Hepatocellular carcinoma (HCC), which accounts for about 90% of all primary liver cancer cases, is the fifth most common malignancy and the second leading cause of cancer-related mortality worldwide. This study aims to analyse the differential costs of HCC-related hospital admissions compared to the general population in Spain.

A retrospective multicenter study analyzed inpatient admissions from a Spanish national discharge database, covering 90% of hospitals between 2010 and 2022. HCC-related admissions were identified using ICD-9 and ICD-10 codes, while control admissions were selected from the general population in the same database without an HCC diagnosis. The direct hospitalization cost was included, covering medical examinations, procedures, medications, surgeries, personnel and equipment. Statistical methods, including nearest-neighbor matching, propensity score matching, and a generalized linear model, were used to estimate differential costs and to ensure comparability based on age, gender, and Charlson Comorbidity Index (CCI).

A total of 199,670 HCC-related hospital admissions and 200,000 control admissions were analyzed. Most HCC-related admissions involved male patients (78%) aged 66-85 years, with an average CCI of 5.18. HCC-related admissions incurred significantly higher costs, with an estimated differential cost of €1,303.68 using GLM, €1,804.25 via propensity score matching, and €1,767.77 using nearest-neighbor matching. Total costs per HCC admission ranged between €1,000 and €31,000.

HCC-related hospital admissions impose a significantly higher economic burden due to the complexity of care. Given the high mortality and resource utilization, advancements in early detection, treatment, and cost-effective interventions are needed to improve patient outcomes and reduce healthcare costs.

Several studies have reported associations between substance use and effort-related decision making, or the degree to which effort expenditure impacts the choice between lower and higher value rewards. However, previous research has not explored effort-related decision making in populations with severe substance use disorder.

Investigate the association between effort-related decision-making and substance use disorder severity.

Adults with substance use disorders (n = 106) enrolled in intensive outpatient treatment completed clinician administered diagnostic interviews and the effort expenditure for rewards task (EEfRT). General linear mixed methods tested the interactive effect of substance use disorder severity and trial-level probability and value on the likelihood of selecting a high-effort choice.

There was a significant interaction between SUD severity and both reward value and reward probability on high-effort choice. The strength of the association between both reward value and probability on high-effort choice significantly increased with SUD severity.

These results support theories of reward sensitivity and behavioral economics and highlight an emerging risk factor that may serve as a useful target for treatment.

Hepatocyte nuclear factor 4 alpha (HNF4α) is a master regulator of hepatocyte differentiation in fetal and adult liver and exerts its transcriptional role in determining physiological functions of the liver. The objective of this review is to address the current knowledge of molecular mechanisms involved in HNF4α regulation in multiple aspects of liver disease pathogenesis.

Based on available literature, this review summarises the current state of knowledge onthe mechanism of HNF4α dysregulation, and the role of HNF4α activity inregulating early to advanced stages of various liver diseases.

Patients with deranged HNF4α expression are at higher risk for the development of liver diseases such as viral hepatitis, alcoholic/nonalcoholic fatty liver disease, hepatocellular carcinoma, and haematological disorders such as coagulopathy and bleeding disorders.

HNF4α interactions with nuclear receptors and target genes promote liver disease pathology by regulating various metabolic pathways. The strong correlation between deranged HNF4α expression and the severity of liver diseases suggests that targeting HNF4α expression can offer potential therapeutic strategy in the prevention of liver disease pathology and haemostatic disorders.

To analyze the burden and trend of idiopathic developmental intellectual disability (IDII) attributed to lead (Pb) exposure in China from 1990 to 2021 and to predict the trend from 2022 to 2035.

We used the Global Burden of Disease Study (GBD) 2021 data to estimate disability-adjusted life years (DALYs) and age-standardized DALY rate (ASDR) of IDII attributable to Pb exposure. The annual average percentage change (AAPCs) was estimated to evaluate the changing trend of IDII ASDR attributable to Pb exposure from 1990 to 2021. The age-period-cohort (APC) and Bayesian age-period-cohort (BAPC) was used to assess and predict changes in the DALYs of IDII attributable to Pb exposure.

From 1990 to 2021, the number of DALYs and rate of the total population, males and females in China showed a fluctuating and decreasing trend. The APC showed that the age deviation had an upward trend and then decreased, the period deviation showed an 'N' shaped trend, and the cohort deviation model showed a trend of first increasing and then decreasing. The BAPC model predicts that the number of DALYs and ASDR will continue to decline, with males declining faster than females, and that by 2035, females will have higher DALYs and ASDR than males.

From 1990 to 2035, the burden of IDII attributed to Pb exposure in China showed a downward trend. But the DALYs and ASDR in females will be higher than that in males in 2035. It is essential to prioritize intervention, prevention, and control measures for females.

Describing cirrhosis and hepatic encephalopathy (HE) burden over time can inform clinical management and resource allocation. Using healthcare claims data, this observational study examined recent trends in the prevalence of cirrhosis and HE and associated healthcare resource utilization among commercially and Medicare-insured adults in the United States.

Data from the MarketScan Commercial Claims and Encounters Database and 100% Medicare Research Identifiable Files were analyzed (2007-2020). Annual prevalence of cirrhosis, HE, overt HE (OHE) hospitalizations, and rifaximin ± lactulose use, and costs per hospitalization per year were calculated. Average year-over-year changes in prevalence of cirrhosis, and HE were estimated. Trends were extrapolated to 2030 using ordinary least-squares regression.

From 2007 to 2020, the prevalence of cirrhosis increased by an average of 4.6% year-over-year in the Commercial population and 8.1% in the Medicare population; the prevalence of HE increased by 4.3% and 2.5%, respectively. Rates of OHE hospitalizations decreased from 27.5% to 5.5% (Commercial) and from 26.2% to 9.5% (Medicare), and rates of liver transplantation increased. Average payer costs (Commercial) and provider charges (Medicare) per OHE hospitalization increased (from $40,881 to $77,699 and from $45,913 to $74,894, respectively). Use of rifaximin ± lactulose showed an increasing trend during the observation period, whereas lactulose use declined steadily.

The healthcare burden of cirrhosis and HE in the United States is increasing. Trends are projected to continue unless action is taken, such as improving medication access and developing policies addressing the contributing factors.

