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Background/Objectives: Gastroesophageal reflux disease (GERD) is one of the common gastrointestinal disorders worldwide. Recent epidemiologic studies have suggested that use of statins may lower the risk of GERD although the results from different studies were inconsistent. This systematic review and meta-analysis were conducted with the aim to summarize all available data. Methods: A systematic literature review was performed using MEDLINE and EMBASE database from inception to December 2017. Cohort, case-control, and cross-sectional studies that compared the risk of GERD among statin users versus nonusers were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. Results: A total of 4 studies (1 case control, 1 cohort, and 2 cross-sectional studies) with 14,505 participants met the eligibility criteria and were included in the meta-analysis. The risk of GERD among statin users was numerically lower than nonusers with the pooled OR of 0.89 but the result did not achieve statistical significance (95% CI, 0.60–1.33). The statistical heterogeneity in this study was moderate (I2 = 54%). Conclusions: The current meta-analysis found that the risk of GERD was numerically lower among statin users although the pooled result did not reach statistical significance. Therefore, more studies are still needed to further clarify this potential benefit of statins. [ABSTRACT FROM AUTHOR]

Background and Objectives: Patients with psoriasis are known to be at a higher risk of several comorbidities, but little is known about their risk of developing schizophrenia. Methods: A systematic review and meta-analysis of cohort and case–control studies that reported relative risk, hazard ratio, odds ratio (OR), or standardized incidence ratio comparing risk of schizophrenia in patients with psoriasis versus subjects without psoriasis was conducted. Pooled OR and 95% confidence interval were calculated using random-effect, generic inverse-variance methods of DerSimonian and Laird. Results: A total of five studies (one retrospective cohort study and four case–control studies) with more than 6 million participants met the eligibility criteria and were included in this meta-analysis. The pooled OR of schizophrenia in patients with psoriasis versus subjects without psoriasis was 1.41 (95% confidence interval, 1.19–1.66). The statistical heterogeneity was low with an I2 of 33%. Conclusion: This systematic review and meta-analysis demonstrated a significantly increased risk of schizophrenia among patients with psoriasis. [ABSTRACT FROM AUTHOR]

Background Non-steroidal anti-inflammatory drugs (NSAIDs) can suppress the proliferation of cholangiocarcinoma (CCA) cells in vitro through inhibition of cyclooxygenase-2. However, the effects of aspirin and NSAIDs on the risk of CCA remain unclear. We performed this meta-analysis to assess the risk of biliary tract cancers in patients who take aspirin and/or NSAIDs. Methods A systematic review was conducted utilizing MEDLINE, EMBASE, Cochrane databases from inception through October 2017 to identify studies that assessed the association of aspirin and/or NSAIDs use with risk of biliary tract cancers including CCA, gallbladder cancer and ampulla of Vater cancer. Effect estimates from the studies were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird. Results Five observational studies with a total of 9 200 653 patients were enrolled. The pooled OR of CCA in patients with aspirin use was 0.56 (95% CI, 0.32–0.96). Egger's regression asymmetry test was performed and showed no publication bias for the association between aspirin use and CCA with P = 0.42. There was no significant association between NSAIDs use and CCA, with a pooled OR of 0.79 (95% CI, 0.28–2.21). One study showed a significant association between aspirin use and reduced risk of gallbladder cancer with OR of 0.37 (0.17–0.80). However, there was no significant association between aspirin and ampulla of Vater cancer with OR of 0.22 (0.03–1.65). Conclusions Our study demonstrates a significant association between aspirin use and a 0.56-fold decreased risk of CCA. However, there is no association between the use of NSAIDs and CCA. