Incidence of liver cancer in young adults according to the Global Burden of Disease database 2019.

BACKGROUND AND AIMS: The worldwide burden of cancer is increasing in younger populations. However, the epidemiology of primary liver cancer remains understudied in young adults compared to other cancer forms. APPROACH AND RESULTS: This study analyzed data from the Global Burden of Disease study between 2010 and 2019 to assess the age-standardized incidence, mortality, and disability-adjusted life years associated with primary liver cancer in the young (15-49 y), stratified by region, nation, sociodemographic index, and sex. The study found a global estimate of 78,299 primary liver cancer cases, 60,602 deaths, and 2.90 million disability-adjusted life years in the young population. The Western Pacific region exhibited the highest burden in 2019, showing the most significant increase compared to other regions between 2010 and 2019. More than half of the countries worldwide have undergone an increase in primary liver cancer incidence rates in young adults. Around 12.51% of deaths due to primary liver cancer occur in young individuals. Throughout the study period, there was a significant decline in primary liver cancer mortality due to most etiologies, except for metabolic dysfunction-associated steatotic liver disease-attributable primary liver cancer (annual percentage change + 0.87%, 95% CI: 0.70%-1.05%) and alcohol-attributable primary liver cancer (annual percentage change + 0.21%, 95% CI: 0.01%-0.42%). The limitations of the Global Burden of Disease database include reliance on the quality of primary data and possible underestimation of alcohol consumption. CONCLUSIONS: Over the past decade, there has been a marked increase in the burden of primary liver cancer, especially that originating from steatotic liver disease. This trend calls for the development of urgent and comprehensive strategies to mitigate this rising burden globally.

Comparative efficacy of pharmacologic therapies for MASH in reducing liver fat content: Systematic review and network meta-analysis.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatohepatitis (MASH) is a leading cause of liver disease. Dynamic changes in MRI proton-density-fat fraction (PDFF) are associated with MASH resolution. We aimed to determine the relative efficacy of therapeutic agents for reducing hepatic fat, assessed by MRI-PDFF. APPROACH AND RESULTS: In this systematic review and network meta-analysis, we searched MEDLINE and Embase from inception until December 26, 2023, for published randomized controlled trials comparing pharmacological interventions in patients with MASH that assessed changes in MRI-PDFF. The primary outcome was the absolute change in MRI-PDFF. The secondary outcome was a ≥30% decline in MRI-PDFF. A surface under-the-curve cumulative ranking probabilities (SUCRA) analysis was performed. Of 1550 records, a total of 39 randomized controlled trials (3311 participants) met the inclusion criteria. For MRI-PDFF decline at 24 weeks, aldafermin (SUCRA: 83.65), pegozafermin (SUCRA: 83.46), and pioglitazone (SUCRA: 71.67) were ranked the most effective interventions. At 24 weeks, efinopegdutide (SUCRA: 67.02), semaglutide + firsocostat (SUCRA: 62.43), and pegbelfermin (SUCRA: 61.68) were ranked the most effective interventions for achieving a ≥30% decline in MRI-PDFF. CONCLUSIONS: This study provides an updated, relative rank-order efficacy of therapies for MASH in reducing hepatic fat. These data may help inform the design and sample size calculation of future clinical trials and assist in the selection of combination therapy.

Vibration-Controlled Transient Elastography-Based Parameters Predict Clinical Outcomes in Liver Transplant Recipients.

