Estimated pulse wave velocity in metabolic dysfunction-associated steatotic liver disease and all-cause/cause-specific mortality.

BACKGROUND AND AIM: Several reports show a significant association between metabolic dysfunction-associated steatotic liver disease (MASLD) and arterial stiffness (estimated pulse wave velocity [ePWV]) as a surrogate marker of vascular age. We investigate whether ePWV as arterial stiffness in MASLD is associated with all-cause/cause-specific mortality. METHODS: This cohort study was based on the third National Health and Nutrition Examination Survey (NHANES, 1988-1994) and NHANES 2007-2014 and linked mortality datasets through 2019. Cox regression models assessed the association between ePWV categorized by quartile and all-cause/cause-specific mortality among individuals with MASLD. RESULTS: During the follow-up of a median of 26.3 years (interquartile range: 19.9-27.9), higher levels of ePWV among individuals with MASLD were associated with increased all-cause mortality, which remained significant after adjusting for demographic, lifestyle, clinical, and metabolic risk factors. Furthermore, higher ePWV in MASLD was associated with higher cardiovascular mortality. There was a 44% (hazard ratio: 1.44, 95% confidence interval: 1.32-1.58) increase in all-cause mortality and a 53% (hazard ratio: 1.53, 95% confidence interval: 1.32-1.77) increase in cardiovascular mortality for every 1 m/s increase in ePWV in MASLD. However, there was no significant association between ePWV and cancer-related mortality. Sensitivity analyses using the NHANES 2007-2014 dataset showed results identical to the original analysis. CONCLUSION: Higher ePWV in MASLD was associated with a higher risk of all-cause and cardiovascular mortality beyond traditional cardiovascular risk factors. Screening for ePWV in individuals with MASLD may be an effective and beneficial approach to reducing all-cause and cardiovascular mortality.

Steatotic liver disease-associated all-cause/cause-specific mortality in the United States.

BACKGROUND: Recently, a panel of multi-society experts proposed steatotic liver disease (SLD) as an alternative terminology for metabolic dysfunction-associated fatty liver disease (MAFLD) or nonalcoholic fatty liver disease (NAFLD). AIMS: We compared the impact of SLD, subtype of SLD, MAFLD and NAFLD on all-cause and cause-specific mortality. METHODS: A total of 7811 individuals in the third National Health and Nutrition Examination Survey and linked mortality through 2019 were analysed. SLD was defined based on ultrasonographic hepatic steatosis. SLD, subtype of SLD and MAFLD were defined using the proposed definitions. The Cox proportional hazard model assessed all-cause/cause-specific mortality. RESULTS: During a median follow-up of 27.1 years, individuals with SLD and MAFLD experienced approximately 13%-23% higher risk of all-cause mortality (hazard ratio [HR]: 1.15, 95% confidence interval [CI]: 1.02-1.29 for SLD; HR: 1.23, 95% CI: 1.09-1.38 for MAFLD; HR: 1.13, 95% CI: 1.01-1.27 for metabolic dysfunction-associated steatotic liver disease [MASLD]). Individuals with MetALD demonstrated a higher risk of all-cause (HR: 1.68, 95% CI: 1.10-2.57) and cancer-related mortality (HR: 2.40, 95% CI: 1.23-4.66). MASLD with advanced fibrosis had an increased risk of all-cause mortality compared to MASLD without advanced fibrosis. CONCLUSIONS: SLD, especially MASLD and MetALD, is associated with increased all-cause mortality among adults in the US. Given this significant association between SLD or subtype of SLD (MASLD and MetALD) and all-cause mortality, adopting the proposed SLD criteria may help identify a sub-group of individuals with SLD who are at an increased risk for all-cause mortality.

The prevalence and predictors of metabolic dysfunction-associated steatotic liver disease and fibrosis/cirrhosis among adolescents/young adults.