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested an increased risk of hip fracture among patients with peripheral arterial disease (PAD), however, the results have been inconsistent. This meta-analysis was conducted with the aim to summarize all available evidence to better characterize the risk of incident hip fracture among these patients. Materials and Methods: A comprehensive literature review was conducted using the MEDLINE and EMBASE databases through October 2017 to identify all cohort and case-control studies that compared the risk of subsequent hip fracture between patients with PAD and individuals without PAD. Effect estimates of the included studies were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird. Results: The systematic review process yielded six eligible cohort studies comprising 15,895 patients with PAD. There was a significant association between incident hip fracture and PAD with the pooled relative risk (RR) of 1.64 (95% CI, 1.17–2.29; I2, 80%), comparing patients with PAD and individuals without PAD. Subgroup analysis by study design revealed significant results for both prospective studies (pooled RR 1.60; 95% CI, 1.12–2.28; I2, 0%) and retrospective studies (pooled RR 1.72; 95% CI, 1.07–2.77; I2, 92%). The funnel plot is relatively asymmetric suggesting publication bias. Conclusion: This study found a significant association between PAD and hip fracture with the pooled RR of 1.64 (95% CI, 1.17–2.29) on comparing patients with PAD and individuals without PAD. Major limitations include high between-study heterogeneity, possibility of publication bias, and lack of data on the characteristics and type of hip fracture which may limit the clinical significance of the observations. [ABSTRACT FROM AUTHOR]

Background/Objectives: The possible relationship between smoking and risk of colonic diverticulosis has been suggested by recent epidemiological studies, although the results were inconsistent. This meta‑analysis was conducted to summarize all available data. Methods: A comprehensive literature review was conducted using the MEDLINE and EMBASE databases through May 2017 to identify all studies that compared the risk of colonic diverticulosis among current and former smokers versus nonsmokers. Effect estimates from each study were extracted and combined together using the random‑effect, generic inverse variance method of DerSimonian and Laird. Results: Of 465 potentially eligible articles, three prospective cohort studies with 130,520 participants met the eligibility criteria and were included in the meta‑analysis. The risk of colonic diverticulosis in current smokers was significantly higher than nonsmokers with the pooled risks ratio of 1.46 (95% confidence interval [CI], 1.13–1.89). However, the risk of colonic diverticulosis in former smokers was not significantly higher than nonsmokers with the pooled risk ratio of 1.13 (95% CI, 0.88–1.44). Conclusions: A significantly increased risk of colonic diverticulosis among current smokers is demonstrated in this study [ABSTRACT FROM AUTHOR]

Aim: This study aims to investigate the association between insomnia or excessive daytime sleepiness (EDS) and risk of nonalcoholic fatty liver disease (NAFLD). Methods: We searched published studies indexed in MEDLINE and EMBASE database from inception to December 2015. Studies that reported odds ratios (ORs), risk ratios, hazard ratios or standardized incidence ratio with 95% confidence intervals (CI) comparing the risk of NAFLD among participants who had insomnia or EDS versus those without insomnia or EDS were included. Pooled ORs and 95% CI were calculated using a random‑effect, generic inverse variance method of DerSimonian and Laird. Cochran’s Q test and I2 statistic were used to determine the between‑study heterogeneity. Results: Our search strategy yielded 2117 potentially relevant articles (781 articles from MEDLINE and 1336 articles from EMBASE). After comprehensive review, seven studies (three cross‑sectional studies and four case–control studies) were found to be eligible and were included in the meta‑analysis. The risk of NAFLD in participants who had insomnia was significantly higher with the pooled OR of 1.13 (95% CI, 1.00–1.27). The statistical heterogeneity was moderate with an I2 of 62%. Elevated risk of NAFLD was also observed among participants with EDS even though the 95% CI was wider and did not reach statistical significance (pooled OR 2.21; 95% CI, 0.84–5.82). The statistical heterogeneity was moderate with an I2 of 62%. Conclusions: Our study demonstrated an increased risk of NAFLD among participants who had insomnia or EDS. Whether this association is causal needs further investigations. [ABSTRACT FROM AUTHOR]