Background: Cirrhosis is associated with significant healthcare utilization, yet data about in-hospital decompensations remain sparse. Additionally, the impact of liver transplant candidacy status on resuscitation and outcomes is largely unknown. Aims:We aimed to evaluate the characteristics of resuscitation events for patients with cirrhosis with acute decompensation, analyzing liver transplant candidacy and intensive care unit (ICU) transfer parameters. Methods: Retrospective single-center review of adult patients with liver cirrhosis who had a rapid response team (RRT) activation during hospitalization and no prior liver transplantation. Results: Patients with cirrhosis who were liver transplant candidates were more likely to be younger (p = .003), have a higher serum total bilirubin (p = .015), higher INR (p < .001), and higher MELD 3.0 (p = .006). There was no significant difference in ICU transfer (p = .170) after RRT activation. Liver transplant candidates had a lower 30- and 60-day mortality (p = .008, p = .014) and were less likely to have a code status discussion after decompensation (p = .001). Lower serum albumin was associated with ICU transfer (p = .001). Patients who transferred to the ICU were more likely to have a code status discussion within 24 h after RRT (p = .011) without significant difference in 30- or 60-day mortality (p = .059, p = .277). Conclusions: Liver transplant candidacy in patients with cirrhosis with acute decompensation is not clearly correlated with ICU transfer. Liver transplant candidates are more likely to be younger, have higher MELD 3.0 scores, less likely to have code status discussed after RRT, and have lower 30- and 60-day mortality rates. Patients who transfer to the ICU are more likely to have a code status discussion without any significant difference in 30- or 60-day mortality.

Background: Patients with end-stage liver disease (ESLD) have complex needs and may benefit from palliative care (PC), which is often underutilized or delayed. Objectives: To characterize patients with ESLD who received inpatient PC consultation and to explore differences in characteristics between those who received PC consultation before (pre-Pall) or after (post-Pall) PC participation at weekly liver transplant (LT) Patient Selection Committee (PSC) meetings. Design: Single-center retrospective cohort study. Setting/Subjects: Hospitalized patients with ESLD who received inpatient PC consultation between February 2017 and February 2019 at an academic LT center in the United States. Measurements: PC referral reasons and timing, code status, hospice referrals, discharge location, and mortality. Results: Two hundred five patients were included. The primary reason for PC was goals of care (88.8%; n = 182). Most (86.8%; n = 178) were Full Code at hospital admission, while 81% (n = 166) were do-not-resuscitate at discharge. Nearly one quarter (22.9%; n = 47) sought life-prolonging care at discharge, while 41.5% (n = 85) were discharged with hospice, and 34.1% (n = 70) died before discharge. By the end of the study, 85.9% (n = 176) were confirmed as deceased. Median time from PC to hospice referral was 12 days [95% confidence interval [CI]: 8-23]. Median time from PC consult to death was 13 days [95% CI: 9-17] and from hospice referral to death was 7 days [95% CI: 4-13]. There were no statistically significant differences between the pre- and post-Pall groups related to PC referral patterns or outcomes. Conclusions: Most PC contacts occurred near end of life, and many led to comfort-focused care. Late referrals may be due to reliance on inpatient consults during acute illness. PC presence at PSC meetings represents an important step in collaboration with LT teams but did not lead to direct impact on PC referral patterns or outcomes.

Alcohol-associated liver disease (ALD) and metabolic associated steatohepatitis (MASH) are leading indications for liver transplant (LT). Data are limited on their trends and association with candidate characteristics.

UNOS database (2002-22) examined on proportion of ALD or of NASH etiology among LT listings comparing 2002-11 vs. 2012-22. Of 169,385 listings, 41,558 (24.5 %) and 21,789 (12.9 %) listed for ALD and MASH respectively. Proportion of ALD increased 2 folds between 2002-11 and 2012-22. Stratified multivariable logistic regression models showed age <35 yrs., females, blacks and Asians, non-diabetics, education below high school, Medicaid insurance, and MELD > 35 with highest increase in ALD. Candidates listed with ALD vs. others had lower 90-d waitlist mortality, SHR 0.85 [0.83-0.87]. Although, AH as listing diagnosis only contributed to 3.2 % of ALD candidates, this subtype of ALD was associated with increasing ALD trends among candidates <35 yrs. of age, with college or higher education, and MELD ≥35. The proportion of MASH increased 3 folds between 2002-11 and 2012-22. Stratified models showed age 35-64 yrs., males, blacks and Asians, diabetics, college or above education, Medicare insurance, and MELD < 25 with highest increase in MASH. Candidates listed with MASH vs. others had similar 90-d waitlist mortality, SHR 0.99 [0.97-1.03].

MASH and ALD in LT listing increased, with differential increase based on candidate characteristics. These findings are relevant in organ allocation and designing public policies to control MASH and ALD.

Alcohol-associated liver disease (ALD) is the foremost cause of liver-related mortality in the United States comprising a spectrum of conditions from simple hepatic steatosis to more severe alcohol-associated cirrhosis and alcohol-associated hepatitis. There has been growing acceptance and application of early liver transplantation (eLT) for ALD. There is robust evidence for excellent patient and graft survival rates for eLT for ALD. Nevertheless, recidivism remains a major concern. This article aims to explore the recent trends in liver transplantation for ALD, as well as the advances in practice and outcomes, with focus on eLT and emerging challenges in this field.

Social determinants of health are key factors driving disease progression. In type 2 diabetes there is limited literature on how distal or intermediate factors (eg, those at the neighborhood level) influence cause-specific mortality or liver disease outcomes.

This was a single-center retrospective study of patients with type 2 diabetes seen at an integrated healthcare system in the United States. The primary outcomes were overall mortality; death due to cardiovascular disease, cancer, or liver disease; or hepatic decompensation. The primary predictors were neighborhood-level (intermediate) factors measuring neighborhood poverty (Area Deprivation Index [ADI], affluence score, disadvantage score) and rurality (Rural-Urban Commuting Area scores). Associations were modeled using Cox proportional hazards or Fine-Grey competing risk models.

28,424 participants were included. Higher neighborhood poverty associated with increased overall mortality, with hazard ratio (HR) 1.11 (95% confidence interval 1.10-1.12, P < .001) per 10 points of ADI and HR 1.32 (95% CI 1.26-1.37, P < .001) for 10 points of disadvantage. Conversely, higher neighborhood affluence associated with lower overall mortality with HR 0.87 (95% CI 0.86-0.89, P < .001) per 10 points of affluence. Living in a rural region associated with increased overall mortality: HR 1.08 (95% CI 1.01-1.15, P = .031). Associations were consistent across cause-specific mortality, though effect sizes were larger for liver-related mortality than for other causes. Living in a more rural neighborhood was associated with increased risk of hepatic decompensation.

