Longitudinal Outcomes Associated With Metabolic Dysfunction-Associated Steatotic Liver Disease: A Meta-analysis of 129 Studies.

BACKGROUND & AIMS: The progression of metabolic dysfunction-associated steatotic liver disease (MASLD) has been found to manifest in a series of hepatic and extrahepatic complications. A comprehensive meta-analysis of the longitudinal outcomes associated with MASLD has yet to be conducted. METHODS: To investigate the longitudinal outcomes associated with MASLD, Medline and Embase databases were searched to identify original studies that evaluated the longitudinal risks of incident clinical outcomes among MASLD patients compared with non-MASLD individuals. DerSimonian Laird random-effects meta-analysis was performed. Pooled effect estimates were calculated, and heterogeneity among studies was evaluated. RESULTS: One hundred twenty-nine studies were included in the meta-analysis. Meta-analysis revealed a significant increase in the risk of cardiovascular outcomes (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.27-1.60; P < .01), various metabolic outcomes such as incident hypertension (HR, 1.75; 95% CI, 1.46-2.08; P < .01), diabetes (HR, 2.56; 95% CI, 2.10-3.13; P < .01), pre-diabetes (HR, 1.69; 95% CI, 1.22-2.35; P < .01), metabolic syndrome (HR, 2.57; 95% CI, 1.13-5.85; P = .02), chronic kidney disease (HR, 1.38; 95% CI, 1.27-1.50; P < .01), as well as all cancers (HR, 1.54; 95% CI, 1.35-1.76; P < .01) among MASLD patients compared with non-MASLD individuals. By subgroup analysis, MASLD patients with advanced liver disease (HR, 3.60; 95% CI, 2.10-6.18; P < .01) were also found to be associated with a significantly greater risk (P = .02) of incident diabetes than those with less severe MASLD (HR, 1.63; 95% CI, 1.0-2.45; P = .02) when compared with non-MASLD. CONCLUSIONS: The present study emphasizes the association between MASLD and its clinical outcomes including cardiovascular, metabolic, oncologic, and other outcomes. The multisystemic nature of MASLD found in this analysis requires treatment targets to reduce systemic events and end organ complications.

The emergence of obesity in type 1 diabetes.

Obesity, a chronic low-grade inflammatory disease represented by multifactorial metabolic dysfunctions, is a significant global health threat for adults and children. The once-held belief that type 1 diabetes is a disease of people who are lean no longer holds. The mounting epidemiological data now establishes the connection between type 1 diabetes and the subsequent development of obesity, or vice versa. Beyond the consequences of the influx of an obesogenic environment, type 1 diabetes-specific biopsychosocial burden further exacerbates obesity. In the course of obesity management discussions, recurring challenges surfaced. The interplay between weight gain and escalating insulin dependence creates a vicious cycle from which patients struggle to break free. In the absence of weight management guidelines and regulatory approval for this population, healthcare professionals must navigate the delicate balance between benefits and risks. The gravity of this circumstance highlights the importance of bringing these topics to the forefront. In this Review, we discuss the changing trends and the biopsychosocial aspects of the intersection between type 1 diabetes and obesity. We highlight the evidence supporting the therapeutic means (i.e., exercise therapy, nutritional therapy, adjunct pharmacotherapy, and bariatric surgery) and directions for establishing a more robust and safer evidence-based approach.

Examining the interim proposal for name change to steatotic liver disease in the US population.

