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Cyrielle Caussy,1– 3 Charlène Telliam,2,4 Bader Al-Nuaimi,2 Marianne Maynard-Muet,5,6 Jérôme Dumortier,3,7 Fabien Zoulim,3,5,6 Emmanuel Disse,1– 3 Cyrille Colin,3,8 Massimo Levrero,3,5,6 Philippe Moulin1,3,4 1CarMen Laboratory, INSERM, INRA, INSA Lyon, Université Claude Bernard Lyon 1, Pierre-Bénite, 69495, France; 2Département Endocrinologie, Diabète et Nutrition, Hôpital Lyon Sud, Hopices Civils de Lyon, Pierre-Bénite, 69495, France; 3Université de Lyon, Université Claude Bernard, Lyon, France; 4Département Endocrinologie, Diabète et Nutrition, Hôpital Cardiologique, Hospices Civils de Lyon, Bron, France; 5Service d’Hépatologie, Hôpital Croix-Rousse, Hospices Civils de Lyon, Lyon, France; 6Centre de Recherche sur le Cancer de Lyon, INSERM, Unité 1052, CNRS, UMR 5286, Lyon, France; 7Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France; 8Unité d’Evaluation Médico-Economique, Pôle Information Médicale Evaluation Recherche, Hospices Civils de Lyon, Lyon, FranceCorrespondence: Cyrielle Caussy, Service d’Endocrinologie, Diabète et Nutrition, Hôpital Lyon Sud, 165 Chemin du Grand Revoyet, Pierre-Bénite, 69495, France, Tel +33478864448, Fax + 33478863019, Email cyrielle.caussy@chu-lyon.frPurpose: A systematic screening for the presence of nonalcoholic fatty liver disease (NAFLD)-related advanced fibrosis is currently recommended in patients with type 2 diabetes mellitus (T2DM) and obesity. However, real-world data of such liver fibrosis risk stratification pathway from diabetology and nutrition clinics towards hepatology clinics are scarce. Therefore, we compared data from two pathways with or without transient elastography (TE) performed in diabetology and nutrition clinics.Patients and Methods: This is a retrospective study comparing the proportion of patients with intermediate/high risk of advanced fibrosis (AF) as defined by a liver stiffness measurement (LSM) ≥ 8kPa, among patients referred in hepatology from two diabetology-nutrition departments at Lyon University Hospital, France between November 1st 2018 to December 31st 2019.Results: Among the two diabetology and nutrition departments using TE or not, 27.5% (62/225) versus 44.2% (126/285) were referred to hepatology, respectively. The pathway using TE in diabetology and nutrition referred to hepatology a higher proportion of patients with intermediate/high risk of AF compared to the pathway without TE: 77.4% versus 30.9%, p< 0.001. In the pathway with TE, the odds of patients with intermediate/high risk of AF referred to hepatology was significantly higher: OR: 7.7, 95% CI: 3.6– 16.7, p< 0.001 after adjustment for age, sex and presence of obesity and T2D compared to the pathway without TE in diabetology and nutrition clinics. However, among the patients not referred, 29.4% had an intermediate/high risk of AF.Conclusion: A pathway-referral using TE performed in diabetology and nutrition clinics, significantly improves the liver fibrosis risk stratification and avoids over-referral. However, collaboration between diabetologist, nutritionists and hepatologists is needed to avoid under-referral.Keywords: nonalcoholic fatty liver disease, FibroScan, cirrhosis, transient elastography, obesity, type 2 diabetes, screening

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Copyright of Obésité is the property of Lavoisier and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Metabolic flexibility (MetF), defined as the ability to switch between fat and glucose oxidation, is increasingly recognised as a critical marker for assessing responses to dietary interventions. Previously, we showed that the consumption of multifibre bread improved insulin sensitivity and reduced low-density lipoprotein cholesterol (LDLc) levels in overweight and obese individuals. As a secondary objective, we aimed to explore whether our intervention could also improve MetF., Methods: In this study, 39 subjects at cardiometabolic risk participated in a double-blind, randomised, crossover trial lasting 8 weeks, repeated twice. During each phase, participants consumed either 150 g of standard bread daily or bread enriched with a mixture of seven dietary fibres. MetF response was assessed using a mixed-meal tolerance test (MMTT), analysing changes in respiratory quotient (∆RQ) measured using indirect calorimetry., Results: Although there were no significant differences in ∆RQ changes induced by dietary fibre between the two diets, these changes were positively correlated with postprandial triglyceride excursion (∆TG) at baseline. Subgroup analysis of baseline fasting and postprandial plasma metabolites was conducted to characterise MetF responders. These responders exhibited higher baseline fasting LDLc levels and greater post-MMTT ∆TG., Conclusion: In conclusion, although dietary fibres did not directly impact MetF in this study, our findings highlight potential determinants of MetF response, warranting further investigation in dedicated future interventions., (© 2024 The Author(s). Journal of Human Nutrition and Dietetics published by John Wiley Sons Ltd on behalf of British Dietetic Association.)

