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Body fat composition determines outcomes before and after liver transplantation in patients with cirrhosis.

ABSTRACT: Cachexia occurs in late stages of liver cirrhosis, and a low-fat mass is potentially associated with poor outcome. This study compared different computed tomography (CT)-derived fat parameters with respect to its prognostic impact on the development of complications and death before and after liver transplantation. Between 2001 and 2014, 612 patients with liver cirrhosis without hepatocellular carcinoma listed for liver transplantation met the inclusion criteria, including abdominal CT scan (±200 days to listing). A total of 109 patients without cirrhosis served as controls. The subcutaneous fat index (SCFI), the paraspinal muscle fat index, and the visceral fat index were assessed at L3/L4 level and normalized to the height (cm² /m² ). Data were collected and analyzed retrospectively. Low SCFI was associated with a higher rate of ascites and increased C-reactive protein levels (p < 0.001). In addition, multivariate Cox regression analysis adjusting for sex, age, body mass index (BMI), and Model for End-Stage Liver Disease showed that decreasing SCFI was also associated with an increased risk of cirrhosis-related complications (p = 0.003) and death on the transplant wait list (p = 0.013). Increased paraspinal and visceral fat were not only positively correlated with creatinine levels (p < 0.001), BMI, and metabolic comorbidities (all p < 0.001) before transplantation, but also predictive for 1-year mortality after transplantation. Conclusion: The distribution of body fat is a major determinant for complications and outcome in cirrhosis before and after liver transplantation.

SUBMITTER: Engelmann C

PROVIDER: S-EPMC9315113 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Liver cirrhosis (LC) is the final usual outcome of liver damage induced by various chronic liver diseases. Because of asymptomatic nature of LC, it is usually diagnosed at late and advanced stages, and patients are easy to miss the best timing for treatment. Thus, the early detection of LC is needed. In the prospective Korean Cancer Prevention Study-II (K-II), we aimed to identify valuable biomarkers for LC using metabolomics to distinguish subjects with incident LC (LC group) from subjects free from LC (control group) during a mean 7-year follow-up period. Metabolic alterations were investigated using baseline serum specimens acquired from 94 subjects with incident LC and 180 age- and sex-matched LC-free subjects via ultra-performance liquid chromatography (UPLC)-linear-trap quardrupole (LTQ)-Orbitrap mass spectrometry (MS). As a result of the metabolic analysis, 46 metabolites were identified. Among them, 11 and 18 metabolite level showed a significant increase and decrease, respectively, in the LC group compared to the control group. Nine metabolic pathways, including glyoxylate and dicarboxylate metabolism, amino acid metabolism, fatty acid metabolism, linoleic acid metabolism, α-linolenic acid metabolism, and arachidonic acid metabolism, were significantly different between the two groups. Logistic regression demonstrated that the LC emergence was independently affected by serum levels of myristic acid, palmitic acid, linoleic acid, eicosapentaenoic acid (EPA), lysophosphatidic acid (LPA) (18:1), glycolic acid, lysophosphatidylcholine (lysoPC) (22:6), and succinylacetone (R 2 = 0.837, P < 0.001). This prospective study revealed that dysregulation of various metabolism had the clinical relevance on the LC development. Moreover, myristic acid, palmitic acid, linoleic acid, EPA, LPA (18:1), glycolic acid, lysoPC (22:6), and succinylacetone were emerged as independent variables influencing the incidence of LC. The results support that the early biomarkers found in this study may useful for predicting and remedying the risk of LC.

Project description:BACKGROUND & AIMS:A diagnosis of cirrhosis can be made on the basis of findings from imaging studies, but these are subjective. Analytic morphomics uses computational image processing algorithms to provide precise and detailed measurements of organs and body tissues. We investigated whether morphomic parameters can be used to identify patients with cirrhosis. METHODS:In a retrospective study, we performed analytic morphomics on data collected from 357 patients evaluated at the University of Michigan from 2004 to 2012 who had a liver biopsy within 6 months of a computed tomography scan for any reason. We used logistic regression with elastic net regularization and cross-validation to develop predictive models for cirrhosis, within 80% randomly selected internal training set. The other 20% data were used as internal test set to ensure that model overfitting did not occur. In validation studies, we tested the performance of our models on an external cohort of patients from a different health system. RESULTS:Our predictive models, which were based on analytic morphomics and demographics (morphomics model) or analytic morphomics, demographics, and laboratory studies (full model), identified patients with cirrhosis with area under the receiver operating characteristic curve (AUROC) values of 0.91 and 0.90, respectively, compared with 0.69, 0.77, and 0.76 for aspartate aminotransferase-to-platelet ratio, Lok Score, and FIB-4, respectively, by using the same data set. In the validation set, our morphomics model identified patients who developed cirrhosis with AUROC value of 0.97, and the full model identified them with AUROC value of 0.90. CONCLUSIONS:We used analytic morphomics to demonstrate that cirrhosis can be objectively quantified by using medical imaging. In a retrospective analysis of multi-protocol scans, we found that it is possible to identify patients who have cirrhosis on the basis of analyses of preexisting scans, without significant additional risk or cost.