Intermediate neighborhood-level socioeconomic status was associated with overall and cause-specific mortality in type 2 diabetes, with larger effects on liver-related mortality than other causes.

Hepatocellular carcinoma (HCC) is a substantial global health challenge owing to its high mortality rate and limited therapeutic options. We aimed to develop an efferocytosis-related gene signature (ER.Sig) and conduct a transcriptomic analysis to predict the prognosis and immunotherapeutic responses of patients with HCC.

Single-cell RNA sequencing data and bulk RNA sequencing data were obtained from public databases. Based on single-sample gene set enrichment analysis and Weighted Gene Co-expression Network analyses, efferocytosis-related genes (ERGs) were selected at both the single-cell and bulk transcriptome levels. A machine-learning framework employing ten different algorithms was used to develop the ER.Sig. Subsequently, a multi-omics approach (encompassing genomic analysis, single-cell transcriptomics, and bulk transcriptomics) was employed to thoroughly elucidate the prognostic signatures.

Analysis of the HCC single-cell transcriptomes revealed significant efferocytotic activity in macrophages, endothelial cells, and fibroblasts within the HCC microenvironment. We then constructed a weighted co-expression network and identified six modules, among which the brown module (168 genes) was most highly correlated with the efferocytosis score (cor = 0.84). Using the univariate Cox regression analysis, 33 prognostic ERGs were identified. Subsequently, a predictive model was constructed using 10 machine-learning algorithms, with the random survival forest model showing the highest predictive performance. The final model, ER.Sig, comprised nine genes and demonstrated robust prognostic capabilities across multiple datasets. High-risk patients exhibited greater intratumoral heterogeneity and higher TP53 mutation frequencies than did low-risk patients. Immune landscape analysis revealed that compared with high-risk patients, low-risk patients exhibited a more favorable immune environment, characterized by higher proportions of CD8+ T and B cells, tumor microenvironment score, immunophenoscore, and lower Tumor Immune Dysfunction and Exclusion scores, indicating better responses to immunotherapy. Additionally, an examination of an independent immunotherapy cohort (IMvigor210) demonstrated that low-risk patients exhibited more favorable responses to immunotherapy and improved prognoses than did their high-risk counterparts.

The developed ER.Sig effectively predicted the prognosis of patients with HCC and revealed significant differences in tumor biology and treatment responses between the risk groups.

Updated data on the survival of patients with cirrhosis are limited, especially for subgroups by specific liver disease aetiology. To inform practice, future modelling studies, and public health planning, our study aimed to provide updated and granular data on survival outcomes of patients with cirrhosis stratified by liver disease aetiology. We also assessed their changes over time.

We analysed 8726 consecutive adult patients with cirrhosis who presented at Stanford university medical center during 1/2005-1/2022.

8726 Patients had the following etiologies: hepatitis C virus (HCV) (28.1%), hepatitis B virus (HBV) (4.8%), alcohol-associated (ALD, 33.3%), metabolic-associated steatotic liver disease (MASLD) (9.5%), autoimmune (9.6%), cryptogenic (8.2%) and other etiologies (6.5%). Patients with cryptogenic cirrhosis had the lowest overall 5-, 10-, and 15-year cumulative survival (57.5%, 34.3% and 21.4%), as well as for liver and nonliver-related death, followed by ALD, MASLD, HCV, and autoimmune, while HBV patients had the best survival (86.0%, 70.1% and 65.1%), respectively. On multivariable Cox regression, cryptogenic cirrhosis (vs. HBV) was associated with the highest risk of all-cause death (aHR: 2.24, 95% CI 1.67-3.00), followed by MASLD and ALD (all p < 0.001). Post-2010 time was associated with a 33% lower risk of all-cause death (p = 0.0011); While in the post-2010 period, MASLD (vs. HBV) was associated with the highest risk of all-cause death (aHR: 1.92, 95% CI 1.32-2.80, p < 0.001) followed by cryptogenic and ALD.

Survival outcomes in patients with cirrhosis varied by aetiology and have changed over time, which should be taken into account for future practice guidelines and modelling studies.

Neurological disorders represent a significant global health issue, leading to severe cognitive impairments and being a major cause of premature mortality and disability. This study aims to utilize data from the Global Burden of Disease (GBD) research website to assess the burden of neurological disorders in the Asian region and its individual countries and territory from 1990 to 2021, with the goal of providing reference for global efforts and decision-making in the prevention, treatment, and management of neurological disorders.

Based on the Global Burden of Disease data, this study assessed the incidence, prevalence, mortality, and disability-adjusted life years (DALYs) of 13 neurological disorders in the Asian region from 1990 to 2021. The epidemiological characteristics of neurological disorders across these Asian regions were analyzed. Joinpoint regression analysis was employed to assess the temporal patterns of the burden of neurological disorders, and the average annual percent change (AAPC) was calculated to determine the overall trend throughout the study period.

In 2021, stroke, migraine, and Alzheimer's disease and other dementias emerged as the primary contributors to neurological burden in Asia, with stroke accounting for 112.87 million disability-adjusted life years (DALYs), followed by migraine (25.4 million) and Alzheimer's disease and other dementias (20.0 million). Stroke was also the leading cause of neurological mortality (5.03 million deaths), trailed by Alzheimer's disease and other dementias (1.0 million). Stroke, migraine, and tension-type headache had the highest prevalence rates among neurological disorders, with 57.3 million, 683.5 million, and 1130.2 million. Temporal trends from 1990 to 2021 revealed a significant decline in age-standardized DALY rates for stroke (estimated annual percentage change [EAPC]: - 1.65%), though absolute DALYs increased (EAPC: 0.06%). In contrast, Alzheimer's disease and other dementias exhibited rising age-standardized (EAPC: 0.14%) and absolute DALYs (EAPC: 2.8%), while infectious neurological diseases (e.g., meningitis, tetanus) demonstrated marked reductions in burden. Sex-specific disparities were evident, with males experiencing a higher total DALY burden (84.8 million vs. 77.05 million), driven by stroke and Parkinson's disease, whereas Alzheimer's disease and other dementias and migraine disproportionately affected females. Geographically, stroke dominated Southeast Asia (67.6% of regional DALYs), while migraine contributed most substantially to West Asia (16%). Nationally, stroke ranked as the leading cause of neurological DALYs in most Asian countries, contrasting with migraine in Israel, Kuwait, Qatar, and the United Arab Emirates. Longitudinal analyses highlighted accelerated declines in stroke DALYs post- 2004 but escalating burdens for Alzheimer's disease and other dementias after 2019, reflecting divergent epidemiological trajectories.