OBJECTIVES: We investigated the current prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and fibrosis/cirrhosis and identified at-risk populations for MASLD and MASLD-related fibrosis among US adolescents and young adults in the United States. METHODS: Utilizing the National Health and Nutrition Examination Survey 2017-2020, the prevalence of MASLD and fibrosis/cirrhosis was assessed via controlled attenuation parameter (CAP) score and liver stiffness measurements by transient elastography in participants aged 12-29 years with at least one cardiometabolic criteria and absence of other chronic liver disease. Multivariable logistic regression was performed to determine predictors of MASLD and MASLD-related fibrosis. RESULTS: The overall prevalence of MASLD was 23.9% (95% CI: 21.3-26.5 for CAP ≥ 263 dB/m) and 17.3% (95% CI: 14.7-20.0 for ≥285 dB/m), respectively. The prevalence of fibrosis and cirrhosis in MASLD was 11.0% and 3.1%, respectively. When categorized by age, the prevalence of MASLD varied from 16.8% (of which 6.2% [fibrosis], 1.8% [cirrhosis]) in early and middle adolescents (12-17 years), to 25.5% (11.8% [fibrosis], 4.8% [cirrhosis]) in late adolescents and young adults (18-24 years), and to 30.4% (of which 13.2% [fibrosis] and 2.1% [cirrhosis]) in older young adults (25-29 years). The independent predictors for MASLD included male sex, Hispanic, non-Hispanic Asian, body mass index, and low HDL-cholesterol. In contrast, diabetes and body mass index were associated with an increased risk of fibrosis in individuals with MASLD. CONCLUSIONS: The prevalence of MASLD and related fibrosis in adolescents and young adults in the United States has reached a significant level, with a substantial proportion of cirrhosis.

Incidence of liver cancer in young adults according to the global burden of disease database 2019.

OBJECTIVE: 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. METHODS: This study analyzed data from the Global Burden of Disease (GBD) study between 2010 and 2019 to assess the age-standardized incidence, mortality, and disability-adjusted life years (DALYs) associated with primary liver cancer in the young (15-49 y), stratified by region, nation, sociodemographic index, and sex. RESULTS: The study found a global estimate of 78,299 primary liver cancer cases, 60,602 deaths, and 2.90 million DALYs in the young population. The Western Pacific region exhibited the highest burden in 2019, showing the most significant increase compared to other regions between 2010-2019. More than half of 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 (MASLD)-attributable primary liver cancer (annual percentage change [APC] +0.87%, 95% confidence interval 0.70-1.05%) and alcohol-attributable primary liver cancer (APC +0.21%, 95% confidence interval 0.01-0.42%). Limitations of the GBD database include reliance on the quality of primary data and possible underestimation of alcohol consumption. CONCLUSION: 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.

The Global Burden of Early-Onset Pancreatic Cancer and Its Risk Factors: A Perspective From Global Burden of Disease Study 2019.

OBJECTIVES: Despite evidence of increased incidence of early-onset pancreatic cancer (EOPC), defined as pancreatic cancer diagnosed in patients below 50 years old, and its risk factors in the Western region, global epidemiological data addressing this issue is still lacking. MATERIALS AND METHODS: Utilizing data from the Global Burden of Disease Study 2019, we aimed to conduct a comprehensive analysis of the incidence, deaths, and disability-adjusted life years (DALYs) associated with EOPC and its risk factors, including smoking, obesity, and diabetes. The analysis examined the annual percentage change (APC) over the period. RESULTS: In 2019, the incidence of EOPC surpassed 35,000 cases worldwide. This burden of EOPC tends to be more prevalent in males, as well as in Europe and high SDI countries. However, there is a noticeable upward trend in the burden of EOPC in the Eastern Mediterranean. While there is a global decline in EOPC mortality attributed to smoking (APC -0.33%), there is a concerning increase in mortality associated with diabetes (APC +2.84%) and obesity (APC +2.12%). CONCLUSIONS: The burden of EOPC has been increasing. The mortality is rising mainly from metabolic factors. There is an urgent need for national policy development for reducing the burden of this disease.