BACKGROUND AND AIMS: Fatty liver is the commonest liver condition globally and traditionally associated with NAFLD. A consensus meeting was held in Chicago to explore various terminologies. Herein, we explore the proposed changes in nomenclature in a population data set from the US. APPROACH AND RESULTS: Statistical analysis was conducted using survey-weighted analysis. Assessment of fatty liver was conducted with vibration-controlled transient elastography. A controlled attenuation parameter of 288 dB/m was used to identify hepatic steatosis. Patients were classified into nonalcoholic steatotic liver disease, alcohol-associated steatotic liver disease, and viral hepatitis steatotic liver disease. Liver stiffness measures at ≥8.8, ≥11.7, and ≥14 kPa were used to identify clinically significant fibrosis, advanced fibrosis, and cirrhosis, respectively. A total of 5102 individuals were included in the analysis. Using a survey-weighted analysis, a total of 25.43%, 6.95%, and 0.73% of the population were classified as nonalcoholic steatotic liver disease, alcohol-associated steatotic liver disease, and viral hepatitis steatotic liver disease, respectively. A sensitivity analysis at controlled attenuation parameter of 248 dB/m and fatty liver index found similar distribution. In a comparison between nonalcoholic steatotic liver disease, alcohol-associated steatotic liver disease, and viral hepatitis steatotic liver disease, there was no significant difference between the odds of advanced fibrosis and cirrhosis between groups. However, viral hepatitis steatotic liver disease individuals were found to have a significantly higher odds of clinically significant fibrosis (OR: 3.76, 95% CI, 1.27-11.14, p =0.02) compared with nonalcoholic steatotic liver disease. CONCLUSIONS: The current analysis assessed the proposed changes based on discussions from the consensus meeting. Although the definitions are an interim analysis of discussions, steatotic liver disease respects the underlying liver etiology and reduces stigma while increasing awareness of FL among viral and alcohol-associated steatosis/steatohepatitis.

The prognostic value of metabolic dysfunction-associated steatotic liver disease in acute myocardial infarction: A propensity score-matched analysis.

AIM: Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are at increased risk of incident cardiovascular disease. However, the clinical characteristics and prognostic importance of MASLD in patients presenting with acute myocardial infarction (AMI) have yet to be examined. METHODS: This study compared the characteristics and outcomes of patients with and without MASLD presenting with AMI at a tertiary centre in Singapore. MASLD was defined as hepatic steatosis, with at least one of five metabolic criteria. Hepatic steatosis was determined using the Hepatic Steatosis Index. Propensity score matching was performed to adjust for age and sex. The Kaplan-Meier curve was constructed for long-term all-cause mortality. Cox regression analysis was used to investigate independent predictors of long-term all-cause mortality. RESULTS: In this study of 4446 patients with AMI, 2223 patients with MASLD were matched with patients without MASLD using propensity scores. The mean follow-up duration was 3.4 ± 2.4 years. The MASLD group had higher rates of obesity, diabetes and chronic kidney disease than their counterparts. Patients with MASLD had early excess all-cause mortality (6.8% vs. 3.6%, p < .001) at 30 days, with unfavourable mortality rates sustained in the long-term (18.3% vs. 14.5%, p = .001) compared with those without MASLD. After adjustment, MASLD remained independently associated with higher long-term all-cause mortality (hazard ratio 1.330, 95% confidence interval 1.106-1.598, p = .002). CONCLUSION: MASLD embodies a higher burden of metabolic dysfunction and is an independent predictor of long-term mortality in the AMI population. Its early identification may be beneficial for risk stratification and provide therapeutic targets for secondary preventive strategies in AMI.

The Global Epidemic of Metabolic Fatty Liver Disease.

PURPOSE OF REVIEW: The objective of this manuscript is to examine the current literature on the epidemiology of metabolic dysfunction-associated steatotic liver disease (MASLD), its correlation with cardiovascular disease (CVD) outcomes, as well as to evaluate the update in nomenclature from non-alcoholic liver disease (NAFLD). RECENT FINDINGS: The update of diagnostic criteria from NAFLD to MASLD reduces the stigma associated with alcohol consumption and poor health choices. It also shines a light on the crucial role of cardiometabolic risk factors in disease pathophysiology. The incidence and prevalence of MASLD are projected to increase significantly in the future as the population burden of cardiometabolic risk factors rises. MASLD is also a potent risk factor for developing CVD that should be tackled by using a multi-disciplinary team with a holistic approach. As the new nomenclature for metabolic liver disease is adopted on a global scale, more research is needed to investigate the applicability of findings from previous trials focusing on NAFLD. It is anticipated that the epidemic of MASLD will continue to increase globally, hence the urgent need for therapeutic approaches to reverse this trend.

Correction: Effectiveness of an Artificial Intelligence-Assisted App for Improving Eating Behaviors: Mixed Methods Evaluation.

[This corrects the article DOI: 10.2196/46036.].

Effectiveness of an Artificial Intelligence-Assisted App for Improving Eating Behaviors: Mixed Methods Evaluation.