Background The association between periodontitis and systemic diseases has been increasingly recognized. However, the data on the association between periodontitis and psoriasis are still limited. Objectives To summarize all available data on the association between periodontitis and the risk of psoriasis. Methods Two investigators independently searched published studies indexed in MEDLINE and EMBASE databases from inception to July 2016 using a search strategy that included terms for psoriasis and periodontitis. Studies were included if the following criteria were met: (i) case-control or cohort study comparing the risk of psoriasis in subjects with and without periodontitis; (ii) subjects without periodontitis were used as comparators in cohort studies while participants without psoriasis were used as controls in case-control studies; and (iii) effect estimates and 95% confidence intervals (CI) were provided. Point estimates and standard errors from each study were extracted and combined together using the generic inverse variance technique described by DerSimonian and Laird. Results Two cohort studies and three case-control studies met the inclusion criteria and were included in the meta-analysis. The pooled risk ratio of psoriasis in patients with periodontitis versus comparators was 1.55 (95% CI, 1.35-1.77). The statistical heterogeneity was insignificant with an I2 of 18%. Subgroup analysis according to study design revealed a significantly higher risk among patients with periodontitis with a pooled RR of 1.50 (95% CI, 1.37-1.64) for cohort studies and a pooled RR of 2.33 (95% CI, 1.51-3.60) for case-control studies. Conclusions Patients with periodontitis have a significantly elevated risk of psoriasis. [ABSTRACT FROM AUTHOR]

Background/Objectives: Nonalcoholic fatty liver disease (NAFLD) is the major concern of public health worldwide. The risk of NAFLD in subjects who regularly drink soda is controversial. The aim of this study was to assess the association between consumption of sugar-sweetened soda and NAFLD. Methods: A literature search was performed using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from inception through June 2015. Studies that reported relative risks, odd ratios, or hazard ratios comparing the risk of NAFLD in patients consuming a significant amount of either sugar or artificially sweetened soda vs. those who did not consume soda were included. Pooled risk ratios (RRs) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. Results: Seven observational studies were included in our analysis to assess the association between consumption of sugarsweetened soda and NAFLD. The pooled RR of NAFLD in patients consuming sugar-sweetened soda was 1.53 (95% CI: 1.34- 1.75, I² = 0). When meta-analysis was limited only to studies with adjusted analysis, the pooled RR of NAFLD was 1.55 (95% CI: 1.36-1.78, I² = 0). The data on association between consumption of artificially sweetened soda and NAFLD were limited; one observational study reported no significant increased risk of NAFLD in artificially sweetened soda consumption. Conclusions: Our study demonstrates statistically significant association between sugar-sweetened soda consumption and NAFLD. This finding may impact clinical management and primary prevention of NAFLD. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal cancers comprise nearly one-third of global mortality from cancer, yet the comprehensive global burden of these cancers remains uninvestigated., Objective: We aimed to assess the global, regional and national burden of gastrointestinal cancers., Designs: Data on oesophagus, gastric, colorectal, liver, pancreas and biliary tract cancers were extracted from the Global Burden of Disease 2021 database. Age-standardised incidence rate (ASIR) and age-standardised death rate (ASDR) were calculated by sex, region and Sociodemographic Index (SDI)., Results: In 2021, there were 5.26 million incidences and 3.70 million deaths from gastrointestinal cancer. The greatest burden is from colorectal, followed by gastric, oesophageal, pancreatic, liver and biliary tract cancer. We noted geographical and socioeconomic differences in ASIR and ASDR across all types of cancers. From 2000 to 2021, ASIR increased for colorectal cancer (annual percent change (APC): 0.10%, 95% CI 0.05% to 0.14%), pancreatic cancer (APC: 0.27%, 95% CI 0.14% to 0.41%), and liver cancer from metabolic dysfunction-associated steatotic liver disease (APC: 0.62%, 95% CI 0.58% to 0.67%) and alcohol-related liver disease (APC: 0.26%, 95% CI 0.22% to 0.30%). ASDR increased for pancreatic cancer (APC: 0.18%, 95% CI 0.02% to 0.34%). Higher SDI countries had higher incidence rates for most types of gastrointestinal cancer., Conclusions: Although the ASIR of oesophageal, gastric and biliary tract cancer has decreased, the ASIR still increased in colorectal, pancreatic and liver cancer from steatotic liver disease. Public policies are important for controlling gastrointestinal cancers-most importantly, reducing alcohol consumption, hepatitis B immunisation and tackling the burden of metabolic diseases., Competing