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Background and Aims: The association between socioeconomic factors and disease severity is not well studied in people living with metabolic dysfunction-associated steatotic liver disease (MASLD). We thus examined if socioeconomic factors influence the presence of, or risk for future, major adverse liver outcomes (MALOs) in people living with MASLD., Methods: We conducted a register-based cohort study that included all individuals with a MASLD diagnosis between 1987 and 2020 in Sweden. Logistic and Cox regression were used to examine the association between socioeconomic factors (country of birth, educational level, and marital status) and the presence of MALOs before or upon MASLD diagnosis or during follow-up, respectively., Results: In total, 14 026 people living with MASLD were identified, among whom the median age was 55 years, 50% were male and 775 (5.5%) had MALOs before or upon diagnosis. The adjusted odds ratio (aOR) for pre-existing MALOs was higher in divorced (aOR = 1.29, 95% confidence interval [CI] = 1.06-1.57) compared to married individuals. The aOR for pre-existing MALOs was lower among those with >12 years of education (aOR = .76, 95% CI = .62-.93) compared to individuals with an education level of 10-12 years. During a 5.2-year median follow-up, several socioeconomic factors were associated with increased rates of developing MALOs in a crude model; however, none were independently associated with incident MALOs after adjustment for confounders., Conclusions: Socioeconomic factors were associated with somewhat higher odds for prevalent, but not incident, MALOs in people living with MASLD, after adjustments. This suggests primarily that risk factors for fibrosis progression are differently distributed across socioeconomic subgroups., (© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.)

Background: Numerous recent studies have explored the association between metabolic dysfunction-associated steatotic liver disease (MASLD) and the risk of various extrahepatic cancers. However, the conclusions were inconclusive. The aim of this study was to clarify this relationship by conducting a robust meta-analysis., Methods: Systematic searches were conducted on PubMed, Embase and Web of Science databases to identify relevant cohort studies published prior to February 2024. Hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CIs) were combined using a random-effects model in this meta-analysis., Results: Eighteen cohort studies (approximately 16.7 million participants) were finally included in this meta-analysis. MASLD was linked to a higher risk of extrahepatic cancers, such as gastric (n = 10, HR = 1.47, 95% CI: 1.07-2.01), colorectal (n = 13, HR = 1.33, 95% CI: 1.16-1.53), pancreatic (n = 8, HR = 1.41, 95% CI: 1.11-1.79), biliary tract (n = 5, HR = 1.27, 95% CI: 1.18-1.37), thyroid (n = 6, HR = 1.46, 95% CI: 1.02-2.09), urinary system (n = 10, HR = 1.45, 95% CI: 1.25-1.69), breast (n = 11, HR = 1.17, 95% CI: 1.08-1.26) and female genital organ cancers (n = 10, HR = 1.36, 95% CI: 1.11-1.66). However, there was no statistically significant association between MASLD and the risk of head and neck (n = 6, HR = 1.03, 95% CI: 99-1.07), oesophageal (n = 9, HR = 1.26, 95% CI: 0.86-1.86), lung (n = 9, HR = 1.01, 95% CI: 0.92-1.10), prostate (n = 9, HR = 1.06, 95% CI: 0.94-1.19) or small intestine cancer (n = 2, HR = 1.75, 95% CI: 1.00-3.06)., Conclusions: This latest large-scale meta-analysis indicated that MASLD was associated with an increased risk of various extrahepatic cancers, such as gastric, colorectal, pancreatic, biliary duct, thyroid, urinary system, breast, skin and female genital cancers. Further research is needed to investigate the mechanisms underlying these associations., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background and Aims: The increasing incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) has led to a gradual increase in MASLD-related hepatocellular carcinomas (HCC). In this context, we aimed to investigate the association between modifiable factors and the risk of incident HCC in patients with MASLD., Methods: Two authors independently searched electronic databases (PubMed, Embase, and the Cochrane Library) from their inception to April 1, 2023. Observational studies reporting an association between modifiable risk factors and MASLD-related HCC were eligible for inclusion. The effect size on the study outcomes was calculated using a random-effects model and was presented as a risk ratio with 95% confidence interval., Results: A total of 31 studies covering 1.02 million individuals were included. Regarding lifestyle factors, smoking and alcohol consumption were associated with 30% (1.30 [1.08-1.57]) and 140% (2.41 [1.03-5.65]) risk increase of MASLD-related HCC. Regarding metabolic risk factors, patients with MASLD who were overweight or obese (1.31 [1.13-1.52]), had diabetes (2.08 [1.71-2.53]) and hypertension (1.42 [1.12-1.80]) had a higher risk of developing HCC, while dyslipidemia was negatively associated with MASLD-HCC (0.78 [0.65-0.93]). The use of metformin, statin, and aspirin was associated with 18% (0.82 [0.68-0.98]), 55% (0.45 [0.36-0.56]), and 36% (0.64 [0.44-0.92]) risk reduction in incident HCC, respectively., Conclusions: This comprehensive systematic review and meta-analysis showed statistically significant increases in the risk of incident HCC inpatients with MASLD due to smoking, alcohol use, obesity, diabetes, and hypertension, whereas metformin, statin, and aspirin therapy might modify disease progression., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The aim of this study was to investigate the associations among sex hormone-binding globulin (SHBG), visceral adipose tissue (VAT), liver fat content, and risk of type 2 diabetes (T2D). In the Netherlands Epidemiology of Obesity study, 5,690 women (53%) and men (47%) without preexisting diabetes were included and followed for incident T2D. SHBG concentrations were measured in all participants, VAT was measured using MRI, and liver fat content was measured using proton magnetic resonance spectroscopy in a random subset of 1,822 participants. We examined associations between SHBG and liver fat using linear regression and bidirectional Mendelian randomization analyses and between SHBG and T2D using Cox regression adjusted for confounding and additionally for VAT and liver fat to examine mediation. Mean age was 56 (SD 6) years, mean BMI was 30 (SD 4) kg/m2, median SHBG was 47 (interquartile range [IQR] 34-65) nmol/L in women and 34 (26-43) nmol/L in men, and median liver fat was 3.4% (IQR 1.6-8.2%) in women and 6.0% (2.9-13.5%) in men. Compared with the highest SHBG quartile, liver fat was 2.9-fold (95% CI 2.4, 3.4) increased in women and 1.6-fold (95% CI 1.3, 1.8) increased in men, and the hazard ratio of T2D was 4.9 (95% CI 2.4, 9.9) in women and 1.8 (1.1, 2.9) in men. Genetically predicted SHBG was associated with liver fat content (women: SD -0.45 [95% CI -0.55, -0.35]; men: natural logarithm, -0.25 [95% CI -0.34, -0.16]). VAT and liver fat together mediated 43% (women) and 60% (men) of the SHBG-T2D association. To conclude, in a middle-aged population with overweight, the association between low SHBG and increased risk of T2D was, for a large part, mediated by increased VAT and liver fat., (© 2024 by the American Diabetes Association.)

Background & Aims: Metabolic dysfunction associated steatotic liver disease (MASLD) has a strong genetic component. The aim of this study was to examine noninvasively the prevalence of MASLD and of advanced fibrosis in relatives of patients with advanced MASLD and the risk factors for liver involvement, with a focus on the contribution of common genetic risk variants., Methods: We prospectively enrolled 98 consecutive probands with advanced fibrosis and/or hepatocellular carcinoma caused by MASLD and 160 nontwin first-degree relatives noninvasively screened for MASLD and advanced fibrosis at 4 Italian centers. We evaluated common genetic determinants and polygenic risk scores of liver disease., Results: Among relatives, prevalence of MASLD was 56.8% overall, whereas advanced fibrosis was observed in 14.4%. At multivariable analysis in relatives, MASLD was associated with body mass index (odds ratio [OR], 1.31 [1.18-1.46]) and tended to be associated with diabetes (OR, 5.21 [0.97-28.10]), alcohol intake (OR, 1.32 [0.98-1.78]), and with female sex (OR, 0.54 [0.23-1.15]), whereas advanced fibrosis was associated with diabetes (OR, 3.13 [1.16-8.45]) and nearly with body mass index (OR, 1.09 [1.00-1.19]). Despite that the PNPLA3 risk variant was enriched in probands (P = .003) and overtransmitted to relatives with MASLD (P = .045), evaluation of genetic risk variants and polygenic risk scores was not useful to guide noninvasive screening of advanced fibrosis in relatives., Conclusions: We confirmed that about 1 in 7 relatives of patients with advanced MASLD has advanced fibrosis, supporting clinical recommendations to perform family screening in this setting. Genetic risk variants contributed to liver disease within families but did not meaningfully improve fibrosis risk stratification., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Recent updates in nomenclature and diagnostic criteria encompass the diverse phenotypes associated with steatotic liver disease (SLD). 1 These updates aim to reflect the current understanding of SLD, promote disease awareness and research, and reduce stigma. Notably, the term metabolic dysfunction-associated steatotic liver disease (MASLD) is defined as hepatic steatosis with at least 1 of 5 cardiometabolic criteria without any other cause of steatosis. A new category, MetALD, includes those with MASLD and high alcohol intake. 1 We aimed to characterize SLD using this nomenclature in the Framingham Heart Study (FHS) and to quantify its association with cardiometabolic risk factors., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Metabolic dysfunction-associated steatotic liver disease (MASLD) poses a significant and ever-increasing health and economic burden worldwide. Substantial epidemiological evidence shows that MASLD is a multisystem disease that is associated not only with liver-related complications but is also associated with an increased risk of developing cardiometabolic comorbidities and extrahepatic cancers (principally gastrointestinal [GI] cancers). GI cancers account for a quarter of the global cancer incidence and a third of cancer-related deaths. In this narrative review, we provide an overview of the literature on (a) the epidemiological data on the risk of non-liver GI cancers in MASLD, (b) the putative mechanisms by which MASLD (and factors linked with MASLD) may increase this risk, and (c) the possible pharmacotherapies beneficially affecting both MASLD and extrahepatic GI cancer risk. There are multiple potential pathophysiological mechanisms by which MASLD may increase extrahepatic GI cancer risk. Although further studies are needed, the current evidence supports a possible extrahepatic carcinogenic role for MASLD, regardless of obesity and diabetes status, thus highlighting the potential role of tailoring cancer screening for individuals with MASLD. Although there are conflicting data in the literature, aspirin, statins and metformin appear to exert some chemo-preventive effects against GI cancer., Competing Interests: Declaration of competing interest The Authors have no potential conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: As metabolic dysfunction-associated steatotic liver disease (MASLD) management extends into primary care, little is known about patterns of specialty referral for affected patients. We determined the proportion of primary care patients with MASLD that received a gastroenterology (GI) consultation and compared advanced fibrosis risk between patients with and without a referral., Methods: This retrospective study of electronic health record data from a primary care clinic included patients with MASLD, no competing chronic liver disease diagnoses, and no history of cirrhosis. Referral to GI for evaluation and management (E/M) any time after MASLD ascertainment was the outcome. Fibrosis-4 Index (FIB-4) scores were calculated, categorized by advanced fibrosis risk, and compared by receipt of a GI E/M referral. Logistic regression models were developed to determine the association of FIB-4 risk with receipt of a GI referral., Results: The cohort included 652 patients of which 12% had FIB-4 scores (≥2.67) at high-risk for advanced fibrosis. Overall, 31% of cohort patients received a GI referral for E/M. There was no difference in the proportion of patients with high (12% vs. 12%, p=0.952) risk FIB-4 scores by receipt of a GI E/M referral. In adjusted logistic regression models, high-risk FIB-4 scores (OR 1.01; 95% CI 0.59 - 1.71) were not associated with receipt of a referral., Conclusions: Only 30% of patients in this primary care MASLD cohort received a GI E/M referral during the study period, and those patients with a referral did not differ by FIB-4 advanced fibrosis risk., Competing Interests: Declaration of competing interest All authors report no conflicts of interest with this work., (Copyright © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