BACKGROUND: A plethora of weight management apps are available, but many individuals, especially those living with overweight and obesity, still struggle to achieve adequate weight loss. An emerging area in weight management is the support for one's self-regulation over momentary eating impulses. OBJECTIVE: This study aims to examine the feasibility and effectiveness of a novel artificial intelligence-assisted weight management app in improving eating behaviors in a Southeast Asian cohort. METHODS: A single-group pretest-posttest study was conducted. Participants completed the 1-week run-in period of a 12-week app-based weight management program called the Eating Trigger-Response Inhibition Program (eTRIP). This self-monitoring system was built upon 3 main components, namely, (1) chatbot-based check-ins on eating lapse triggers, (2) food-based computer vision image recognition (system built based on local food items), and (3) automated time-based nudges and meal stopwatch. At every mealtime, participants were prompted to take a picture of their food items, which were identified by a computer vision image recognition technology, thereby triggering a set of chatbot-initiated questions on eating triggers such as who the users were eating with. Paired 2-sided t tests were used to compare the differences in the psychobehavioral constructs before and after the 7-day program, including overeating habits, snacking habits, consideration of future consequences, self-regulation of eating behaviors, anxiety, depression, and physical activity. Qualitative feedback were analyzed by content analysis according to 4 steps, namely, decontextualization, recontextualization, categorization, and compilation. RESULTS: The mean age, self-reported BMI, and waist circumference of the participants were 31.25 (SD 9.98) years, 28.86 (SD 7.02) kg/m2, and 92.60 (SD 18.24) cm, respectively. There were significant improvements in all the 7 psychobehavioral constructs, except for anxiety. After adjusting for multiple comparisons, statistically significant improvements were found for overeating habits (mean -0.32, SD 1.16; P<.001), snacking habits (mean -0.22, SD 1.12; P<.002), self-regulation of eating behavior (mean 0.08, SD 0.49; P=.007), depression (mean -0.12, SD 0.74; P=.007), and physical activity (mean 1288.60, SD 3055.20 metabolic equivalent task-min/day; P<.001). Forty-one participants reported skipping at least 1 meal (ie, breakfast, lunch, or dinner), summing to 578 (67.1%) of the 862 meals skipped. Of the 230 participants, 80 (34.8%) provided textual feedback that indicated satisfactory user experience with eTRIP. Four themes emerged, namely, (1) becoming more mindful of self-monitoring, (2) personalized reminders with prompts and chatbot, (3) food logging with image recognition, and (4) engaging with a simple, easy, and appealing user interface. The attrition rate was 8.4% (21/251). CONCLUSIONS: eTRIP is a feasible and effective weight management program to be tested in a larger population for its effectiveness and sustainability as a personalized weight management program for people with overweight and obesity. TRIAL REGISTRATION: ClinicalTrials.gov NCT04833803; https://classic.clinicaltrials.gov/ct2/show/NCT04833803.

Outcomes of Nonalcoholic Steatohepatitis After Liver Transplantation: An Updated Meta-Analysis and Systematic Review.

BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) is the fastest growing indication of liver transplantation (LT) and is projected to be the leading cause of LT in the near future. The systemic pathogenesis of NASH increases risks of adverse clinical outcomes in patients with NASH receiving LT. Thus, this study aimed to conduct a time-dependent survival analysis between LT recipients with and without NASH using hazard ratios. METHODS: A search was conducted on Medline and Embase databases for articles relating to LT outcomes for NASH recipients. A survival analysis was conducted of hazard ratios using the DerSimonian and Laird random-effects model with meta-regression. To account for censoring, survival data were reconstructed from published Kaplan-Meier curves and pooled to derive more accurate hazard estimates and all-cause mortality in NASH patients after LT. Pairwise meta-analysis was conducted to analyze secondary outcomes. RESULTS: Fifteen studies involving 119,327 LT recipients were included in our analysis with a prevalence of NASH of 20.2% (95% CI, 12.9-30.2). The pooled 1-year, 5-year, and 10-year all-cause mortality in NASH patients after LT were 12.5%, 24.4%, and 37.9%, respectively. Overall survival was comparable between LT recipients for NASH vs non-NASH (hazard ratio, 0.910; 95% CI, 0.760 to 1.10; P = .34). Meta-regression showed that a higher model for end-stage liver disease score was associated with significantly worse overall survival in NASH compared with non-NASH after LT (95% CI, -0.0856 to -0.0181; P = .0026). CONCLUSIONS: This study shows that patients undergoing LT for NASH cirrhosis have comparable complication rates, overall survival, and graft survival compared with non-NASH patients, although close monitoring may be indicated for those with higher model for end-stage liver disease scores.