The aim of the current study is to demonstrate the feasibility of radiofrequency (RF) pulses generated via an optimal control (OC) algorithm to perform magnetic resonance elastography (MRE) and quantify the mechanical properties of materials with very short transverse relaxation times (T2 < 5 ms) for the first time. OC theory applied to MRE provides RF pulses that bring isochromats from the equilibrium state to a fixed target state, which corresponds to the phase pattern of a conventional MRE acquisition. Such RF pulses applied with a constant gradient allow to simultaneously perform slice selection and motion encoding in the slice direction. Unlike conventional MRE, no additional motion-encoding gradients (MEGs) are needed, enabling shorter echo times. OC pulses were implemented both in turbo spin echo (OC rapid acquisition with refocused echoes [RARE]) and ultrashort echo time (OC UTE) sequences to compare their motion-encoding efficiency with the conventional MEG encoding (classical MEG MRE). MRE experiments were carried out on agar phantoms with very short T2 values and on an ex vivo bovine tendon. Magnitude images, wave field images, phase-to-noise ratio (PNR), and shear storage modulus maps were compared between OC RARE, OC UTE, and classical MEG MRE in samples with different T2 values. Shear storage modulus values of the agar phantoms were in agreement with values found in the literature, and that of the bovine tendon was corroborated with rheometry measurements. Only the OC sequences could encode motion in very short T2 samples, and only OC UTE sequences yielded magnitude images enabling proper visualization of short T2 samples and tissues. The OC UTE sequence produced the best PNRs, demonstrating its ability to perform anatomical and mechanical characterization. Its success warrants in vivo confirmation in further studies., (© 2024 John Wiley & Sons Ltd.)

Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with obesity. We aimed to assess the impact of obesity on the performance of different noninvasive tests, including liver stiffness measurement (LSM) and Agile3+ (A3+), to detect advanced fibrosis (AF) in a population of patients with MASLD encompassing a wide range of BMI values., Methods: A total of 479 patients with MASLD were consecutively included (Lyon Hepatology Institute). Clinical data and noninvasive tests, including FibroTest, LSM, A3+, Fibrosis-4 (FIB-4), magnetic resonance elastography, and liver biopsies, were collected. AF was determined by a composite endpoint, i.e., histological stage ≥ F3, overt diagnosis of cirrhosis by magnetic resonance elastography, or concordant LSM ≥ 9.6 kPa and FibroTest ≥ F3., Results: The median BMI was 35.0 kg/m 2 , and the prevalence of AF was 28.6%. Patients with BMI ≥ 35 versus <35 had a lower proportion of AF, i.e., 19.3% versus 38.1% (p < 0.001), but higher indeterminate status for AF (34.2% vs. 15.4%; p < 0.001). In the case of BMI ≥ 35, LSM had lower specificity to rule in AF (77.9%) versus A3+ (90.4%), but A3+ had decreased sensitivity to rule out AF. A sequential LSM/A3+ strategy achieved high specificity to rule in AF and lowered the proportion of indeterminate cases in patients with BMI ≥ 35., Conclusions: The grade of obesity affects the detection of MASLD-related AF. A sequential use of LSM/A3 + could improve AF detection in patients with BMI ≥ 35., (© 2024 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as NAFLD, is increasingly recognized as a prevalent global burden. Type 2 diabetes mellitus (T2DM), another important metabolic disease, is considered a major contributor to the development of MASLD. MASLD and T2DM have a strong association with each other due to shared pathogenic mechanisms. The co-existence of the 2 diseases increases the risk of liver-related adverse outcomes and imposes a heavier burden on extrahepatic outcomes, representing a substantial public health issue. Effective assessment and management of T2DM combined with MASLD necessitate a multidisciplinary approach. The emergence of numerous RCTs has shed light on the treatment of T2DM combined with MASLD. This review uncovers the epidemiology of the intertwined T2DM and MASLD, offers insights into the evaluation of hepatic fibrosis in patients with T2DM, glucose monitoring in the MASLD population, and provides comprehensive co-management strategies for addressing both diseases., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Growing evidence highlights the significant impact