Metabolic-dysfunction associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is increasingly recognized as a prevalent global burden. Type 2 diabetes mellitus (T2DM), another important metabolic disease, is considered a major contributor to the development of MASLD. MASLD and T2DM have a strong association with each other due to shared pathogenic mechanisms. The co-existence of the two diseases increases the risk of liver-related adverse outcomes, and imposes a heavier burden on extrahepatic outcomes, representing a substantial public health issue. Effective assessment and management of T2DM combined with MASLD necessitate a multidisciplinary approach. The emergence of numerous randomized clinical trials has shed light on the treatment of T2DM combined with MASLD. This review uncovered the epidemiology of the intertwined T2DM and MASLD, offer insights into the evaluation of hepatic fibrosis in T2DM patients, glucose monitoring in MASLD population, and provide comprehensive co-management strategies for addressing both diseases.
BACKGROUND: One challenge for primary care providers caring for patients with nonalcoholic fatty liver disease is to identify those at the highest risk for clinically significant liver disease. AIM: To derive a risk stratification tool using variables from structured electronic health record (EHR) data for use in populations which are disproportionately affected with obesity and diabetes. METHODS: We used data from 344 participants who underwent Fibroscan examination to measure liver fat and liver stiffness measurement [LSM]. Using two approaches, multivariable logistic regression and random forest classification, we assessed risk factors for any hepatic fibrosis (LSM > 7 kPa) and significant hepatic fibrosis (> 8 kPa). Possible predictors included data from the EHR for age, gender, diabetes, hypertension, FIB-4, body mass index (BMI), LDL, HDL, and triglycerides. RESULTS: Of 344 patients (56.4% women), 34 had any hepatic fibrosis, and 15 significant hepatic fibrosis. Three variables (BMI, FIB-4, diabetes) were identified from both approaches. When we used variable cut-offs defined by Youden's index, the final model predicting any hepatic fibrosis had an AUC of 0.75 (95% CI 0.67-0.84), NPV of 91.5% and PPV of 40.0%. The final model with variable categories based on standard clinical thresholds (i.e., BMI ≥ 30 kg/m2; FIB-4 ≥ 1.45) had lower discriminatory ability (AUC 0.65), but higher PPV (50.0%) and similar NPV (91.3%). We observed similar findings for predicting significant hepatic fibrosis. CONCLUSIONS: Our results demonstrate that standard thresholds for clinical risk factors/biomarkers may need to be modified for greater discriminatory ability among populations with high prevalence of obesity and diabetes.
Metabolic dysfunction-associated steatohepatitis (MASH) is a leading etiology of chronic liver disease worldwide, with increasing incidence and prevalence in the setting of the obesity epidemic. MASH is also a leading indication for liver transplantation, given its associated risk of progression to end-stage liver disease. A key challenge in managing MASH is the lack of approved pharmacotherapy. In its absence, lifestyle interventions with a focus on healthy nutrition and regular physical activity have been the cornerstone of therapy. Real-world efficacy and sustainability of lifestyle interventions are low, however. Pharmacotherapy development for MASH is emerging with promising data from several agents with different mechanisms of action (MOAs) in phase 3 clinical trials. In this review, we highlight ongoing challenges and potential solutions in drug development for MASH and provide an overview of available data from emerging therapies across multiple MOAs.
Fatty Liver , Humans , Fatty Liver/therapy , Fatty Liver/metabolism , Animals , Metabolic Diseases/metabolism , Metabolic Diseases/therapy
BACKGROUND & AIMS: Food insecurity (FI) is a risk factor for nonalcoholic fatty liver disease (NAFLD) and advanced fibrosis in the general population, but its impact on liver disease in people with HIV (PWH) is unknown. METHODS: We examined the association of FI with prevalence of NAFLD and fibrosis in a diverse cohort of PWH. PWH aged ≥ 18 years on antiretroviral therapy, HIV RNA <200 copies/mL, and without other known liver diseases were screened for NAFLD (controlled attenuated parameter ≥263 decibels/meter) and advanced fibrosis (liver stiffness measurement ≥11 kilopascals) by vibration controlled transient elastography at 8 U.S. CENTERS: Participants were categorized as food insecure using the Six-Item Short Form Household Food Security Survey. We used multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of NAFLD and advanced fibrosis by FI status. RESULTS: Among 654 PWH, NAFLD was present in 348 (53%) and advanced fibrosis in 41 (6%). FI was present in 203 of participants (31%), including 97/348 with NAFLD (28%) and 18/41 with advanced fibrosis (44%). In multivariable analysis, FI was associated with lower odds of NAFLD (OR, 0.57; 95% CI, 0.37-0.88) and a greater, but nonsignificant, odds of advanced fibrosis (OR, 1.38; 95% CI, 0.65-2.90). We identified a significant interaction between FI and diabetes (P = .02) on fibrosis risk, with greater odds of fibrosis among food insecure PWH and diabetes (OR, 3.83; 95% CI, 1.15-12.73) but not among food insecure nondiabetics (OR, 1.12; 95% CI, 0.47-2.98). CONCLUSIONS: FI is highly prevalent among PWH and associated with lower odds of NAFLD, and among PWH with diabetes, there is greater odds of advanced fibrosis. FI may contribute to hepatic fibrosis through mechanisms other than steatosis in PWH.
