Individual and combined effects of muscle strength and visceral adiposity on incident prediabetes and type 2 diabetes in a longitudinal cohort of midlife Asian women.

AIM: To investigate the independent and combined effects of muscle strength and visceral adiposity on prediabetes and type 2 diabetes incidence among midlife women. MATERIALS AND METHODS: In this prospective study of midlife women (mean age 56.4 years), visceral adiposity, defined as visceral adipose tissue (VAT) >131 cm2 measured by dual energy X-ray absorptiometry, and poor combined muscle strength, defined as handgrip strength <18 kg and/or five-time repeated chair stand test performance ≥12 s, were determined at baseline between 2014 and 2016. After 6.6 years, the effects of VAT and muscle strength on risk of incident prediabetes (fasting blood glucose 5.6-6.9 mmol/L) and type 2 diabetes (fasting blood glucose levels ≥7 mmol/L, medication use, or physician diagnosis) were examined using modified Poisson regression analysis. RESULTS: Among the 733 initially normoglycaemic participants, 150 (20.5%) developed prediabetes or type 2 diabetes. Women with both poor combined muscle strength and high VAT had the highest risk for both prediabetes and type 2 diabetes (adjusted relative risk [aRR] 2.63, 95% confidence interval [CI] 1.81-3.82). In comparison, high VAT alone increased risk by 1.78-fold (95% CI 1.12-2.84). Stratification analyses showed that among women with low muscle strength, high VAT demonstrated increased risks of prediabetes and type 2 diabetes (aRR 2.84, 95% CI 1.95-4.14) compared to those with normal strength (aRR 1.66, 95% CI 1.04-2.65). CONCLUSIONS: Low combined muscle strength with high VAT poses a greater risk for the development of prediabetes and type 2 diabetes than high VAT alone. Muscle strengthening should be promoted alongside weight loss in diabetes prevention.

Integrin-α9 overexpression underlies the niche-independent maintenance of leukemia stem cells in acute myeloid leukemia.

Leukemia stem cells (LSCs) are widely believed to reside in well-characterized bone marrow (BM) niches; however, the capacity of the BM niches to accommodate LSCs is insufficient, and a significant proportion of LSCs are instead maintained in regions outside the BM. The molecular basis for this niche-independent behavior of LSCs remains elusive. Here, we show that integrin-α9 overexpression (ITGA9 OE) plays a pivotal role in the extramedullary maintenance of LSCs by molecularly mimicking the niche-interacting status, through the binding with its soluble ligand, osteopontin (OPN). Retroviral insertional mutagenesis conducted on leukemia-prone Runx-deficient mice identified Itga9 OE as a novel leukemogenic event. Itga9 OE activates Akt and p38MAPK signaling pathways. The elevated Myc expression subsequently enhances ribosomal biogenesis to overcome the cell integrity defect caused by the preexisting Runx alteration. The Itga9-Myc axis, originally discovered in mice, was further confirmed in multiple human acute myeloid leukemia (AML) subtypes, other than RUNX leukemias. In addition, ITGA9 was shown to be a functional LSC marker of the best prognostic value among 14 known LSC markers tested. Notably, the binding of ITGA9 with soluble OPN, a known negative regulator against HSC activation, induced LSC dormancy, while the disruption of ITGA9-soluble OPN interaction caused rapid cell propagation. These findings suggest that the ITGA9 OE increases both actively proliferating leukemia cells and dormant LSCs in a well-balanced manner, thereby maintaining LSCs. The ITGA9 OE would serve as a novel therapeutic target in AML.

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.

Evaluating Chatbot responses to patient questions in the field of glaucoma.

Objective: The aim of this study was to evaluate the accuracy, comprehensiveness, and safety of a publicly available large language model (LLM)-ChatGPT in the sub-domain of glaucoma. Design: Evaluation of diagnostic test or technology. Subjects participants and/or controls: We seek to evaluate the responses of an artificial intelligence chatbot ChatGPT (version GPT-3.5, OpenAI). Methods intervention or testing: We curated 24 clinically relevant questions in the domain of glaucoma. The questions spanned four categories: pertaining to diagnosis, treatment, surgeries, and ocular emergencies. Each question was posed to the LLM and the responses obtained were graded by an expert grader panel of three glaucoma specialists with combined experience of more than 30 years in the field. For responses which performed poorly, the LLM was further prompted to self-correct. The subsequent responses were then re-evaluated by the expert panel. Main outcome measures: Accuracy, comprehensiveness, and safety of the responses of a public domain LLM. Results: There were a total of 24 questions and three expert graders with a total number of responses of n = 72. The scores were ranked from 1 to 4, where 4 represents the best score with a complete and accurate response. The mean score of the expert panel was 3.29 with a standard deviation of 0.484. Out of the 24 question-response pairs, seven (29.2%) of them had a mean inter-grader score of 3 or less. The mean score of the original seven question-response pairs was 2.96 which rose to 3.58 after an opportunity to self-correct (z-score - 3.27, p = 0.001, Mann-Whitney U). The seven out of 24 question-response pairs which performed poorly were given a chance to self-correct. After self-correction, the proportion of responses obtaining a full score increased from 22/72 (30.6%) to 12/21 (57.1%), (p = 0.026, χ2 test). Conclusion: LLMs show great promise in the realm of glaucoma with additional capabilities of self-correction. The application of LLMs in glaucoma is still in its infancy, and still requires further research and validation.