of diet to modify low-grade inflammation closely linked to cardiometabolic profile. Multifunctionnal diets, combining several compounds have been shown to beneficially impact metabolic parameters., Objective: This study synthesizes the knowledge on the impact of RCTs combining dietary multifunctional compounds on low-grade inflammation in humans. We investigate whether the effects of dietary multifunctional interventions on inflammatory markers were parallel to alterations of cardiometabolic parameters., Methodology: We considered both the integrated dietary interventions (ID, i.e. global diets such as Mediterranean, Nordic…) and the dietary interventions based on selected bioactive mix (BM) compounds, in healthy individuals and those at cardiometabolic risk. Out of 221 screened publications, we selected 27 studies: 11 for BM (polyphenols and/or omega-3 fatty acids and/or antioxidants and/or dietary fiber) and 16 for ID (Mediterranean, paleo, Nordic, Dietary Approaches to Stop Hypertension (DASH) diet…)., Results: ID studies reflected significant improvements in inflammatory markers (CRP, IL-6, IL-10, IL-1b), concomitantly with beneficial changes in metabolic parameters. In BM studies, pronounced effects on low-grade inflammatory markers were observed, while improvements in metabolic parameters were not consistent. Both types of studies suggested a favorable impact on oxidative stress, a factor closely linked to the inflammatory profile., Conclusion: Our findings showed that multifunctional RCT diets have differential role in managing low-grade inflammation and cardiometabolic health, with a large heterogeneity in explored inflammatory markers. Further research is imperative to elucidate the link between low-grade inflammation and other cardiometabolic risk factors, such as intestinal inflammation or postprandial inflammatory dynamics, aiming to attain a comprehensive understanding of the mechanisms involved in these processes. These future investigations not only have the potential to deepen our insights into the connections among these elements but also pave the way for significant advancements in the prevention and management of conditions related to the cardiovascular and metabolic systems., Competing Interests: SV is employee of the Nutrition Department, Mondelez International R&D. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2024 Hornero-Ramirez, Aubin, Michalski, Vinoy, Caussy and Nazare.)

Background & Aims: If alcohol-related liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are now the two main indications for liver transplantation (LT), it has been recognized that both conditions can coexist in varying degrees and the concept of dual-aetiology fatty liver disease (DAFLD) has been proposed. This retrospective study aimed to evaluate, in a cohort of patients transplanted for ALD and NAFLD, the prevalence of DAFLD before LT and the impact on liver graft outcome., Methods: From 1990 to 2010, all patients who underwent LT for the so-called ALD or NAFLD in our centre were included. Before LT, DAFLD was defined as patients with a history of excessive alcohol consumption and obesity associated with either diabetes or hypertension. Before LT, patients were separated into three groups: DAFLD, ALD, and NAFLD. Fatty liver graft disease was classified according to the FLIP algorithm., Results: Out of 907, adult LT recipients were identified: 33 DAFLD patients, 333 ALD patients, and 24 NAFLD patients. After LT, ALD patients experienced significantly more alcohol relapse than DAFLD patients, who had twice more post-LT metabolic syndrome. Out of 926, post-LT biopsies, DAFLD patients had significantly more fatty liver graft disease due to metabolic syndrome features than ALD patients., Conclusion: Our results support that DAFLD recently emerged as an indication of LT. In the future, this particular population needs to be identified as a specific entity since post-LT outcome on the graft is different from ALD and more similar to NAFLD patients., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)