Comparative Burden of Metabolic Dysfunction in Lean NAFLD vs Non-lean NAFLD - A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is traditionally associated with obesity. However, there is a subtype of NAFLD, namely NAFLD in lean, that occurs without obesity. However, a recent call to redefine NAFLD to metabolic-associated fatty liver disease focuses on obesity and metabolic dysfunction. Criticism has arisen from the perceived over emphasis on systemic comorbidities, which may disadvantage the lean. The current analysis seeks to quantify the degree of metabolic dysfunction in NAFLD in lean and compare with NAFLD in overweight and obese and non-NAFLD. METHODS: Medline and Embase databases were searched from inception to March 3, 2022. The inclusion criteria were articles with NAFLD in lean patients presenting with baseline metabolic parameters. Comparisons were conducted with subgroup analysis. RESULTS: Eighty-five articles were included in the meta-analysis. NAFLD in lean accounted for 13.11% (95% confidence interval [CI], 10.26%-16.62%) of the global population and 14.55% (95% CI, 11.32%-18.51%) in Asia. The degree of metabolic dysfunction was weight dependent with significantly less metabolic dysfunction in NAFLD in lean subjects as compared with NAFLD in overweight counterparts. For NAFLD in lean, only 19.56% (95% CI, 15.28%-24.69%) of the subjects were diabetic, whereas 45.70% (95% CI, 35.01%-56.80%) of obese subjects with NAFLD had diabetes (P < .01). Fasting blood glucose and systolic and diastolic blood pressure values were significantly lower in subjects with NAFLD in lean than in overweight and obese. CONCLUSION: The current analysis highlights the weight-dependent nature of metabolic dysfunction in NAFLD. Lean subjects with NAFLD were significantly less metabolically unhealthy than were obese and overweight persons with NAFLD. An overreliance on metabolic dysfunction in defining fatty liver will be a flaw in potentially excluding previously characterized NAFLD.

An Observational Data Meta-analysis on the Differences in Prevalence and Risk Factors Between MAFLD vs NAFLD.

BACKGROUND & AIMS: The shift to redefine nonalcoholic fatty liver disease (NAFLD) as metabolic associated fatty liver disease (MAFLD) can profoundly affect patient care, health care professionals, and progress within the field. To date, there remains no consensus on the characterization of NAFLD vs MAFLD. Thus, this study sought to compare the differences between the natural history of NAFLD and MAFLD. METHODS: Medline and Embase databases were searched to include articles on prevalence, risk factors, or outcomes of patients with MAFLD or NAFLD. Meta-analysis of proportions was conducted using the generalized linear mix model. Risk factors and outcomes were evaluated in conventional pairwise meta-analysis. RESULTS: Twenty-two articles involving 379,801 patients were included. Pooled prevalence of MAFLD was 39.22% (95% confidence interval [CI], 30.96%-48.15%) with the highest prevalence in Europe and Asia, followed by North America. The current MAFLD Definition only accounted for 81.59% (95% CI, 66.51%-90.82%) of NAFLD diagnoses. Patients had increased odds of being diagnosed with MAFLD compared with NAFLD (odds ratio, 1.37; 95% CI, 1.16-1.63; P < .001). Imaging modality resulted in a significantly higher odds of being diagnosed with MAFLD compared with NAFLD, but not biopsy. MAFLD was significantly associated with males, higher body mass index, hypertension, diabetes, lipids, transaminitis, and greater fibrosis scores compared with NAFLD. CONCLUSIONS: There were stark differences in the prevalence and risk factors between MAFLD and NAFLD. However, in the use of the MAFLD Definition, a greater emphasis on the management of concomitant metabolic diseases and a collaborative effort is required to explore the complex pathophysiologic mechanisms underlying the disease.

The Spectrum and Impact of Metabolic Dysfunction in MAFLD: A Longitudinal Cohort Analysis of 32,683 Overweight and Obese Individuals.

