Dataset Information

The relationship between frailty and cirrhosis etiology: From the Functional Assessment in Liver Transplantation (FrAILT) Study.

ABSTRACT:

Background & aims

Cirrhosis leads to malnutrition and muscle wasting that manifests as frailty, which may be influenced by cirrhosis aetiology. We aimed to characterize the relationship between frailty and cirrhosis aetiology.

Methods

Included were adults with cirrhosis listed for liver transplantation (LT) at 10 US centrer who underwent ambulatory testing with the Liver Frailty Index (LFI; 'frail' = LFI ≥ 4.4). We used logistic regression to associate aetiologies and frailty, and competing risk regression (LT as the competing risk) to determine associations with waitlist mortality (death/delisting for sickness).

Results

Of 1,623 patients, rates of frailty differed by aetiology: 22% in chronic hepatitis C, 31% in alcohol-associated liver disease (ALD), 32% in non-alcoholic fatty liver disease (NAFLD), 21% in autoimmune/cholestatic and 31% in 'other' (P < .001). In univariable logistic regression, ALD (OR 1.53, 95% CI 1.12-2.09), NAFLD (OR 1.64, 95% CI 1.18-2.29) and 'other' (OR 1.58, 95% CI 1.06-2.36) were associated with frailty. In multivariable logistic regression, only ALD (OR 1.40; 95% 1.01-1.94) and 'other' (OR 1.59; 95% 1.05-2.40) remained associated with frailty. A total of 281 (17%) patients died/were delisted for sickness. In multivariable competing risk regression, LFI was associated with waitlist mortality (sHR 1.05, 95% CI 1.03-1.06), but aetiology was not (P > .05 for each). No interaction between frailty and aetiology on the association with waitlist mortality was found (P > .05 for each interaction term).

Conclusions

Frailty is more common in patients with ALD, NAFLD and 'other' aetiologies. However, frailty was associated with waitlist mortality independent of cirrhosis aetiology, supporting the applicability of frailty across all cirrhosis aetiologies.

SUBMITTER: Xu CQ

PROVIDER: S-EPMC8522207 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Publications

The relationship between frailty and cirrhosis etiology: From the Functional Assessment in Liver Transplantation (FrAILT) Study.

Xu Chelsea Q CQ Mohamad Yara Y Kappus Matthew R MR Boyarsky Brian B Ganger Daniel R DR Volk Michael L ML Rahimi Robert S RS Duarte-Rojo Andres A McAdams-DeMarco Mara M Segev Dorry L DL Ladner Daniela P DP Verna Elizabeth C EC Grab Joshua J Tincopa Monica M Dunn Michael A MA Lai Jennifer C JC

Liver international : official journal of the International Association for the Study of the Liver 20210714 10

<h4>Background & aims</h4>Cirrhosis leads to malnutrition and muscle wasting that manifests as frailty, which may be influenced by cirrhosis aetiology. We aimed to characterize the relationship between frailty and cirrhosis aetiology.<h4>Methods</h4>Included were adults with cirrhosis listed for liver transplantation (LT) at 10 US centrer who underwent ambulatory testing with the Liver Frailty Index (LFI; 'frail' = LFI ≥ 4.4). We used logistic regression to associate aetiologies and frailty, and ...[more]

PMID: 34219362

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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.

