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Acute-on-chronic liver failure in liver transplant candidates with non-alcoholic steatohepatitis.

ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease worldwide. It is expected that non-alcoholic steatohepatitis (NASH), NASH-related cirrhosis and its decompensated forms will increase further in the next two decades. Acute-on-chronic liver failure (ACLF) is a distinct syndrome characterized by rapid deterioration of liver function in patients with chronic liver disease that is associated with development of one or more organ failures, and carries a very high short-term mortality. There is a paucity of data on ACLF in patients with NASH cirrhosis. Recent studies have shown that although ACLF incidence due to NASH is lower when compared to other etiologies, NASH is the fastest growing liver disease etiology among all ACLF hospitalizations. Higher rates of infections, as a precipitating factor, and circulatory failure were noted in this population. Metabolic derangements such as obesity and diabetes might also play a confounding role in the pathophysiology, clinical course, and prognosis of NASH patients with ACLF. Patients with ACLF due to NASH have shown a lower inpatient mortality despite a longer hospital length-of-stay and a higher 28- and 90-day mortality. Patients with ACLF should be promptly transferred to a transplant center and evaluated for liver transplantation (LT). Optimal prognostic scores, timing of LT, and the best bridge to LT therapy and treatment of post-LT complications need to be elucidated in prospective studies.

SUBMITTER: Doycheva I

PROVIDER: S-EPMC7063516 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Acute-on-chronic liver failure in liver transplant candidates with non-alcoholic steatohepatitis.

Doycheva Iliana I Thuluvath Paul J PJ

Translational gastroenterology and hepatology 20200705

Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease worldwide. It is expected that non-alcoholic steatohepatitis (NASH), NASH-related cirrhosis and its decompensated forms will increase further in the next two decades. Acute-on-chronic liver failure (ACLF) is a distinct syndrome characterized by rapid deterioration of liver function in patients with chronic liver disease that is associated with development of one or more organ failures, and carries a very high shor ...[more]

PMID: 32632389

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Project description:Background & aimsLittle is known about outcomes of liver transplantation for patients with non-alcoholic steatohepatitis (NASH). We aimed to determine the frequency and outcomes of liver transplantation for patients with NASH in Europe and identify prognostic factors.MethodsWe analysed data from patients transplanted for end-stage liver disease between January 2002 and December 2016 using the European Liver Transplant Registry database. We compared data between patients with NASH versus other aetiologies. The principle endpoints were patient and overall allograft survival.ResultsAmong 68,950 adults undergoing first liver transplantation, 4.0% were transplanted for NASH - an increase from 1.2% in 2002 to 8.4% in 2016. A greater proportion of patients transplanted for NASH (39.1%) had hepatocellular carcinoma (HCC) than non-NASH patients (28.9%, p <0.001). NASH was not significantly associated with survival of patients (hazard ratio [HR] 1.02, p = 0.713) or grafts (HR 0.99; p = 0.815) after accounting for available recipient and donor variables. Infection (24.0%) and cardio/cerebrovascular complications (5.3%) were the commonest causes of death in patients with NASH without HCC. Increasing recipient age (61-65 years: HR 2.07, p <0.001; >65: HR 1.72, p = 0.017), elevated model for end-stage liver disease score (>23: HR 1.48, p = 0.048) and low (<18.5 kg/m2: HR 4.29, p = 0.048) or high (>40 kg/m2: HR 1.96, p = 0.012) recipient body mass index independently predicted death in patients transplanted for NASH without HCC. Data must be interpreted in the context of absent recognised confounders, such as pre-morbid metabolic risk factors.ConclusionsThe number and proportion of liver transplants performed for NASH in Europe has increased from 2002 through 2016. HCC was more common in patients transplanted with NASH. Survival of patients and grafts in patients with NASH is comparable to that of other disease indications.Lay summaryThe prevalence of non-alcoholic fatty liver disease has increased dramatically in parallel with the worldwide increase in obesity and diabetes. Its progressive form, non-alcoholic steatohepatitis, is a growing indication for liver transplantation in Europe, with good overall outcomes reported. However, careful risk factor assessment is required to maintain favourable post-transplant outcomes in patients with non-alcoholic steatohepatitis.