BACKGROUND AND AIMS: Vibration-controlled transient elastography (VCTE) is used in clinical practice to risk-stratify liver transplant (LT) recipients; however, there are currently little data demonstrating the relationship between VCTE and clinical outcomes. METHODS: A total of 362 adult LT recipients with successful VCTE examination between 2015 and 2022 were included. Presence of advanced fibrosis was defined as liver stiffness measurement (LSM) ≥10.5 kPa and hepatic steatosis as controlled attenuation parameter (CAP) ≥270 dB/m. The outcomes of interest included all-cause mortality, myocardial infarction (MI), and graft cirrhosis using cumulative incidence analysis that accounted for the competing risks of these outcomes. RESULTS: The LSM was elevated in 64 (18%) and CAP in 163 (45%) LT recipients. The baseline LSM values were similar in patients with elevated vs normal CAP values. After a median follow-up of 65 (interquartile range, 20-140) months from LT to baseline VCTE, 66 (18%) patients died, 12 (3%) developed graft cirrhosis, and 18 (5%) experienced an MI. Baseline high LSM was independently associated with all-cause mortality (hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.11-3.50; P = .02) and new onset cirrhosis (HR, 6.74; 95% CI, 2.08-21.79; P < .01). A higher CAP value was significantly and independently associated with increased risk of experiencing a MI over study follow-up (HR, 4.14; 95% CI, 1.29-13.27; P = .017). CONCLUSIONS: The VCTE-based parameters are associated with clinical outcomes and offer the potential to be incorporated into clinical risk-stratification strategies to improve outcomes among LT recipients.

Global Prevalence, Clinical Characteristics, Surveillance, Treatment Allocation, and Outcomes of Alcohol-Associated Hepatocellular Carcinoma.

BACKGROUND: Although the burden of alcohol-associated hepatocellular carcinoma (HCC) is increasing with rising alcohol consumption, clinical presentation and outcomes of alcohol-associated HCC have not been systematically assessed. We aimed to determine the prevalence, clinical characteristics, surveillance rates, treatment allocation, and outcomes of alcohol-associated HCC. METHODS: Medline and Embase were searched from inception to January 2023. Proportional data were analyzed using a generalized linear mixed model. The odds ratio (OR) or mean difference comparing alcohol-associated HCC and other causes was obtained with pairwise meta-analysis. Survival outcomes were evaluated using a pooled analysis of hazard ratios. RESULTS: Of 4824 records identified, 55 articles (86,345 patients) were included. Overall, 30.4% (95% confidence interval [CI], 24.0%-37.7%) of HCC was alcohol associated, with the highest proportion in Europe and the lowest in the Americas. People with alcohol-associated HCC were more likely male but were similar in age and comorbidities compared with other causes. A total of 20.8% (95% CI, 11.4%-34.9%) of people with alcohol-associated HCC underwent surveillance compared with 35.0%, 31.6%, and 21.4% in hepatitis B virus, hepatitis C virus, and metabolic dysfunction-associated HCC, respectively (all P < .05). Alcohol-associated HCC had a lower likelihood of Barcelona Clínic Liver Cancer C stage (0/A) (OR, 0.7; 95% CI, 0.6-0.9; P = .018) and curative therapy (24.5% vs 33.9%; OR, 0.7; 95% CI, 0.5-0.9; P = .003), and higher mortality (HR, 1.3; 95% CI, 1.1-1.5; P = .012) when compared with other causes. CONCLUSIONS: Alcohol-associated HCC is associated with lower surveillance rates, more advanced BCLC stage, lower likelihood of receiving curative therapy, and poorer survival. These data call for measures to reduce heavy alcohol consumption and improve strategies for effective HCC surveillance in high-risk individuals.

The Burden of Overweight and Obesity-Associated Gastrointestinal Cancers in Low and Lower-Middle-Income Countries: A Global Burden of Disease 2019 Analysis.

INTRODUCTION: Obesity is associated with cancer, including gastrointestinal (GI). Data from low (LICs) and lower-middle-income countries (MICs) are limited. METHODS: We utilized data from the Global Burden of Disease Study 2019 to determine the mortality from GI cancer risk of high body mass index (BMI) in these countries. RESULTS: Mortality rates of GI cancers from high BMI increased in LICs and lower MICs, while burdens decreased or remained stable in high and middle-income countries. DISCUSSION: The GI cancer-related burden from high BMI increased in LICs and lower MICs, necessitating a concerted effort to tackle the obesity pandemic.

