scholarly journals Liver Histopathology in Late Protocol Biopsies after Pediatric Liver Transplantation

Children ◽  
2021 ◽  
Vol 8 (8) ◽  
pp. 671
Author(s):  
Małgorzata Markiewicz-Kijewska ◽  
Sylwia Szymańska ◽  
Michal Pyzlak ◽  
Piotr Kaliciński ◽  
Joanna Teisseyre ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Biochemical Tests ◽  
Term Survival ◽  
Antibody Mediated Rejection ◽  
Liver Histopathology ◽  
Biochemical Status ◽  
Protocol Biopsies ◽  
Liver Biopsies ◽  
End Stage ◽  
Liver Tests

Liver transplantation has become a routine treatment for children with end stage liver failure. Recently, the long term survival of pediatric patients after liver transplantation has improved, with a life expectancy much longer than that of adult recipients, but also with longer exposition of the graft to various injuries, including immunological, inflammatory and others. Biochemical tests, although important, do not always reflect graft injury. The aim of our study was to analyze the histopathology of the graft in late protocol biopsies and correlate it with the clinical and biochemical status of these patients. We analyzed 61 protocol liver biopsies taken from 61 patients. Biopsies were taken 9.03–17.09 years (mean 12.68, median 11.74 years) after transplantation. Liver specimens were examined particularly for the presence and stage of liver fibrosis, inflammation, steatosis, and acute or chronic cellular and humoral rejection. We did not find any abnormalities in 26 (42.6%) liver specimens. None of the patients had signs of cellular or antibody mediated rejection or chronic rejection. In 23 liver biopsies (37.7%), we found non-specific lymphoid infiltrates. Another problem was fibrosis (equal to or more than three on the Ishak scale)—we found it in 17 patients, including seven liver specimens (11.5%) with severe fibrosis (Ishak 5–6). Conclusions: Various pathomorphological abnormalities were found in more than half of patients with a median 11.74 years post-transplant follow-up. Most of them presented normal laboratory liver tests at the same time, suggesting a slow subclinical process leading to pathomorphological abnormalities. No single factor for the development of these abnormalities was found, but our study supports the need for protocol liver biopsies even in patients with normal/almost normal biochemical liver tests.

scholarly journals Efficiency of Machine Learning Algorithms for the Determination of Macrovesicular Steatosis in Frozen Sections Stained with Sudan to Evaluate the Quality of the Graft in Liver Transplantation

Sensors ◽  
2021 ◽  
Vol 21 (6) ◽  
pp. 1993
Author(s):  
Fernando Pérez-Sanz ◽  
Miriam Riquelme-Pérez ◽  
Enrique Martínez-Barba ◽  
Jesús de la Peña-Moral ◽  
Alejandro Salazar Nicolás ◽  
...  
Keyword(s):  
Machine Learning ◽  
Liver Transplantation ◽  
Learning Algorithms ◽  
Selection Procedure ◽  
Machine Learning Algorithms ◽  
Liver Biopsies ◽  
Convenient Technique ◽  
End Stage ◽  
Macrovesicular Steatosis

Liver transplantation is the only curative treatment option in patients diagnosed with end-stage liver disease. The low availability of organs demands an accurate selection procedure based on histological analysis, in order to evaluate the allograft. This assessment, traditionally carried out by a pathologist, is not exempt from subjectivity. In this sense, new tools based on machine learning and artificial vision are continuously being developed for the analysis of medical images of different typologies. Accordingly, in this work, we develop a computer vision-based application for the fast and automatic objective quantification of macrovesicular steatosis in histopathological liver section slides stained with Sudan stain. For this purpose, digital microscopy images were used to obtain thousands of feature vectors based on the RGB and CIE L*a*b* pixel values. These vectors, under a supervised process, were labelled as fat vacuole or non-fat vacuole, and a set of classifiers based on different algorithms were trained, accordingly. The results obtained showed an overall high accuracy for all classifiers (>0.99) with a sensitivity between 0.844 and 1, together with a specificity >0.99. In relation to their speed when classifying images, KNN and Naïve Bayes were substantially faster than other classification algorithms. Sudan stain is a convenient technique for evaluating ME in pre-transplant liver biopsies, providing reliable contrast and facilitating fast and accurate quantification through the machine learning algorithms tested.