BACKGROUND AND AIMS: The patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 variant is associated with Steatotic Liver Disease (SLD) and its progression. We examined the association between PNPLA3 and the development of major adverse liver outcomes (MALO) and how non-modifiable and modifiable conditions modify this relationship. APPROACH AND RESULTS: 2,075 adults with biopsy-confirmed Metabolic-Associated SLD (MASLD) were enrolled in the MASLD CRN studies and followed prospectively until death, transplant, or withdrawal of consent. 104 MALOs were recorded during an average of 4.3 years. PNPLA3 G-allele (Adj. SubHazard ratio (sHR): 1.4, 95% confidence interval (CI): 1.07-1.8), advanced fibrosis (AF) (Adj. sHR: 7.8, 95% CI: 4.4-13.8), age >60 years (Adj. sHR: 2.9, 95% CI: 1.3-6.8), and type 2 diabetes mellitus (T2DM) (Adj. sHR: 2.8, 95% CI: 1.8-4.2) were associated with MALO. Among participants with AF, those carrying the G-allele displayed the highest cumulative incidence of MALO (85%) vs. noncarriers (53%), p=0.03, and p value for interaction<0.01. The strength of the association between PNPLA3 and MALO was statistically significantly greater among older than 60 years (sHR: 2.1, 95% CI: 1.5-2.8), women (sHR: 1.4, 95% CI: 1.1-1.9), and those with AF (sHR: 1.9, 95% CI: 1.5-2.4) or T2DM (sHR: 2.1, 95% CI: 1.5-2.8) as compared with their counterparts, p value for interaction between PNPLA3 and each factor<0.01. CONCLUSIONS: The deleterious effects of PNPLA3 rs738409 on the risk of MALO are significantly worsened by advanced fibrosis, age, T2DM, and sex.
BACKGROUND: A multi-society consensus group proposed a new nomenclature for steatotic liver disease (SLD) including metabolic-dysfunction associated steatotic liver disease (MASLD), MASLD and increased alcohol intake (MetALD) and alcohol-associated liver disease (ALD). However, the risk of liver-related events, major adverse cardiovascular events (MACE) and all-cause mortality among various sub-groups is unknown. AIMS: To evaluate the risk of liver-related events, MACE and death among patients with SLD. METHODS: We conducted a nationwide, population-based study and enrolled 761,400 patients diagnosed with MASLD, MetALD or ALD. The primary endpoint was the occurrence of liver-related events, MACE and death in patients with MASLD, MetALD and ALD. RESULTS: The cumulative incidence of liver-related events and death were highest in ALD, followed by MetALD and MASLD (p < 0.001 for both liver-related events and death), while the incidence of MACE was highest in MASLD, followed by MetALD and ALD (p < 0.001). Using MASLD as the reference and adjusting for age, sex, smoking, diabetes mellitus, dyslipidaemia and hypertension, the adjusted hazard ratios (95% confidence intervals) for liver-related events, MACE and death in MetALD were 1.42 (1.1-1.8), 0.68 (0.63-0.73) and 1.13 (0.98-1.3), respectively. In ALD, they were 3.42 (2.6-4.6), 0.58 (0.49-0.67) and 1.60 (1.3-2.0), respectively, for liver-related events, MACE and death. CONCLUSIONS: The new consensus nomenclature can be used to stratify the risk of complications and prognosis. The nomenclature is beneficial for risk stratification and identifying new mechanisms for disease-specific therapeutic implications.