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.

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.

THE TRENDS AND INCIDENCE OF ALCOHOL-ASSOCIATED HEPATITIS HOSPITALIZATIONS FROM 2016-2020 AND THE IMPACT OF THE COVID-19 PANDEMIC.

INTRODUCTION: The impact of the COVID-19 pandemic on hospitalizations for alcohol-associated hepatitis (AH) is poorly understood. Here we explore AH trends from 2016-2020 and evaluate demographic disparities including sex and race. METHODS: A retrospective analysis of the 2016-2020 Healthcare Cost and Utilization Project National Inpatient Sample was performed to assess temporal trends in hospitalizations for AH. The 2020 dataset was evaluated to compare AH hospitalizations between those with and without an additional diagnosis of COVID-19. RESULTS: Included were 607,140 weighted inpatient AH discharges per 145,055,152 all-cause discharges from 2016-2020. AH hospitalizations increased at a rate of 23.4 hospitalizations per 100,000 all-cause discharges per year between 2016-2019 and increased to 113 hospitalizations per 100,000 all-cause discharges in 2020. Mortality was higher in females despite lower rates of hospitalization than males. The adjusted odds of hospitalization for AH in 2020 were higher than in 2016-2019 (aOR= 1.28, p < 0.001). The Hispanic population had greater odds of hospitalization with AH and COVID-19 compared to other races (aOR= 2.71, p <0.001). DISCUSSION: Increased efforts toward primary prevention of excessive alcohol use and greater social support for those with alcohol used disorder are needed. More research is required to elucidate the racial disparities among the Hispanic population with AH and COVID-19.

The Global Burden of Alcohol-associated Cirrhosis and Cancer in Young and Middle-aged Adults.

Alcohol is a substance that impacts premature mortality and morbidity.1 The liver is invariably subjected to the impact of alcohol, which can result in cirrhosis and cancer. Alcohol also has detrimental effects that extend beyond the liver. While traditionally associated with advanced age, emerging data reported a rising burden of cancers and alcohol-associated liver disease in the young.1-3 Thus, the primary objective was to evaluate the trend of alcohol-associated cirrhosis and cancer in young and middle-aged adults (aged 15-49) utilizing the Global Burden of Disease Study (GBD) 2019.4 We chose the age group less than 50 years old based on the definition of early-onset cancer and the inherent selection of the age group in the GBD database.4-6 The detailed methods are provided in the Supplementary Appendix. Briefly, data were sourced from population-based cancer registries, vital registration systems, or verbal autopsy studies. Verbal autopsy is a well-established approach for monitoring health, providing valuable information on mortality patterns and the reasons behind deaths in areas lacking robust medical death certification processes. The researchers employed the Cause of Death Ensemble model to estimate the burden linked to cancer and cirrhosis associated with alcohol use.

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.

Impact of the COVID-19 pandemic on hospitalizations with hepatocellular carcinoma in the United States.

BACKGROUND: We studied the temporal trends of hepatocellular carcinoma (HCC)-related hospitalizations and potential predictors of in-hospital mortality around the COVID-19 pandemic. RESEARCH DESIGN AND METHODS: Using the International Classification of Diseases code, we used the National Inpatient Sample 2019-2020 and defined HCC and its underlying etiology. To assess the impact of the COVID-19 pandemic on hospitalization and in-hospital mortality, the study period was divided into the pre-COVID-19 era (2019 Q1-2020 Q1) and the COVID-19 era (2020 Q2-2020 Q4). Quarterly trends in etiology-based hospitalizations with HCC and predictors of in-hospital mortality among hospitalizations with HCC were determined. RESULTS: Hospitalization rates for HCC, as well as viral hepatitis-related HCC hospitalization rates, remained stable, while hospitalizations with alcohol-related liver disease (ALD, quarterly percentage change [QPC]: 2.1%; 95% confidence interval [CI]: 0.1%-4.2%) increased steadily. Hospitalization related to nonalcoholic fatty liver disease (NAFLD)-related HCC increased significantly steeper in the COVID-19 era (QPC: 6.6%; 95% CI: 4.0%-9.3%) than in the pre-COVID-19 era (QPC: 0.7%; 95% CI: 0.2%-1.3%). COVID-19 infection was independently associated with in-hospital mortality among hospitalizations with HCC (odds ratio: 1.94, 95% CI: 1.30-2.88). CONCLUSION: Hospitalization rates for viral hepatitis-related HCC remained stable, while those for HCC due to ALD and NAFLD increased during the COVID-19 pandemic.