In 2021, the burden of neurological disorders in Asia remained substantial, with stroke, migraine, and Alzheimer's disease and other dementias being the top three contributors to DALYs. The study also revealed significant differences in the burden of neurological disorders across various subregions and countries in Asia, highlighting the need for enhanced international collaboration, sharing of best practices, provision of technical support, and optimization of healthcare resource allocation.

Liver cirrhosis seriously harms human health and fibrosis is the essential pathological process of cirrhosis. Recently, circular RNAs (circRNAs) were found to play critical roles in liver fibrosis, but the key circRNAs and precise mechanisms remained unclear. This study aimed to investigate the effect of circ_0098181 in fibrogenesis and explore its mechanism.

RNA sequencing was conducted to identify circRNA signatures in human liver cirrhotic tissues. Hepatic stellate cells (HSCs) (including primary rat HSCs, LX2, HSC-T6) and carbon tetrachloride (CCl4) induced liver cirrhosis model were used to explore the role of circ_0098181 on HSC activation and liver fibrogenesis in vitro and in vivo. RNA sequencing, RNA pull-down, mass spectrometry, and RNA immunoprecipitation (RIP) experiments were performed to elucidate the mechanism.

Circ_0098181 was obviously reduced in human fibrotic liver tissues and activated HSCs. Exogenous administration of circ_0098181 blocked the activation, proliferation, and migration of HSCs in vitro and mitigated the progression of CCl4-induced liver fibrosis in vivo. Mechanistically, adenosine deaminase acting on RNA1 (ADAR1) combined with the intronic complementary sequences (ICSs) in the flanking regions, thereby regulating the biogenesis of circ_0098181. RNA sequencing and qRT-PCR revealed the suppression of circ_0098181 on pro-inflammation cytokines expression (TNFα, Fas, Cxcl11, etc.). RNA pull-down, mass spectrometry, and RIP experiments indicated that pyruvate kinase M2 (PKM2) was the direct target of circ_0098181. Circ_0098181 bound to PKM2, restrained its nuclear translocation and phosphorylation.

In conclusion, circ_0098181 exerts a significant anti-fibrotic effect by binding PKM2 to repress its nuclear translocation and inhibiting hepatic inflammation, suggesting the promising therapeutic merit in liver cirrhosis.

Aim: To evaluate the clinical characteristics and healthcare resource utilization for acute care and its costs for patients with primary biliary cholangitis (PBC) with or without cirrhosis. Materials & methods: This retrospective observational cohort study was conducted using two datasets (Komodo's Healthcare Map™ [Komodo Health] and Optum Clinformatics® Data Mart [CDM] database) between 2015 and 2023. Patients (≥18 years) with PBC were identified based on ≥1 inpatient or ≥2 outpatient claims. Healthcare resource utilization for acute care (hospitalizations and emergency department [ED] visits [not leading to hospitalization]) were assessed in both datasets, and associated medical costs were evaluated in Optum CDM. Results: In Komodo Health, of the 29,758 patients with PBC (mean age: 59.2 years), 21.6% had cirrhosis and 50.4% of patients with cirrhosis had Medicaid or Medicare coverage. Of the total 8143 patients in Optum CDM (mean age: 67.0 years), 20.7% had cirrhosis, and most were enrolled in Medicare (69.7%). There was a larger proportion of men in the cirrhosis group compared with the no-cirrhosis group in Komodo Health (31.7 vs 16.3%) and Optum CDM (29.7 vs 16.5%). Annually, among patients with cirrhosis who had a hospitalization, 69.3% had additional hospitalizations, and among patients who had an ED visit, 52.9% had additional ED visits in Komodo Health; similar results were observed in Optum CDM. Among patients with at least one acute-care event, the mean annual acute-care costs with and without cirrhosis were $113,568 and $47,436, respectively. Conclusion: Data from two large healthcare claims databases showed that the majority of patients who had at least one acute-care event experienced additional acute-care events, particularly among those with cirrhosis. Timely treatment to avoid hospitalization and disease progression may help mitigate the clinical and economic burden for patients with PBC.

Liver cancer (LC) is a major concern in the Asia-Pacific region, particularly in China, Korea, and Japan. In this study, we aimed to investigate the burden, trends, and predictions related to LC in these countries.

Using data from the Global Burden of Disease Study 2021, the epidemiological characteristics [incidence, deaths, and disability-adjusted life-years (DALYs)] for LC were analysed and stratified by specific etiologies in China, Japan, and South Korea. We examined temporal trends in LC burden over the last 32 years and projected changes over the following 25 years. The risk factors associated with LC deaths and DALYs were also investigated.

In 2021, the highest LC-related incidence, mortality, and DALYs were recorded in China (196,637 incidents, 172,068 mortalities, and 4,890,023 DALYs), and the lowest in South Korea (18,642 incidents, 13,674 deaths, and 326,336 DALYs). South Korea recorded the highest age-standardized rates (ASRs) of incidence, mortality, and DALYs for LC (19.94 per 100,000, 14.53 per 100,000, and 354.57 per 100,000), and Japan the lowest (9.89, 7.29, and 145.74, respectively). From 1990 to 2021, LC incidents and deaths in the three countries increased, and the trends in ASRs decreased. LC incidents and deaths caused by five etiologies also increased in the past 32 years, and non-alcoholic steatohepatitis (NASH) was the largest increasing etiologies in China. Infections with hepatitis B virus remained the leading cause of LC in China and South Korea, while hepatitis C virus was the prevailing cause in Japan. High body mass index (BMI) was the most sharply increasing risk factor in China. Alcohol and drug use were the main risk factors for LC in South Korea and Japan, respectively. The LC burden in the three countries was projected to rise steadily between 2022 and 2046.

LC remains a significant disease burden in China, Japan, and South Korea now and over the next 25 years. Regarding etiologies and risk factors, NASH and high BMI in China, alcohol use in South Korea, and drug use in Japan should receive significant attention.

"Healthcare contact days" is a patient-centered quantitative proxy for time toxicity, which can be informative for liver transplant (LT) decision-making. We aimed to (i) quantify contact days in patients with cirrhosis pre-LT and post-LT and (ii) identify clinical and demographic features associated with contact days.