Liver Transplantation for the Gastroenterologist

2015 ◽  
Author(s):  
Andreea M. Catana ◽  
Michael P. Curry
Keyword(s):  
United States ◽  
Liver Transplantation ◽  
Liver Disease ◽  
Organ Procurement ◽  
The United States ◽  
Waiting Lists ◽  
Liver Graft ◽  
Term Survival ◽  
End Stage Liver Disease ◽  
End Stage

The first liver transplantation (LT) was performed in 1963, and currently more than 65,000 people in the United States are living with a transplanted liver. In 2012, the number of adults who registered on the LT waiting list decreased for the first time since 2002; 10,143 candidates were added compared with 10,359 in 2011. LT offers long-term survival for complications of end-stage liver disease and prolongs life in properly selected patients, but problems such as donor deficit, geographic disparities, and long waiting lists remain. This overview of LT for the gastroenterologist details the indications for LT and patient selection, evaluation, liver organ allocation, prioritization for transplantation, transplantation benefit by the Model for End-Stage Liver Disease (MELD), MELD limitations, sources of liver graft, strategies employed to decrease the donor deficit, complications, and outcomes. Figures include indications for LT in Europe and the United States, Organ Procurement and Transplantation Network regions in the United States, the number of transplants and size of active waiting lists, mortality by MELD, regional disparity, patient survival rates with and without hepatitis C virus, and unadjusted patient and graft survival. Tables list LT milestones, indications for LT, contraindications for LT, minimal listing criteria for LT, criteria for LT in acute liver failure, LT evaluation process, adult recipient listing status 1A, and early posttransplantation complications. This review contains 7 highly rendered figures, 8 tables, and 46 references. 

Prognostic value of endogenous and exogenous metabolites in liver transplantation

2020 ◽  
Vol 14 (12) ◽  
pp. 1165-1181
Author(s):  
Xiao-fu Xiong ◽  
Ding-ding Chen ◽  
Huai-jun Zhu ◽  
Wei-hong Ge
Keyword(s):  
Liver Transplantation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Immunosuppressive Agents ◽  
Graft Function ◽  
Individual Variability ◽  
Pathological Examination ◽  
Biochemical Tests ◽  
Monitoring Method ◽  
End Stage

Liver transplantation has been widely accepted as an effective intervention for end-stage liver diseases and early hepatocellular carcinomas. However, a variety of postoperative complications and adverse reactions have baffled medical staff and patients. Currently, transplantation monitoring relies primarily on nonspecific biochemical tests, whereas diagnosis of multiple complications depends on invasive pathological examination. Therefore, a noninvasive monitoring method with high selectivity and specificity is desperately needed. This review summarized the potential of endogenous small-molecule metabolites as biomarkers for assessing graft function, ischemia-reperfusion injury and liver rejection. Exogenous metabolites, mainly those immunosuppressive agents with high intra- and inter-individual variability, were also discussed for transplantation monitoring.

Pre-Liver Transplantation Evaluation and Listing

2019 ◽  
Vol 03 (04) ◽  
pp. 255-262
Author(s):  
Alexander Pan ◽  
Sean Koppe
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Comprehensive Evaluation ◽  
Organ Distribution ◽  
Post Transplantation ◽  
Term Survival ◽  
Transplant Candidates ◽  
Liver Transplant Waiting List ◽  
End Stage ◽  
Survival Risk

AbstractLiver transplantation provides a curative treatment option for patients with both acute and chronic liver disease, but the decision to list a patient for transplant should be an informed one to maximize post-transplantation benefit and survivability. Potential candidates meeting transplantation indications must undergo a comprehensive evaluation consisting of both physical, as well as psychiatric, assessment to be considered for transplantation. Once listed, a candidate's place on the liver transplant waiting list is determined predominantly by his or her Model for End-Stage Liver Disease (MELD)-Na score, which is a reliable tool to stratify short-term survival risk. The severity of certain conditions, however, is not accurately reflected by the MELD-Na score, and these particular diagnoses may be assigned MELD exception points. Herein, we discuss common indications for liver transplantation: the MELD system and its exceptions, the physical and psychosocial evaluation of potential transplant candidates, and some limitations of the current organ allocation system and efforts to reduce disparity in organ distribution.

scholarly journals The role of the gut microbiome in graft fibrosis after pediatric liver transplantation

