INTRODUCTION We developed the strength training intervention (STRIVE), a home-based exercise program targeting physical function in patients with cirrhosis. In this pilot study, we aimed to evaluate the safety and efficacy of STRIVE. METHODS Eligible were adult patients with cirrhosis at 3 sites. Patients were randomized 2:1–12 weeks of STRIVE, a 30-minute strength training video plus a health coach or standard of care (SOC). Physical function and quality of life were assessed using the Liver Frailty Index (LFI) and Chronic Liver Disease Questionnaire (CLDQ), respectively. RESULTS Fifty-eight and 25 were randomized to STRIVE and SOC arms, respectively: 43% women, median age was 61 years, MELDNa, Model for End-Stage Liver Disease Sodium was 14, and 54% were Child-Pugh B/C. Baseline characteristics were similar in the STRIVE vs SOC arms except for rates of hepatic encephalopathy (19 vs 36%). LFI @ 12 weeks was available in 43 STRIVE and 20 SOC participants. After 12 weeks, the median LFI improved from 3.8 to 3.6 (ΔLFI −0.1) in the STRIVE arm and 3.7 to 3.6 (ΔLFI −0.1) in the SOC arm (P = 0.65 for ΔLFI difference). CLDQ scores improved from 4.6 to 5.2 in STRIVE participants (ΔCLDQ 0.38) and did not change in SOC participants (4.2–4.2; ΔCLDQ −0.03) (P = 0.09 for ΔCLDQ difference). One patient died (SOC arm) of bleeding. Only 14% of STRIVE participants adhered to the strength training video for 10–12 weeks. No adverse events were reported by STRIVE participants. DISCUSSION STRIVE, a home-based structured exercise program for patients with cirrhosis, was safely administered at 3 sites, but adherence was low. Although all participants showed minimal improvement in the LFI, STRIVE was associated with a substantial improvement in quality of life.
Frailty, a state of decreased physiological reserve, has been associated with dysregulation of the immune system. We hypothesized that frailty is associated with differential rates of acute cellular rejection (ACR) in liver transplantation (LT) recipients. Our study included LT recipients from 2014 to 2016 who had a pre‐LT frailty assessment using the liver frailty index (LFI). Frailty was defined as an LFI ≥4.5. ACR at 3 months was ascertained from pathology reports, and immunosuppression regimens were collected from chart review. There were 241 LT recipients who were included: 46 (19%) were classified as frail before LT. Median tacrolimus trough levels, mycophenolate doses, and corticosteroid doses at discharge and 3 months were similar between frail and nonfrail patients. Within 3 months after LT, 7 (15%) frail patients versus 10 (5%) nonfrail patients experienced ACR (P = 0.02). In the univariate analysis, frailty was associated with a higher odds of ACR at 3 months (OR, 3.3; 95% confidence interval, 1.2‐9.3; P = 0.02). Bivariate analyses were conducted with covariates that were associated with ACR in the univariate analysis or that were previously associated with either frailty (age and female sex) or ACR (Model for End‐Stage Liver Disease score and ascites), as well as relevant immunosuppression variables. In the bivariate analyses, frailty remained significantly associated with ACR at 3 months with an odds ratio relatively similar to the unadjusted value. In conclusion, frailty is associated with an increased rate of ACR within 3 months, despite similar immunosuppression regimens, suggesting that frailty should be considered in immediate post‐LT management.
Background. Frailty has emerged as a critical determinant of mortality in patients with cirrhosis. Currently, the United Network for Organ Sharing registry only includes the Karnofsky Performance Status (KPS) scale, which captures a single component of frailty. We determined the associations between frailty, as measured by the Liver Frailty Index (LFI), and KPS with waitlist mortality. Methods. Included were 247 adult patients with cirrhosis listed for liver transplantation without hepatocellular carcinoma from February 2014 to June 2019, who underwent outpatient assessments using the LFI and KPS within 30 days of listing. “Frail” was defined using the established LFI cutoff of ≥4.4. Competing risk models assessed associations between the LFI and KPS with waitlist mortality (death/delisting for sickness). Results. At a median 8 months follow-up, 25 (10%) patients died/were delisted. In this cohort, median Model for End-Stage Liver Disease-Sodium was 17, LFI was 3.9 (interquartile range 3.4–4.5), and KPS was 80 (interquartile range 70–90). In multivariable analysis, LFI (sub-hazard ratio 1.07, per 0.1 unit; 95% confidence interval, 1.01-1.12) was associated with waitlist mortality while KPS was not (sub-hazard ratio 1.00, per 10 units; 95% confidence interval, 0.78-1.29). Conclusions. Our data suggest that frailty, as measured by the LFI, may be more appropriate at capturing mortality risk than KPS and provide evidence in support of using the LFI more broadly in clinical transplant practice in the outpatient setting.
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.
Frailty has commonly been defined as a distinct biologic state of decreased physiologic reserve and increased vulnerability to health stressors that predispose individuals to adverse health outcomes. 1 As originally conceptualized in the field of geriatrics, frailty is a multidimensional construct that encompasses physical as well as psychological factors. A number of instruments have been developed in the field of geriatrics to operationalize the multidimensionality of this construct; however, in patients with cirrhosis, instruments used to measure frailty have largely focused on the physical aspects of frailty. 2 Our team developed the Liver Frailty Index from a cohort of patients with cirrhosis awaiting liver transplantation that includes hand grip strength, chair stands, and balance testing. 3 While we have demonstrated that the Liver Frailty Index accurately captures the construct of physical frailty, little is known of its association with psychological contributors to health outcomes. One psychological construct that has been recognized to be associated with frailty in noncirrhotic populations is resilience. 4-8 Resilience is a modifiable quality that describes an individual's capability to thrive
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