Using a national health system database, we calculated healthcare contact days (inpatient, outpatient hospital [e.g. observation], ambulatory, emergency, mental health, other) for patients with cirrhosis before and after LT.

Between 2008 and 2023, 2,708 patients underwent LT (median age 59 years [interquartile range 52-65], 66% male, 68% non-Hispanic White). Total mean contact days were 76.0 (SD, 58.6) 1 year pre-LT, increasing to 92.3 (SD, 63.2) 1 year post-LT, then decreasing to 39.7 (SD, 43.3) and 30.9 (SD, 35.6) 2 years and 3 years post-LT, respectively. The mean inpatient contact days were 33.6 (SD, 47.5) 1 year pre-LT, increasing to 49.6 (SD, 59.1) 1 year post-LT, then decreasing to 11.9 (SD, 32.0) and 6.7 (SD, 19.8) 2 years and 3 years post-LT, respectively. In multivariable analysis, pre-LT contact days were not associated with post-LT days (incidence rate ratio [IRR] 1.00 [1.00-1.00]). Post-LT, female gender (IRR 1.09 [1.03-1.15]), Black race (IRR 1.11 [1.00-1.23]), and pre-LT dialysis (IRR 1.21 [1.10-1.34]) were associated with increased total contact days.

Healthcare contact days provide interpretable prognostic information to inform expectations regarding LT for cirrhosis and can be useful for patients, providers, and policymakers alike.

Recent epidemiological evidence indicates a significant rise in cirrhosis burden over the past 2 decades in all parts of the world, with cirrhosis incidence rates and related deaths escalating quickly. Women face unique risk factors and susceptibility to chronic liver diseases compared with men, underscoring the need for a sex-specific approach in early identification, reversal of causative factors, and complication prevention. This review aims to explore epidemiological trends and sex-specific factors contributing to the global epidemiology of cirrhosis among female patients today. While cirrhosis prevalence remains higher in male patients globally, the incidence rate from 2010 to 2019 grew faster among female patients. The female-to-male incidence ratio of metabolic dysfunction-associated steatotic liver disease-related cirrhosis globally in 2019 was 1.3, indicating a shifting trend toward new diagnoses among women now surpassing that of men. Alcohol-associated cirrhosis epidemiology is also changing, with trends toward an equal incidence of alcohol-associated cirrhosis between both sexes, particularly in industrialized nations with increased alcohol accessibility. Cirrhosis from viral hepatitis remains the main etiology among female patients in endemic regions. Sex differences in epidemiology are likely multifactorial, influenced by varying risk factors, susceptibility, and behaviors between sexes. Further research is necessary to better understand these disparities and to tailor sex-specific interventions toward improved management and treatment strategies, ultimately enhancing outcomes for women with cirrhosis and providing better patient-centered care.

Alcohol-associated liver disease (ALD) disproportionately impacts men, racial and ethnic minorities, and individuals of low socioeconomic status; however, it's unclear how recent increases in ALD burden have impacted these disparities. We aimed to describe trends in racial, ethnic and socioeconomic disparities in alcohol-associated hospital encounters.

We conducted a retrospective cohort study of adult hospital encounters with alcohol-associated diagnoses from three health systems between January 2016 and December 2021. The cohort was divided into three eras: a 'Historical Era,' (Oct 2016-June 2018, used only for trends); 'Era 1' (July 2018-March 2020); and 'Era 2' (April 2020-December 2021). Kaplan Meier and Cox regression analyses were performed to identify factors associated with overall survival.

We identified 19,295 individuals with alcohol-associated encounters (44.7% White, 29.8% Hispanic, and 21.8% non-Hispanic Black (NHB) individuals), with a greater increase observed between eras 1 and 2 than the historical era and Era 1 (8.7% vs. 5.0%, p < 0.01). By age and sex, the greatest increases in encounters were observed in the youngest and oldest females but only the oldest males. By race and ethnicity, Hispanic individuals had greater increases in encounters compared to Black and White individuals (14.8% vs. 7.5% and 6.3%, p < 0.01). Older age (aSHR: 1.03, 95% CI: 1.03-1.0), higher MELD (aSHR: 1.08, 95% CI: 1.0-1.09), hepatic encephalopathy (aSHR: 1.42, 95% CI: 1.06-1.90), and hepatocellular carcinoma (HCC) (aSHR: 3.20, 95% CI: 2.29-4.49) were associated with increased mortality.

The highest increases of alcohol-associated encounters were observed amongst young Hispanic and NHB women, highlighting variation in trends by age, sex, race and ethnicity. These disparities merit further investigation to elucidate underlying mechanisms and develop tailored interventions to improve ALD burden and outcomes.

Introduction. The study of gut microbiota is now an essential dimension in many clinical studies. For instance, microbiota diversity investigation can help us to better manage cirrhotic patients by the identification of markers of severity and the identification of possible sources of pathogens.Hypothesis/Gap Statement. Conducting clinical research on gut microbiota for fragile patients in intensive care units, such as cirrhotic patients, poses significant challenges.Aim. In this study, we developed a comprehensive toolkit for investigating gut microbiota in fragile patients using rectal swabbing combined with straightforward lifestyle and clinical questionnaires.Methodology . We applied this prospective approach to 49 well-phenotyped cirrhotic patients as a function of their compensation status (compensated patients with outpatients' recruitment vs decompensated patients in intensive care units).Results . Our results, consistent with the literature, showed that liver function impairment is associated with lower microbiota diversity. Additionally, we monitored aerobic microbiota in decompensated cirrhotic patients, observing the invasion of extended spectrum beta-lactamase (ESBL)-producing Escherichia coli in the gut's aerobic microbiota prior to severe infection caused by these pathogens.Conclusion. We propose this pragmatic methodology for larger cohort studies, aiming to enhance the monitoring of immunocompromised patients by using microbiota analysis as a predictive tool for the severity of associated pathologies and the identification of agents responsible for severe infections.

Falls are a major threat to the well-being of patients with cirrhosis. We are performing a clinical trial to determine whether lactulose, TeleTai-Chi, or their combination will reduce falls in HE and improve health-related quality of life (HRQOL) among patients with cirrhosis.