BACKGROUND & AIMS: The natural progression of hepatic decompensation in metabolic dysfunction-associated steatotic liver disease (MASLD) is not well-characterised. We aimed to describe it by conducting a retrospective analysis. METHODS: This longitudinal, retrospective analysis of well-characterised MASLD cohorts followed for hepatic decompensation and death. The sequence of liver-related events was evaluated, and the median time between hepatic decompensation episodes and death versus. transplantation was measured. RESULTS: Of the 2016 patients identified, 220 (11%) developed at least one episode of hepatic decompensation during a median follow-up of 3.2 years. Ascites was the most common first liver-related event [153 (69.5%)], followed by hepatic encephalopathy (HE) [55 (25%)] and variceal haemorrhage (VH) [30 (13.6%)]. Eighteen out of the 220 (8.1%) patients had more than one liver-related event as their first hepatic decompensation. Among the patients who had the first episode, 87 (39.5%) had a second episode [44 (50.5%) HE, 31 (35.6%) ascites, and 12 (13.7%) VH]. Eighteen out of 220 (8.1%) had a third episode [10 (55.5%) HE, 6 (33.3%) VH, and 2 (11.1%) ascites]. Seventy-three out of 220 (33.1%) died, and 31 (14%) received liver transplantation. The median time from the first episode to the second was 0.7 years and 1.3 years from the second episode to the third. The median survival time from the first episode to death or transplantation was 2.0 years. CONCLUSION: The most common first liver-related event in MASLD patients is ascites. The median survival from the first hepatic decompensation to either death or transplantation is 2 years.
OBJECTIVES: Multicenter studies reporting outcomes following tracheostomy in children with congenital heart disease are limited, particularly in patients with single ventricle physiology. We aimed to describe clinical characteristics and outcomes in a multicenter cohort of patients with single ventricle physiology who underwent tracheostomy before Fontan operation. DESIGN: Multicenter retrospective cohort study.SETTING: Twenty-one tertiary care pediatric institutions participating in the Collaborative Research from the Pediatric Cardiac Intensive Care Society. PATIENTS: We reviewed 99 children with single ventricle physiology who underwent tracheostomy before the Fontan operation at 21 institutions participating in Collaborative Research from the Pediatric Cardiac Intensive Care Society between January 2010 and December 2020, with follow-up through December 31, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Death occurred in 51 of 99 patients (52%). Cox proportional hazard analysis was performed to determine factors associated with death after tracheostomy. Results are presented as hazard ratio (HR) with 95% CIs. Nonrespiratory indication(s) for tracheostomy (HR, 2.21; 95% CI, 1.14-4.32) and number of weeks receiving mechanical ventilation before tracheostomy (HR, 1.06; 95% CI, 1.02-1.11) were independently associated with greater hazard of death. In contrast, diagnosis of tricuspid atresia or Ebstein's anomaly was associated with less hazard of death (HR, 0.16; 95% CI, 0.04-0.69). Favorable outcome, defined as survival to Fontan operation or decannulation while awaiting Fontan operation with viable cardiopulmonary physiology, occurred in 29 of 99 patients (29%). Median duration of mechanical ventilation before tracheostomy was shorter in patients who survived to favorable outcome (6.1 vs. 12.1 wk; p < 0.001), and only one of 16 patients with neurologic indications for tracheostomy and 0 of ten patients with cardiac indications for tracheostomy survived to favorable outcome. CONCLUSIONS: For children with single ventricle physiology who undergo tracheostomy, mortality risk is high and should be carefully considered when discussing tracheostomy as an option for these children. Favorable outcomes are possible, although thoughtful attention to patient selection and tracheostomy timing are likely necessary to achieve this goal.
Obesity and metabolic syndrome affect the majority of the US population. Patients with obesity are at increased risk of developing type 2 diabetes (T2DM), obstructive sleep apnea (OSA), and metabolic dysfunction-associated steatotic liver disease (MASLD), each of which carry the risk of further complications if left untreated and lead to adverse outcomes. The rising prevalence of obesity and its comorbidities has led to increased mortality, decreased quality of life, and rising healthcare expenditures. This phenomenon has resulted in the intensive investigation of exciting therapies for obesity over the past decade, including more treatments that are still in the pipeline. In our present report, we aim to solidify the relationships among obesity, T2DM, OSA, and MASLD through a comprehensive review of current research. We also provide an overview of the surgical and pharmacologic treatment classes that target these relationships, namely bariatric surgery, the glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon receptor agonists.