As morbidity and mortality related to potentially preventable liver diseases are on the rise globally, early detection of liver fibrosis offers a window of opportunity to prevent disease progression. Early detection of non-alcoholic fatty liver disease allows for initiation and reinforcement of guidance on bodyweight management, risk stratification for advanced liver fibrosis, and treatment optimisation of diabetes and other metabolic complications. Identification of alcohol-related liver disease provides the opportunity to support patients with detoxification and abstinence programmes. In all patient groups, identification of cirrhosis ensures that patients are enrolled in surveillance programmes for hepatocellular carcinoma and portal hypertension. When considering early detection strategies, success can be achieved from applying ad-hoc screening for liver fibrosis in established frameworks of care. Patients with type 2 diabetes are an important group to consider case findings of advanced liver fibrosis and cirrhosis, as up to 19% have advanced fibrosis (which is ten times higher than the general population) and almost 70% have non-alcoholic fatty liver disease. Additionally, patients with type 2 diabetes with alcohol use disorders have the highest proportion of liver-related morbidity of people with type 2 diabetes generally. Patients with type 2 diabetes receive an annual diabetes review as part of their routine clinical care, in which the health of many organs are considered. Yet, liver health is seldom included in this review. This Viewpoint argues that augmenting the existing risk stratification strategy with an additional liver health check provides the opportunity to detect advanced liver fibrosis, thereby opening a window for early interventions to prevent end-stage liver disease and its complications, including hepatocellular carcinoma., Competing Interests: Conflict of interests LV reports consulting fees from Gilead, Pfizer, Astra Zeneca, Novo Nordisk, Intercept Pharmaceuticals, Diatech Pharmacogenetics, IONIS, and Boehringer Ingelheim; grant support from Gilead; and speaker fees from MSD, Gilead, AlfaSigma, AbbVie, and Viatris. JFD reports consulting fees from Intelligent Ultrasound and speaker fees for Gilead and GE systems. AMA reports consulting fees from NovoNordisk and grant support from Target, Novo Nordisk, and Pfizer. MN reports consulting fees from Altimmune, Cytodyn, 89bio, GlaxoSmithKline, Madrigal, Merck, Novo Nordisk, Northsea Therapeutics, Perspectum, Terns, and Takeda; grant support from Allergan, Akero, Bristol Myers Squibb, Gilead, Galectin, Genfit, GlaxoSmithKline, Conatus, Corcept, Enanta, Madrigal, Novartis, Novo Nordisk, Shire, Takeda, Terns, Viking, and Zydus; and stock options with Rivus Pharma, CIMA, Cytodyn, and ChronWell. MER reports consulting fees from Intercept Pharmaceuticals, Gilead Sciences, Genfit, NGM Biopharmaceuticals, Enanta, Immuron, Fractyl, Prociento, Gelesis, Merck, Bristol Myers Squibb, Metacrine, Viking Therapeutics, Allergan, Cymabay, Boehringer Ingelheim, Genentech, 89bio, Galecto, Terns, Sagimet, Thetis, Fractyl, Lipicine, GSK, Coherus, and Novartis. FT reports consulting fees for Allergan, AstraZeneca, Bayer, Gilead, Bristol Myers Squibb, Boehringer, Intercept, Ionis, Inventiva, Merz, Pfizer, Alnylam, NGM Biopharma, CSL Behring, Madrigal, Novo Nordisk, and Novartis; grant support from Allergan, Bristol Myers Squibb, Inventiva, and Gilead (funding to institution); speaker fees from Gilead, AbbVie, Falk, Merz, Intercept, Sanofi, and AstraZeneca; expert testimony for Alnylam; participation on a data safety monitoring board for Pfizer; and travel support from Gilead. SF reports consulting fees from AbbVie, Actelion, Aelin Therapeutics, Aligos Therapeutics, Allergan, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Meyers Squibb, CSL Behring, Coherus, Echosens, Eisai, Enyo, Galapagos, Galmed, Genentech, Genfit, Gilead Sciences, Intercept, Inventiva, Janssens Pharmaceutica, Julius Clinical, Madrigal, Medimmune, Merck Sharp & Dohme, NGM Bio, Novartis, Novo Nordisk, Promethera, and Roche; research grants from Astellas, Falk Pharma, Genfit, Gilead Sciences, GlympsBio, Janssens Pharmaceutica, Inventiva, Merck Sharp & Dohme, Pfizer, and Roche; and speaker fees from AbbVie, Allergan, Bayer, Eisai, Genfit, Gilead Sciences, Janssens Cilag, Intercept, Inventiva, Merck Sharp & Dohme, Novo Nordisk, and Promethera. MT reports speaker fees from Echosens and Siemens Healthcare. PNN reports consulting fees from Boehringer Ingelheim, Intercept, Madrigal, Bristol Myers Squibb, AstraZeneca, Gilead, Pfizer, GlaxoSmithKline, Novo Nordisk, Poxel Pharamceuticals, and Sun Pharma and grant support from Novo Nordisk. ING reports grant support from Gilead. JMS reports consulting fees from Apollo Endosurgery, Albireo Pharma, Bayer, Boehringer Ingelheim, Gilead Sciences, GlaxoSmithKline, Intercept Pharmaceuticals, Ipsen, Inventiva