Patients with cirrhosis and portal hypertension without HE will be enrolled in 3 US states and followed participants for 24 weeks. In stage 1 (12 wk), participants will be randomized to receive either lactulose therapy or enhanced usual care. In stage 2 (12 wk), participants will be randomized to either TeleTai-Chi or usual care. The primary outcome is a hierarchical composite: Injurious falls, noninjurious falls, incident HE, and death/transplantation. Secondary outcomes include cognitive function, days-alive and out-of-hospital, and HRQOL. After completion of the interventions, participants will be followed for 48 weeks for health and financial outcomes.

Our study has a central institutional review board with individual site IRB review. Dissemination includes the publication of study findings and patient-focused educational webinars.

Acute alcohol-associated hepatitis (AH) is a syndrome that occurs in heavy and long-term drinkers and results in severe jaundice and liver failure. The mortality rate in severe cases is 20%-50% at 28 days, and in cases that do not improve despite appropriately timed corticosteroid therapy, the mortality rate reaches 70% at 6 months. The only curative treatment is early liver transplantation, but less than 2% of patients with severe AH are eligible. In order to improve the prognosis, diagnostic tools are needed to detect appropriate cases at risk of severe conditions, and new therapies need to be developed that can replace corticosteroids. Recent research has revealed that the pathogenesis of AH involves a complex of factors, including changes in the gut microbiota, inflammatory and cytokine signalling, oxidative stress and mitochondrial dysfunction, and abnormalities in the hepatic regenerative capacity. Non-invasive diagnostic tools focusing on these specific pathologies have been reported in recent years. In addition, several novel agents targeting specific pathways are currently being developed and tested in clinical trials. This review will provide an overview of alcohol-associated hepatitis and focus on the latest diagnostic tools, particularly non-invasive biomarkers, and novel therapies.

This review emphasizes a novel, multidisciplinary, coordinated approach in the management of chronic liver diseases (CLDs).

Chronic liver diseases represent a significant global health burden, marked by a notable shift in the prevalence patterns from virus-related to metabolic and alcohol-related entities. Malnutrition, frailty, and sarcopenia exert a substantial impact on patients with cirrhosis, affecting 75%-90% of cases and escalating as the disease progresses. The European Association for the Study of the Liver recommends a comprehensive approach to nutritional care, emphasizing the need for detailed assessments in patients with cirrhosis, using diverse tools such as computed tomography scans, bioelectrical impedance analysis, and evaluations of muscle function. Considering the prevalence of nutritional and psychological disorders in the CLD population, the treatment of these patients should be founded indispensably on a multidisciplinary approach.

A systematic search was conducted of the PubMed, MEDLINE, and SCOPUS databases to identify trials investigating the health effects of nutritional and psychological assessments in patients with CLD.

In dealing with the treatment of patients with CLD, an exploration of the psychological domain emerges as crucial, because psychological distress, especially depression, exerts a tangible influence on patient outcomes. Thus, the engagement of psychologists and/or psychotherapists, who might use techniques such as cognitive behavioral therapy, could enhance patients' comprehension of nutritional implications in their treatment and make them more aware of their illness.

The review emphasizes the relevance of both nutritional and psychological assessments in patients with CLD that could improve patient education on the pivotal role of nutrition in disease management. Randomized controlled trials evaluating the combined impact of nutritional and psychological support are recommended to further investigate this complex clinical landscape.

Patients with liver cirrhosis face high infection risks due to immune dysfunction and hospital-related factors, increasing mortality rates when sepsis occurs. While various biomarkers predict outcomes in cirrhosis, few are accessible and reliable. This study addresses the gap by evaluating the prognostic potential of the lactate-to-albumin ratio (LAR).

We retrospectively analyzed data from patients with cirrhosis and sepsis who were admitted to the intensive care unit at Beth Israel Deaconess Medical Center between 2008 and 2022. LAR was calculated from the ratio obtained from the first measurement taken within 24 h of admission. The optimal LAR threshold was determined using R statistical software. Kaplan-Meier analysis was used to compare mortality risks between two patient groups, while multivariate Cox proportional hazards regression models were used to assess the association between LAR and mortality risk in patients with cirrhosis and concomitant sepsis. A restricted cubic spline (RCS) was used to explore potential dose-response relationships between LAR and mortality. Receiver operating characteristic (ROC) analyses were used to assess the predictive ability, sensitivity, and specificity of LAR for all-cause mortality in patients with cirrhosis and combined sepsis, and the area under the curve (AUC) was calculated. Finally, subgroup analyses were performed to assess the relationship between LAR and prognosis across different populations.

A total of 1731 patients were included in the study. The optimal LAR threshold was identified as 1.0 using R statistical software. Kaplan-Meier analysis indicated that patients with higher LAR levels had a higher risk of 14-day, 28-day, and 90-day all-cause mortality (all log-rank P < 0.001). Multivariate Cox proportional hazards models indicated independent associations between higher LAR levels and all-cause mortality at 14-day, 28-day, and 90-day before and after adjusting for confounders. RCS analysis revealed a nonlinear association between LAR and short- and long-term all-cause mortality in patients with cirrhosis and sepsis. ROC curve analysis showed that although the predictive value of LAR for the prognosis of patients with cirrhosis combined with sepsis was slightly inferior to that of the Model for End-Stage Liver Disease score, it was significantly better than that of lactate, albumin, and the Sequential Organ Failure Assessment. Subgroup analyses showed no significant interactions between LAR and any specific subgroup.

LAR has good predictive value for the prognosis of patients with cirrhosis and sepsis.

The role of diet in reducing the burden of liver disease and mortality attributed to cirrhosis is very imperative. The present study scrutinized the relationship between dietary advanced glycation end products (AGEs) and mortality in patients with cirrhosis. This research was a prospective cohort study on 166 ambulatory cirrhotic patients who had been diagnosed with cirrhosis for a maximum of six months. Follow-up of patients continued for 5 years until May 2024. To determine the incidence of mortality in the quartiles of dietary AGEs, cox regression models were used with the adjustment of potential confounding variables. Although the first model of the analysis by adjusting the results for age and sex failed to show a significant increase in the risk of mortality in patients (HRQ4 vs. Q1 = 2.64; 95% CI = 0.9-7.5, P trend = 0.075), after adjusting the results for further confounders in the second (HRQ4 vs. Q1 = 3.56; 95% CI = 1.1-11.6, P trend = 0.040) and third (HRQ4 vs. Q1 = 3.3; 95% CI = 1.79-13.7, P trend = 0.048) models, the P trend for the risk of mortality during the quartiles of AGEs became significant. In addition, along with increasing trend of dietary AGEs, the number of deaths increased significantly (P = 0.024). Higher mortality risk was generally attributed to higher dietary AGEs in patients with cirrhosis.