We aim to evaluate the prevalence of steatotic liver disease (SLD) in United States (US) adolescents and explore whether metabolic dysfunction-associated steatotic liver disease (MASLD) can identify individuals with clinically significant fibrosis (CSF) in this study. The prevalence of SLD and its categories, including MASLD, metabolic dysfunction and alcohol associated liver disease (MetALD), alcohol related liver disease (ALD) and other SLD were determined. Weighted multivariable logistic regression analysis was conducted to evaluate the association between MASLD and CSF in adolescents with SLD. Among the total 1,446 US adolescents, SLD was present in 291 (20.1%) of individuals, including 260 (17.9%) for MASLD, 9 (0.6%) for MetALD and 5 (0.3%) for ALD. Only 58 (4%) had CSF. Patients with SLD showed a higher prevalence of CSF (9.6% vs. 2.6%, p < 0.001). Among patients with SLD, 89.3% met the MASLD criteria. The risk of CSF in patients with MASLD was not significantly different (odds ratio [OR] = 1.07, 95% confidence interval [CI] = 0.30-3.83, p = 0.9180) compared with those without MASLD. MASLD was met by most of the US adolescents with SLD. Moreover, MASLD was not associated with higher prevalence of CSF among adolescents with SLD., (© 2024. The Author(s).)

Background/objectives: We investigated the effects of ultraprocessed food (UPF) consumption on metabolic disorders (e.g., adiposity, metabolic associated steatotic liver disease [MASLD], and insulin resistance) in children and adolescents with obesity to improve dietary guidelines and public health strategies., Methods: The dietary intake of 149 participants (aged 8-17 years) was assessed with food diaries. The NOVA classification system was used to classify food according to the degree of processing. Metabolic outcomes, including the fat mass index (FMI), hepatic fat percentage, and insulin resistance, were measured via dual-energy X-ray absorptiometry (DXA), magnetic resonance imaging proton density fat fraction (MRI-PDFF), and biochemical analysis, respectively., Results: Greater UPF consumption from baseline to the 6-month follow-up was significantly associated with increased insulin and decreased total cholesterol and LDL-cholesterol. UPF consumption was positively associated with the prevalence of MASLD (liver MRI-PDFF ≥ 5%; odds ratio T3 vs. T1 = 1.75; 95% confidence interval [CI] 1.03, 3.00), moderate-to-severe MASLD (liver MRI-PDFF ≥ 10%; OR T3 vs. T1 = 4.19; 95% CI 1.72, 10.22), and insulin resistance (OR T3 vs. T1 = 2.44; 95% CI 1.33, 4.48), after adjusting for covariates. A linear dose-response relationship was observed between UPF consumption and the odds of moderate-to-severe MASLD and insulin resistance., Conclusions: Greater UPF consumption was strongly associated with MASLD and insulin resistance in children and adolescents with obesity, underscoring the importance of reducing UPF consumption through dietary guidelines and public health interventions to mitigate the risk of obesity-related metabolic conditions in young populations., Competing Interests: The authors declare no conflicts of interest.

Aim: This study aims to explore the relationship between niacin intake and the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) within a large, multi-ethnic cohort., Methods: A total of 2946 participants from the National Health and Nutrition Examination Survey (NHANES) were carefully selected based on strict inclusion and exclusion criteria. Participants meeting the eligibility criteria underwent two dietary recall interviews, and niacin intake was calculated using the USDA's Food and Nutrient Database for Dietary Studies (FNDDS). Liver steatosis was diagnosed using a Controlled Attenuation Parameter (CAP) of 248 dB/m, and MASLD diagnosis was based on metabolic indicators. Weighted multivariate logistic regression was utilized to analyze the correlation between niacin intake and MASLD prevalence, with potential nonlinear relationships explored through restricted cubic spline (RCS) regression., Results: Analysis of baseline data revealed that MASLD patients had lower niacin intake levels and poorer metabolic biomarker profiles. Both RCS analysis and multivariate logistic regression indicated a U-shaped association between niacin intake and MASLD prevalence. Specifically, there was a non-linear dose-response relationship, with the odds of MASLD gradually decreasing with increasing niacin intake until reaching a threshold of 23.6 mg, beyond which the odds of MASLD began to increase., Conclusion: This study confirms a U-shaped nonlinear relationship between niacin intake and MASLD prevalence within the diverse American population., (© 2024. The Author(s).)

We aimed to compare the associations of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) with coronary artery calcification (CAC). Patients who simultaneously underwent ultrasonography to diagnose hepatic steatosis and cardiac computed tomography to detect CAC were included. The presence and severity of CAC were defined with CAC-score thresholds of > 0 and > 300, respectively, and patients were divided into the following groups: no MASLD or MAFLD (reference), MASLD-only, MAFLD-only, and overlapping groups. Overall, 1,060/2,773 (38.2%) patients had CAC, of which 196 (18.5%) had severe CAC. The MASLD and MAFLD prevalence rates were 32.6% and 45.2%, respectively, with an overlap of 30.7%. In an ASCVD risk score-adjusted model, both MASLD (adjusted odd ratios [aOR], 1.21; 95% confidence interval [CI], 1.02-1.44; p = 0.033) and MAFLD (aOR 1.20; 95% CI 1.01-1.42, p = 0.034) were associated with CAC, whereas only MASLD (aOR 1.38; 95% CI 1.01-1.89, p = 0.041) was associated with severe CAC. Compared to the reference group, the overlapping group showed an association with CAC (aOR 1.22; 95% CI 1.01-1.47; p = 0.038); however, the MASLD and MAFLD subgroups did not differ in their association with CAC. MASLD may predict a higher risk of ASCVD more effectively than MAFLD., (© 2024. The Author(s).)

Objective: The objective of this study was to determine the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) in young compared with older adults., Methods: Individuals (n = 1420) with (63%) and without type 2 diabetes mellitus (T2D; 37%) who attended internal medicine clinics and did not have a known history of MASLD underwent laboratory evaluation and transient elastography to assess for hepatic steatosis and fibrosis. Magnetic resonance elastography and liver biopsy were recommended when indicated., Results: A total of 243 participants were ages <45 years, and 1177 were ages ≥45 years. Obesity, T2D, and metabolic syndrome were highly prevalent in young adults. Frequencies of steatosis and fibrosis were high in young adults (50.2% and 7.5% vs. older adults 52.7% and 9.9%, respectively) and were significantly higher in those with both obesity and T2D (71.1% and 15.7%, respectively; p < 0.01). In young adults, T2D and obesity were the strongest risk factors for hepatic fibrosis (odds ratios 4.33 [95% CI: 1.37-13.68] and 1.16 [95% CI: 1.07-1.25], respectively; p < 0.05)., Conclusions: There is a high prevalence of clinically significant hepatic fibrosis in young adults with cardiometabolic risk factors. Up to one in seven young adults with obesity and T2D had clinically significant hepatic fibrosis on elastography. This highlights the need to screen young adults with cardiometabolic risk factors for MASLD for early detection and intervention., (© 2024 The Obesity Society.)