BACKGROUND: Acute kidney injury is a common postoperative complication of paediatric cardiac surgery associated with increased morbidity and mortality. The purpose of this study is to characterise associations between haemodynamic parameters, clinical parameters, and medical interventions, on acute kidney injury. METHODS: Nine patients with univentricular physiology undergoing the Norwood procedure from a single-centre tertiary care paediatric cardiac ICU were included (September 2022 to March 2023). Patients were monitored with the T3 software. Data were analysed using a Fisher exact test, Mann-Whitney-U test, LASSO-based machine learning techniques, and receiver operator curve analyses. RESULTS: Over 27,000 datapoints were included. Acute kidney injury occurred in 2 patients (22%) during this period. Net fluid balance and renal oxygen extraction were independently associated with acute kidney injury, while commonly used metrics of pressure (systolic, diastolic, or mean arterial blood pressure) were not. The resulting acute kidney injury risk score was (4.1 × fluid balance) + (1.9 × renal oxygen extraction). The risk score was significantly higher in acute kidney injury with a score of 32.9 compared to 7.9 (p < 0.01). Optimal cut-offs for fluid balance (7 mL/hr) and renal oxygen extraction (29%) were identified. Higher serum creatinine:baseline creatinine ratio was associated with a higher mean airway pressure, higher renal oxygen extraction, higher mean arterial blood pressure, higher vasoactive inotropic score, and fluid balance. CONCLUSION: Among patients with univentricular physiology undergoing the Norwood procedure, renal oxygen extraction and a higher net fluid balance are independently associated with increased risk of acute kidney injury. Renal perfusion pressure is not significantly associated with acute kidney injury.
BACKGROUND: There are limited data on the prevalence and treatment of at-risk metabolic dysfunction-associated steatohepatitis (MASH) among patients with type 2 diabetes (T2DM) in the United States. AIM: To estimate the prevalence of at-risk MASH in a prospectively recruited cohort of adults with T2DM using new nomenclature endorsed by multiple societies. METHODS: This prospective study enrolled adults aged ≥50 with T2DM from primary care and endocrinology clinics in southern California from 2016 to 2023. Metabolic dysfunction-associated steatotic liver disease (MASLD) was defined by an magnetic resonance imaging proton density fat fraction ≥5% and at least one metabolic risk factor without any other chronic liver disease or secondary cause for hepatic steatosis. RESULTS: We included 530 adult patients with T2DM. The mean (±SD) age and body mass index (BMI) were 64.4 (±8.1) years and 31.5 (±6.1) kg/m2, respectively. Among patients with T2DM, the prevalence of MASLD, at-risk MASH and cirrhosis was 69.6%, 13.6% and 6.8%, respectively. Among patients with co-existing T2DM and obesity, the prevalence of MASLD, at-risk MASH and cirrhosis was 77.8%, 15.9% and 9.0%, respectively, and was higher than in participants without obesity (p < 0.0001, 0.0543 and 0.0128, respectively). CONCLUSION: Among adults aged ≥50 years with T2DM, the prevalence of MASLD, at-risk MASH and cirrhosis is high, posing a significant risk for liver-related morbidity and mortality. Approximately 14% of patients with T2DM may be candidates for pharmacologic therapies specific to MASH-related fibrosis.
INTRODUCTION: This study investigates the applicability of the new MASLD nomenclature to the real-world TARGET-NASH US adult cohort. METHODS: The new MASLD/MASH nomenclature was applied to patients enrolled with pragmatic diagnoses of NAFL, NASH and NASH cirrhosis and concordance was determined between the definitions. RESULTS: 99% of TARGET-NASH participants met the new MASLD diagnostic criteria. 1484/1541 (96.3%, kappa 0.974) NAFL patients (MASL), 2195/2201 (99.7%, kappa 0.998) NASH patients (MASH), and 1999/2003 (99.8%, kappa 0.999) NASH cirrhosis patients met the new criteria. CONCLUSION: The new MASLD nomenclature is highly concordant with the prior TARGET-NASH pragmatic definitions.
This commentary discusses how clinicians and various stakeholders can utilize the recently published American Association for the Study of Liver Diseases nonalcoholic fatty liver disease (AASLD NAFLD) Practice Guidance in light of the change in the nomenclature to steatotic liver disease and its subcategories. The new terminologies explained in this commentary make it easier for the readers to interchangeably use metabolic dysfunction-associated steatotic liver disease (MASLD) in place of NAFLD and metabolic-dysfunction associated steatohepatitis (MASH) instead of nonalcoholic steatohepatitis (NASH), respectively, as they read the NAFLD Practice Guidance. The guidance document is relevant and can be utilized for the diagnosis, risk stratification, and management of patients with MASLD. This commentary serves as an accompanying article to the NAFLD Practice Guidance and helps it clinical application in the light of the new nomenclature.