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.

What Is New in Metabolic Dysfunction-Associated Steatotic Liver Disease in Lean Individuals: From Bench to Bedside.

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects more than 30% of the world's adult population. While it is associated with obesity and metabolic syndrome, emerging evidence has shown that a substantial number of MASLD patients have a normal body mass index ("lean individuals with MASLD"). In this article, we provide an overview of the definition, epidemiology, pathogenesis, and clinical outcomes associated with lean individuals with MASLD and updates on current management.

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.

The incidence of adverse outcome in donors after living donor liver transplantation: A meta-analysis of 60,829 donors.

The scarcity of liver grafts has prompted developments in living donor liver transplantations (LDLT), with previous literature illustrating similar outcomes in recipients compared to deceased donor transplants. However, significant concerns regarding living donor morbidity and mortality have yet to be examined comprehensively. This study aims to provide estimates of the incidence of various outcomes in living liver donors. In this meta-analysis, Medline and Embase were searched from inception to July 2022 for articles assessing the incidence of outcomes in LDLT donors. Complications in the included studies were classified into respective organ systems. Analysis of incidence was conducted using a generalized linear mixed model with Clopper-Pearson intervals. Eighty-seven articles involving 60,829 living liver donors were included. The overall pooled incidence of complications in LDLT donors was 24.7% (CI: 21.6%-28.1%). The incidence of minor complications was 17.3% (CI: 14.7%-20.3%), while the incidence of major complications was lower at 5.5% (CI: 4.5%-6.7%). The overall incidence of donor mortality was 0.06% (CI: 0.0%-0.1%) in 49,027 individuals. Psychological complications (7.6%, CI: 4.9%-11.5%) were the most common among LDLT donors, followed by wound-related (5.2%, CI: 4.4%-6.2%) and respiratory complications (4.9%, CI: 3.8%-6.3%). Conversely, cardiovascular complications had the lowest incidence among the subgroups at 0.8% (CI: 0.4%-1.3%). This study presents the incidence of post-LDLT outcomes in living liver donors, illustrating significant psychological, wound-related, and respiratory complications. While significant advancements in recent decades have contributed towards decreased morbidity in living donors, our findings call for targeted measures and continued efforts to ensure the safety and quality of life of liver donors post-LDLT.

Rising global burden of cancer attributable to high BMI from 2010 to 2019.

BACKGROUND: High body mass index (BMI) is a major risk factor for cancer development, but its impact on the global burden of cancer remains unclear. METHODS: We estimated global and regional temporal trends in the burden of cancer attributable to high BMI, and the contributions of various cancer types using the framework of the Global Burden of Disease Study. RESULTS: From 2010 to 2019, there was a 35 % increase in deaths and a 34 % increase in disability-adjusted life-years from cancers attributable to high BMI. The age-standardized death rates for cancer attributable to high BMI increased over the study period (annual percentage change [APC] +0.48 %, 95 % CI 0.22 to 0.74 %). The greatest number of deaths from cancer attributable to high BMI occurred in Europe, but the fastest-growing age-standardized death rates and disability-adjusted life-years occurred in Southeast Asia. Liver cancer was the fastest-growing cause of cancer mortality (APC: 1.37 %, 95 % CI 1.25 to 1.49 %) attributable to high BMI. CONCLUSION: The global burden of cancer-related deaths attributable to high BMI has increased substantially from 2010 to 2019. The greatest increase in age-standardized death rates occurred in Southeast Asia, and liver cancer is the fastest-growing cause of cancer mortality attributable to high BMI. Urgent and sustained measures are required at a global and regional level to reverse these trends and slow the growing burden of cancer attributed to high BMI.