Background and Aim: The steatosis-associated fibrosis estimator (SAFE) score has been developed to distinguish clinically significant fibrosis in patients with steatotic liver disease (SLD). However, validation of its performance in Asian subjects is limited. This study aimed to evaluate the performance of the SAFE score in Asian subjects with biopsy-proven SLD and in different subgroups according to age, sex, and body mass index., Methods: We retrospectively analyzed 6383 living liver donors who underwent a liver biopsy between 2005 and 2023. Of these, 1551 subjects with biopsy-proven SLD were included. The performance of the SAFE score was evaluated using areas under the curve and compared with those of the nonalcoholic fatty liver disease fibrosis score (NFS) and fibrosis-4 index (FIB-4)., Results: The prevalence of clinically significant fibrosis in the cohort was 2.2%. The proportion of subjects with a "low-risk" SAFE score was the highest (91.0%), followed by those with "intermediate-risk" (7.8%) and "high-risk" (1.2%) scores. The prevalence of fibrosis in subjects with low-risk, intermediate-risk, and high-risk scores was 1.6%, 6.6%, and 21.1%, respectively. The SAFE outperformed FIB-4 and NFS (area under the curve: 0.70 vs 0.64 for both NFS and FIB-4). However, it showed low diagnostic accuracy and sensitivity (27%) at the low cutoff (SAFE < 0) in subjects aged 30-39 years (fibrosis: 1.2%), despite having a high negative predictive value (0.99)., Conclusion: While the SAFE score demonstrates superior performance compared with other noninvasive tests in Asian subjects with SLD, its performance varies across age groups. In younger subjects, particularly, its performance may be more limited., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Objective: To quantify the burden of metabolic dysfunction-associated steatotic liver disease (MASLD) and related metabolic disorders in premenopausal women., Patients and Methods: Between 2010 and 2019, global evaluations of prevalence, mortality, disability-adjusted life years (DALYs), and their age-standardized rate (ASR) were conducted for metabolic conditions such as MASLD, type 2 diabetes mellitus, dyslipidemia, hypertension (HTN), obesity, and polycystic ovarian syndrome. Subgroup assessments were conducted according to geographical regions and the sociodemographic index. The predictive models were established to estimate mortality and DALYs through 2040., Results: In 2019, the most significant ASR of deaths was found in HTN (11.37; 9.52 to 13.45), followed by obesity (10.49; 7.57 to 13.64). In contrast, the greatest ASR of DALYs was attributed to obesity (816.13; 581.41 to 1073.32), followed by HTN (634.73; 536.75 to 744.77). The mortality rates for dyslipidemia ( - 0.55%) and HTN ( - 0.72%) have been decreasing over time, but there has been an increase in obesity ( + 0.58%), type 2 diabetes mellitus ( + 0.85%), and MASLD ( + 0.51%). Lower sociodemographic index countries exhibit a higher disability-to-prevalence ratio. In 2040, obesity is predicted to cause the most deaths ( + 41.59% from 2019)., Conclusion: The escalating impact of metabolic syndrome, the rising trends in death rates linked to obesity, and the disparities based on region and socioeconomic status in premenopausal women underscore the alarming increase in the global burden of metabolic syndrome., (Copyright © 2024 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

The most common chronic liver illness worldwide is metabolic dysfunction linked to fatty liver disease (MAFLD), which is poorly understood by doctors and patients. Many people with this disease develop steatohepatitis, cirrhosis and its consequences, as well as extrahepatic manifestations; these conditions are particularly common if they are linked to diabetes mellitus or obesity. A breakthrough with numerous benefits is the switch from NAFLD to MAFLD in terms of terminology and methodology. The diagnosis of MAFLD is based on affirmative criteria; unlike NAFLD, it is no longer based on exclusion. The diagnosis of MAFLD and the evaluation of steatosis and fibrosis is achieved using liver biopsy and non-invasive laboratory or radiographic techniques. We briefly address the most recent developments in MAFLD epidemiology and diagnosis., (© 2024. The Author(s).)

Weight gain poses a rising concern post-liver transplantation (LT), and metabolic dysfunction-associated steatotic liver disease might impair graft health. The timing is crucial when considering bariatric surgery (BS) in a population with liver disease or transplantation. BS can be considered for post-LT weight gain, although the evidence is limited and the long-term outcome still uncertain. We conducted a national retrospective analysis in 5 Belgian transplant centers and included 25 patients with an LT followed by a bariatric procedure. A total of 187 LT patients without BS were included for comparison. Clinical, biochemical, and outcome data were retrospectively retrieved. In our nationwide cohort, 25 patients had undergone BS post-LT, at a median 3.5 years after LT. Twenty-one (84.0%) patients received a sleeve gastrectomy (SG). Patients were predominantly male (72.0%), with a lower age at time of transplantation compared with the non-BS population (54.5 vs. 60.6, p <0.001). Weight loss was significant and sustained, with a decrease in body mass index from 41.0±4.5 pre-BS to 32.6±5.8 1-3 years post-BS ( p <0.001) and 31.1±5.8 3-5 years post-BS ( p <0.001). Three pre-BS (12.0%) patients presented with recurrent and one (4.0%) de novo metabolic dysfunction-associated steatotic liver disease after LT, with 100% resolution post-BS ( p =0.016). Notable reductions were observed in alanine transaminase levels (40.5±28.5 U/L to 27.1±25.1 U/L post-BS, p =0.05) and HbA1c levels (6.9±1.6 to 6.0±1.4 post-BS, p <0.001). Three patients were re-transplanted, and eight patients died, of which five (20.0%) due to a nonhepatic malignancy and one (4.0%) due to liver failure. SG is the favored BS post-LT and has proven to be safe and feasible in a post-LT setting with favorable metabolic consequences. SG post-LT is a valid treatment for de novo and recurrent metabolic dysfunction-associated steatotic liver disease post-LT. Although we report on the largest cohort to date, there is still a need for larger cohorts to examine the effect of BS on patient and graft survival., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Background and Aim: Few population-based studies have investigated the association between metabolic dysfunction-associated steatotic liver disease (MASLD) and depression. Additionally, it remains unclear if depression affects progression to major adverse liver outcomes (MALO) in MASLD., Methods: All patients in Sweden with newly diagnosed MASLD between 2006 and 2020 were identified from the National Patient Register. Each patient was matched on age, sex, inclusion year, and municipality with up to 10 comparators from the general population. Cox regression was used to compare rates of severe depression in persons with MASLD to the comparators. In persons with MASLD, Cox regression was used to estimate rates of MALO using severe depression before baseline or diagnosed during follow-up as a time-varying exposure., Results: We included 11 301 persons with MASLD and 104 205 comparators who were followed for a median of 3.9 (IQR 1.5-7.6) and 4.9 years (IQR 2.3-8.7), respectively. The median age was 56 years and 5576 of 11 301 (49.3%) persons with MASLD were male. Incident severe depression developed in 228 of 11 301 (2.0%) persons with MASLD and 1160 of 104 205 (1.1%) comparators (fully adjusted hazard ratio [HR] = 1.8, 95% CI = 1.5-2.1). Of persons with MASLD, 25 of 1229 (2.0%) of those with severe depression before or after baseline progressed to MALO compared to 322 of 10 326 (3.1%) of those without severe depression (fully adjusted HR = 1.0, 95% CI = .6-1.5)., Conclusions: We confirm an association between MASLD and severe depression. However, no association between severe depression and incident MALO was found, but conclusions are limited by few observed outcomes., (© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.)

Liver disease prevalence, severity, outcomes and hepatic risk factors (for example, unhealthy diet) are heavily affected by socioeconomic status and food insecurity. Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent liver disease globally and is likely to co-occur with other liver diseases associated with food insecurity. Though weight reduction and adopting a healthy diet can reverse the course of MASLD, gaps between recommendations and practice transcend individual responsibility and preference. Broader sociocultural determinants of food choices (social nutrition) include food insecurity, community and social norms and the local environment, including commercial pressures that target people experiencing poverty, ethnic minorities and children. Food insecurity is a barrier to a healthy diet, as a low-quality diet is often less expensive than a healthy one. Consequently, food insecurity is an 'upstream' risk factor for MASLD, advanced fibrosis and greater all-cause mortality among patients with liver disease. Intervening on food insecurity at four major levels (environment, policy, community and health care) can reduce the burden of liver disease, thereby reducing social and health inequities. In this Review, we report on the current research in the field, the need for implementing proven interventions, and the role liver specialists can have., (© 2024. Springer Nature Limited.)

Metabolic dysfunction-associated fatty liver disease (MAFLD) and viral hepatitis due to chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection are common liver diseases worldwide. Excessive alcohol consumption and alcoholic liver disease (ALD) are also emerging health problems. Therefore, in clinical practice, we may encounter subjects with dual etiology of liver diseases such as coexisting MAFLD/HBV, MAFLD/HCV, and MAFLD/ALD. In this review, we summarize the epidemiology, clinical features, and mutual interactions of MAFLD with coexisting HBV, HCV, or ALD. The impact of MAFLD on the progression of liver diseases and treatment outcomes in patients with chronic viral hepatitis and the clinical questions to be addressed regarding dual MAFLD and ALD are also discussed., (© 2024. Asian Pacific Association for the Study of the Liver.)

Aim: To elucidate the effects of sleep parameters and renal function on the risk of developing new-onset severe metabolic dysfunction-associated steatotic liver disease (MASLD)., Materials and Methods: The primary analysis involved a cohort of 305 257 participants. Multivariable Cox models were employed to calculate hazard ratios and 95% confidence intervals. Traditional mediation and two-step Mendelian randomization (MR) analyses were conducted to assess the associations and mediating roles of renal function indicators between sleep and new-onset severe MASLD., Results: Poor sleep score and renal function biomarker score (RFS) were associated with an increased risk of new-onset severe MASLD (all p trend  <0.001). Participants with poor sleep patterns and the highest RFS had a 5.45-fold higher risk of new-onset severe MASLD, compared to those with healthy sleep patterns and the lowest RFS (p < 0.001). The RFS could explain 10.08% of the correlations between poor sleep score and risk of new-onset severe MASLD. Additionally, MR analyses supported a causal link between insomnia and new-onset severe MASLD and revealed a mediating role of chronic kidney disease in the connection between insomnia and new-onset severe MASLD risk., Conclusions: This study highlights the independent and combined associations of sleep parameters and renal function indicators with new-onset severe MASLD, underscoring the bidirectional communication of the liver-kidney axis and providing modifiable strategies for preventing MASLD., (© 2024 John Wiley & Sons Ltd.)