From Shadows to Spotlight: Exploring the Escalating Burden of Alcohol-Associated Liver Disease and Alcohol Use Disorder in Young Women.

INTRODUCTION: The burden of alcohol-related complications is considerable, particularly alcohol-associated liver disease and alcohol use disorder (AUD). However, there are deficiencies in comprehensive epidemiological research focusing on these issues, especially among young women who display higher susceptibility to such complications compared with their male counterparts. We thus aimed to determine the global burden of these conditions in this vulnerable group. METHODS: Leveraging data from the Global Burden of Disease Study 2019, we analyzed the prevalence, mortality, and disability-adjusted life years of alcohol-associated cirrhosis (AC), liver cancer from alcohol, and AUD in young women. The findings were categorized by region, nation, and sociodemographic index. RESULTS: The highest age-standardized prevalence rates were observed in AUD (895.96 [95% uncertainty interval (UI) 722.6-1,103.58]), followed by AC (65.33 [95% UI 48.37-86.49]) and liver cancer from alcohol (0.13 [95% UI 0.09-0.19]) per 100,000 people. The highest age-standardized mortality rates were observed in AC (0.75 [95% UI 0.55-0.97]), followed by AUD (0.48 [95% UI 0.43-0.53]) and liver cancer from alcohol (0.06 [95% UI 0.04-0.09]). The highest burdens of AC and AUD were observed in Central Europe, whereas the high-income Asia Pacific had the highest burden of liver cancer from alcohol. DISCUSSION: Throughout the past decade, the trend of AUD varied among regions while the impact of alcohol-associated liver disease has increased, requiring urgent public health strategy to mitigate these complications, particularly in female patients in Europe and the Asia-Pacific region.

Disparities among ethnic groups in mortality and outcomes among adults with MASLD: A multicenter study.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease and 10%-20% occurs in lean individuals. There is little data in the literature regarding outcomes in an ethnically-diverse patient populations with MASLD. Thus, we aim to investigate the natural history and ethnic disparities of MASLD patients in a diverse population, and stratified by body mass index categories. METHODS: We conducted a retrospective multicenter study on patients with MASLD at the Banner Health System from 2012 to 2022. Main outcomes included mortality and incidence of cirrhosis, cardiovascular disease, diabetes mellitus (DM), liver-related events (LREs), and cancer. We used competing risk and Cox proportional hazard regression analysis for outcome modelling. RESULTS: A total of 51 452 (cross-sectional cohort) and 37 027 (longitudinal cohort) patients were identified with 9.6% lean. The cohort was 63.33% European ancestry, 27.96% Hispanic ancestry, 3.45% African ancestry, and 2.31% Native American/Alaskan ancestry. Median follow-up was 45.8 months. After adjusting for confounders, compared to European individuals, Hispanic and Native American/Alaskan patients had higher prevalence of cirrhosis and DM, and individuals of Hispanic, African, and Native American/Alaskan ancestry had higher mortality and incidence of LREs and DM. Lean patients had higher mortality and incidence of LREs compared with non-lean patients. CONCLUSION: Native American/Alaskan, Hispanic, and African patients had higher mortality and incidence of LREs and DM compared with European patients. Further studies to explore the underlying disparities and intervention to prevent LREs in lean patients, particularly several ethnic groups, may improve clinical outcomes.

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.

Development of Clinical Algorithm Utilizing Vibration-Controlled Transient Elastography to Detect Advanced Hepatic Fibrosis in Liver Transplant Recipients.