Project description:BackgroundNon-alcoholic steatohepatitis (NASH) is the second-leading indication for liver transplantation (LT) worldwide and is projected to become the leading indication. Our study aimed to determine clinical variables that predict post-LT survival in NASH.MethodsA systematic review and meta-analysis was performed. On June 18, 2020 and April 28, 2022, Ovid MEDLINE ALL, Ovid Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials were searched. No date limits were applied. Inclusion criteria specified the type of study and our study's population/comparison and outcome/timepoints. Pediatric, animal, retransplantation-only, and studies classifying cryptogenic cirrhosis patients with body mass index (BMI) <30 as NASH were excluded. Studies with duplicate cohorts and missing information were excluded from the meta-analysis. Studies were appraised using the Newcastle-Ottawa Scale. This study was preregistered in PROSPERO (CRD42020196915).FindingsOut of 8583 studies identified, 25 studies were included in the systematic review, while 5 studies were included in the meta-analysis. Our quantitative review suggested that the following variables were predictive of post-LT NASH patient survival: recipient age, functional status, pre-LT hepatoma, model for end-stage liver disease (MELD) score, diabetes mellitus (DM), pre-LT dialysis, hepatic encephalopathy, portal vein thrombosis, hospitalization/ICU at LT, and year of LT. Predictors of graft survival included recipient age, BMI, pre-LT dialysis, and DM. Our pooled meta-analyses included five predictors of patient survival. Increased patient mortality was associated with older recipient age (HR=2·07, 95%CI: 1·71-2·50, I2=0, τ2=0, p=0·40) and pretransplant DM (HR=1·18, 95%CI: 1·08-1·28, I2=0, τ2=0, p=0·76).InterpretationOur systematic review and meta-analysis aimed to synthesise predictive variables of mortality in LT NASH patients. Clinically, this might help to identify modifiable risk factors that can be optimized in the post-transplant setting to improve patient outcomes and optimises decision making in the resource-limited LT setting.FundingToronto General and Western Hospital Foundation.

Project description:This paper is based upon the "Charles Lieber Satellite Symposia" organized by Manuela G. Neuman at the Research Society on Alcoholism (RSA) Annual Meetings, 2013 and 2014. The present review includes pre-clinical, translational and clinical research that characterize alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH). In addition, a literature search in the discussed area was performed. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD. The liver biopsy can confirm the etiology of NASH or alcoholic steatohepatitis (ASH) and assess structural alterations of cells, their organelles, as well as inflammatory activity. Three histological stages of ALD are simple steatosis, ASH, and chronic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes such as cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Alcohol mediated hepatocarcinogenesis, immune response to alcohol in ASH, as well as the role of other risk factors such as its co-morbidities with chronic viral hepatitis in the presence or absence of human immunodeficiency virus are discussed. Dysregulation of hepatic methylation, as result of ethanol exposure, in hepatocytes transfected with hepatitis C virus (HCV), illustrates an impaired interferon signaling. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota are suggested. The clinical aspects of NASH, as part of metabolic syndrome in the aging population, are offered. The integrative symposia investigate different aspects of alcohol-induced liver damage and possible repair. We aim to (1) determine the immuno-pathology of alcohol-induced liver damage, (2) examine the role of genetics in the development of ASH, (3) propose diagnostic markers of ASH and NASH, (4) examine age differences, (5) develop common research tools to study alcohol-induced effects in clinical and pre-clinical studies, and (6) focus on factors that aggravate severity of organ-damage. The intention of these symposia is to advance the international profile of the biological research on alcoholism. We also wish to further our mission of leading the forum to progress the science and practice of translational research in alcoholism.

Dataset Information

Acute-on-chronic liver failure in liver transplant candidates with non-alcoholic steatohepatitis.

Publications

Acute-on-chronic liver failure in liver transplant candidates with non-alcoholic steatohepatitis.

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