Metabolic dysfunction-associated steatotic liver disease (MASLD) brings heavy clinical and economic burdens to patients worldwide. High fasting plasma glucose (HFPG) was proven to be an important modifiable risk factor. However, the global burden distribution of HFPG-attributable MASLD has not been fully studied. This study aimed to describe the epidemiological distribution and trends of the burden of HFPG-attributable MASLD worldwide. The data source was the 2021 Global Burden of Disease Study. Descriptive statistics were mainly conducted using disability-adjusted life years (DALYs) and deaths of HFPG-attributable MASLD from 1990 to 2021, as well as their age-standardized rates (ASRs) and population-attributable fractions. Subgroup analyses were conducted by region, age group, and sex. We found that 213.48 thousand DALYs and 10.02 thousand deaths in MASLD were attributable to HFPG worldwide in 2021, with an increase of 2.96 and 3.32 times compared with 1990, respectively. Over the past 32 years, age-standardized DALY rates (ASDRs) have fluctuated upward, reaching 2.45 per 100,000 people in 2021, with an increase of 81.21%. The ASDRs continued to rise in low, low-middle, and high social demographic index (SDI) regions, fluctuated upward at high levels in middle SDI regions, and were relatively low in high-middle SDI regions. People aged 50-69 accounted for the largest proportion of DALYs, while people over 70 had the largest increase of 3.73 times. Men had higher ASDRs, and the sex difference has been gradually expanding over the past 32 years, peaking at the age of 45-49. In conclusion, the burden of HFPG-attributable MASLD has continued to increase globally, with differences in geographical area, age, and sex distribution. HFPG, as a modifiable risk factor, should be given more importance. The implementation of targeted health intervention strategies is recommended for each country based on trends in the burden of HFPG-attributable MASLD., (© 2024. The Author(s).)

Aims: To examine whether an extended lifestyle metrics incorporating sleep quality improves risk stratification for metabolic dysfunction-associated fatty liver disease (MAFLD), at-risk metabolic dysfunction-associated steatohepatitis (MASH) and significant fibrosis., Methods: A total of 5011 participants with abdominal ultrasound from Imaging sub-cohort of South China Cohort (ISSCC) and 3672 participants underwent vibration controlled transient elastography from US National Health and Nutrition Examination Survey (US NHANES) were included. Liver Essential 5 was constructed by incorporating sleep quality into traditional healthy lifestyles (HLS)., Results: A total of 4.66-17.72% of the association between traditional HLS and MAFLD was mediated by sleep quality regardless of the detection techniques, and their joint associations on MAFLD were significant in both cohorts. ORs for individuals with poor sleep and unfavorable HLS were 1.72 (1.29-2.30) in ISSCC and 2.25 (1.55-3.26) in US NHANES, respectively. Around half of the participants previously considered as following a favorable HLS were re-classified by Liver Essential 5 with significantly higher prevalences of MAFLD in both cohorts (P < 0.001). Similar results were also found on at-risk MASH and significant fibrosis in US NHANES. ORs of participants with per one increment increase in Liver Essential 5 were 0.82 (0.77-0.89) and 0.79 (0.70-0.88) for MAFLD in ISSCC and US NHANES, 0.62 (0.48-0.78) for at-risk MASH and 0.78 (0.65-0.93) for significant fibrosis., Conclusions: Liver Essential 5, which incorporates sleep quality and traditional lifestyle factors, provides additional risk stratification for MAFLD-related outcomes., (© 2024. The Author(s).)

Elevated liver enzymes are a common finding in primary care medicine, with an estimated prevalence of 8 %. Steatotic liver diseases are the most frequently encountered etiologies and r-epresent the main cause of liver-related morbidity and mortality. This article looks at the latest developments in these diseases, with a particular focus on MASLD (Metabolic dysfunction associated steatotic liver disease). Recommendations include biological monitoring every 1-3 years in the presence of risk factors, and the use of the FIB-4 score to detect fibrosis in cases of MASLD. Therapeutic management aims to improve metabolic function by treating risk factors and through lifestyle and dietary measures., Competing Interests: Les auteur-ices n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Objective: To assess the relationship between dietary intake of α -carotene, β -carotene, β -cryptoxanthin, lycopene and lutein+zeaxanthin (LZ) and occurrence of metabolic dysfunction-associated fatty liver disease (MAFLD)., Design: Cross-sectional study design. The MAFLD diagnosis was based on hepatic steatosis and metabolic dysregulation. Carotenoid intake was adjusted for using an energy-adjusted model. Logistic regression and restricted cubic spline (RCS) analyses were used to assess the relationships, with sensitivity analysis to validate the findings. Weighted quantile sum regression (WQS) was used to explore the combined effect of these carotenoids on MAFLD. Subgroup analyses were conducted to identify population-specific associations., Setting: National Health and Nutrition Examination Survey (NHANES) 2017-March 2020., Participants: This study included 5098 individuals aged 18 years and older., Results: After adjusting for potential confounders, a weak inverse association was observed between α -carotene and β -carotene intakes and MAFLD occurrence (all P value <0·05). The highest quartile of β -carotene intake showed a significantly lower occurrence of MAFLD compared with the lowest quartile (OR = 0·65; 95 % CI: 0·44, 0·97). RCS analysis showed that a significantly lower occurrence of MAFLD was associated with a higher intake of the four carotenoids, excluding lycopene. Furthermore, the WQS analysis revealed a negative relationship between combined carotenoid intake and MAFLD occurrence (OR = 0·95, 95 % CI: 0·90, 1·00, P = 0·037). Subgroup analyses showed dietary carotenoid intake was associated with reduced MAFLD occurrence in populations aged 50-69 years, females, physically active individuals and non-drinkers., Conclusion: Higher dietary intake of carotenoids is associated with lower MAFLD occurrence. However, this relationship varies among individuals of different ages, sexes and lifestyles.

Background : Consumption of flavonoid-rich orange juice has been shown to reduce adiposity and liver steatosis in murine models of diet-induced obesity. However, little is known about the effects of whole orange intake, independent of body weight changes, on liver function and steatosis in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD). The goal is to understand the direct impact of orange consumption on metabolic health. Methods : Sixty-two men and women aged 30-65 with MASLD (Controlled Attenuation Parameter, (CAP) > 275 dB/m) were randomly assigned to consume either 400 g of whole oranges or non-citrus fruits daily for 4 weeks. Baseline evaluations included medical assessments, blood tests, and body composition. Liver health was assessed using transient elastography (FibroScan ® ) for steatosis and fibrosis, conducted by blinded personnel. This clinical trial was registered at ClinicalTrials.gov (NCT05558592). Results : After 4 weeks of orange supplementation, liver steatosis decreased in the treatment group, with 70.9% showing steatosis compared to 100% in controls ( p < 0.004), indicating a 30% reduction in liver disease prevalence. There were no significant changes in fibrosis or plasma liver enzymes, though plasma gamma glutaril transferase (GGT) levels decreased significantly. Body weight, waist circumference, body composition, lipid profile, fasting glucose, insulin, and C-reactive protein levels remained unchanged. Dietary analysis revealed no change in caloric intake, but vitamins C, A, thiamine, and riboflavin increased in the orange group. Conclusions : Our findings suggest that phytochemical-rich foods, especially whole fruits like oranges, may enhance liver function as an adjunct treatment for MASLD. The notable reduction in liver steatosis prevalence occurred independently of body weight changes. Further studies are needed to investigate the long-term effects of orange supplementation on steatosis and fibrosis progression and to identify the specific bioactive compounds and mechanisms involved.

People with type 2 diabetes mellitus (T2DM) show a high prevalence of steatotic liver disease (SLD), and especially metabolic dysfunction-associated steatotic liver disease (MASLD), with liver fibrosis. Their health-related quality of life (HRQL) is affected by multiple in part overlapping factors and aggravated by metabolic and liver-related comorbidities, including liver fibrosis stage. The aim of this study was to investigate the effect size of advanced fibrosis (AF) on the HRQL in people with T2DM. A total of 149 individuals with T2DM treated at a primary care provider within the German disease management program (DMP) were included in the final analysis. Vibration-controlled transient elastography (VCTE) was used to non-invasively detect steatosis and AF. The EQ-5D-3L questionnaire was used to assess the HRQL. Uni- and multivariable linear regression models were used to identify independent predictors of impaired HRQL. The majority was male (63.1%), and the median age was 67 years (IQR 59; 71). In the entire cohort, the prevalence of MASLD and AF was 70.7% and 19.5%, respectively. People with T2DM and AF had an overall lower HRQL in comparison to those without AF (p < 0.001). Obesity (β: - 0.247; 95% CI - 0.419, - 0.077) and AF (β: - 0.222; 95% CI - 0.383, - 0.051) remained independent predictors of a poor HRQL. In turn, T2DM-related comorbidities were not predictive of an impaired HRQL. Obesity and AF negatively affect the HRQL in patients with SLD and T2DM in primary care. Awareness of liver health and specific interventions may improve patient-reported and liver-related outcomes in people with T2DM., (© 2024. The Author(s).)