BACKGROUND: Metabolic associated fatty liver disease (MAFLD) was recently proposed as an alternative name change for better encapsulation of disease. However, there exists a spectrum of MAFLD where both metabolically healthy (MH) and metabolically unhealthy (MU) individuals are included. In view of limited evidence, we sought to examine the prevalence, clinical characteristics, and differences in outcomes of MH-MAFLD at the population level. METHODS: Data were used from the United States National Health and Nutrition Examination Survey 1999 to 2018. Multivariate logistic regression analysis was used to obtain odds ratios for the estimation of events. Survival analysis was conducted with Cox regression and the Fine-Gray subdistribution model. RESULTS: There were 32,683 overweight and obese individuals included in the analysis. In MAFLD patients, the prevalence of MH-MAFLD was 6.92% (95% confidence interval [CI], 6.58%-7.27%), and 93.08% (95% CI, 92.73%-93.42%) were considered as MU-MAFLD. Multivariate analysis found a significantly higher risk of MACE (odds ratio, 1.38; 95% CI, 1.28-1.49; P < .01), all-cause (hazard ratio, 1.24; 95% CI, 1.17-1.32; P < .01), cardiovascular disease (SHR, 1.20; 95% CI, 1.02-1.42; P = .03), and cancer mortality (SHR, 1.24; 95% CI, 1.07-1.44; P < .01) in MU-MAFLD relative to non-MAFLD. However, MH-MAFLD individuals were not associated with a statistically significant increased risk of these adverse outcomes compared with non-MAFLD. MU-MAFLD diabetics were also at a higher risk of adverse events compared with non-diabetics. CONCLUSIONS: This study reports on the heterogeneity and spectrum of metabolic dysfunction that exists in overweight and obese MAFLD. Although MAFLD may potentially be advantageous in improving awareness and patient outcomes, there remains substantial heterogeneity within patients included in MAFLD on the basis of the underlying metabolic burden.

Placebo Adverse Events in Non-alcoholic Steatohepatitis Clinical Trials: A Pooled Analysis of 2,944 Participants.

INTRODUCTION: In the absence of an effective treatment for non-alcoholic steatohepatitis (NASH), a randomized, placebo-controlled trial (RCT) remains the current gold standard study design in NASH. As NASH is a largely asymptomatic disease, the side effects of potential therapies require careful evaluation, therefore a pooled rate of the adverse events (AEs) in placebo-treated patients serves as a useful comparator for safety. Therefore, we performed a systematic review and meta-analysis to estimate the rate of AEs among participants in the placebo arm of NASH RCTs. METHODS: Medline, Embase and Cochrane Central Register of Controlled Trials were searched to include clinical trials in phase 2-4 NASH RCTs with placebo treatment arms. A pooled proportions of AEs were analyzed using a generalized linear mixed model with Clopper-Pearson intervals. RESULTS: A total of 41 RCTs (2,944 participants on placebo) were included in this meta-analysis. A total of 68% (confidence interval [CI] 55%-77%) of participants on placebo experienced an AE, 7.8% (5.7%-10%) experienced serious AEs and 3.1% (CI: 1.9%-5.1%) experienced AEs leading to discontinuation. A significantly higher proportion of participants experienced serious AEs in phase 3 studies compared to in phase 2 studies ( P < 0.01) and in pharmaceutical funded studies as compared to studies which were federal-funded studies ( P < 0.01). An analysis of clinical trials evaluating bile acid modulating agents determined that 10% (CI: 5.5%-18%) of participants receiving placebo developed pruritus. DISCUSSION: The present study summarizes the AEs with NASH placebo. Among participants in the placebo arm in NASH, two-third experienced an AE, and nearly 10% experienced a serious AE.

Efficacy and safety of tirzepatide for treatment of overweight or obesity. A systematic review and meta-analysis.