INTRODUCTION: Vibration-controlled transient elastography (VCTE) based liver stiffness measurement (LSM) is an excellent 'rule-out' test for advanced hepatic fibrosis in liver transplant (LT) recipients, however, its ability to 'rule-in' the disease is suboptimal. The study aimed to improve diagnostic performance of LSM in LT recipients. METHODS: Adult LT recipients with a liver biopsy and VCTE were included (N = 150). Sequential covering analysis was performed to create rules to identify patients at low or high risk for advanced fibrosis (stage 3-4). RESULTS: Advanced hepatic fibrosis was excluded in patients with either LSM < 7.45 kPa (n = 72) or 7.45 ≤ LSM < 12.1 kPa and time from LT < 5.6 years (n = 25). Conversely, likelihood of advanced fibrosis was 95% if patients had LSM > 14.1 and controlled attenuation parameter > 279 dB/m (n = 21). Thus, 118 (79%) were correctly identified and 32 (21%) would have required a biopsy to establish the diagnosis. Compared to previously established LSM based cutoff values of 10.5 kPa (Youden index) and 13.3 kPa (maximized specificity), the false positive rates of sequential covering analysis was 1% compared to 16.5% with LSM ≥ 10.5 kPa and 8.3% with LSM ≥ 13.3 kPa. The true positive rates were comparable at 87% for sequential covering analysis, 93% for LSM ≥ 10.5 kPa and 83% for LSM ≥ 13.3 kPa. CONCLUSION: The proposed clinical sequential covering analysis allows for better risk stratification when evaluating for advanced fibrosis in LT recipients compared to LSM alone. Additional efforts are necessary to further reduce the number of patients with indeterminate results in whom a liver biopsy may be required.

Sex and Race-Ethnic Disparities in Metabolic Dysfunction-Associated Steatotic Liver Disease: An Analysis of 40,166 Individuals.

BACKGROUND: To overcome the limitations of the term "non-alcoholic fatty liver disease" (NAFLD), the term metabolic-associated steatotic liver disease (MASLD) was introduced. While epidemiologic studies have been conducted on MASLD, there is limited evidence on its associated sex and ethnic variations. AIMS: This study assesses the differences across sex and race-ethnicity on the prevalence, associated risk factors and adverse outcomes in individuals with MASLD. METHODS: Data retrieved from the National Health and Nutrition Examination Survey between 1999 to 2018 was analyzed. Prevalence, clinical characteristics, and outcomes were evaluated according to sex and race-ethnicity. Adverse outcomes and mortality events were analyzed using multivariate analyses. RESULTS: Of 40,166 individuals included, 37.63% had MASLD. There was a significant increase in MASLD prevalence from 1999 to 2018 among Mexican Americans (Annual Percentage Change [APC] + 1.889%, p < 0.001), other Hispanics (APC + 1.661%, p = 0.013), NH Whites (APC + 1.084%, p = 0.018), NH Blacks (APC + 1.108%, p = 0.007), and females (APC + 0.879%, p = 0.030), but not males. Females with MASLD were at lower risk of all-cause (HR: 0.766, 95%CI 0.711 to 0.825, p < 0.001), cardiovascular disease-related (CVD) (SHR: 0.802, 95% CI 0.698 to 0.922, p = 0.002) and cancer-related mortality (SHR: 0.760, 95% CI 0.662 to 0.873, p < 0.001). Significantly, NH Blacks have the highest risk of all-cause and CVD-related mortality followed by NH Whites then Mexican Americans. CONCLUSION: There has been an increase in prevalence in most race-ethnicities over time. While the change in definition shows no significant differences in previous associations found in NAFLD, the increased mortality in NH Whites relative to Mexican Americans remains to be explored.

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.

Type 2 diabetes mellitus and cardiometabolic outcomes in metabolic dysfunction-associated steatotic liver disease population.