Metabolic Diseases , Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/therapy
Importance: Aspirin may reduce severity of metabolic dysfunction-associated steatotic liver disease (MASLD) and lower the incidence of end-stage liver disease and hepatocellular carcinoma, in patients with MASLD. However, the effect of aspirin on MASLD is unknown. Objective: To test whether low-dose aspirin reduces liver fat content, compared with placebo, in adults with MASLD. Design, Setting, and Participants: This 6-month, phase 2, randomized, double-blind, placebo-controlled clinical trial was conducted at a single hospital in Boston, Massachusetts. Participants were aged 18 to 70 years with established MASLD without cirrhosis. Enrollment occurred between August 20, 2019, and July 19, 2022, with final follow-up on February 23, 2023. Interventions: Participants were randomized (1:1) to receive either once-daily aspirin, 81 mg (n = 40) or identical placebo pills (n = 40) for 6 months. Main Outcomes and Measures: The primary end point was mean absolute change in hepatic fat content, measured by proton magnetic resonance spectroscopy (MRS) at 6-month follow-up. The 4 key secondary outcomes included mean percentage change in hepatic fat content by MRS, the proportion achieving at least 30% reduction in hepatic fat, and the mean absolute and relative reductions in hepatic fat content, measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF). Analyses adjusted for the baseline value of the corresponding outcome. Minimal clinically important differences for study outcomes were not prespecified. Results: Among 80 randomized participants (mean age, 48 years; 44 [55%] women; mean hepatic fat content, 35% [indicating moderate steatosis]), 71 (89%) completed 6-month follow-up. The mean absolute change in hepatic fat content by MRS was -6.6% with aspirin vs 3.6% with placebo (difference, -10.2% [95% CI, -27.7% to -2.6%]; P = .009). Compared with placebo, aspirin treatment significantly reduced relative hepatic fat content (-8.8 vs 30.0 percentage points; mean difference, -38.8 percentage points [95% CI, -66.7 to -10.8]; P = .007), increased the proportion of patients with 30% or greater relative reduction in hepatic fat (42.5% vs 12.5%; mean difference, 30.0% [95% CI, 11.6% to 48.4%]; P = .006), reduced absolute hepatic fat content by MRI-PDFF (-2.7% vs 0.9%; mean difference, -3.7% [95% CI, -6.1% to -1.2%]; P = .004]), and reduced relative hepatic fat content by MRI-PDFF (-11.7 vs 15.7 percentage points; mean difference, -27.3 percentage points [95% CI, -45.2 to -9.4]; P = .003). Thirteen participants (32.5%) in each group experienced an adverse event, most commonly upper respiratory tract infections (10.0% in each group) or arthralgias (5.0% for aspirin vs 7.5% for placebo). One participant randomized to aspirin (2.5%) experienced drug-related heartburn. Conclusions and Relevance: In this preliminary randomized clinical trial of patients with MASLD, 6 months of daily low-dose aspirin significantly reduced hepatic fat quantity compared with placebo. Further study in a larger sample size is necessary to confirm these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT04031729.
Anti-Inflammatory Agents , Aspirin , Fatty Liver , Liver , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Anti-Inflammatory Agents/adverse effects , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Aspirin/adverse effects , Aspirin/pharmacology , Aspirin/therapeutic use , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/prevention & control , Double-Blind Method , End Stage Liver Disease/etiology , End Stage Liver Disease/prevention & control , Fatty Liver/complications , Fatty Liver/diagnostic imaging , Fatty Liver/drug therapy , Fatty Liver/metabolism , Follow-Up Studies , Liver/diagnostic imaging , Liver/drug effects , Liver Cirrhosis , Liver Neoplasms/etiology , Liver Neoplasms/prevention & control , Proton Magnetic Resonance Spectroscopy
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.