Interests: Competing interests: MBW declared the conflict of interest as designated below: Consulting: Cosmo/Aries Pharmaceuticals, Verily, Boston Scientific, Endiatix, Intervenn, AlphaMed UAE, Fujifilm. Research grants: Fujifilm, Boston Scientific, Olympus, Medtronic, Ninepoint Medical, Cosmo/Aries Pharmaceuticals. Stock/Stock Options: Virgo Inc. Consulting on behalf of Mayo Clinic: Boston Scientific, Microtek. General payments/Minor Food and Beverage: Boston Scientific and Cook Medical. All other coauthors denied conflict of interest. LRR has been on advisory boards for AstraZeneca, Bayer, Eisai, Exact Sciences, Focus Medical Communication, Gilead Sciences, GRAIL, Inc., Novartis Venture Fund, Pontifax, and Roche. LR has received research support from Bayer, Boston Scientific, Exact Sciences, Fujifilm Medical Systems, Genentech, Gilead Sciences, Glycotest, Inc., HERMES, Innovo Bioanalysis, RedHill Biopharma, and TARGET Real World Evidence., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

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., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background/aims: Multi-society experts proposed the adoption of new terminology, metabolic dysfunction-associated steatotic liver disease (MASLD) and steatotic liver disease (SLD). We studied the current prevalence of SLD and its subcategories in the US., Methods: Using the recent National Health and Nutrition Examination Survey from 2017 to 2023, we analyzed data from 12,199 participants (≥18 years) who completed transient elastography. SLD and its subcategories, including MASLD, metabolic and alcohol-related liver disease (MetALD), and alcohol-related liver disease (ALD), were categorized according to consensus nomenclature., Results: The age-adjusted prevalence of SLD (cut-off: 285 dB/m) was 35.0% (95% confidence interval [CI]: 33.4-36.7). Within this category, the age-adjusted prevalence for MASLD was 31.9% (95% CI: 30.4-33.4), MetALD 2.2% (95% CI: 1.8-2.6), and ALD 0.8% (95% CI: 0.6-1.1). The prevalence of SLD and MASLD showed a statistically insignificant decrease during COVID-19, while ALD increased without significance. In contrast, the prevalence of advanced fibrosis in SLD was significantly higher during the COVID-19 era, at 9.8% for 285 dB/m and 7.8% for 263 dB/m, compared to 7.4% (P=0.039) and 6% (P=0.041) in the pre-COVID-19 era. The proportion of advanced fibrosis and cirrhosis in individuals with ALD was two-fold higher than MASLD and MetALD, largely due to increases during the COVID-19 era., Conclusion: While the prevalence of SLD and its subcategories remained stable, there was a significant increase in advanced fibrosis among SLD individuals during the COVID-19 era, with ALD having a proportion of advanced fibrosis and cirrhosis that was twice as high as MASLD and MetALD.

Background: Alcohol is linked to various cancers. While many studies have focused on developed countries, the burden of alcohol-related cancers in developing countries remains underexplored., Methods: We analyzed data from the Global Burden of Disease Study (2000-2019) to assess mortality and disability-adjusted life years (DALYs) from alcohol-related cancers in low and low-to-middle sociodemographic index (SDI) countries., Results: In 2019, there were 494 730 mortality from alcohol-related cancer. Low and low-middle SDI countries contributed over 15% of global mortality of alcohol-related cancer. Among multiple types of cancer, other pharyngeal cancers in these countries accounted for over 30% of global mortality of alcohol-related cancer. Primary liver cancer exhibited the highest mortality (n = 16 090) in low and low-middle SDI countries. While deaths and DALYs rates from alcohol-related cancers decreased globally between 2000 and 2019, the related burden increased in low and low-middle SDI countries with a rise in all types of alcohol-related cancers, except for primary liver cancer. The most rapidly growing mortality rates in low SDI were from other pharyngeal cancers (+2.25%), whereas in low-middle SDI countries, colorectal cancer evidenced the highest increase (+2.76%)., Conclusion: The burden from alcohol-related cancer has risen in countries with low and low-to-middle SDI, especially other pharyngeal cancers and colorectal cancer. Policymakers should focus on improving alcohol-related policies as well as screening availability to tackle the associated burden of cancer in resource-constrained countries. However, the difficulty in isolating the impact of alcohol due to limited data on other confounders necessitates caution in interpreting these findings., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Substance use disorders (SUDs) play a major role in global preventable disability and mortality. Even though they impact patients of all ages, adolescents and young adults (AYAs) are at increased risk of substance use at a later age. We aim to assess the burden of SUDs and alcohol-related harms in AYAs., Methods: This study employed the Global Burden of Disease Study 2019 data. We assessed the prevalence, incidence, years of life lost, years of living with disability, and disability-adjusted life years (DALYs) of SUDs, alcohol use disorder (AUD), and alcohol-related burden in AYAs (10-24 years)., Results: Among multiple SUDs, AUD had the highest prevalence (13.31 million), followed by cannabis use disorder (10.69 million) and opioid use disorder (4.27 million). From 2010-2019, while many SUDs saw a decrease in prevalence and incidence rates, opioid use disorder experienced increases across prevalence and incidence rates. Geographically, Europe and the Americas recorded the highest SUD burden. Higher Socio-demographic Index (SDI) levels correlated with increased SUD burden. Females showed a lower burden from SUDs and related health issues compared to males. The distribution of DALYs relative to prevalence varied across different SUDs and SDIs. The largest mortality caused by alcohol use were road injuries, interpersonal violence, and self-harm., Conclusion: The worldwide burden of SUDs, particularly AUD, cannabis use disorder, opioid use disorder, and alcohol-induced harms (particularly injuries) among AYAs, is significant. Addressing this issue urgently requires the implementation of effective policies targeting SUDs., Competing Interests: Declaration of Competing Interest Mazen Noureddin has been on the advisory board for 89BIO, Gilead, Intercept, Pfizer, Novo Nordisk, Blade, EchoSens, Fractyl, Terns, Siemens, and Roche diagnostic; has received research support from Allergan, BMS, Gilead, Galmed, Galectin, Genfit, Conatus, Enanta, Madrigal, Novartis, Pfizer, Shire, Viking and Zydus; and is a minor shareholder or has stocks in Anaetos, Rivus Pharma and Viking. Vincent Chen’s institution has received research grants from KOWA and AstraZeneca. Hirokazu Takahashi received a research grant from Astellas Pharma, AbbVie GK and Sysmex. Gerald Scott Winder: consulting fees from Alexion and GSK. Lorenzo Leggio is a federal employee at the National Institutes of Health Intramural Research Program and is supported by NIDA and NIAAA. Jessica Mellinger has received consulting fees from GlaxoSmithKline, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: In patients with metabolic dysfunction-associated steatotic liver disease (MASLD), there are limited data on how changes in FIB4 and liver stiffness measurement (LSM) correlate in non-biopsy cohorts., Aims: Our objective was to evaluate associations between changes in FIB4 and LSM in MASLD patients., Methods: We included MASLD patients with serial VCTE from 2015-2022. The primary predictors were change in FIB4 and presence of diabetes, obesity, and high alanine aminotransferase (ALT). The primary outcome, applied only to patients with LSM1 < 8 kPa, was incident significant fibrosis (SF) defined as a ≥ 20% increase in LSM2 vs. LSM1 and LSM2 ≥ 8 kPa. A secondary outcome was LSM progression with a similar definition but applied to all participants, not only those with LSM1 < 8 kPa., Results: Of 285 included patients, 216 had LSM1 < 8 kPa and were included in the primary analysis; of these, 34 (16%) had incident SF. Changes in FIB4 correlated with changes in LSM (R = 0.16, p = 0.016). Independent predictors of incident SF included comorbid diabetes mellitus (OR 2.43, 95% CI 1.04-6.56), obesity (OR 3.88, 95% CI 1.63-9.25), and baseline ALT ≥ 30 (OR 8.55, 95% CI 1.10-66.29). A model including ALT, diabetes, and obesity outperformed a model with FIB4 change alone., Conclusion: Among patients with MASLD, changes in FIB4 correlated with changes in LSM but more significant correlates of incident significant fibrosis included diabetes mellitus, obesity, and high baseline ALT., Competing Interests: Declarations Conflict of interest VLC received grants from KOWA, Ipsen, and AstraZeneca (paid to his institution). The remaining authors have no conflicts of interest to disclose., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background/aims: Liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) is recommended for risk stratification of patients with nonalcoholic fatty liver disease (NAFLD). More recently, AGILE3 + and AGILE4 have combined LSM with clinical parameters to identify patients with advanced fibrosis and cirrhosis, respectively. However, there are limited data on prognostic performance of these scores in key