2020 ◽  
Author(s):  
Tian Qin ◽  
Jingyuan Fu ◽  
Henkjan J. Verkade
Keyword(s):  
Liver Transplantation ◽  
Gut Microbiome ◽  
Current Knowledge ◽  
Solid Organ Transplantation ◽  
Short Chain Fatty Acids ◽  
Solid Organ ◽  
Microbial Composition ◽  
Term Survival ◽  
End Stage

Abstract Liver transplantation (LT) is a life-saving option for children with end-stage liver disease. However, about 50% of patients develop graft fibrosis in 1 year after LT, with normal liver function. Graft fibrosis may progress to cirrhosis, resulting in graft dysfunction and ultimately the need for re-transplantation. Previous studies have identified various risk factors for the post-LT fibrogenesis, however, to date, neither of the factors seems to fully explain the cause of graft fibrosis. Recently, evidence has accumulated on the important role of the gut microbiome in outcomes after solid organ transplantation. As an altered microbiome is present in pediatric patients with end-stage liver diseases, we hypothesize that the persisting alterations in microbial composition or function contribute to the development of graft fibrosis, for example by bacteria translocation due to increased intestinal permeability, imbalanced bile acids metabolism, and/or decreased production of short-chain fatty acids (SCFAs). Subsequently, an immune response can be activated in the graft, together with the stimulation of fibrogenesis. Here we review current knowledge about the potential mechanisms by which alterations in microbial composition or function may lead to graft fibrosis in pediatric LT and we provide prospective views on the efficacy of gut microbiome manipulation as a therapeutic target to alleviate the graft fibrosis and to improve long-term survival after LT.

Liver transplantation in children: an overview on organ allocation and surgical management

2021 ◽  
Vol 17 ◽  
Author(s):  
Chiara Grimaldi ◽  
Marco Spada ◽  
Giuseppe Maggiore
Keyword(s):  
Liver Transplantation ◽  
Organ Shortage ◽  
Perioperative Mortality ◽  
Term Survival ◽  
Early Referral ◽  
End Stage Liver Disease ◽  
Metabolic Defects ◽  
Partial Liver Transplantation ◽  
End Stage

: Liver transplantation is the standard of treatment for children with end-stage liver disease, primary hepatic neoplasms, or liver-localized metabolic defects. Perioperative mortality is almost absent, and long-term survival exceeds 90%. Organ shortage is managed thanks to advances in organ retrieval techniques. Living donation and partial liver transplantation almost eliminated waiting list mortality, thus leading to expanding indications for transplantation. The success of pediatric liver transplantation depends on the prompt and early referral of patients to transplant centers and on the close and integrated multidisciplinary collaboration between pediatricians, hepatologists, surgeons, intensivists, oncologists, pathologists, coordinating nurses, psychologists, and social workers.

scholarly journals Hepatorenal Syndrome

2019 ◽  
Vol 14 (5) ◽  
pp. 774-781 ◽  
Author(s):  
Claire Francoz ◽  
François Durand ◽  
Jeffrey A. Kahn ◽  
Yuri S. Genyk ◽  
Mitra K. Nadim
Keyword(s):  
Liver Transplantation ◽  
Systemic Inflammation ◽  
Hepatorenal Syndrome ◽  
Prognostic Information ◽  
Term Survival ◽  
Tubular Necrosis ◽  
Volume Activation ◽  
Central Volume ◽  
Definition Of ◽  
End Stage

Hepatorenal syndrome is a severe complication of end-stage cirrhosis characterized by increased splanchnic blood flow, hyperdynamic state, a state of decreased central volume, activation of vasoconstrictor systems, and extreme kidney vasoconstriction leading to decreased GFR. The contribution of systemic inflammation, a key feature of cirrhosis, in the development of hepatorenal syndrome has been highlighted in recent years. The mechanisms by which systemic inflammation precipitates kidney circulatory changes during hepatorenal syndrome need to be clarified. Early diagnosis is central in the management and recent changes in the definition of hepatorenal syndrome help identify patients at an earlier stage. Vasoconstrictive agents (terlipressin in particular) and albumin are the first-line treatment option. Several controlled studies proved that terlipressin is effective at reversing hepatorenal syndrome and may improve short-term survival. Not all patients are responders, and even in responders, early mortality rates are very high in the absence of liver transplantation. Liver transplantation is the only curative treatment of hepatorenal syndrome. In the long term, patients transplanted with hepatorenal syndrome tend to have lower GFR compared with patients without hepatorenal syndrome. Differentiating hepatorenal syndrome from acute tubular necrosis (ATN) is often a challenging yet important step because vasoconstrictors are not justified for the treatment of ATN. Hepatorenal syndrome and ATN may be considered as a continuum rather than distinct entities. Emerging biomarkers may help differentiate these two conditions and provide prognostic information on kidney recovery after liver transplantation, and potentially affect the decision for simultaneous liver–kidney transplantation.