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.

Sex-based Disparities in Liver Transplantation for Hepatocellular Carcinoma and the Impact of the Growing Burden of NASH.

Background: The cause of liver disease is changing, but its impact on liver transplantation (LT) for hepatocellular carcinoma (HCC) in women and men is unclear. We performed a nationwide study to assess the prevalence and posttransplant survival outcomes of the various causes of liver disease in women and men with HCC. Methods: Data were obtained from the United Network for Organ Sharing database from 2000 to 2022. Data related to the listing, transplant, waitlist mortality, and posttransplant mortality for HCC were extracted. The proportion of HCC related to the various causes of liver disease among LT candidates and recipients and posttransplant survival were compared between women and men. Results: A total of 51 721 individuals (39 465 men, 12 256 women) with HCC were included. From 2000 to 2022, nonalcoholic steatohepatitis (NASH) was the fastest-growing cause of liver disease among female LT candidates with HCC (P < 0.01), followed by alcohol-associated liver disease. NASH overtook chronic hepatitis C as the leading cause of liver disease in 2020 and 2022 among waitlisted women and men with HCC, respectively. Female patients with HCC spent a significantly longer time on the LT waitlist compared with male patients (ß: 8.73; 95% confidence interval [CI], 2.91-14.54). Female patients with HCC from alcohol-associated liver disease also have a lower probability of receiving LT (subdistribution hazard ratio: 0.90; 95% CI, 0.82-0.99). Among transplant recipients with NASH HCC, female sex was associated with lower posttransplant mortality compared with male sex (hazard ratio: 0.79; 95% CI, 0.70-0.89; P < 0.01). Conclusions: Women have a significantly longer waitlist duration compared with men. NASH is now the leading cause of liver disease among both female and male LT candidates and recipients with HCC.

Changing global epidemiology of chronic hepatitis C virus-related outcomes from 2010 to 2019: cirrhosis is the growing burden of hepatitis C virus-related disease.

BACKGROUND: Chronic infection with hepatitis C virus (HCV) has a long-term impact on hepatic consequences. A comprehensive evaluation of the global burden of HCV-related health outcomes can help to develop a global HCV prevention and treatment program. METHODS: We used the 2019 Global Burden of Disease (GBD) Study to comprehensively investigate burden and temporal trends in incidence, mortality and disability-adjusted life-years (DALYs) of HCV-related diseases, including liver cancer and cirrhosis and other liver diseases across 264 countries and territories from 2010 to 2019. RESULTS: Globally, there were 152 225 incident cases, 141 811 deaths and approximately 2.9 million DALYs because of HCV-related liver cancer, and 551 668 incident cases, 395 022 deaths and about 12.2 million DALYs because of HCV-related cirrhosis in 2019. Worldwide, during the 2010-2019 period, liver cancer incidence declined, however, there was a 62% increase in cirrhosis incidence. In 2019, the Eastern Mediterranean was the region with the highest rates of incidence and mortality of both liver cancer and cirrhosis. Africa was the region with the fastest-growing trend of incidence of cirrhosis in the 2010-2019 period [annual percentage change (APC) = 2.09, 95% confidence interval (CI): 1.93-2.25], followed by the Western Pacific region (APC = 1.17, 95% CI: 1.09-1.22). Americas were the only region observing increased trends in liver cancer and cirrhosis mortality (APC = 0.70 and 0.12, respectively). We identified three patterns of temporal trends of mortality rates of liver cancer and cirrhosis in countries that reported HCV treatment rates. CONCLUSION: Urgent measures are required for diagnosis, treatment and research on HCV-related cirrhosis at global, regional and country levels, particularly in Africa, the Western Pacific and the Eastern Mediterranean.

Ultrasound Surveillance in Melanoma Management: Bridging Diagnostic Promise with Real-World Adherence: A Systematic Review and Meta-Analysis.