Pharma, Madrigal, MSD, Northsea Therapeutics, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi, and Siemens Healthineers; grant support from Gilead Sciences, Boehringer Ingelheim, and Siemens Healthcare; and speaker fees from Boehringer Ingelheim, Echosens, MedPublico, Novo Nordisk, and Madrigal Pharmaceuticals. AB reports consulting fees from Inventiva and grant support from Boehringer Ingelheim. AGH reports consulting fees from Inventiva, Echosens, Novo Nordisk, Gilead, and Julius Clinical. CC reports consulting fees from Novo Nordisk, Gilead, AstraZeneca, Bayer, E-Scopics, Intercept, and Lilly; research support from Echosens, E-scopics, and Gilead; and speaker fees from Madrigal, AstraZeneca, Gilead, Novo Nordisk, Lilly, and LVL. KC reports consulting fees from Altimmune, Arrowhead, AstraZeneca, Boehringer Ingelheim, Covance, 89bio, Bristol Myers Squibb, Lilly, Madrigal, Merck, Myovant, Novo Nordisk, Prosciento, Quest, Sagimet, Sonic Incytes, and Terns and grant support from Echosens, Inventiva, Novo Nordisk, Nordic Bioscience, Poxel, Labcorp, and Zydus. MR reports consulting fees from Boehringer, Pfizer, Novo Nordisk, and Eli Lilly and grant support from Boehringer, Novo Nordisk, Nutricia Danone, and Sanofi. HH reports consulting fees from AstraZeneca and grant support from AstraZeneca, EchoSens, Gilead, Intercept, MSD, and Pfizer. VW-SW reports consulting fees from AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Inventiva, Novo Nordisk, Pfizer, Sagimet Biosciences, TARGET PharmaSolutions, and Visirna; speaker fees from AbbVie, Gilead Sciences, Novo Nordisk, and Unilab; travel support from AbbVie and Gilead Sciences; grant support from Gilead Sciences; and stock options for Illuminatio Medical Technology. LC reports consulting fees from Echosens, Madrigal, MSD, Novo Nordisk, Pfizer, Sagimet, and Siemens Healthineers and speaker fees from Echosens, Inventiva, and Novo Nordisk. JVL reports grants and speaker fees from AbbVie, Gilead Sciences, MSD, and Roche Diagnostics and speaker fees from Intercept, Jannsen, Novo Nordisk, and ViiV, outside of the submitted work. EAT reports consulting fees from Alexion, Novo Nordisk, Pfizer, Boehringer, Orphalan, and Univar and speaker fees from Novo Nordisk, Orphalan, and Dr Falk. All other authors report no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The flexibility between the wide array of hepatic functions relies on calcium (Ca 2+ ) signalling. Indeed, Ca 2+ is implicated in the control of many intracellular functions as well as intercellular communication. Thus, hepatocytes adapt their Ca 2+ signalling depending on their nutritional and hormonal environment, leading to opposite cellular functions, such as glucose storage or synthesis. Interestingly, hepatic metabolic diseases, such as obesity, type 2 diabetes and non-alcoholic fatty liver diseases, are associated with impaired Ca 2+ signalling. Here, we present the hepatocytes' toolkit for Ca 2+ signalling, complete with regulation systems and signalling pathways activated by nutrients and hormones. We further discuss the current knowledge on the molecular mechanisms leading to alterations of Ca 2+ signalling in hepatic metabolic diseases, and review the literature on the clinical impact of Ca 2+ -targeting therapeutics., Competing Interests: Declaration of Competing Interest All the authors declare no conflict of interests., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Undernutrition has been previously identified as a deleterious factor in acute infections. In covid-19 infection, obesity is a risk-factor of severe evolution, but initial undernutrition has not been evaluated yet., Methods: We retrospectively analyzed correlation between nutritional status at admission and severe outcomes (intensive care unit admission, invasive mechanical ventilation requirement and death) of patients hospitalized for confirmed covid-19 infection., Results: Risk of intensive care unit admission and invasive mechanical ventilation requirement was not significantly different between undernutrition and normoweight sub-groups, but increased in excessive weight sub-group (ODDR (IC 95%) 1.048 (1.011-1.086), p = 0.011). Risk of death was the same in all sub-groups., Conclusion: Undernutrition didn't appear as a factor of severe outcomes in covid-19 infection., Competing Interests: The authors declare that they have no competing interests. All authors read and approved the final manuscript., (© 2022 The Authors.)