Clinical Outcome of Orthotopic Liver Transplantation

2002 ◽  
Vol 25 (10) ◽  
pp. 935-938 ◽  
Author(s):  
G.A. Berlakovich
Keyword(s):  
Liver Transplantation ◽  
Clinical Outcome ◽  
Orthotopic Liver Transplantation ◽  
Hepatic Failure ◽  
Patient Survival ◽  
Standard Procedure ◽  
Survival Rates ◽  
Acute Hepatic Failure ◽  
Term Survival ◽  
End Stage

Orthotopic liver transplantation (OLT) has become a standard procedure for end-stage cirrhosis. The purpose of this anlysis is to give a brief overview on the clinical outcome of OLT. According to a current survey of primary indications for liver transplantation in Europe, virus-induced cirrhosis represents the largest proportion with 25%. The next frequent indication is alcoholic cirrhosis with 19%. Cholestatic diseases amount to 13%, malignancy in cirrhosis 10%, and acute hepatic failure 10%. The outcome of these main indications will be discussed and critical considerations pointed out. Patient survival rates demonstrate for cirrhosis at 1-and 5-year about 80% and 70%, respectively. In acute hepatic failure, more patients are lost in the perioperative period. Not surprisingly, patients transplanted for malignancy show decreased long-term survival. Considering an average of 5-year survival in patients with end-stage liver disease of 20% or less, excellent patient survival can be achieved by liver transplantation.

scholarly journals Cirrhosis Risk Score of the Donor Organ Predicts Early Fibrosis Progression after Liver Transplantation

2019 ◽  
Vol 28 (1) ◽  
pp. 53-61
Author(s):  
Anca Zimmermann ◽  
Felix Darstein ◽  
Maria Hoppe-Lotichius ◽  
Gerrit Toenges ◽  
Anja Lautem ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Risk Score ◽  
Donor Organ ◽  
Fibrosis Progression ◽  
Hazard Ratios ◽  
Protocol Biopsies ◽  
Liver Biopsies ◽  
Early Fibrosis ◽  
The Impact ◽  
Group D

Background & Aims: Fibrosis progression (FP) after liver transplantation (LT) increases morbidity and mortality. Biomarkers are needed for early prediction of FP. A recipient’s seven-gene cirrhosis risk score (CRS) has been associated with FP, especially in non-transplant cohorts. A broader validation of CRS, including the genotype of the donor-organ and HCV-negative patients is lacking. We therefore analyzed the impact of donor- and recipient-specific genotypes on FP after LT in a large cohort of HCV-positive and -negative patients.Method: Genotyping from liver biopsies (n=201 donors) and peripheral blood (n=442 recipients) was performed. Cirrhosis risk score was correlated with FP at 1 and 5 years after LT.Results: Fibrosis ≥F2 was documented in 26.5% of the recipients’ CRS group (R-CRS) (defined by recipient’s genotype) and in 23.4% of the donors’ CRS- group (D-CRS) (defined by donor’s genotype). Cumulative incidence for fibrosis ≥F2 was higher in patients with D-CRS >0.7 (p=0.03). While the R-CRS showed no prognostic relevance, D-CRS >0.7 was associated with higher hazard ratios (HRs) for fibrosis ≥F2 (HR=2.04; p=0.01), especially in HCV-negative patients (HR=2.59, p=0.03). Donors’ CRS >0.7 was associated with higher risk for ≥F2 in 1-year protocol biopsies (p<0.001). Among the patients in whom both the recipient’s and donor’s CRS were available, fibrosis ≥F2 was encountered more frequently in patients with a D-CRS >0.7, in combination with any R-CRS, compared to patients with D-CRS scores ≤0.7 (p=0.034). Donors’ AZIN1, STXBP5L, TRPM5 genotypes carried a higher risk for fibrosis ≥F2 in subgroups.Conclusion: High D-CRS >0.7 predicted early FP after LT, especially in HCV negative patients.

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