Dataset Information

Frailty and the Burden of Concurrent and Incident Disability in Patients With Cirrhosis: A Prospective Cohort Study.

ABSTRACT: Frailty results from the chronic effects of malnutrition and muscle wasting in patients with cirrhosis. It is well-established that frailty is strongly associated with mortality in this population. However, little is known of its relationship with physical disability, a critical patient-centered outcome. Adults with cirrhosis underwent outpatient testing of frailty using the Liver Frailty Index (LFI) and disability using activities of daily living (ADL; range 0-6) and Instrumental ADL (IADL; range 0-8) scales at one center between 2012 and 2016. We used adjusted multilevel logistic mixed-effects regression to test the association between frailty and current disability (impairment with ?1 ADL or IADL) and incident disability at 6 months among those without baseline disability. Of the 983 participants, 20% were robust, 32% were less robust, 33% were prefrail, and 15% were frail; 587 (60%) had at least 1 assessment. The percentage of participants with at least 1 baseline ADL or IADL impairment was 28% and 37%, respectively. In adjusted regression models, each point LFI increase was associated with a 3.3 and 4.6 higher odds of current difficulty with at least 1 ADL and IADL (P < 0.001 for each), respectively. Among participants without baseline disability, each point LFI increase was associated with a 2.6 and 1.7 higher odds of having difficulty with at least 1 ADL and IADL at 6 months, respectively. Conclusion: Frailty is strongly associated with concurrent and incident disability in patients with cirrhosis. In the clinic, the LFI can be used to identify those in greatest need for additional support/resources to maintain functional independence. In research settings, the LFI may help to identify an enriched population for clinical trials of interventions aimed at those most vulnerable to disability.

SUBMITTER: Lai JC

PROVIDER: S-EPMC6939546 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Frailty and the Burden of Concurrent and Incident Disability in Patients With Cirrhosis: A Prospective Cohort Study.

Lai Jennifer C JC Dodge Jennifer L JL McCulloch Charles E CE Covinsky Kenneth E KE Singer Jonathan P JP

Hepatology communications 20191031 1

Frailty results from the chronic effects of malnutrition and muscle wasting in patients with cirrhosis. It is well-established that frailty is strongly associated with mortality in this population. However, little is known of its relationship with physical disability, a critical patient-centered outcome. Adults with cirrhosis underwent outpatient testing of frailty using the Liver Frailty Index (LFI) and disability using activities of daily living (ADL; range 0-6) and Instrumental ADL (IADL; ran ...[more]

PMID: 31909360

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Project description:Background & Aims:Body composition, particularly sarcopenia, is associated with mortality in patients with decompensated cirrhosis undergoing transplant evaluation. Similar data are limited for non-transplant eligible or compensated patients. Methods:A total of 274 patients with cirrhosis were followed prospectively for ?5 years after a CT scan. We utilized Analytic Morphomics® to measure body composition (fat, muscle, and bone) which was rendered into relative values (percentiles) in relation to a reference population. The model for end-stage liver disease (MELD) score was used as a reference model for survival prediction. We validated our models in a separate cohort. Results:Our cohort had a mean Child-Pugh score of 7.0 and a mean MELD of 11.3. The median follow-up time was 5.05 years. The proportion of patients alive at 1, 3 and 5 years was 86.5%, 68.0%, and 54.3%; 13 (4.6%) underwent liver transplantation. Child-Pugh B/C (vs. A) cirrhosis was associated with decreased muscle, subcutaneous, and visceral fat area but increased subcutaneous/visceral fat density. Decreased normal density muscle mass was associated with mortality (hazard ratio [HR] 0.984, p <0.001) as well as visceral and subcutaneous fat density (HR 1.013 and 1.014, respectively, p <0.001). Models utilizing these features outperformed MELD alone for mortality discrimination in both the derivation and validation cohort, particularly for those with compensated cirrhosis (C-statistics of 0.74 vs. 0.58). Using competing risk analysis, we found that subcutaneous fat density was most predictive of decompensation (subdistribution HR 1.018, p = 0.0001). Conclusion:The addition of body composition features to predictive models improves the prospective determination of prognosis in patients with cirrhosis, particularly those with compensated disease. Fat density, a novel feature, is associated with the risk of decompensation. Lay summary:Am I at high risk of getting sicker and dying? This is the key question on the mind of patients with cirrhosis. The problem is that we have very few tools to help guide our patients, particularly if they have early cirrhosis (without symptoms like confusion or fluid in the belly). We found that how much muscle and fat the patient has and what that muscle or fat looks like on a CT scan provide helpful information. This is important because many patients have CT scans and this information is hiding in plain sight.