Background/aims: Young Korean men are obligated to serve in the military for 18 to 21 months. We investigated the effects of military service on steatotic liver disease (SLD) and other metabolic parameters., Methods: Pre-enlistment health check-up performed from 2019 to 2022 and in-service health check-up performed from 2020 to 2022 were merged as paired data. SLD was defined as a hepatic steatosis index of 36 or higher. Hypertension (HTN) and hypertriglyceridemia were also included in the analysis., Results: A total of 503,136 paired cases were included in the analysis. Comparing pre-enlistment and in-service health check-ups, the prevalence of SLD (22.2% vs 17.6%, p<0.001), HTN (7.6% vs 4.3%, p<0.001), and hypertriglyceridemia (8.1% vs 2.9%, p<0.001) decreased during military service. In terms of body mass index, the proportion of underweight (8.2% vs 1.4%, p<0.001) and severely obese (6.1% vs 4.9%, p<0.001) individuals decreased over time. Regarding factors associated with SLD development and resolution, age was positively associated with SLD development (odds ratio, 1.146; p<0.001) and a health check-up interval of <450 days was a protective factor for SLD development (odds ratio, 0.746; p<0.001). Those serving in the marines were less likely to develop SLD, whereas those serving in the navy were more likely to develop SLD. Serving in the army or the navy was negatively associated with SLD resolution, whereas serving in the air force was positively associated with SLD resolution., Conclusions: The prevalence of SLD, HTN, and hypertriglyceridemia decreased substantially during Korean military service.

Background: The neutrophil-to-high-density lipoprotein cholesterol ratio (NHR) has emerged as a promising biomarker for assessing inflammation and lipid dysregulation. Increasing evidence indicates that these metabolic disturbances play a crucial role in the development of metabolic dysfunction-associated steatotic liver disease(MASLD). This study aims to investigate the association between NHR, MASLD, and liver fibrosis., Methods: This cross-sectional study analyzed data from the 2017-2020 National Health and Nutrition Examination Survey (NHANES). Weighted multivariate logistic regression models were used to investigate the association between NHR and both MASLD and liver fibrosis. Smoothed curve fitting and threshold effect analysis were performed to detect potential nonlinear relationships. Subgroup analyses were conducted to assess the consistency of these associations across different groups., Results: The study involved 4,761 participants. We observed a significant positive association between NHR and MASLD (OR = 1.20, 95% CI: 1.09-1.31). However, there was no significant association between NHR and liver fibrosis (OR = 1.01; 95% CI: 0.94-1.09). The analysis of smoothed curve fitting and threshold effect revealed an inverted U-shaped relationship between NHR and MASLD, with a turning point at 5.63., Conclusion: Our findings indicate a positive correlation between elevated NHR levels and MASLD prevalence. However, we did not observe a significant association between NHR and liver fibrosis prevalence. Further prospective research is needed to validate these findings in a longitudinal setting., (© 2024. The Author(s).)

Objective: Alzheimer's Disease (AD) is increasingly recognized as being associated with metabolic disorders, including Metabolic Associated Steatotic Liver Disease (MASLD). This study aimed to assess the relative risk of AD in individuals with MASLD., Methods: In this retrospective cohort study, we analyzed data from individuals aged over 65 who underwent health check-ups between January 2018 and June 2023. MASLD was diagnosed based on ultrasound findings and cardiometabolic criteria. AD incidence was identified using ICD-10 codes and self-reports. Poisson regression models estimated the relative risk of AD in relation to MASLD, adjusting for age, BMI, sex, SBP, HbA1c, HDL-c, triglycerides, hs-CRP, GGT, and estimated GFR., Results: The study included 4,582 MASLD patients and 6,318 controls. MASLD patients showed a higher incidence of AD (127 cases) compared to controls (61 cases). The fully adjusted Poisson regression model indicated an increased AD risk in MASLD patients [RR: 2.80 (95% CI: 1.79-4.38)]., Conclusion: Our findings suggested MASLD as an independent risk factor for AD, underlining the role of metabolic dysfunctions in AD pathogenesis. The study emphasized the need for comprehensive metabolic health management in AD prevention strategies, particularly among high-risk groups., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Wang, Hou, Wu, Wang, Fan, Zhang, Yuan, Sun, Lu and Zheng.)

Importance: Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most common chronic liver disease worldwide and is increasingly being diagnosed at younger ages, affecting more than one-third of young people with obesity., Objective: To evaluate associations between perinatal conditions and risk of MASLD and associated progressive liver disease., Design, Setting, and Participants: This nationwide, population-based case-control study included all biopsy-confirmed cases of MASLD in Sweden. Individuals aged 25 years or younger (hereafter, young individuals) with biopsy-proven MASLD between January 1, 1992, and December 31, 2016, were matched to up to 5 general population control individuals. Granular data on maternal and perinatal characteristics were retrieved from the Swedish Medical Birth Register. Data were analyzed from June 2023 to June 2024., Exposures: Birth weight (low [<2500 g], reference [2500 to <4000 g], or high [≥4000 g]), gestational age (GA), and birth weight for GA (small for GA [SGA; <10th percentile], appropriate for GA [10th-90th percentile], or large for GA [LGA; >90th percentile]), compared between patients and matched controls., Main Outcomes and Measures: The main outcome was odds of biopsy-proven MASLD and MASLD-associated progressive liver disease (ie, liver fibrosis or cirrhosis) according to birth weight, GA, and birth weight for GA, adjusted for matching factors., Results: In total, 165 young individuals with biopsy-proven MASLD (median age at diagnosis: 12.0 years [IQR, 4.4-16.9 years]; 100 [60.6%] male) were matched with 717 controls. There was an association between low birth weight and future development of MASLD (adjusted odds ratio [AOR], 4.05; 95% CI, 1.85-8.88) but no association between high birth weight and odds of MASLD (AOR, 0.64; 95% CI, 0.38-1.08) compared with the reference birth weight. An association was seen for SGA (AOR, 3.36; 95% CI, 2.00-5.64) compared with appropriate size for GA (reference category) but not for LGA (AOR, 0.57; 95% CI, 0.27-1.20). Progressive liver disease was more common in individuals born with low birth weight (AOR, 6.03; 95% CI, 1.66-21.87) or SGA (AOR, 4.90; 95% CI, 2.15-11.14)., Conclusions and Relevance: In this nationwide study of young individuals with biopsy-proven MASLD, low birth weight and SGA were associated with development of MASLD and progressive liver disease, suggesting a need for structured screening measures to diagnose these conditions early in high-risk individuals.

Background: Globally, viral hepatitis is decreasing, but nonalcoholic fatty liver disease (NAFLD), now metabolic dysfunction-associated steatotic liver disease (MASLD), is increasing. We assessed the burden and trends of MASLD and viral hepatitis in Saudi Arabia., Methods: Prevalence, death, and disability data due to MASLD, hepatitis C virus (HCV), and hepatitis B virus (HBV) were obtained from 2019 Global Burden of Disease (GBD) database for Saudi Arabia. Time trends were assessed by annual percent change (APC) from joinpoint regression., Results: From 2012 through 2019, MASLD prevalence in children and adults increased from 28.02% ( n = 8.34 million) to 33.11% ( n = 11.83 million); APC +2.43% (95% confidence interval: 2.33% to 2.54%). HBV prevalence decreased from 1.83% ( n = 0.54 million) to 1.53% ( n = 0.55 million); APC -1.74% (-2.66% to -0.81%). HCV prevalence stabilized from 0.72% ( n = 0.21 million) to 0.73% ( n = 0.26 million): APC +0.32% (-0.13% to 0.78%). Among adults (>20 years), MASLD prevalence increased from 40.64% to 43.95% (APC = +1.15%, 1.12% to 1.18%), HBV prevalence decreased from 2.67% to 2.05% (APC = -2.96%, -3.90% to -2.01%), and HCV leveled from 0.88% to 0.86% (APC = -0.30%, -0.75% to 0.16%). MASLD liver mortality rate from liver cancer and cirrhosis increased: APC of +1.15% (0.82% to 1.48%) from 1.31 to 1.43 (per 100,000). HBV and HCV liver mortality increased at slower rates (APC = +0.78%, 0.38% to 1.19%): 2.07 to 2.20 (per 100,000) and (APC = +0.55%, 0.09% to 0.89%): 6.32 to 6.61 (per 100,000), respectively., Conclusions: MASLD burden is increasing, while HBV and HCV burden is decreasing/remaining stable. Early prevention and diagnosis health policies for MASLD are needed., (Copyright © 2024 Copyright: © 2024 Saudi Journal of Gastroenterology.)

Background: The cardiometabolic index (CMI) is a new type of obesity index that is based on a combination of lipid levels and abdominal obesity indicators. It is closely correlated with the occurrence of diabetes mellitus, atherosclerosis, hypertension, and other diseases, thus playing an important role in the screening of metabolic diseases. This is coupled with hepatic steatosis and fibrosis which are characterized by excessive liver fat deposition. The aim of this study was to investigate the possible association between CMI and hepatic steatosis and liver fibrosis., Methods: A cross-sectional investigation was conducted using the 2017-2020 National Health and Nutrition Examination Survey (NHANES) dataset to probe the relationship between CMI and hepatic steatosis and liver fibrosis, while multiple linear regression models were used to test the linear association between CMI and controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). Smooth-fit curves and threshold effects analysis were used to describe the nonlinear relationships. Subgroup analyses were performed according to gender, age, body mass index (BMI), hypertension, diabetes, cardiovascular disease, and smoking status., Results: A total of 3084 adults aged 18-80 years were included in this analysis, and after controlling for a variety of variables, there was a significant positive correlation between CMI and CAP [20.38 (16.27,24.49)]. When subgroups were analyzed, this positive correlation was found to be stronger in the female population than in the male (P for interaction = 0.0303). Furthermore, the association between CMI and CAP was nonlinear. Using multiple regression analysis, it was shown that the linear relationship between CMI and liver fibrosis was not significant [-0.09 (-0.47,0.29)]., Conclusions: The findings suggest that elevated CMI levels are associated with hepatic steatosis, but that CMI is not linked to liver fibrosis. Larger prospective investigations are needed to confirm our findings., (© 2024. The Author(s), under exclusive licence to Hellenic Endocrine Society.)