To investigate the trends in alcohol-associated liver disease (ALD), liver cancer from alcohol, and alcohol use disorder (AUD) burden among older adults in the United States (US).

We gathered the ALD, liver cancer from alcohol, and AUD prevalence, mortality, and age-standardized rates (ASRs) from the Global Burden of Disease (GBD) Study 2021 between 2010 and 2021. We estimated the annual percent change (APC) with confidence intervals (CIs) for the burden of ALD, liver cancer from alcohol, and AUD in older adults (>70 years) in the United States. The findings were contrasted with global estimates and categorized by sex and state.

In 2021, there were approximately 512,340 cases of AUD, 56,990 cases of ALD, and 4490 cases of primary liver cancer from alcohol among older adults in the United States. In contrast to declining ASRs of prevalence and mortality in the global burden, these parameters were increased in older adults in the United States. From 2000 to 2021, prevalence from AUD (APC: 0.54%, 95% CI 0.43% to 0.65%), ALD (APC + 0.54%, 95% CI 0.22% to 0.86%), and primary liver cancer from alcohol (APC 2.93%, 95% CI 2.76% to 3.11%) increased. Forty states in the United States exhibited a rise in the prevalence rates of ALD in older adults.

Our findings highlighted the increased prevalence and mortality of AUD, ALD, and primary liver cancer from alcohol among older adults in the United Sates, contrasting with the decline in global trends. Public health strategies on ALD, AUD, and primary liver cancer from alcohol, which targets older adults, are urgently needed.

Morbidity and mortality from cirrhosis are substantial and increasing. Health disparities in cirrhosis and liver transplantation are reflective of inequities along the entire spectrum of chronic liver disease care, from screening and diagnosis to prevention and treatment of liver-related complications. The key populations experiencing disparities in health status and healthcare delivery include racial and ethnic minority groups, sexual and gender minorities, people of lower socioeconomic status and underserved rural communities. These disparities lead to delayed diagnosis of chronic liver disease and complications of cirrhosis (for example, hepatocellular carcinoma), to differences in treatment of chronic liver disease and its complications, and ultimately to unequal access to transplantation for those with end-stage liver disease. Calling out these disparities is only the first step towards implementing solutions that can improve health equity and clinical outcomes for everyone. Multi-level interventions along the care continuum for chronic liver disease are needed to mitigate these disparities and provide equitable access to care.

This study aims to explore racial disparities in immediate outcomes of Transjugular Intrahepatic Portosystemic Shunt (TIPS) among Native Americans, a group that have higher prevalence of liver cirrhosis but were the "invisible group" in previous TIPS studies due to their small population size.

The study identified Native Americans and Caucasians who underwent TIPS in National/Nationwide Inpatient Sample (NIS) database from Q4 2015-2020. Preoperative factors, including demographics, indications for TIPS, comorbidities, etiologies for liver disease, primary payer status, and hospital characteristics, were matched by 1:5 propensity score matching. In-hospital post-TIPS outcomes were then compared between the two cohorts.

There were 6,658 patients who underwent TIPS, where 101 (1.52%) were Native Americans and 4,574 (68.70%) were Caucasians. Native Americans presented as younger, with a lower socioeconomic status, and displayed higher rates of alcohol abuse and related liver diseases. After propensity-score matching, Native Americans had comparable in-hospital post-TIPS outcomes including mortality (8.33% vs 9.09%, p = 1.00), hepatic encephalopathy (18.75% vs 25.84%, p = 0.19), acute kidney injury (28.13% vs 30.62%, p = 0.71), and other adverse events. Native Americans also had similar wait from admission to operation (2.15 ± 0.30 vs 2.87 ± 0.21 days, p = 0.13), hospital length of stay (7.43 ± 0.63 vs 8.62 ± 0.47 days, p = 0.13), and total costs (158,299 ± 14,218.2 vs 169,425 ± 8,600.7 dollars, p = 0.50).

Native Americans had similar immediate outcomes after TIPS compared to their propensity-matched Caucasians. While these results underscore effective healthcare delivery of TIPS to Native Americans, it is imperative to pursue further research for long-term post-procedure outcomes.

Background: Portal hypertension is a major complication of chronic liver diseases, leading to serious issues such as esophageal variceal bleeding. The increase in portal vein pressure is driven by both an organic component and a functional component, including tonic contraction of hepatic stellate cells. These processes result in a pathological rise in intrahepatic vascular resistance, stemming from partial impairment of hepatic microcirculation, which is further exacerbated by abnormalities in extrahepatic vessels, including increased portal blood flow. Objectives: This review aims to provide a comprehensive overview of the evolving pharmacological therapies for portal hypertension, with consideration and discussion of pathophysiological mechanisms, clinical complications, and pharmacogenetic considerations, highlighting potential directions for future research. Methods: A review of recent literature was performed to evaluate current knowledge and potential therapeutic strategies in portal hypertension. Results: For over 35 years, non-selective beta-blockers have been the cornerstone therapy for portal hypertension by reducing portal vein inflow as an extrahepatic target, effectively preventing decompensation and variceal hemorrhages. However, since not all patients exhibit an adequate response to non-selective beta-blockers (NSBBs), and some may not tolerate NSBBs, alternative or adjunctive therapies that enhance the effects of NSBBs on portal pressure are being investigated in preclinical and early clinical studies. Conclusions: A better understanding of pharmacogenetic factors and pathophysiological mechanisms could lead to more individualized and effective treatments for portal hypertension. These insights highlight potential directions for future research.

Organ fibrosis is gradually becoming a human health and safety problem, and various organs of the body are likely to develop fibrosis. The ultimate pathological feature of numerous chronic diseases is fibrosis, and few interventions are currently available to specifically target the pathogenesis of fibrosis. The medical detection of organ fibrosis has gradually matured. However, there is currently no effective treatment method for these diseases. Therefore, we need to strive for developing effective and reliable drugs or substances to treat and prevent fibrotic diseases. Lactoferrin (LF) is a multifunctional glycoprotein with many pathological and physiologically active effects, such as antioxidant, anti-inflammatory and antimicrobial effects, and it protects against pathological and physiological conditions in various disease models. This review summarizes the effects and underlying mechanisms of LF in preventing organ fibrosis. As a naturally active substance, LF can be used as a promising and effective drug for the prevention and remission of fibrotic diseases.

