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Background: Mucosal-associated invariant T (MAIT) cells promote inflammation in obesity and are implicated in the progression of non-alcoholic fatty liver disease (NAFLD). However, as the intrahepatic MAIT cell response to lifestyle intervention in NAFLD has not been investigated, this work aimed to examine circulating and intrahepatic MAIT cell populations in patients with NAFLD, after either 12 weeks of dietary intervention (DI) or aerobic exercise intervention (EI)., Methods: Multicolour flow cytometry was used to immunophenotype circulating and intrahepatic MAIT cells and measure MAIT cell expression (median fluorescence intensity, MFI) of the activation marker CD69 and apoptotic marker CD95. Liver histology, clinical parameters, and MAIT cell populations were assessed at baseline (T0) and following completion (T1) of DI or EI., Results: Forty-five patients completed the study. DI participants showed decreased median (interquartile range) expression of the activation marker CD69 on circulating MAIT cells (T0: 104 (134) versus T1 27 (114) MFI; p = 0.0353) and improvements in histological steatosis grade post-intervention. EI participants showed increased expression of the apoptotic marker CD95, both in circulating (T0: 1549 (888) versus T1: 2563 (1371) MFI; p = 0.0043) and intrahepatic MAIT cells (T0: 2724 (862) versus T1: 3117 (1622) MFI; p = 0.0269). Moreover, the percentage of intrahepatic MAIT cells significantly decreased after EI (T0: 11.1 (14.4) versus T1: 5.3 (9.3)%; p = 0.0029), in conjunction with significant improvements in fibrosis stage and hepatocyte ballooning., Conclusions: These data demonstrate independent benefits from dietary and exercise intervention and suggest a role for intrahepatic MAIT cells in the observed histological improvements in NAFLD.

Objective: End-stage chronic liver disease is associated with accelerated ageing and increased frailty. Frailty measures have provided clinical utility in identifying patients at increased risk of poor health outcomes, including those awaiting liver transplantation. However, there is limited data on the prevalence and severity of frailty in patients with non-cirrhotic non-alcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the prevalence of frailty and prefrailty in patients with non-cirrhotic NAFLD and correlate with severity of liver disease., Design: A cross-sectional analysis of functional and laboratory frailty assessments, including the Fried frailty index (FFI), a self-reported frailty index (SRFI) and a lab-based frailty index (FI-LAB), was performed in a cohort of 109 patients with NAFLD, and results compared with fibrosis staging based on transient elastography., Results: Patients with NAFLD had a high prevalence of prefrailty and frailty, with a median SRFI score of 0.18 (IQR: 0.18), FFI of 1 (IQR: 1) and FI-LAB of 0.18 (IQR: 0.12). Using the SRFI, 45% of F0/F1 patients were classified as prefrail and 20% were classified as frail, while in F2/F3 patients this increased to 36% and 41%, respectively. SRFI, 30 s sit-to-stand and FI-LAB scores increased with increasing liver fibrosis stages (p=0.001, 0.006 and <0.001, respectively). On multivariate linear regression, female gender was identified as a significant predictor of elevated frailty scores., Conclusion: This study identifies a high prevalence of frailty in individuals with non-cirrhotic NAFLD. Addressing frailty through early rehabilitation interventions may reduce overall morbidity and mortality in this population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