Project description:IntroductionCirrhosis is the main cause of morbidity and mortality globally, accounting for approximately 1.2 million deaths annually. Impaired aerobic capacity, muscle wasting and reduced muscle strength are significant complications in patients with cirrhosis. Preoperative exercise intervention "prehabilitation" has been recognised as a potential approach to optimise muscle strength, aerobic capacity and body composition as well as quality of life in patients awaiting abdominal surgery. However, there is little evidence on the effects of preoperative exercise on older adults with cirrhosis and awaiting liver transplant. Thus, the primary objective of this systematic review and meta-analysis will be to assess the effects of exercise interventions in improving aerobic capacity, muscle strength and body composition of older adults with cirrhosis and awaiting liver transplant.Methods and analysisThis systematic review and metaanalysis protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This systematic review will include all peer-reviewed randomised controlled trials (RCTs), including cluster RCTs, controlled (non-controlled), complex clinical trials (CCTs) or cluster trials, cohort, observational studies published in English from inception until July 2024. The following electronic databases will be searched: MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL (EBSCO) and Scopus (Elsevier) and supplemented by a secondary screening of the reference lists of all included articles. Searches will involve studies with both male and female participants aged ≥ 18 years with cirrhosis and awaiting liver transplant. Primary outcomes will include muscle strength, and aerobic capacity. The secondary outcomes include body composition (e.g. body mass index, and thigh circumference). The Cochrane Collaboration Risk of Bias Tool will be used to evaluate quality of the studies and Review Manager (RevMan) V.5.3 (Copenhagen, Denmark: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). Effect sizes will be expressed as a standardised mean difference, and their 95% confidence intervals will be calculated and presented as a forest plot. The standard χ2 and I2 tests will be used to test heterogeneity.ConclusionThis systematic review and meta-analysis is anticipated to provide meaningful and contemporary evidence on the effects of preoperative exercise in older adults living with cirrhosis and awaiting liver transplant. In addition, the findings will help clinicians with developing safe and effective preoperative exercise regimens for these patients.

Project description:UnlabelledCirrhosis is characterized by sarcopenia and malnutrition, leading to progressive functional decline. We aimed to objectively measure functional decline in patients with cirrhosis awaiting liver transplantation and its association with waiting list mortality. Consecutive adults listed for liver transplantation with laboratory Model for End-Stage Liver Disease (MELD) ≥12 at a single center underwent functional status assessments at every outpatient visit using the Short Physical Performance Battery (0 = impaired to 12 = robust), consisting of gait, chair stands, and balance tests. Joint linear time-to-event analyses modeled the simultaneous impact of the longitudinal trajectory of physical function on waiting list mortality (=death or delisted for being too sick for liver transplantation). Included were 309 liver transplantation candidates. Median laboratory MELD was 15, serum albumin was 3.0 g/dL, 28% had ascites, 18% had hepatic encephalopathy, and 83% were Child class B or C. At a median follow-up of 14 months, 15% died or were delisted and 28% underwent liver transplantation. Average physical function worsened per 3 months on the waiting list: -0.38 kg in grip strength, -0.05 meters/second in gait, 0.03 seconds in chair stands, and -0.16 Short Physical Performance Battery points. In joint models of longitudinal trajectories of physical function and waiting list mortality adjusted for MELD-Na, albumin, hepatocellular carcinoma, and baseline physical function, the longitudinal trajectories of each physical function measure were significantly associated with waiting list mortality: grip (hazard ratio = 0.89, 95% confidence interval 0.83-0.95), gait (hazard ratio = 0.72, 95% confidence interval 0.62-0.84), chair stands (hazard ratio = 1.17, 95% confidence interval 1.09-1.25), and Short Physical Performance Battery <10 (hazard ratio = 1.45, 95% confidence interval 1.15-2.20).ConclusionLiver transplantation candidates experience significant functional decline on the waiting list, despite modest wait time and low baseline MELD; decline in physical function is associated with an increased risk of death or delisting, independent of liver disease severity.

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Body fat composition determines outcomes before and after liver transplantation in patients with cirrhosis.

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