BACKGROUND: Recent studies suggest that tirzepatide, a dual glucose-dependent insulinotropic-peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA), has significant weight loss effects. This systematic review and meta-analysis aims to assess the efficacy and safety of tirzepatide for weight loss in patients with overweight or obesity. METHODS: Medline, Embase and Cochrane CENTRAL were searched for randomized controlled trials (RCTs) on tirzepatide's weight loss efficacy for these patients. A single arm meta-analysis of proportions estimated primary outcomes, ≥5%, ≥10%, and ≥15% weight loss, and adverse events (AEs); while meta-analysis of means estimated secondary outcomes. Comparative meta-analysis was conducted between tirzepatide and control arms where mean differences and odds ratios were estimated for continuous and dichotomous outcomes respectively. RESULTS: RCTs included in this study revealed that among 5800 patients, 78.22% (95% CI: 72.15% to 83.73%), 55.60% (95% CI: 46.54% to 64.47%), 32.28% (95% CI: 23.17% to 42.12%) achieved ≥5%, ≥10%, and ≥15% weight loss, respectively. Tirzepatide 5 mg demonstrated weight loss superiority relative to placebo (MD: -12.47 kg, 95% CI: -13.94 kg to -11.00 kg) and semaglutide (n = 1409, MD: -1.90 kg, 95% CI: -2.97 kg to -0.83 kg) with dose-dependent increase for 10 mg and 15 mg doses. The comparison between tirzepatide and semaglutide was examined in the SURPASS-2 trial that was included in this systematic review. For AEs, there was increase odds of experiencing gastrointestinal AEs with tirzepatide compared to placebo, but no significant difference with semaglutide. CONCLUSION: Tirzepatide has significant potential as a weight loss drug in patients with overweight and obesity, with little increase in AEs compared to other weight loss drugs. With its ability to concurrently target multiple aspects of metabolic syndrome, it should be considered as the next helm of weight loss therapies.

De novo metabolic syndrome after liver transplantation: a meta-analysis on cumulative incidence, risk factors, and outcomes.

Post-transplant metabolic syndrome (PTMS) has been associated with increased cardiovascular risk which significantly impacts the morbidity and mortality rates of liver transplant (LT) recipients. This study sought to conduct a meta-analysis and systematic review on the cumulative incidence, risk factors, and cardiovascular outcomes associated with de novo PTMS.Medline and Embase were searched for articles describing the incidence, risk factors, and cardiovascular outcomes of de novo PTMS. Meta-analysis of proportions was conducted to calculate incidence. Conventional pairwise analysis using random effects model was used to tabulate OR and hazard ratio for risk factors and cardiovascular outcomes, respectively. Fifteen studies involving 2683 LT recipients were included. Overall rate of de novo PTMS was 24.7% (CI: 18.0%-32.9%) over a mean follow-up period of 15.3 months and was highest in patients with NAFLD (60.0%, CI: 52.0%-67.5%) compared with other liver diseases. Older age (OR: 1.05, CI: 1.01-1.09, p = 0.02) and pre-LT type II diabetes mellitus (OR: 5.00, CI: 4.17-5.99, p < 0.01) were predictive factors of de novo PTMS. Patients with de novo PTMS had significantly higher likelihood of cardiovascular disease events compared with those who did not (hazard ratio: 2.42, CI: 1.54-3.81, p < 0.01). De novo PTMS is a common complication and is significantly associated with increased cardiovascular disease morbidity. High-risk patients such as elderly recipients, those with pre-LT type II diabetes mellitus, or NASH-related cirrhosis should undergo routine screening to allow timely intervention.

Placebo effect on progression and regression in NASH: Evidence from a meta-analysis.

BACKGROUND AND AIMS: The evaluation of the natural history of NASH has been limited. Currently, liver biopsy remains the gold standard in the assessment of NASH. Placebo-controlled trials represent a controlled environment with paired biopsies for the evaluation of NASH. This meta-analysis thus seeks to quantify the change severity of NASH over time, with patients on placebo arms from randomized controlled trials (RCTs) to examine the natural history of NASH. METHODS: A search was conducted to include NASH RCTs with placebo treatment arms. Primary outcomes were (1) the resolution of NASH without worsening of fibrosis, (2) two-point reduction in NAFLD activity score without worsening of fibrosis, and (3) at least one-point reduction in fibrosis. Generalized linear mix model was used to estimate pooled proportion and mean differences. RESULTS: This meta-analysis of 43 RCTs included 2649 placebo-treated patients. The pooled estimate of NASH resolution and two-point NAFLD activity score reduction without worsening of fibrosis was 11.65% (95% CI: 7.98-16.71) and 21.11% (95% CI: 17.24-25.57). The rate of ≥1 stage reduction and progression of fibrosis was 18.82% (95% CI: 15.65-22.47) and 22.74% (CI: 19.63-26.17), respectively. Older age and African American ethnicity was associated with lower NASH resolution rate in placebo-treated patients. CONCLUSIONS: Despite the absence of any pharmacological interventions, a significant proportion of patients in the placebo arm demonstrated improvements in liver histology, highlighting the possibility that NASH is a disease that can not only progress but regress spontaneously over time. Additionally, histologic response in placebo-treated patients is helpful in future design of phase 2B and phase 3 trials.