Postoperative atrioventricular block may occur after pediatric cardiac surgery. A small proportion of those who develop atrioventricular block will require pacemaker placement. The primary aim of this study was to determine factors associated with postoperative atrioventricular block. Secondary aims included determining factors associated with pacemaker placement in those with atrioventricular block. Data from the PHIS data were utilized to identify patients under 18 years of age who underwent cardiac surgery. Those who did and did not develop atrioventricular block. Univariable analyses and regression analyses were conducted to determine factors associated with postoperative atrioventricular block. Similar analyses were conducted to determine factors associated with pacemaker placement in those with atrioventricular block. A total of 43,716 admissions were identified. Of these, 2093 (5%) developed atrioventricular block and 480 (1% of total admissions) underwent pacemaker placement. Approximately 70% of those with atrioventricular block received steroids but this was not associated with a decrease in pacemaker placement. Risk factors (congenital malformations of the heart, comorbidities, medications) associated with increased risk of atrioventricular block and pacemaker placement were identified. Postoperative atrioventricular block occurred in 5% of pediatric admissions for cardiac surgery. Of these admissions with postoperative atrioventricular block, 23% required pacemaker placement. Isoproterenol and steroids were not associated with a reduction in the likelihood of pacemaker placement.
Atrioventricular Block , Cardiac Surgical Procedures , Heart Defects, Congenital , Pacemaker, Artificial , Child , Humans , Adolescent , Atrioventricular Block/epidemiology , Atrioventricular Block/etiology , Atrioventricular Block/therapy , Pacemaker, Artificial/adverse effects , Cardiac Surgical Procedures/adverse effects , Heart Defects, Congenital/complications , Postoperative Complications/etiology , Steroids
BACKGROUND: The prevalence of at-risk metabolic dysfunction-associated steatohepatitis (at-risk MASH) has not been systematically assessed. AIM: To delineate the prevalence of at-risk MASH in a large population-based cohort. METHODS: We conducted a cross-sectional analysis of 40,189 patients in the UK Biobank who underwent liver MRI. Hepatic steatosis was determined by proton density fat fraction (PDFF) ≥5%. Based on AASLD criteria, participants were classified as alcohol-associated steatotic liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), combined metabolic alcoholic liver disease (MetALD) and at-risk MASH. RESULTS: Among 40,189 patients, 10,886 (27.0%) had a PDFF ≥5%, indicating SLD. Among patients with SLD, 1% had ALD, 89.0% had MASLD, 7.9% had MetALD and 2.2% had at-risk MASH. The at-risk MASH group, which included 0.6% of the general population, had the highest mean liver fat on MRI and the highest BMI. Serum biomarkers highlighted increased inflammation and metabolic changes in at-risk MASH. The prevalence of MASLD was significantly higher among men with a BMI ≥30 kg/m2. Non-obese women showed only a 12% risk of MASLD. Conversely, MetALD had similar prevalence in obese men and women and was absent in non-obese women. CONCLUSIONS: MASLD is prevalent among patients with elevated PDFF on MRI. There are different sex- and BMI-specific prevalence of different steatotic liver disorders. At-risk MASH demonstrates the most severe metabolic and inflammatory profiles. This study provides novel estimates for the at-risk MASH population that will be eligible for treatment with pharmacologic therapy when approved by regulatory authorities.
Fatty Liver, Alcoholic , Magnetic Resonance Imaging , Humans , Male , Female , Middle Aged , Cross-Sectional Studies , Prevalence , Aged , United Kingdom/epidemiology , Fatty Liver, Alcoholic/epidemiology , Fatty Liver, Alcoholic/complications , Adult , Risk Factors , Fatty Liver/epidemiology , Liver/metabolism , Liver/pathology , Liver/diagnostic imaging
In June 2023, under the patronage of the American Association for Study of Liver Disease, the European Association for Study of the Liver, and the Asociación Latinoamericana para el Estudio del Hígado with the involvement of 236 participants from around the world, a new nomenclature and definition for nonalcoholic fatty liver disease (NAFLD) has been proposed. Metabolic dysfunction-associated steatotic liver disease (MASLD) was defined as presence of hepatic steatosis and at least one of the cardiometabolic risk factors with alcohol intake less than 140 g/wk for women and 210 g/wk for men and no other causes of steatosis. A new entity called combined metabolic dysfunction- and alcohol-associated liver disease (MetALD) was created outside of pure MASLD for patients with metabolic dysfunction and alcohol intake greater than that allowed for MASLD (i.e., 140-350 g/wk for women and 210-420 g/wk for men). Recent studies have confirmed a 95% overlap between NAFLD and the new MASLD diagnostic criteria. Natural history, biomarkers, and thresholds of alcohol intake in MetALD group remains to be studied and validated.
Liver Diseases, Alcoholic , Metabolic Diseases , Non-alcoholic Fatty Liver Disease , Male , Humans , Female , Non-alcoholic Fatty Liver Disease/complications , Alcohol Drinking/adverse effects