COVID-19 is a major public health pandemic. Risk factors for severe infection and poorer outcomes include cardiovascular disease, obesity, type 2 diabetes mellitus and non-alcoholic fatty liver disease (NAFLD). Lifestyle interventions, including diet and physical activity modifications, are the current recommended treatment for NAFLD. In this communication, the authors discuss the crossover link between NAFLD and severe COVID-19 infection and the impact of essential public health measures to suppress the spread of COVID-19 on exercise and physical activity participation in patients with NAFLD. The future of exercise prescription and the potential use of digital technology in addressing NAFLD healthcare needs in the COVID-19 era are also explored., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Physical activity (PA) is an important non-pharmacological treatment for non-alcoholic fatty liver disease (NAFLD). This study investigated the determinants of PA engagement and awareness of the World Health Organization (WHO) PA guidelines in patients with NAFLD., Methods: Study participants were 101 patients with NAFLD (median age: 54 [IQR = 15] y; 53 men and 48 women) who completed 4 questionnaires: (1) a PA guideline awareness questionnaire; (2) a PA questionnaire assessing PA levels; and (3) 2 questionnaires assessing perceived barriers and motivators for engaging in PA. Binary logistic regression was performed to assess predictors of PA levels., Results: Twenty-four percent of participants correctly identified the recommended WHO weekly PA guidelines, and 39% adhered to the guidelines. Lack of willpower, time, and energy were the most frequently cited barrier domains. Scores for lack of willpower (odds ratio [OR] = 1.445, 95% CI = 1.088-1.919) and lack of resources (OR = 1.378, 95% CI = 1.003-1.893), and reporting 3 or more "significant" barrier domains (OR = 5.348, 95% CI = 1.792-15.873) were significant predictors of PA levels. Maintaining health and fitness was the most cited motivator domain and was a significant predictor (OR = 2.551, 95% CI = 1.253-5.208) of PA levels., Conclusions: This study highlights the lack of awareness of the WHO PA guidelines and the key determinants of PA participation in patients with NAFLD. Determinants of PA should be identified at the individual level to create a personalized approach for PA maintenance for people with NAFLD to promote lifelong participation in PA., Impact: This study closes a gap in the published data on the determinants of PA engagement in patients with NAFLD., Lay Summary: Physical inactivity is the fourth leading cause of global mortality and contributes to many chronic inflammatory diseases, including obesity, type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease (NAFLD). People with NAFLD engage in less physical activity compared with people who are healthy, and this study provides new information that clinicians can use to help these patients increase their physical activity participation., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Lifestyle interventions are the primary treatment for metabolic (dysfunction) associated fatty liver disease (MAFLD). However, the histological and cardiometabolic effects of aerobic exercise in MAFLD remain unclear., Aims: To assess the effects of a 12-week aerobic exercise intervention on histological and cardiometabolic endpoints in MAFLD., Methods: Patients with biopsy-confirmed MAFLD participated in a 12-week aerobic exercise intervention. Liver histology, cardiorespiratory fitness (estimated V̇O 2max ), physical activity, anthropometry and biochemical markers were assessed at baseline, intervention completion, and 12 and 52 weeks after intervention completion., Results: Twenty-four patients completed the exercise intervention (exercise group n = 16, control group n = 8). In the exercise group, 12 weeks of aerobic exercise reduced fibrosis and hepatocyte ballooning by one stage in 58% (P = 0.034) and 67% (P = 0.020) of patients, with no changes in steatosis (P = 1.000), lobular inflammation (P = 0.739) or NAFLD activity score (P = 0.172). Estimated V̇O 2max increased by 17% compared to the control group (P = 0.027) but this level of improvement was not maintained at 12 or 52 weeks after the intervention. Patients with fibrosis and ballooning improvement increased estimated V̇O 2max by 25% (P = 0.020) and 26% (P = 0.010), respectively. Anthropometric reductions including body mass (P = 0.038), waist circumference (P = 0.015) and fat mass (P = 0.007) were also observed, but no patient achieved 7%-10% weight loss., Conclusion: This study highlights the potential benefits of a 12-week aerobic exercise intervention in improving histological endpoints of MAFLD. The development of strategies to ensure continued engagement in aerobic exercise in MAFLD are needed., (© 2020 John Wiley & Sons Ltd.)

Objectives Physical activity (PA) is an important non-pharmacological treatment for non-alcoholic fatty liver disease (NAFLD). This study investigated the determinants of PA engagement and awareness of the World Health Organization (WHO) PA guidelines in patients with NAFLD. Methods Study participants were 101 patients with NAFLD (median age: 54 [IQR = 15] y; 53 men and 48 women) who completed 4 questionnaires: (1) a PA guideline awareness questionnaire; (2) a PA questionnaire assessing PA levels; and (3) 2 questionnaires assessing perceived barriers and motivators for engaging in PA. Binary logistic regression was performed to assess predictors of PA levels. Results Twenty-four percent of participants correctly identified the recommended WHO weekly PA guidelines, and 39% adhered to the guidelines. Lack of willpower, time, and energy were the most frequently cited barrier domains. Scores for lack of willpower (odds ratio [OR] = 1.445, 95% CI = 1.088–1.919) and lack of resources (OR = 1.378, 95% CI = 1.003–1.893), and reporting 3 or more "significant" barrier domains (OR = 5.348, 95% CI = 1.792–15.873) were significant predictors of PA levels. Maintaining health and fitness was the most cited motivator domain and was a significant predictor (OR = 2.551, 95% CI = 1.253–5.208) of PA levels. Conclusions This study highlights the lack of awareness of the WHO PA guidelines and the key determinants of PA participation in patients with NAFLD. Determinants of PA should be identified at the individual level to create a personalized approach for PA maintenance for people with NAFLD to promote lifelong participation in PA. Impact This study closes a gap in the published data on the determinants of PA engagement in patients with NAFLD. Lay Summary Physical inactivity is the fourth leading cause of global mortality and contributes to many chronic inflammatory diseases, including obesity, type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease (NAFLD). People with NAFLD engage in less physical activity compared with people who are healthy, and this study provides new information that clinicians can use to help these patients increase their physical activity participation. [ABSTRACT FROM AUTHOR]