BACKGROUND: Ultrasound surveillance has become the new standard of care in stage III melanoma after the 2017 Multicenter Selective Lymphadenectomy Trial II (MSLT-II) demonstrated non-inferior 3-year survival compared with complete lymph node dissection. OBJECTIVE: We aimed to quantify diagnostic performance and adherence rates of ultrasound surveillance for melanoma locoregional metastasis, offering insights into real-world applicability. METHODS: Conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, we systematically searched the Medline, Embase, Cochrane Library, CINAHL, Scopus, and Web of Science databases from inception until 11 October 2023. All primary studies that reported data on the diagnostic performance or adherence rates to ultrasound surveillance in melanoma were included. R statistical software was used for data synthesis and analysis. Sensitivity and specificity were aggregated across studies using the meta-analytic method for diagnostic tests outlined by Rutter and Gatsonis. Adherence rates were calculated as the ratio of patients fully compliant to planned follow-up to those who were not. RESULTS: A total of 36 studies including 18,273 patients were analysed, with a mean age of 56.6 years and a male-to-female ratio of 1:1.11. The median follow-up duration and frequency was 36 and 4 months, respectively. The pooled sensitivity of ultrasound examination was 0.879 (95% confidence interval [CI] 0.878-0.879) and specificity was 0.969 (95% CI 0.968-0.970), representing a diagnostic odds ratio of 224.5 (95% CI 223.1-225.9). Ultrasound examination demonstrated a substantial improvement in absolute sensitivity over clinical examination alone, with a number needed to screen (NNS) of 2.95. The overall adherence rate was 77.0% (95% CI 76.0-78.1%), with significantly lower rates in the United States [US] (p <  0.001) and retrospective studies (p <  0.001). CONCLUSION: Ultrasound is a powerful diagnostic tool for locoregional melanoma metastasis. However, the real applicability to surveillance programmes is limited by low adherence rates, especially in the US. Further studies should seek to address this adherence gap.

Overcoming low initial coulombic efficiencies of Si anodes through prelithiation in all-solid-state batteries.

All-solid-state batteries using Si as the anode have shown promising performance without continual solid-electrolyte interface (SEI) growth. However, the first cycle irreversible capacity loss yields low initial Coulombic efficiency (ICE) of Si, limiting the energy density. To address this, we adopt a prelithiation strategy to increase ICE and conductivity of all-solid-state Si cells. A significant increase in ICE is observed for Li1Si anode paired with a lithium cobalt oxide (LCO) cathode. Additionally, a comparison with lithium nickel manganese cobalt oxide (NCM) reveals that performance improvements with Si prelithiation is only applicable for full cells dominated by high anode irreversibility. With this prelithiation strategy, 15% improvement in capacity retention is achieved after 1000 cycles compared to a pure Si. With Li1Si, a high areal capacity of up to 10 mAh cm-2 is attained using a dry-processed LCO cathode film, suggesting that the prelithiation method may be suitable for high-loading next-generation all-solid-state batteries.

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.

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.

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.

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.

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.

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

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

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.

Donor Diabetes and Steatosis Affects Recipient Survival Following Liver Transplantation Based on Etiology of Liver Cirrhosis.

BACKGROUND: Liver transplantation (LT) offers patients with decompensated cirrhosis the best chance at long-term survival. With the rising prevalence of diabetes, further clarity is needed on the impact of receiving a liver allograft from a donor with diabetes on post-LT outcomes. This study aims to evaluate the impact of donor diabetes on clinical outcomes after LT. METHODS: This is a retrospective analysis of the United Network for Organ Sharing registry data of LT recipients from January 1, 2000, to December 31, 2021. Outcomes analysis was performed using Cox proportional model for all-cause mortality and graft failure. Confounding was reduced by coarsened exact matching causal inference analysis. RESULTS: Of 66 960 donors identified, 7178 (10.7%) had diabetes. Trend analysis revealed a longitudinal increase in the prevalence of donor diabetes ( P < 0.001). Importantly, donor diabetes was associated with increased all-cause mortality (hazard ratio [HR]: 1.13; 95% confidence interval [CI], 1.07-1.19; P < 0.001) and graft failure (HR: 1.16; 95% CI, 1.11-1.22; P < 0.001). Receiving donor organ with diabetes reduced graft survival in patients who received LT for nonalcoholic steatohepatitis cirrhosis (HR: 1.26; 95% CI, 1.13-1.41; P < 0.001) but not other etiologies of cirrhosis. CONCLUSIONS: Donor diabetes was associated with worse outcomes post-LT, particularly in patients receiving LT for nonalcoholic steatohepatitis cirrhosis. Future studies are needed to better understand the mechanism underlying this association to develop better risk stratification and clinical practice to improve the outcomes of the transplanted patients.

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.