The metabolic syndrome, characterized by type 2 diabetes mellitus (T2DM), hypertension, hyperlipidemia, and obesity, collectively increases the risk of cardiovascular diseases. Nonalcoholic fatty liver disease (NAFLD) is a prominent manifestation, affecting over a third of the global population with a concerning annual increase in prevalence. Nearly 70 % of overweight individuals have NAFLD, and NAFLD-related deaths are predicted to rise, especially among young adults. The association of T2DM and NAFLD has led to the proposal of "metabolic dysfunction-associated steatotic liver disease" (MASLD) terminology, encompassing individuals with T2DM, overweight/obesity, hypertension, hypertriglyceridemia, or low HDL-cholesterol. Patients with MASLD will likely have double the risk of developing T2DM, and the combination of insulin resistance, overweight/obesity, and MASLD significantly elevates the risk of T2DM. Cardiovascular diseases remain the leading cause of mortality in the MASLD and T2DM population, with MASLD directly associated with coronary artery disease, compounded by coexisting insulin resistance and T2DM. Urgency lies in early detection of subclinical cardiovascular diseases among patients with T2DM and MASLD. Novel strategies targeting multiple pathways offer hope for effectively improving cardiometabolic health. Understanding and addressing the intertwined factors contributing to these disorders can pave the way towards better management and prevention of cardiometabolic complications.

NAFLD and NAFLD-related HCC in Asia: Burden and Surveillance.

Non-alcoholic fatty liver disease (NAFLD) is rapidly emerging as a leading etiology of chronic liver disease (CLD) in Asia. The increasing incidence of NAFLD is projected to drive a surge in NAFLD-related hepatocellular carcinoma (HCC). A notable characteristic of NAFLD-HCC is its capacity for development in individuals without cirrhosis in more than a third of patients. Most practice guidelines recommend biannual ultrasound screening for patients with cirrhosis. In cases of severe limitations to ultrasound visualisation, cross-sectional abdominal imaging may be warranted. Improved strategies for HCC risk stratification are required for people with NAFLD but without cirrhosis. In this Review, we discuss the evolving trends of NAFLD and HCC in Asia, and implications for surveillance.

Global and regional burden of alcohol-associated liver disease and alcohol use disorder in the elderly.

Background & Aims: Alcohol-associated liver diseases (ALDs) and alcohol use disorder (AUD) pose a global health risk. AUD is underrecognized in the elderly, and the burden of AUD complications, including ALD, may increase with aging populations and rising alcohol intake. However, there is a lack of epidemiological evidence on AUD and ALD in the elderly. Methods: Using the Global Burden of Disease Study 2019, we analyzed the prevalence, mortality, disability-adjusted life years (DALYs), age-standardized rates (ASRs), and temporal change from 2000 to 2019 of ALD and AUD in the overall population and the elderly (65-89 years). The findings were categorized by sex, region, nation, and sociodemographic index. Results: The prevalence rates of ALD in the elderly were higher than those in adolescents and young adults, whereas AUD levels were lower than those in adolescents and young adults. In 2019, there were 9.39 million cases (8.69% of cases in the overall population) of AUD, 3.23 million cases (21.8% of cases in the overall population) of alcohol-associated cirrhosis, and 68,468 cases (51.27% of cases in the overall population) of liver cancer from alcohol among the elderly. ASRs of the prevalence of ALD and AUD in the elderly increased in most regions; on the contrary, ASRs of death and DALYs decreased in most regions. Nevertheless, ASRs of death and DALYs from liver cancer from alcohol increased in many areas. Conclusions: Our findings highlighted the increased prevalence of ALD in the elderly, with a burden of AUD comparable with that in the overall population. Public health strategies on ALD and AUD targeting the elderly are urgently needed. Impact and implications: The burden of alcohol-associated liver disease (ALD) and alcohol use disorder (AUD) is increasing. Advances in healthcare and education have resulted in a remarkable spike in life expectancy and a consequential population aging. Nevertheless, little is known about the epidemiology of ALD and AUD in the elderly. Our study indicates the increasing burden of ALD and AUD in the elderly population, necessitating early detection, intervention, and tailored care to the unique needs and complexities faced by older individuals grappling with these conditions.

The Global Burden of Early-Onset Biliary Tract Cancer: Insight From the Global Burden of Disease Study 2019.