Proton Pump Inhibitors Increases Longitudinal Risk of Mortality, Decompensation, and Infection in Cirrhosis: A Meta-Analysis.

BACKGROUND/AIMS: Proton pump inhibitors (PPIs) are frequently prescribed to cirrhotic patients, but there is limited longitudinal evidence regarding their effects. This study aimed to assess the impact of PPIs on adverse events in cirrhotic patients. METHODS: A comprehensive search was conducted using the Medline and Embase databases to identify relevant articles. Pooled hazard ratios (HRs) using DerSimonian and Laird random-effects model were calculated to evaluate the risk of adverse events such as long-term mortality, hepatic decompensation, hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP), and overall infection in cirrhotic patients with PPI use. RESULTS: The analysis included 28 studies with 260,854 cirrhotic patients. The prevalence of PPI use among cirrhotic patients was 55.93%. The use of PPIs was not significantly associated with short-term mortality in cirrhotic patients. However, long-term mortality (HR 1.321, 95% CI 1.103-1.581, P = 0.002), decompensation (HR 1.646, 95% CI 1.477-1.835, P < 0.001), HE (HR 1.968, 95% CI 1.372-2.822, P < 0.001), SBP (HR 1.751, 95% CI 1.649-1.859, P < 0.001), and infection (HR 1.370, 95% CI 1.148-1.634, P < 0.001) were significantly associated with PPI use. Sensitivity analysis with prospective studies yielded similar results. CONCLUSION: PPIs should be reserved for appropriate indications at lowest effective dose for cirrhotic patients due to the potential harm.

Associations between metabolic hyperferritinaemia, fibrosis-promoting alleles and clinical outcomes in steatotic liver disease.

BACKGROUND & AIMS: Ferritin has been investigated as a biomarker for liver fibrosis and iron in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). However, whether metabolic hyperferritinaemia predicts progression of liver disease remains unknown. In this study, we sought to understand associations between hyperferritinaemia and (1) adverse clinical outcomes and (2) common genetic variants related to iron metabolism and liver fibrosis. METHODS: This was a retrospective analysis of adults with MASLD seen at the University of Michigan Health System, where MASLD was defined by hepatic steatosis on imaging, biopsy or vibration-controlled transient elastography, plus metabolic risk factors in the absence of chronic liver diseases other than hemochromatosis. The primary predictor was serum ferritin level, which was dichotomized based on a cut-off of 300 or 450 mcg/L for women or men. Primary outcomes included (1) incident cirrhosis, liver-related events, congestive heart failure (CHF), and mortality and (2) distribution of common genetic variants associated with hepatic fibrosis and hereditary hemochromatosis. RESULTS: Of 7333 patients with MASLD, 1468 (20%) had elevated ferritin. In multivariate analysis, ferritinaemia was associated with increased mortality (HR 1.68 [1.35-2.09], p < .001) and incident liver-related events (HR 1.92 [1.11-3.32], p = .019). Furthermore, elevated ferritin was associated with carriage of cirrhosis-promoting alleles including PNPLA3-rs738409-G allele (p = .0068) and TM6SF2-rs58542926-T allele (p = 0.0083) but not with common HFE mutations. CONCLUSIONS: In MASLD patients, metabolic hyperferritinaemia was associated with increased mortality and higher incidence of liver-related events, and cirrhosis-promoting alleles but not with iron overload-promoting HFE mutations.

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.