Aim: The association of overweight/obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) in young adulthood with subclinical atherosclerosis [coronary artery calcification (CAC) and abdominal aortic calcification (AAC)] by middle age is unknown., Method: In total, 2274 participants aged 28-39 years from the coronary artery risk development in young adults study at year 10 (1995-1996) who were re-examined 15 years later were included. CAC and AAC were measured at year 25 using computed tomography. We examined the utility of three young adult phenotypes (lean group; overweight/obese group; overweight/obese MASLD group) at year 10 in predicting CAC or AAC by middle age. Modified Poisson regression was used to estimate the association between groups and CAC, and AAC. Independent determinates of CAC and AAC were determined with linear regression models., Results: Compared with individuals categorized as lean in young adulthood, the relative risk for CAC by middle age was 1.09 (95% confidence interval: 0.93-1.28) for those with overweight/obesity and 1.32 (95% confidence interval: 1.08-1.61) for those with overweight/obesity-related MASLD. For AAC, no difference was observed between these three groups. Group, systolic blood pressure and group × systolic blood pressure interaction were all the independent determinates for CAC., Conclusion: In this study, young adults with overweight/obesity-related MASLD have a higher risk of developing CAC by middle age. These abnormalities are only partially explained by traditional cardiovascular risk factors, and overweight/obesity-related MASLD has an independent impact on CAC. Our study provides evidence for identifying young adults at higher risk of developing subclinical atherosclerosis., (© 2024 John Wiley & Sons Ltd.)

Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiometabolic conditions affect populations across economic strata. Nevertheless, there are limited epidemiological studies addressing these diseases in low (LICs) and lower-middle-income countries (lower MICs). Therefore, an analysis of the trend of MASLD and cardiometabolic conditions in these countries is necessary., Methods: From 2000 to 2019, jointpoint regression analysis was employed to calculate the prevalence, mortality, and disability-adjusted life years (DALYs) for cardiometabolic conditions including MASLD, type 2 diabetes mellitus (T2DM), dyslipidemia (DLP), hypertension (HTN), obesity, peripheral artery disease (PAD), atrial fibrillation and flutter (AF/AFL), ischemic heart disease (IHD), stroke, and chronic kidney disease from HTN and T2DM, in LICs and lower MICs (according to the World Bank Classification 2019) using the Global Burden of Disease 2019 data., Results: Among the eleven cardiometabolic conditions, MASLD (533.65 million), T2DM (162.96 million), and IHD (76.81 million) had the highest prevalence in LICs and Lower MICs in 2019. MASLD represented the largest proportion of global prevalence in these countries (43 %). From 2000 to 2019, mortality in LICs and lower MICs increased in all cardiometabolic conditions, with obesity-related mortality having the highest increase (+134 %). During this timeframe, there were increased age-standardized death rates (ASDR) from obesity, PAD, and AF/AFL. From all conditions, the DALYs-to-prevalence ratio was higher in LICs and lower MICs than the global average., Conclusion: The burden of MASLD and cardiometabolic conditions is increasing worldwide, with LICs and lower MICs experiencing higher (DALYs) disability per prevalence. As these conditions are preventable, counteracting these trends requires not only the modification of ongoing actions but also the strategizing of immediate interventions., Competing Interests: Declaration of competing interest Mazen Noureddin has been on the advisory board for 89BIO, Gilead, Intercept, Pfizer, Novo Nordisk, Blade, EchoSens, Fractyl, Terns, Siemens, and Roche diagnostic; has received research support from Allergan, BMS, Gilead, Galmed, Galectin, Genfit, Conatus, Enanta, Madrigal, Novartis, Pfizer, Shire, Viking and Zydus; and is a minor shareholder or has stocks in Anaetos, Rivus Pharma and Viking. Vincent Chen's institution has received research grants from KOWA and AstraZeneca. Christos S. Mantzoros: reports grants through his institution from Merck, Massachusetts Life Sciences Center, and Boehringer Ingelheim; he reports personal consulting fees and support through his institution from Ansh Inc., collaborative research support from LabCorp Inc., reports personal consulting fees from Nestle, Olympus, Genfit, Lumos, Novo Nordisk, Amgen, Corcept, Intercept, 89 Bio, Madrigal, Aligos, Esperion, Biodexa and Regeneron, reports educational activity meals through his institution or national conferences from Esperion, Merck, Boehringer Ingelheim and travel support and fees from UptoDate, TMIOA, Elsevier, and the Cardio Metabolic Health Conference. None is related to this manuscript. Peer review of this manuscript was handled by an associate editor independently of the EIC and their research groups. As EIC recused himself from handling this manuscript. Naim Alkhouri reports grant/research support from 89Bio, Akero, Arbutus, AstraZeneca, Better Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Corcept, Cymabay, DSM, Galectin, Genentech, Genfit, Gilead, Hepagene, Healio, Intercept, Inventiva, Ionis, Ipsen, Madrigal, Merck, NGM, Noom, NorthSea, Novo Nordisk, Perspectum, Pfizer, Poxel, Viking, and Zydus; speaker's fees from AbbVie, Alexion, Echosens, Eisai, Gilead, Intercept, Ipsen, Madrigal, Perspectum, Salix, and Theratechnologies; Consultant for 89Bio, Boehringer Ingelheim, Echosens, Fibronostics, Gilead, Intercept, Madrigal, NorthSea, Novo Nordisk, Perspectum, Pfizer, and Zydus. Cheng Han Ng: CHN has served as a consultant to Boxer Capital. Jeffrey V. Lazarus: acknowledges grants to ISGlobal from AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Madrigal, MSD, Novo Nordisk, Pfizer, and Roche Diagnostics, consulting fees from Echosens, NovoVax, GSK, Novo Nordisk and Pfizer and payment or honoraria for lectures from AbbVie, Echosens, Gilead Sciences, Janssen, Moderna, MSD, Novo Nordisk and Pfizer, outside of the submitted work. The other authors declares there are no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) contributes to cardiovascular events. Therefore, we aimed to identify the association of MASLD, as indicated by the fatty liver index (FLI), on sudden cardiac arrest (SCA) in young adults., Methods: We analyzed data from adults aged 20-39 years, who underwent health examinations between 2009 and 2012, sourced from the Korean National Health Insurance Service database. The presence of MASLD was determined using the FLI, which was calculated based on an individual's body mass index, waist circumference, gamma-glutamyl transferase and triglyceride levels. The primary outcome was the occurrence of SCA during the follow-up period, until December 2020., Results: Of the total 5,398,082 individuals analyzed, 4,021,056 (74.5 %) had a normal FLI (FLI <30), 837,943 (15.5 %) were within the intermediate range (30-60), and 539,083 (10.0 %) demonstrated a high FLI (≥60). Individuals with a high FLI were older, and comprised a higher proportion of men with hypertension, diabetes mellitus, dyslipidemia, heart failure, and myocardial infarction. During follow-up, SCA occurred in 4255 individuals (0.08 %). The group with a high FLI exhibited an increased incidence (incidence rate, 0.19) and elevated risk of SCA (hazard ratio, 3.04). Adjustment of covariates revealed a 55 % increased risk of SCA in the high FLI group (adjusted hazard ratio 1.55, 95 % confidence interval 1.41-1.70, p < 0.001). Moreover, the influence of a high FLI on SCA risk was more pronounced in women compared to men. Additionally, an increase in relevant cardiometabolic conditions was associated with an elevated risk of SCA., Conclusions: Among young adults, a high risk of MASLD, as indicated by the FLI, revealed an increased risk of SCA. Furthermore, the association of FLI with the risk of SCA varied by sex and cardiometabolic conditions., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: To examine the cardiovascular disease (CVD) risks associated with metabolic dysfunction-associated steatotic liver disease (MASLD) and different numbers of cardiometabolic risk factors (CMRFs) in patients with inflammatory bowel disease (IBD) based on a long-term prospective cohort., Methods: Prevalent IBD patients at baseline who were free of CVD, cancer, alcoholic liver disease, cancer and hepatitis B/C virus seropositive were included (N = 4204). MASLD, MASLD subtypes [pure MASLD, MASLD with increased alcohol intake (MetALD)], lean/non-lean MASLD and CMRFs at baseline were defined according to the latest criteria proposed by AASLD and EASL. The primary outcome was incident CVD, including ischaemic heart disease (IHD), heart failure (HF) and stroke. Multivariable Cox proportional hazard models were used to estimate the relationship., Results: Overall, 1528 (36.4%) were diagnosed with MASLD at baseline. During a median of 13.1-year follow-up, 503 incident CVDs were identified. Compared with IBD-only, IBD-MASLD patients had an increased risk of CVD (HR = 1.77, 95%CI: 1.26-2.49), especially in those with MetALD (HR = 2.34, 1.34-4.11) and lean MASLD (HR = 2.30, 1.13-4.66). As the number of CMRFs increased, the risks of CVD were significantly increased (p trend  <0.001), with a 116% and 92% excess risk in MASLD with 3 CMRFs (HR = 2.16, 1.48-3.15) and ≥4 CMRFs (HR = 1.92, 1.27-2.91). Similar excess risk of incident IHD and HF was observed in IBD-MASLD, either pure MASLD or MetALD, as well as lean/non-lean MASLD., Conclusions: MASLD is associated with increased CVD risk in IBD patients, with greater risk as number of CMRFs increased and evidently higher risk in MetALD and lean MASLD patients., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Significance of autoantibodies in pediatric metabolic dysfunction-associated steatotic liver disease (MASLD) is unknown. Our aim was to determine the prevalence and significance of autoantibodies in MASLD. PubMed and Scopus were searched and six articles (689 [487 males] MASLD patients) were identified. Antinuclear antibodies (ANA) was positive in 28% (95% confidence interval [CI]: 17%-39%, n = 6 studies), antismooth muscle antibodies (ASMA) in 28% (95% CI: 8%-50%, n = 5 studies), actin-positive in 15% (95% CI: 10%-20%, n = 2 studies) and elevated immunoglobulin G in 17% (95% CI: 1%-39%, n = 4 studies). Anti-liver-kidney-microsomal antibody was not present in any patient. There was no significant association of ANA positivity with degree of liver steatosis, liver fibrosis or nonalcoholic fatty liver disease activity score (NAS) but patients with ASMA positivity had advanced fibrosis (pooled risk ratio [RR] 1.77; 95% CI 1.16-2.71) and higher risk of NAS ≥5 (pooled RR 1.21; 95% CI: 1.01-1.44, n = 2 studies, 243 patients). To conclude, non-organ specific autoantibodies are present in over one-fourth of children with MASLD and the presence of ASMA maybe associated with increased disease severity., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background and Aims: Sarcopenia is a common complication in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). However, the prevalence and its impact on the survival of sarcopenia in patients with MASLD is unknown. In this study, we aimed to assess the prevalence and effects of sarcopenia in patients with MASLD., Methods: Systematic review and meta-analysis of full texts of relevant studies were searched from inception until June 12, 2024 in five databases (PubMed, Cochrane Library, Embase, Web of Science, and the China National Knowledge Infrastructure). Next, we assessed the prevalence of sarcopenia in MASLD, and calculated the ORs and HRs between sarcopenia and MASLD based on the adjusted data from individual studies. Statistical analyses were performed using Stata 11.0., Results: Of the 2984 records considered, 29 studies recruiting 63,330 patients were included. The pooled prevalence of sarcopenia in patients with MASLD was 23.5% overall (95% CI; 19.1%-27.9%, I 2  = 99.6%), and was higher in Asian patients, male, cross-sectional studies, when BIA were employed to measure muscle mass, one criterion of diagnosis sarcopenia, MASLD was diagnosed employing MRI, and moderate-quality studies. Sarcopenia was associated with MASLD patients (adjusted odds ratio [aOR] 2.08, 95% CI 1.58-2.74, I 2  = 93.6%) with similar findings in subgroups stratified by age, study design, methods for measuring muscle mass, assessment method to detect sarcopenia, and study quality. The association between all-cause mortality further supports the association between sarcopenia and poor prognosis with MASLD (aHR 1.59, 95% CI 1.33-1.91, I 2  = 0%)., Conclusions: Sarcopenia was strongly associated with MASLD progression and was a risk factor not only for MASLD pathogenesis but was also markedly correlated with MASLD-associated mortality., Competing Interests: Conflict of interest These authors declare that there exists no potential conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD)-related cirrhosis has been increasing these last decades. There are no data regarding the prevalence of MASLD-related cirrhosis in intensive care unit (ICU)., Methods: Prospective single-centre study in a cohort of patients hospitalized in the ICU of Hepatology La Pitié-Salpêtrière Hospital between January 2019 and September 2021. We analysed three groups of patients: MASLD-cirrhosis (alcohol ≤210 g for men and 140 g weekly for women), ALD (alcohol-related liver disease, alcohol>140 g weekly for women or >210 g for men)-cirrhosis alone and MetALD (metabolic and alcohol-related liver disease)-cirrhosis. Endpoints were 1-year transplant-free survival (TFS), further acute decompensation (AD) and re-admission., Results: A total of 410 patients were hospitalized, and 315 analysed: 39 in MASLD, 160 in ALD and 116 in MetALD groups. The global prevalence was 10% for MASLD, 41% ALD and 29.7% for MetALD. Patients in the MASLD group were significantly older (65 vs. 57 and 59 years, p < 0.001), and had lower Child-Pugh (8 vs. 11 vs. 10, p < 0.001) and MELD score (17 vs. 22 vs. 21, p < 0.001). The 1-year TFS was not different between groups (53% vs. 54% vs. 54%, p = 0.96). Cardiovascular mortality was <5% in all groups. The 1-year probability of developing hepatic encephalopathy was significantly higher in the MASLD group (73% vs. 27% and 21%, p < 0.001). There was no difference regarding the development of other complications between groups., Conclusion: MASLD or MetALD was responsible for 1/3 of the causes of cirrhosis in the ICU. MASLD-related cirrhosis is as severe as ALD-related cirrhosis. Liver transplantation should be rapidly discussed., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Objective: The association of appendicular skeletal muscle mass (ASM), grip strength and fat-to-muscle ratio (FMR) and the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) are not well known., Materials and Methods: This study included participants older than 40 years who underwent bioelectrical impedance assessment in Prevalence of Metabolic Diseases and Risk Factors in Shunde (SPEED-Shunde). We measured grip strength with an electronic grip strength metre. ASM and grip strength were adjusted by dividing body mass index (BMI). FMR was calculated as total fat mass to total muscle mass. Liver steatosis and liver fibrosis were evaluated by vibration-controlled transient elastography. Multifactorial logistic regression was used to analyse the relationship between ASM, grip strength, FMR, and MASLD or MASLD-associated liver fibrosis. We performed subgroup analyses according to sex, age and BMI. Interaction tests and linear trend tests were also conducted., Results: This study included a total of 3277 participants. FMR was positively associated with MASLD (OR: 1.89, 95% CI: 1.66-2.15) and MASLD-associated liver fibrosis (OR: 1.70, 95% CI: 1.22-2.37). While ASM/BMI (OR: 0.59, 95% CI: 0.52-0.67) or grip strength/BMI (OR: 0.72, 95% CI: 0.66-0.78) were negatively associated with MASLD. Interactions were observed between ASM/BMI and age, grip strength and sex in MASLD, as well as FMR and MASLD-associated liver fibrosis., Conclusion: In a middle-to-elderly aged population, FMR was positively associated with the risk of MASLD and MASLD-associated liver fibrosis, and muscle mass and grip strength were negatively associated with MASLD, rather than MASLD-associated liver fibrosis.