Backgrounds/objectives: The escalating incidence of early-onset gastrointestinal cancers is becoming a primary global health concern. Biliary tract cancer (BTC) has been relatively understudied in this regard. We conducted an epidemiological study regarding the burden of this condition. Methods: We utilized data from the Global Burden of Disease Study 2019 to investigate the temporal trends in early-onset BTC (EOBTC), encompassing the estimation of frequencies and age-standardized rates (ASRs) of EOBTC incidence, mortality, and disability-adjusted life-years (DALYs), from 2010 to 2019. Results: EOBTC constituted nearly 7%of all BTC cases worldwide. The incidence rates of EOBTC decreased significantly in most regions, except in the Eastern Mediterranean (annual percentage change +1.04 %), where the incidence is rising. Stratified by the sociodemographic index (SDI), countries with low middle SDI (annual percentage change +0.5 %) show increasing incidence of EOBTC. The ASR of death and DALYs decreased in most regions. The ASR of EOBTC-related death and disability attributable to high body mass index increased in most regions, with the highest increase in Southeast Asia and low, middle SDI strata. Conclusions: There was a reduction in the burden of EOBTC globally, except for Eastern Mediterranean countries and low-middle SDI countries.

Gut-liver axis: Potential mechanisms of action of food-derived extracellular vesicles.

Food-derived extracellular vesicles (FEVs) are nanoscale membrane vesicles obtained from dietary materials such as breast milk, plants and probiotics. Distinct from other EVs, FEVs can survive the harsh degrading conditions in the gastrointestinal tract and reach the intestines. This unique feature allows FEVs to be promising prebiotics in health and oral nanomedicine for gut disorders, such as inflammatory bowel disease. Interestingly, therapeutic effects of FEVs have recently also been observed in non-gastrointestinal diseases. However, the mechanisms remain unclear or even mysterious. It is speculated that orally administered FEVs could enter the bloodstream, reach remote organs, and thus exert therapeutic effects therein. However, emerging evidence suggests that the amount of FEVs reaching organs beyond the gastrointestinal tract is marginal and may be insufficient to account for the significant therapeutic effects achieved regarding diseases involving remote organs such as the liver. Thus, we herein propose that FEVs primarily act locally in the intestine by modulating intestinal microenvironments such as barrier integrity and microbiota, thereby eliciting therapeutic impact remotely on the liver in non-gastrointestinal diseases via the gut-liver axis. Likewise, drugs delivered to the gastrointestinal system through FEVs may act via the gut-liver axis. As the liver is the main metabolic hub, the intestinal microenvironment may be implicated in other metabolic diseases. In fact, many patients with non-alcoholic fatty liver disease, obesity, diabetes and cardiovascular disease suffer from a leaky gut and dysbiosis. In this review, we provide an overview of the recent progress in FEVs and discuss their biomedical applications as therapeutic agents and drug delivery systems, highlighting the pivotal role of the gut-liver axis in the mechanisms of action of FEVs for the treatment of gut disorders and metabolic diseases.

Metabolic Syndrome and Metabolic Dysfunction-Associated Steatotic Liver Disease in Premenopausal Women: Global Trends and Projections to 2040.

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.

Meta-analysis: Prevalence and impact of alcohol abstinence in alcohol-associated cirrhosis.

BACKGROUND: Although alcohol abstinence may be an effective intervention for alcohol-associated cirrhosis, its association with prognosis has not been systematically assessed or quantified. AIMS: To determine the prevalence of alcohol abstinence, factors associated with alcohol abstinence and the impact of abstinence on morbidity and overall survival in people with alcohol-associated cirrhosis. METHODS: We searched Medline and Embase from inception to 15 April 2023 for prospective and retrospective cohort studies describing alcohol abstinence in people with known alcohol-associated cirrhosis. Meta-analysis of proportions for pooled estimates was performed. The method of inverse variance, employing a random-effects model, was used to pool the hazard ratio (HR) comparing outcomes of abstinent against non-abstinent individuals with alcohol-associated cirrhosis. RESULTS: We included 19 studies involving 18,833 people with alcohol-associated cirrhosis. The prevalence of alcohol abstinence was 53.8% (CI: 44.6%-62.7%). Over a mean follow-up duration of 48.6 months, individuals who continued to consume alcohol had significantly lower overall survival compared to those who were abstinent (HR: 0.611, 95% CI: 0.506-0.738). These findings remained consistent in sensitivity/subgroup analysis for the presence of decompensation, study design and studies that assessed abstinence throughout follow-up. Alcohol abstinence was associated with a significantly lower risk of hepatic decompensation (HR: 0.612, 95% CI: 0.473-0.792). CONCLUSIONS: Alcohol abstinence is associated with substantial improvement in overall survival in alcohol-associated cirrhosis. However, only half of the individuals with known alcohol-associated cirrhosis are abstinent.