Hepatic steatosis and advanced hepatic fibrosis are independent predictors of long-term mortality in acute myocardial infarction.

AIM: To examine the prevalence and prognosis of hepatic steatosis and fibrosis in post-acute myocardial infarction (AMI) patients. METHODS: Patients presenting with AMI to a tertiary hospital were examined from 2014 to 2021. Hepatic steatosis and advanced hepatic fibrosis were determined using the Hepatic Steatosis Index and fibrosis-4 index, respectively. The primary outcome was all-cause mortality. Cox regression models identified determinants of mortality after adjustments and Kaplan-Meier curves were constructed for all-cause mortality, stratified by hepatic steatosis and advanced fibrosis. RESULTS: Of 5765 patients included, 24.8% had hepatic steatosis, of whom 41.7% were diagnosed with advanced fibrosis. The median follow-up duration was 2.7 years. Patients with hepatic steatosis tended to be younger, female, with elevated body mass index and an increased metabolic burden of diabetes, hypertension and hyperlipidaemia. Patients with hepatic steatosis (24.6% vs. 20.9% mortality, P < .001) and advanced fibrosis (45.6% vs. 32.9% mortality, P < .001) had higher all-cause mortality rates compared with their respective counterparts. Hepatic steatosis (adjusted hazard ratio 1.364, 95% CI 1.145-1.625, P = .001) was associated with all-cause mortality after adjustment for confounders. Survival curves showed excess mortality in patients with hepatic steatosis compared with those without (P = .002). CONCLUSIONS: Hepatic steatosis and advanced fibrosis have a substantial prevalence among patients with AMI. Both are associated with mortality, with an incrementally higher risk when advanced fibrosis ensues. Hepatic steatosis and fibrosis could help risk stratification of AMI patients beyond conventional risk factors.

Complete alcohol abstinence increases the risk of NAFLD but not severity. A population analysis with transient elastography.

BACKGROUND & AIMS: As the global prevalence of non-alcoholic fatty liver disease (NAFLD) continues to rise, ubiquity of alcohol use has also prompted discussion regarding the potential interactions between the two. This study aims to examine the effects of modest alcohol consumption on the prevalence and complications of NAFLD in a multi-ethnic population. METHODS: This study analyses the 2017-2018 cycles of NHANES that examined liver fibrosis and steatosis with vibration controlled transient elastography. A coarsened exact matching was conducted to reduce confounding. Logistic regression was done with a multivariate model to assess the relationship between alcohol consumption (modest drinkers and non-drinkers) and risk of NAFLD and its complications. RESULTS: 2,067 individuals were found to have NAFLD and 284 NAFLD patients had a total history of alcohol abstinence. After coarsened exact matching, the prevalence of NAFLD was 49% (CI: 0.41 - 0.58) in non-drinkers and 33% (CI: 0.26 - 0.41) in modest drinkers. Non-drinkers had twice the odds of NAFLD compared to modest drinkers (OR: 1.99, CI: 1.22 - 3.22, p<.01) after adjustment for confounders. There were no significant differences in the odds of significant fibrosis, advance fibrosis, cirrhosis, cardiovascular disease and stroke between non-drinkers and modest drinkers. The odds of malignancy in non-drinkers were almost significantly less than modest drinkers (OR: 0.28, CI:0.08 - 1.02, p=.053). CONCLUSION: Interestingly, modest alcohol consumption is associated with decreased odds of NAFLD. Further investigations are required to examine the relationship between alcohol consumption and NAFLD and subsequently the potential impact on NAFLD management.

Barriers and Facilitators to Engagement With a Weight Management Intervention in Asian Patients With Overweight or Obesity: A Systematic Review.