Project description:ImportanceFemale liver transplant candidates experience higher rates of wait list mortality than male candidates. Frailty is a critical determinant of mortality in patients with cirrhosis, but how frailty differs between women and men is unknown.ObjectiveTo determine whether frailty is associated with the gap between women and men in mortality among patients with cirrhosis awaiting liver transplantation.Design, setting, and participantsThis prospective cohort study enrolled 1405 adults with cirrhosis awaiting liver transplant without hepatocellular carcinoma seen during 3436 ambulatory clinic visits at 9 US liver transplant centers. Data were collected from January 1, 2012, to October 1, 2019, and analyzed from August 30, 2019, to October 30, 2020.ExposuresAt outpatient evaluation, the Liver Frailty Index (LFI) score was calculated (grip strength, chair stands, and balance).Main outcomes and measuresThe risk of wait list mortality was quantified using Cox proportional hazards regression by frailty. Mediation analysis was used to quantify the contribution of frailty to the gap in wait list mortality between women and men.ResultsOf 1405 participants, 578 (41%) were women and 827 (59%) were men (median age, 58 [interquartile range (IQR), 50-63] years). Women and men had similar median scores on the laboratory-based Model for End-stage Liver Disease incorporating sodium levels (MELDNa) (women, 18 [IQR, 14-23]; men, 18 [IQR, 15-22]), but baseline LFI was higher in women (mean [SD], 4.12 [0.85] vs 4.00 [0.82]; P = .005). Women displayed worse balance of less than 30 seconds (145 [25%] vs 149 [18%]; P = .003), worse sex-adjusted grip (mean [SD], -0.31 [1.08] vs -0.16 [1.08] kg; P = .01), and fewer chair stands per second (median, 0.35 [IQR, 0.23-0.46] vs 0.37 [IQR, 0.25-0.49]; P = .04). In unadjusted mixed-effects models, LFI was 0.15 (95% CI, 0.06-0.23) units higher in women than men (P = .001). After adjustment for other variables associated with frailty, LFI was 0.16 (95% CI, 0.08-0.23) units higher in women than men (P < .001). In unadjusted regression, women experienced a 34% (95% CI, 3%-74%) increased risk of wait list mortality than men (P = .03). Sequential covariable adjustment did not alter the association between sex and wait list mortality; however, adjustment for LFI attenuated the mortality gap between women and men. In mediation analysis, an estimated 13.0% (IQR, 0.5%-132.0%) of the gender gap in wait list mortality was mediated by frailty.Conclusions and relevanceThese findings demonstrate that women with cirrhosis display worse frailty scores than men despite similar MELDNa scores. The higher risk of wait list mortality that women experienced appeared to be explained in part by frailty.

Project description:BackgroundCardiac dysfunction is increasingly recognized in patients with liver cirrhosis. Nevertheless, the presence or absence of structural alterations such as diffuse myocardial fibrosis remains unclear. We aimed to investigate myocardial structural changes in cirrhosis, and explore left ventricular (LV) structural and functional changes induced by liver transplantation.MethodsThis study included 33 cirrhosis patients listed for transplantation and 20 healthy controls. Patients underwent speckle-tracking echocardiography and cardiovascular magnetic resonance (CMR) with extracellular volume fraction (ECV) quantification at baseline (n = 33) and 1 year after transplantation (n = 19).ResultsCMR-based LV ejection fraction (CMRLV-EF) and echocardiographic LV global longitudinal strain (LV-GLS) demonstrated hyper-contractile LV in cirrhosis patients (CMRLV-EF: 67.8 ± 6.9% in cirrhosis vs 63.4 ± 6.4% in healthy controls, P = 0.027; echocardiographic GLS: - 24.2 ± 2.7% in cirrhosis vs - 18.6 ± 2.2% in healthy controls, P < 0.001). No significant differences in LV size, wall thickness, mass index, and diastolic function between cirrhosis patients and healthy controls were seen (all P > 0.1). Only one of the cirrhosis patients showed late gadolinium enhancement. However, cirrhosis patients showed a higher ECV (31.6 ± 5.1% vs 25.4 ± 1.9%, P < 0.001) than healthy controls. ECV showed a positive correlation with Child-Pugh score (r = 0.564, P = 0.001). Electrocardiogram-based corrected QT interval was prolonged in cirrhosis (P < 0.001). One-year post-transplantation, echocardiographic LV-GLS (from - 24.9 ± 2.4% to - 20.6 ± 3.4%, P < 0.001) and ECV (from 30.9 ± 4.5% to 25.4 ± 2.6%, P = 0.001) moved to the normal ranges. Corrected QT interval decreased after transplantation (from 475 ± 41 to 429 ± 30 msec, P = 0.001).ConclusionsMyocardial extracellular volume expansion with augmented resting LV systolic function was characteristic of cirrhotic cardiomyopathy, which normalizes 1-year post-transplantation. Thus, myocardial extracellular expansion represents a structural component of myocardial changes in cirrhosis.

Dataset Information

The relationship between frailty and cirrhosis etiology: From the Functional Assessment in Liver Transplantation (FrAILT) Study.

Background & aims

Methods

Results

Conclusions

Publications

The relationship between frailty and cirrhosis etiology: From the Functional Assessment in Liver Transplantation (FrAILT) Study.

Similar Datasets

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