Long-term exposure to lead is associated with an increased risk of diabetic kidney disease (DKD). However, limited data exist on global trends in DKD burden attributable to lead exposure, especially across diverse regions categorized by socioeconomic level. We aimed to assess the spatiotemporal changes in DKD burden attributable to lead exposure from 1990 to 2019 across 204 countries and regions with varying socio-demographic index (SDI) metrics. This retrospective analysis utilized data from the Global Burden of Disease Study 2019 (GBD2019) database. We estimated the burden of DKD attributable to lead exposure using the age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life year rate (ASDR), accounting for sex, age, nationality, and SDI. The annual percentage change (APC) and average annual percentage change (AAPC) were calculated using the Joinpoint model to evaluate trends in the ASMR and ASDR attributable to lead exposure from 1990 to 2019. Gaussian process regression was used to model the relationship between the SDI and ASMR/ASDR. Globally, the burden of DKD attributable to lead exposure has significantly increased since 1990, especially among elderly men and in regions such as Asia, Central Latin America, North Africa, the Middle East, and low-SDI regions. In 2019, the ASMR and ASDR of DKD attributable to lead exposure were 0.68 (95% CI: 0.40, 0.98) per 100,000 people and 15.02 (95% CI: 8.68, 22.26) per 100,000 people, respectively. From 1990 to 2019, the global ASMR and ASDR attributable to lead-associated DKD changed by 15.45% and -1.78%, respectively. The global AAPCs of the ASMR and ASDR were 0.55 (95% CI: 0.45, 0.65) and -0.01 (95% CI: -0.12, 0.1), respectively. Significant declining trends were observed in the high-income Asia Pacific region, eastern sub-Saharan Africa, North Africa, the Middle East, and other regions with high SDIs. Over this 30-year study period, the global burden of DKD attributable to lead exposure has increased, particularly in regions with low SDI. Lead exposure remains a significant concern in the global burden of diabetic kidney disease.

Due to current challenges in the early detection, less than 40% of individuals diagnosed with hepatocellular carcinoma (HCC) are viable candidates for surgical intervention. Therefore, validating and launching of a novel precise diagnostic approach is essential for early diagnosis. Based on developing evidence using circulating tumor cells and their derivatives, circulating miRNAs, and extracellular vesicles (EVs), liquid biopsy may offer a reliable platform for the HCC's early diagnosis. Each liquid biopsy analyte may provide significant areas for diagnosis, prognostic assessment, and treatment monitoring of HCC patients depending on its kind, sensitivity, and specificity. The current review addresses potential clinical applications, current research, and future developments for liquid biopsy in HCC management.

The COVID-19 pandemic has resulted in a greater incidence of alcohol-associated liver disease (ALD) and simultaneously magnified health-related inequalities. We evaluated the impact of race and ethnicity on ALD-related hospitalizations in Brazil.

An interrupted time series analysis was used to estimate ALD-related hospitalization in public hospitals in Brazil. Monthly hospitalization rates for 34 consecutive months before and after the point of interruption (March 2020) were calculated using the Sistema de Informações Hospitalares database across four ethnic groups: Black, Pardo, Black, and Pardo combined, and Others (White and Unknown Ethnicity).

A total of 84,787 ALD-related hospitalizations were recorded during the study period. The mean age of hospitalized patients was 53 years (SD=12.5); 83.6% were male. Immediately after the start of the pandemic, there was a statistically significant decrease in monthly ALD-related hospitalization rates for the whole population and for all ethnic groups. Subsequently, compared to pre-pandemic rates, there was a statistically significant trend increase in the referred hospitalization rates for the total population (0.065, 95% CI= 0.045 to 0.085, p<0.01), black population (0.0028, 95% CI= 0.006 to 0.050, p<0.05), pardo population (0.077, 95% CI= 0.063 to 0.090, p<0.01), and for black and pardo combined population (0.066, 95% CI= 0.053 to 0.079, p<0.01); however, the increase in hospitalization rates among the Others population (0.059, 95% CI= -0,014 to 0.133, p>0.1) was not statistically significant.

The pandemic impacted ALD-related monthly hospitalization rates and disproportionately impacted Black and Pardo populations in Brazil.

The fatty liver disease represents a complex, multifaceted challenge, requiring a multidisciplinary approach for effective management and research. This article uses conventional and advanced imaging techniques to explore the etiology, imaging patterns, and quantification methods of hepatic steatosis. Particular emphasis is placed on the challenges and advancements in the imaging diagnostics of fatty liver disease. Techniques such as ultrasound, CT, MRI, and elastography are indispensable for providing deep insights into the liver's fat content. These modalities not only distinguish between diffuse and focal steatosis but also help identify accompanying conditions, such as inflammation and fibrosis, which are critical for accurate diagnosis and management.

Alcohol-related liver disease (ALD) has emerged as a significant public health concern, particularly among younger populations. ALD remains the leading cause of alcohol-attributable deaths. This study aims to forecast ALD mortality trends up to 2030, focusing on individuals under 55 years.

We utilized data from the CDC WONDER database (1999-2022) to examine ALD-related deaths, identified by ICD-10 codes (K70.0-K70.9). Crude mortality rates (CMRs) per 100 000 were analyzed and temporal trends were assessed using annual and average annual percent changes (APC/AAPC) with empirical quantile confidence intervals. An Autoregressive Integrated Moving Average (ARIMA) model was employed to project mortality rates until 2030, validated through time series cross-validation.

From 1999 to 2022, there were 181 862 ALD-related deaths among individuals under 55, with mortality rates increasing from 3.9 per 100 000 in 1999 to 9.7 per 100 000 in 2022 (AAPC 4.66%, 95% CI: 3.90%-5.86%). Projections suggest rates will continue to rise, reaching 14.4 per 100 000 by 2030. From 1999 to 2022, the 25-34 age group experienced the highest increase, with an AAPC of 10.27% (95% CI: 9.19%-11.35%), while the 35-44 and 45-54 age groups showed more moderate increases, with AAPCs of 5.03% and 4.38%, respectively. Projections indicate an AAPC of 3.86% for ages 25-34, 3.90% for ages 35-44, and 6.17% for ages 45-54 by 2030.

Forecasts indicate a continued rise in ALD mortality among individuals under 55, necessitating immediate public health strategies to mitigate this trend.