Background and Aims: Patients with nonalcoholic fatty liver disease (NAFLD) cirrhosis benefit from referral to subspecialty care. While several clinical prediction rules exist to identify advanced fibrosis, the cutoff for excluding cirrhosis due to NAFLD is unclear. This analysis compared clinical prediction rules for excluding biopsy-proven cirrhosis in NAFLD., Methods: Adult patients were enrolled in the NASH Clinical Research Network (US) and the Newcastle Cohort (UK). Clinical and laboratory data were collected at enrolment, and a liver biopsy was taken within 1 year of enrolment. Optimal cutoffs for each score (eg, FIB-4) to exclude cirrhosis were derived from the US cohort, and sensitivity, specificity, positive predictive value, negative predictive value and AUROC were calculated. The cutoffs were evaluated in the UK cohort., Results: 147/1483 (10%) patients in the US cohort had cirrhosis. All prediction rules had similarly high NPV (0.95-0.97). FIB-4 and NAFLD fibrosis scores were the most accurate in characterising patients as having cirrhosis (AUROC 0.84-0.86). 59/494 (12%) patients in the UK cohort had cirrhosis. Prediction rules had high NPV (0.92-0.96), and FIB-4 and NAFLD fibrosis score the most accurate in the prediction of cirrhosis in the UK cohort (AUROC 0.87-0.89)., Conclusions: This cross-sectional analysis of large, multicentre international datasets shows that current clinical prediction rules perform well in excluding cirrhosis with appropriately chosen cutoffs. These clinical prediction rules can be used in primary care to identify patients, particularly those who are white, female, and <65, unlikely to have cirrhosis so higher-risk patients maintain access to specialty care., (© 2022 John Wiley & Sons Ltd.)

Peroxisome proliferator-activated receptors (PPAR), ligand-activated transcription factors of the nuclear hormone receptor superfamily, have been identified as key metabolic regulators in the liver, skeletal muscle, and adipose tissue, among others. As a leading cause of liver disease worldwide, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) cause a significant burden worldwide and therapeutic strategies are needed. This review provides an overview of the evidence on PPAR-targeted treatment of NAFLD and NASH in individuals with type 2 diabetes mellitus. We considered current evidence from clinical trials and observational studies as well as the impact of treatment on comorbid metabolic conditions such as obesity, dyslipidemia, and cardiovascular disease. Future areas of research, such as possible sexually dimorphic effects of PPAR-targeted therapies, are briefly reviewed.

Objective: This study assessed the impact of a history of metabolic and bariatric surgery (MBS) on the clinical outcomes in patients with type 2 diabetes (T2D) and severe obesity hospitalized for COVID-19., Methods: In this post hoc analysis from the nationwide observational CORONADO (Coronavirus SARS-CoV2 and Diabetes Outcomes) study, patients with T2D and a history of MBS were matched with patients without MBS for age, sex, and BMI either at the time of MBS or on admission for COVID-19. The composite primary outcome (CPO) combined invasive mechanical ventilation and/or death within 7 and 28 days following admission., Results: Out of 2,398 CORONADO participants, 20 had a history of MBS. When matching for BMI at the time of MBS and after adjustment for diabetes duration, the CPO occurred less frequently within 7 days (3 vs. 17 events, OR: 0.15 [0.01 to 0.94], p = 0.03) and 28 days (3 vs. 19 events, OR: 0.11 [0.01 to 0.71], p = 0.02) in patients with MBS (n = 16) vs. controls (n = 44). There was no difference in CPO rate between patients with MBS and controls when matching for BMI on admission., Conclusions: These data are reassuring regarding COVID-19 prognosis in patients with diabetes and a history of MBS compared with those without MBS., (© 2021 The Obesity Society.)