Background: Continuous glucose monitoring (CGM) devices provide detailed information on daily glucose control and glycemic variability. Yet limited population-based studies have explored the association between CGM metrics and fatty liver. We aimed to investigate the associations of CGM metrics with the degree of hepatic steatosis., Methods: This cross-sectional study included 1180 participants from the Guangzhou Nutrition and Health Study. CGM metrics, covering mean glucose level, glycemic variability, and in-range measures, were separately processed for all-day, nighttime, and daytime periods. Hepatic steatosis degree (healthy: n = 698; mild steatosis: n = 242; moderate/severe steatosis: n = 240) was determined by magnetic resonance imaging proton density fat fraction. Multivariate ordinal logistic regression models were conducted to estimate the associations between CGM metrics and steatosis degree. Machine learning models were employed to evaluate the predictive performance of CGM metrics for steatosis degree., Results: Mean blood glucose, coefficient of variation (CV) of glucose, mean amplitude of glucose excursions (MAGE), and mean of daily differences (MODD) were positively associated with steatosis degree, with corresponding odds ratios (ORs) and 95% confidence intervals (CIs) of 1.35 (1.17, 1.56), 1.21 (1.06, 1.39), 1.37 (1.19, 1.57), and 1.35 (1.17, 1.56) during all-day period. Notably, lower daytime time in range (TIR) and higher nighttime TIR were associated with higher steatosis degree, with ORs (95% CIs) of 0.83 (0.73, 0.95) and 1.16 (1.00, 1.33), respectively. For moderate/severe steatosis (vs. healthy) prediction, the average area under the receiver operating characteristic curves were higher for the nighttime (0.69) and daytime (0.66) metrics than that of all-day metrics (0.63, P < 0.001 for all comparisons). The model combining both nighttime and daytime metrics achieved the highest predictive capacity (0.73), with nighttime MODD emerging as the most important predictor., Conclusions: Higher CGM-derived mean glucose and glycemic variability were linked with higher steatosis degree. CGM-derived metrics during nighttime and daytime provided distinct and complementary insights into hepatic steatosis., (© 2024. The Author(s).)

Background: Albuminuria is considered an early and sensitive marker of kidney dysfunction, but also an independent cardiovascular risk factor. Considering the possible relationship among metabolic liver disease, cardiovascular disease and chronic kidney disease, we aimed to evaluate the risk of developing albuminuria regarding the presence of epicardial adipose tissue and the steatotic liver disease status., Methods: A retrospective long-term longitudinal study including 181 patients was carried out. Epicardial adipose tissue and steatotic liver disease were assessed by computed tomography. The presence of albuminuria at follow-up was defined as the outcome., Results: After a median follow up of 11.2 years, steatotic liver disease (HR 3.15; 95% CI, 1.20-8.26; p = 0.02) and excess amount of epicardial adipose tissue (HR 6.12; 95% CI, 1.69-22.19; p = 0.006) were associated with an increased risk of albuminuria after adjustment for visceral adipose tissue, sex, age, weight status, type 2 diabetes, prediabetes, hypertriglyceridemia, hypercholesterolemia, arterial hypertension, and cardiovascular prevention treatment at baseline. The presence of both conditions was associated with a higher risk of developing albuminuria compared to having steatotic liver disease alone (HR 5.91; 95% CI 1.15-30.41, p = 0.033). Compared with the first tertile of visceral adipose tissue, the proportion of subjects with liver steatosis and abnormal epicardial adipose tissue was significantly higher in the second and third tertile. We found a significant correlation between epicardial fat and steatotic liver disease (rho = 0.43 [p < 0.001])., Conclusions: Identification and management/decrease of excess adiposity must be a target in the primary and secondary prevention of chronic kidney disease development and progression. Visceral adiposity assessment may be an adequate target in the daily clinical setting. Moreover, epicardial adipose tissue and steatotic liver disease assessment may aid in the primary prevention of renal dysfunction., (© 2024. The Author(s).)

