatitis. Use of high-risk grafts permitted transplantation of 83% of patients, but was responsible for higher mortality.

The predictive value of four scoring systems in liver transplant recipients.

OBJECTIVE: To compare 4 general severity classification scoring systems concerning prognosis of outcome in 123 liver transplant recipients. The compared scoring systems were: the mortality prediction model (admission model and 24 h model); the simplified acute physiology score; the acute physiology and chronic health evaluation (Apache II) and the acute organ systems failure score. DESIGN: Retrospective, consecutive sample. SETTING: Adult intensive care unit in a university hospital. PATIENTS: 123 adult liver allograft recipients after admission to the intensive care unit. MEASUREMENTS AND MAIN RESULTS: The scoring systems were calculated as described by the authors to classify the severity of illness after admission of the allograft recipients to the intensive care unit. The mean and median values of survivors and the group of patients, that died during hospital stay were compared. Receiver-operating characteristics were plotted for all scoring systems and the areas under the curves of receiver-operating characteristics were calculated. The predictive value of the 4 scoring systems was tested using a variety of sensitivity analyses. The mortality prediction model (24 h model) was found to have a high significance (p < 0.001) in predicting mortality and showed the greatest area under the curve (0.829). Simplified acute physiology score (p < 0.001) and acute physiology and chronic health evaluation (Apache II) (p < 0.01) had a high significance as well, but did not hit the level of prognosis of mortality prediction model, as shown in the area under the curves. Accordingly, sensitivity was highest in MPM-24 h (83%), followed by SAPS (72%) and Apache II (71%). MPM-24 h had a total misclassification rate of 22% (SAPS = 32%, Apache II = 33%). MPM-admission failed in predicting mortality (sensitivity = 52%). Organ systems failure score seemed not to be useful in liver transplant recipients. CONCLUSION: General disease classification systems, such as the mortality prediction model, simplified acute physiology score or acute physiology and chronic health evaluation are good mortality prediction models in patients after liver transplantation. We suggest that there is no need for improvement of a special scoring system.

Trasplante hepático en niños

El trasplante hepático es reconocido hoy en día como el tratamiento de elección para la falla hepática terminal. El trasplante hepático en niños ha sido históricamente el trasplante que ha ocupado el inicio de varias series en el mundo, como ocurrió con la de Denver/Pittsburgh de Thomas Starzl cuando en 1965 trasplantó una niña de año y medio (1). Varios avances son responsables de los mejores resultados en este campo: el advenimiento de la ciclosporina (CyA), por Borel en 1981, dividió en dos la era de los trasplantes, los avances técnicos en la preservación del órgano, el uso del bypass veno-venoso, la reducción anatómica que ha permitido tomar segmentos de hígado para trasplante en niños, el manejo de la inmunosupresión y del rechazo, las pequeñas dosis de prednisona y su pronta suspensión, que ha permitido practicar en gran número trasplante pediátrico sin los efectos colaterales de esta medicación. Todo esto ha contribuido a que los resultados pediátricos sean mejores que en los adultos.