Magnetic Resonance Elastography (MRE) quantifies the mechanical properties of tissues, typically applying motion encoding gradients (MEG). Multifrequency results allow better characterizations of tissues using data usually acquired through sequential monofrequency experiments. High frequencies are difficult to reach due to slew rate limitations and low frequencies induce long TEs, yielding magnitude images with low SNR. We propose a novel strategy to perform simultaneous multifrequency MRE in the absence of MEGs: using RF pulses designed via the Optimal Control (OC) theory. Such pulses control the spatial distribution of the MRI magnetization phase so that the resulting transverse magnetization reproduces the phase pattern of an MRE acquisition. The pulse is applied with a constant gradient during the multifrequency mechanical excitation to simultaneously achieve slice selection and motion encoding. The phase offset sampling strategy can be adapted according to the excitation frequencies to reduce the acquisition time. Phantom experiments were run to compare the classical monofrequency MRE to the OC based dual-frequency MRE method and showed excellent agreement between the reconstructed shear storage modulus G'. Our method could be applied to simultaneously acquire low and high frequency components, which are difficult to encode with the classical MEG MRE strategy., (© 2022. The Author(s).)

Introduction: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and is associated with obesity and metabolic comorbidities. Liver steatosis can progress to nonalcoholic steatohepatitis (NASH) exhibiting a relevant risk of fibrosis and ultimately liver failure. To date, no approved treatment for NASH to reduce its clinical and humanistic burden has been developed., Areas Covered: We undertook a literature review to identify English language, national and international clinical guidelines for NAFLD regarding diagnosis, assessment and management, and determined their points of agreement and difference. Additionally, we investigated published literature relating to real-world management of NAFLD and NASH., Expert Opinion: National (China, England/Wales, Italy, the USA) and international society (Asia-Pacific, Europe, World Gastroenterology Organization) guidelines were identified and analyzed. All guidelines addressed identifying and diagnosing subjects with likely NAFLD, as well as assessment and management of individuals with risk factors for advanced disease, including fibrosis. Real-world practice reveals widespread suboptimal awareness and implementation of guidelines. In the absence of proven therapeutics, such gaps risk failure to recognize patients in need of specialist care and monitoring, highlighting the need for clear, easy-to-apply care pathways to aid in reducing the clinical and humanistic burden of NAFLD and NASH.

Objective: Previous studies have unveiled a relationship between the severity of coronavirus disease 2019 (COVID-19) pneumonia and obesity. The aims of this multicenter retrospective cohort study were to disentangle the association of BMI and associated metabolic risk factors (diabetes, hypertension, hyperlipidemia, and current smoking status) in critically ill patients with COVID-19., Methods: Patients admitted to intensive care units for COVID-19 in 21 centers (in Europe, Israel, and the United States) were enrolled in this study between February 19, 2020, and May 19, 2020. Primary and secondary outcomes were the need for invasive mechanical ventilation (IMV) and 28-day mortality, respectively., Results: A total of 1,461 patients were enrolled; the median (interquartile range) age was 64 years (40.9-72.0); 73.2% of patients were male; the median BMI was 28.1 kg/m 2 (25.4-32.3); a total of 1,080 patients (73.9%) required IMV; and the 28-day mortality estimate was 36.1% (95% CI: 33.0-39.5). An adjusted mixed logistic regression model showed a significant linear relationship between BMI and IMV: odds ratio = 1.27 (95% CI: 1.12-1.45) per 5 kg/m 2 . An adjusted Cox proportional hazards regression model showed a significant association between BMI and mortality, which was increased only in obesity class III (≥40; hazard ratio = 1.68 [95% CI: 1.06-2.64])., Conclusions: In critically ill COVID-19 patients, a linear association between BMI and the need for IMV, independent of other metabolic risk factors, and a nonlinear association between BMI and mortality risk were observed., (© 2021 The Obesity Society.)

Type 2 diabetes mellitus (T2DM) is a frequent comorbidity in patients with cirrhosis that is projected to rise in prevalence due to the worldwide burden of obesity, insulin-resistance and non-alcoholic fatty liver disease. The management of T2DM in patients with cirrhosis is complex given the requirement for accurate adaptation according to the level of liver function impairment, with lack of summary of the little evidence available in the literature. Here, we summarise the data available with respect to the epidemiology and the impact of T2DM in patients with cirrhosis, as well as those on the management of T2DM in these patients. We provide guidance for the diagnosis of T2DM and the monitoring of glycaemic control in patients with cirrhosis, and for the management of nutrition and pharmacological treatments in relation to the level of liver dysfunction., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)