Project description:BACKGROUND & AIMS: The effectiveness of surveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is limited, due to inadequate risk stratification and suboptimal performance of current screening modalities.METHODS: We developed a multicenter prospective cohort of patients with cirrhosis undergoing surveillance with MRI and applied global untargeted metabolomics to 612 longitudinal serum samples from 203 patients. Among them, 37 developed HCC during follow-up.RESULTS: We identified 150 metabolites with significant abundance changes in samples collected prior to HCC (Cases) compared to samples from patients who did not develop HCC (Controls). Tauro-conjugated bile acids and gamma-glutamyl amino acids were increased, while acyl-cholines and deoxycholate derivatives were decreased. Seven amino acids including serine and alanine had strong associations with HCC risk, while strong protective effects were observed for N-acetylglycine and glycerophosphorylcholine. Machine learning using the 150 metabolites, age, gender, and PNPLA3 and TMS6SF2 single nucleotide polymorphisms, identified 15 variables giving optimal performance. Among them, N-acetylglycine had the highest AUC in discriminating Cases and Controls. When restricting Cases to samples collected within 1 year prior to HCC (Cases-12M), additional metabolites including microbiota-derived metabolites were identified. The combination of the top six variables identified by machine learning (alpha-fetoprotein, 6-bromotryptophan, N-acetylglycine, salicyluric glucuronide, testosterone sulfate and age) had good performance in discriminating Cases-12M from Controls (AUC 0.88, 95% CI 0.83-0.93). Finally, 23 metabolites distinguished Cases with LI-RADS-3 lesions from Controls with LI-RADS-3 lesions, with reduced abundance of acyl-cholines and glycerophosphorylcholine-related lysophospholipids in Cases.CONCLUSIONS: This study identified N-acetylglycine, amino acids, bile acids and choline-derived metabolites as biomarkers of HCC risk, and microbiota-derived metabolites as contributors to HCC development.

Project description:BACKGROUND:Frailty is a state of vulnerability to diverse stressors. We assessed the impact of frailty on outcomes after discharge in older surgical patients. METHODS:We prospectively followed patients 65 years of age or older who underwent emergency abdominal surgery at either of 2 tertiary care centres and who needed assistance with fewer than 3 activities of daily living. Preadmission frailty was defined according to the Canadian Study of Health and Aging Clinical Frailty Scale as "well" (score 1 or 2), "vulnerable" (score 3 or 4) or "frail" (score 5 or 6). We assessed composite end points of 30-day and 6-month all-cause readmission or death by multivariable logistic regression. RESULTS:Of 308 patients (median age 75 [range 65-94] yr, median Clinical Frailty Score 3 [range 1-6]), 168 (54.5%) were classified as vulnerable and 68 (22.1%) as frail. Ten (4.2%) of those classified as vulnerable or frail received a geriatric consultation. At 30 days after discharge, the proportions of patients who were readmitted or had died were greater among vulnerable patients (n = 27 [16.1%]; adjusted odds ratio [OR] 4.60, 95% confidence interval [CI] 1.29-16.45) and frail patients (n = 12 [17.6%]; adjusted OR 4.51, 95% CI 1.13-17.94) than among patients who were well (n = 3 [4.2%]). By 6 months, the degree of frailty independently and dose-dependently predicted readmission or death: 56 (33.3%) of the vulnerable patients (adjusted OR 2.15, 95% CI 1.01-4.55) and 37 (54.4%) of the frail patients (adjusted OR 3.27, 95% CI 1.32-8.12) were readmitted or had died, compared with 11 (15.3%) of the patients who were well. INTERPRETATION:Vulnerability and frailty were prevalent in older patients undergoing surgery and unlikely to trigger specialized geriatric assessment, yet remained independently associated with greater risk of readmission for as long as 6 months after discharge. Therefore, the degree of frailty has important prognostic value for readmission. TRIAL REGISTRATION FOR PRIMARY STUDY:ClinicalTrials.gov, no. NCT02233153.

Dataset Information

Frailty and the Burden of Concurrent and Incident Disability in Patients With Cirrhosis: A Prospective Cohort Study.

Publications

Frailty and the Burden of Concurrent and Incident Disability in Patients With Cirrhosis: A Prospective Cohort Study.

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