Background and Objectives: The trends in metabolic dysfunction-associated steatotic liver disease (MASLD) and related metabolic dysfunctions in Japan are unknown. Thus, we aimed to clarify these trends before the novel coronavirus disease 2019 pandemic in Japan. Materials and Methods: We included Japanese individuals aged 25-79 years who underwent health examinations at our center. We analyzed anthropometry, lifestyle-related disease, and nutritional intake in relation to MASLD trends from 2010-2019. Results: The prevalence of MASLD increased in all ages and body mass index (BMI) classes, reaching 30.3% in males and 16.1% in females, with MASLD accounting for 75% of steatotic liver cases and more than half of all type 2 diabetes mellitus (T2DM) and high waist circumference (HWC) cases. The increase in the prevalence of MASLD was thought to be largely attributable to an increase in that of the incidence of steatotic liver itself, and there was no increase in the prevalence of other factors, such as overweight, T2DM, hypertension, and dyslipidemia. The prevalence of glucose metabolic disorders (GMDs) and hypertension decreased. National nutritional data showed an increase in energy intake, total fat, saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids, which correlated with a decrease in GMDs. Salt intake also decreased, which correlated with hypertension. The MASLD group had a higher prevalence of all related metabolic factors than the non-MASLD group, especially HWC, T2DM, and hyperlipidemia. Conclusions: The prevalence of MASLD increased with that of steatotic liver, regardless of age or BMI. A relationship between increased dietary fat, increased steatotic liver, and decreased GMDs was suggested.

Background: With the fast pace of modern life, people have less time for meals, but few studies have examined the association between the habit of fast eating and metabolic diseases., Objective: Combining the results of the current study and the prior ones, we aimed to investigate the possible relationship between fast eating and the risk of metabolic dysfunction-associated steatotic liver disease (MASLD)., Methods: This is a sub-analysis of a multicenter cross-sectional study of 1965 participants investigated the association between fast eating and MASLD in Chinese. Fast eating was defined as meal time less than five minutes and participants were divided into three categories based on their self-reported frequency of fast eating: ≤1 time/month, ≤1 time/week and ≥2 times/week. We further conducted a literature search for available studies published before November, 2023 as well as a meta-analysis to investigate the association between fast eating and MASLD., Results: The proportion of MASLD was 59.3%, 50.5%, and 46.2% in participants with fast eating ≥2 times/week, ≤1 time/week and ≤1 time/month, respectively (P for trend <0.001). The frequency of fast eating was independently associated with risk of MASLD after multiple adjustment for sex, age, demographics, smoking and drinking status, BMI and clinical metabolic parameters (OR, 1.29; 95%CI, 1.09-1.53). Participants who ate fast frequently (≥2 times/week) had 81% higher risk of MASLD (P = 0.011). A meta-analysis of five eligible studies confirmed that frequent fast eating was associated with increased risk of MASLD (pooled OR, 1.22; 95%CI, 1.07-1.39)., Conclusions: Frequent fast eating was associated with an increased risk of MASLD., (© 2024. The Author(s).)

Physical activity is a cornerstone of a healthy lifestyle, with benefits in managing chronic diseases. This study investigates the relationship between physical activity and liver-related outcomes with or without steatotic liver diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD) and MASLD and increased alcohol intake (MetALD). The primary outcomes of interest were overall survival in the entire population, individuals without steatotic liver disease, patients with MASLD, and those with MetALD. The secondary outcomes included the incidence of liver cirrhosis. Participants were categorized based on physical activity frequency and Kaplan-Meier survival curves and Cox proportional hazards models were used for analysis. Higher physical activity was associated with significantly better survival in the overall cohort and MASLD cohort before and after inverse probability of treatment weighting (IPTW). In participants without steatotic liver disease and the MetALD cohort, higher physical activity showed significant survival improvement after IPTW. For the incidence of liver cirrhosis, higher physical activity showed significant associations before IPTW in the overall cohort and MASLD cohort, but these associations were not significant after IPTW. Marginal significance was observed in the MetALD cohort before and after IPTW. In conclusion. promoting physical activity may be key in improving liver-related outcomes.

Aim: To date, there are limited clinical studies and real-world evidence investigating whether sodium-glucose cotransporter-2 inhibitors (SGLT2i) are associated with improved hepatic steatosis. This study aimed to evaluate the effectiveness of SGLT2i compared with that of dipeptidyl peptidase-4 inhibitors (DPP4i) in improving the fatty liver index (FLI) in patients with type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD)., Materials and Methods: This retrospective cohort study included new users of SGLT2i or DPP4i with T2DM and MASLD from a large claims database (JMDC Claims Database). The primary outcome was the incidence of improvement of the FLI. Cox proportional hazard models, weighted using propensity scores for predicting the initiation of treatment, were fitted to estimate hazard ratios with 95% confidence intervals (CIs). Time-course changes in the FLI values were also assessed., Results: This study included 9127 SGLT2i and 12 286 DPP4i initiators. SGLT2i showed a higher incidence of improvement in the FLI (≥30%, ≥40% and ≥50% reduction from baseline FLI) compared with DPP4i, and the weighted hazard ratios were 1.27 (95% CI 1.18-1.38), 1.24 (95% CI 1.13-1.37) and 1.19 (95% CI 1.05-1.33), respectively. SGLT2i indicated a greater decreased in FLI values compared with DPP4i at up to 3 years of the follow-up period., Conclusion: SGLT2is use appeared to be associated with a greater improvement of the FLI than DPP4i use in patients with T2DM and MASLD. In the absence of direct head-to-head comparisons from clinical studies, our study, using real-world data, may support physicians' decision-making in clinical practice., (© 2024 John Wiley & Sons Ltd.)

People living with HIV are particularly susceptible to developing metabolic disorders, including metabolic dysfunction-associated steatotic liver disease and other forms of SLD. However, people living with HIV have been historically excluded from clinical trials and large cohort studies of SLD. Therefore, our understanding of the risk factors and natural history of SLD in this population is poor. Moreover, relevant knowledge gaps on the epidemiology and barriers for adequate health care, such as stigma, hamper adequate responses to the ongoing HIV and SLD syndemic. This Viewpoint provides a comprehensive perspective on how to tackle SLD in people living with HIV by examining the role of social determinants of health in the development of liver disease and metabolic syndrome comorbidities among this population, emphasising the importance of prioritising SLD management, summarising the most urgent needs in the field, and offering recommendations for advancing research to fill key data gaps and protect liver health of people living with HIV., Competing Interests: Declaration of interests JMP reports having received consulting fees from Boehringer Ingelheim, MSD and Novo Nordisk. He has received speaking fees from Gilead, Intercept, and Novo Nordisk, and travel expenses from Gilead, Rubió, Pfizer, Astellas, MSD, CUBICIN, and Novo Nordisk. He has received educational and research support from Madrigal, Gilead, Pfizer, Astellas, Accelerate, Novartis, AbbVie, ViiV, and MSD. CR reports honoraria for speaking activities from ViiV Healthcare. GG reports speaking fees from ViiV Healthcare. AB acknowledges having received consulting fees from Boehringer Ingelheim and speaking fees by GE Healthcare and Hologic. GW received research grants from Gilead Sciences and Roche Diagnostics. MBB has received grant support from National Institute of Health, US Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health, Pfizer, The Kinetix Group, Histoindex, and serves as a consultant for The Kinetix Group, Madrigal, Pfizer, Theratechnologies, Fibronostics, Novo Nordisk, and GSK. JN has received honoraria, speaking fees, and financial support for attending conferences from AbbVie, Gilead Sciences, Janssen-Cilag, Merck Sharp & Dohme, and ViiV Healthcare, and consulting fees from ViiV Healthcare, Gilead Sciences, Janssen Cilag, and Merck Sharp & Dohme, outside the submitted work. JVL acknowledges grants from AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Madrigal, MSD, Novo Nordisk, Pfizer, and Roche Diagnostics; speaker fees from AbbVie, Echosens, Gilead Sciences, Janssen, Moderna, MSD, Novo Nordisk, and Pfizer; and consulting fees from Echosens, NovoVax, GSK, Novo Nordisk, and Pfizer, all outside the current work. JVL also acknowledges participation on the advisory board for the “Same-visit hepatitis C testing and treatment to accelerate cure among people who inject drugs (The QuickStart Study): a cluster randomised control trial–Australia” trial; had roles in the following committees: Member, European Association for the Study of the Liver, Public Health and Policy Committee; Healthy Livers, Health Livers (formed by AASLD, ALEH, APASL, European Association for the Study of the Liver) Global NASH Council; and was the Co-chair of HIV Outcomes. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most common chronic liver disease globally, affecting more than a third of the world's adult population. This comprehensive narrative review summarizes the global incidence and prevalence rates of MASLD and its related adverse hepatic and extrahepatic outcomes. We also discuss the substantial economic burden of MASLD on healthcare systems, thus further highlighting the urgent need for global efforts to tackle this common and burdensome liver condition. We emphasize the clinical relevance of early interventions and a holistic approach that includes public health strategies to reduce the global impact of MASLD., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)