Upper limit of normal ALT levels in health and metabolic diseases: Pooled analysis of 423,355 individuals with bootstrap modelling.

INTRODUCTION: Given the global rise in obesity-related metabolic diseases, the upper limit of normal (ULN) alanine aminotransferase (ALT) in individuals with and without metabolic diseases may have changed. We performed a meta-analysis combined with bootstrap modelling to estimate the ALT ULN levels for individuals with and without metabolic diseases. METHODS AND RESULTS: Two separate searches of the PubMed, Embase and Cochrane databases were performed, one to identify healthy individuals which yielded 12 articles (349,367 individuals); another to include those with potential metabolic diseases but without known liver disease which yielded 35 articles (232,388 individuals). We estimated the mean ALT using a random-effects mixed model and the ULN level (95th-percentile value) via a bootstrap model with 10,000 resamples. In individuals without metabolic diseases and known liver disease, the ALT ULN levels were 32 U/L overall; 36 U/L in males and 28 U/L in females. In analyses that included individuals with metabolic diseases, the ALT ULN levels were 40 U/L among the overweight/obese (29 U/L if normal weight) and 36 U/L among those with type 2 diabetes mellitus (T2DM) (33 U/L if no T2DM). On meta-regression of study-level factors, body mass index (coefficient 1.49, 95% CI 0.11-2.86, p = 0.03), high-density lipoprotein (coefficient -0.47, 95% CI -0.85-(-0.08), p = 0.02) and triglycerides (coefficient 0.19, 95% CI 0.12-0.25, p < 0.0001) correlated with ALT. CONCLUSION: We provide expected ranges of ALT ULN levels for individuals without known liver disease without metabolic diseases and those with or without T2DM and/or are normal weight or overweight/obese. These data may have implications for clinical care and screening.

Socio-economic association of alcohol use disorder and cardiovascular and alcohol-associated liver disease from 2010 to 2019.

BACKGROUNDS AND AIMS: Alcohol use leads to disabilities and deaths worldwide. It not only harms the liver but also causes alcohol use disorder (AUD) and heart disease. Additionally, alcohol consumption contributes to health disparities among different socio-economic groups. METHODS: We estimated global and regional trends in the burden of AUD, liver disease, and cardiovascular disease from alcohol using the methodology of the Global Burden of Disease study. RESULTS: In 2019, the highest disability-adjusted life years rate per 100,000 population was due to AUD (207.31 [95% Uncertainty interval (UI) 163.71-261.66]), followed by alcohol-associated liver disease (ALD) (133.31 [95% UI 112.68-156.17]). The prevalence rate decreased for AUD (APC [annual percentage change] -0.38%) and alcohol-induced cardiomyopathy (APC -1.85%) but increased for ALD (APC 0.44%) and liver cancer (APC 0.53%). Although the mortality rate for liver cancer from alcohol increased (APC 0.30%), mortality rates from other diseases decreased. Between 2010 and 2019, the burden of alcohol-associated complications increased in countries with low and low-middle sociodemographic index (SDI), contributing more significantly to the global burden. CONCLUSION: The global burden of AUD, liver, and cardiovascular disease has been high and increasing over the past decade, particularly for liver complications. Lower SDI countries are contributing more to this global burden. There is a pressing need for effective strategies to address this escalating burden.