OBJECTIVE: The obesity epidemic is a global health concern with Asian countries facing one of the most rapid rises in obesity rates. However, given the underwhelming long-term efficacy of weight loss strategies, especially in Asia, this review aimed to explore barriers and facilitators to weight management of patients with overweight and obesity in Asia. METHODS: Medline, CINAHL, PsycINFO, and Web of Science were searched for articles discussing barriers and facilitators of treatment to obesity from the perspectives of both health care professionals (HCPs) and patients. Qualitative and mixed method studies from Asia were included. Key quotes were extracted, coded, and thematically analyzed according to the methodology of Thomas and Harden. RESULTS: A total of 26 articles were included in this review. From patient perspectives, 3 main themes were identified: factors influencing poor eating behavior, inhibiting lifestyle modifications, and facilitating lifestyle modifications. Patients highlighted several barriers including the lack of social support, physiologic limitations to exercise, and low health literacy. Rigid sociocultural norms and lack of accessible health care services, exercise facilities, and healthy food exacerbated the barriers. Facilitators to lifestyle modifications consisted of strong support systems and high health literacy. HCPs agreed that low health literacy, lack of social support, and patient motivation impeded patients' weight loss attempts but were unaware of the other barriers they faced. CONCLUSION: There are discrepancies between ideas of barriers and facilitators of HCPs and patients. A mixture of population level, primary care, and personal interventions are required to address this disparity, and enhanced health literacy can improve weight loss outcomes.

A Meta-analysis on Associated Risk of Mortality in Nonalcoholic Fatty Liver Disease.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) affects much of the worldwide population and poses a significant burden to the global healthcare. The rising numbers of individuals with NAFLD and instances of mortality point toward the importance of understanding the association causes of mortality in NAFLD. This meta-analysis aimed to seek the associations of NAFLD with all-cause, cardiovascular disease (CVD)-related, liver-related, and cancer-related mortality. METHODS: MEDLINE and Embase were searched for articles relating to causes of mortality between NAFLD and non-NAFLD. The DerSimonian and Laird random-effects model was used to analyze adjusted hazard ratios (HR), and a sensitivity analysis was conducted to reduce heterogeneity through a graphical display of study heterogeneity. RESULTS: Fifteen studies involving 10 286 490 patients were included. Individuals with NAFLD exhibited an increased risk of all-cause mortality (HR, 1.32; 95% CI, 1.09-1.59; P < .01; I2 = 96.00%), CVD-related mortality (HR, 1.22; 95% CI, 1.06-1.41; P < .01; I2 = 81.00%), and cancer-related mortality (HR, 1.67; 95% CI, 1.15-2.41; P < .01; I2 = 95.00%). However, no significant association was found between liver-related mortality and NAFLD (HR, 3.58; 95% CI, 0.69-18.46; P =.13; I2 = 96.00%). The sensitivity analysis conducted with graphic display of heterogeneity and only population-based studies found similar results. CONCLUSION: NAFLD was associated with an increased risk of all-cause, CVD-related, and cancer-related mortality but not liver-related mortality. The finding is likely because of low fibrosis prevalence in the community. However, the significant burden in other causes of mortality beyond the liver points to a need for multidisciplinary efforts to reduce the mortality risks.

Type 2 diabetes mellitus in metabolic-associated fatty liver disease vs. type 2 diabetes mellitus non-alcoholic fatty liver disease: a longitudinal cohort analysis.

INTRODUCTION AND OBJECTIVES: Type 2 Diabetes Mellitus (T2DM) is comorbidity commonly presenting with fatty liver. A recently proposed definition of "metabolic associated fatty liver disease" (MAFLD) is thought to replace non-alcoholic fatty liver disease (NAFLD). Yet, despite the significant prevalence of T2DM among fatty liver, there remains limited evidence on the impact of the change in the definition of T2DM. MATERIALS AND METHODS: The current study uses data from the United States National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Survival analysis was conducted with a cox regression and sub-distribution hazard ratio for competing risk events. RESULTS: 6727 patients had a diagnosis of T2DM. 4982 individuals with T2DM had MAFLD and 2032 were MAFLD(+)/NAFLD(-), while 2950 patients were MAFLD(+)/NAFLD(+). The new definition increased fatty liver diagnosis by 68.89%. Patients who were classified as MAFLD(+)/NAFLD(-) were at a higher risk of major adverse cardiovascular events, advanced fibrosis, all-cause and cardiovascular-related mortality compared to MAFLD(+)/NAFLD(+). In MAFLD(+)/NAFLD(-), viral hepatitis significantly increases the odds of advanced fibrosis (OR: 6.77, CI: 3.92 to 11.7, p < 0.001) and all-cause mortality (HR: 1.75, CI: 1.29 to 2.40, p < 0.001). CONCLUSIONS: The identification and treatment of NAFLD in patients with T2DM is a major concern and the premature change to MAFLD results in an over-diagnosis of fatty liver, exaggerated mortality, and morbidity in patients with T2DM. The definition of MAFLD causes further heterogeneity in fatty liver disease/NAFLD.