at-risk subgroups such as those with diabetes and obesity compared to LSM alone., Methods: This is a retrospective cohort study including 1903 adult patients with NAFLD from tertiary care centers in the United States and Singapore undergoing VCTE between 2015 and 2022. Primary predictors were FAST, LSM, AGILE3 + , and AGILE4 scores and the primary outcome was liver-related events (LRE). Patients were further stratified by diabetes and obesity status. Prognostic performance was measured using the time-dependent area under the receiver operating characteristic curve (tAUC) at 5 years., Results: In total, 25 LRE occurred and the overall incidence rate of LRE was 4.4 per 1000 person-years. tAUC for predicting LRE in the overall group was significantly higher with AGILE3 + (0.94 [95% CI: 0.90-0.98]) and AGILE4 (0.94 [95% CI: 0.90-0.98]) compared to LSM (0.87 [95% CI: 0.80-0.94]) (p = 0.001 and 0.009, respectively) and FAST (0.73 [95% CI: 0.59-0.86]) (p < 0.001 for both). Similarly, tAUC was significantly higher in those with T2D for AGILE3 + compared to LSM (0.92 vs 0.86, respectively) (p = 0.015) and FAST (0.92 vs 0.73, respectively) (p = 0.008). Among people with obesity, tAUC was significantly higher for AGILE3 + compared to LSM (0.95 vs 0.89, respectively) (p = 0.005) and FAST (0.95 vs 0.76, respectively) (p = 0.0035). Though AGILE4 had a higher tAUC in these subgroups compared to LSM, it did not reach statistical significance., Conclusion: AGILE3 + significantly outperforms LSM and FAST for predicting LRE in patients with NAFLD including in those with diabetes or obesity., Competing Interests: Declarations Conflict of interest YJW was supported by the Nurturing Clinician Scientist Scheme, Medicine Academic Clinical Program, Singhealth. VLC was supported in part by National Institute of Diabetes and Digestive and Kidney Diseases (K08 DK132312)., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aim: Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a leading cause of chronic liver disease worldwide. A new entity termed MetALD has also been described and is defined as individuals with MASLD and increased alcohol intake. However, the natural history of MetALD compared with MASLD is unknown. We aimed to compare longitudinal outcomes in patients with MASLD versus MetALD., Methods: This study was performed using data from the National Health and Nutrition Examination Survey from 2011 to 2018. MASLD patients (defined by the United States Fatty Liver Index > 30) who met cardiometabolic criteria including body mass index (BMI) > 25 (BMI > 23 in Asians), hypertension, diabetes mellitus, dyslipidemia, and hypertriglyceridemia were included. MetALD was defined as MASLD with increased alcohol intake (3-6 standard drinks per day in males; 2-5 standard drinks per day in females). A comparison of overall, cardiovascular, cancer-related, and other causes of mortality in patients with MASLD versus MetALD was performed., Results: A total of 2838 individuals with MASLD and 2557 individuals with MetALD were included with a median follow-up time of 56 months. MetALD patients were at increased risk of cancer-related mortality compared with patients with MASLD (hazard ratio 1.32; 95% confidence interval 1.14-1.53; P < 0.01). However, there was no significant difference in overall, cardiovascular, and other causes of mortality., Conclusions: Patients with MetALD were at higher risk for cancer-related mortality than MASLD. Close attention to regular cancer surveillance and accurate classification of alcohol consumption in individuals with diagnosed MASLD is warranted to help improve patient care and outcome., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background & Aims: The epidemiology of adult primary liver cancer continues to evolve, owing to the increasing prevalence of metabolic disease, rising alcohol consumption, advances in vaccination for HBV, and antiviral therapy for HCV. Disparities in care and the burden of liver cancer between populations persist. We assess trends in the burden of liver cancer and contributions by various etiologies across 204 countries and territories from 2010 to 2021., Methods: Utilizing the methodological framework of the Global Burden of Disease Study 2021, we analyzed global and regional temporal trends in incidence and mortality, and the contributions of various etiologies of liver disease., Results: In 2021, there were an estimated 529,202 incident cases and 483,875 deaths related to liver cancer. From 2010 to 2021, global liver cancer incident cases and deaths increased by 26% and 25%, respectively. Global age-standardized incidence rates (ASIRs) and death rates (ASDRs) for liver cancer declined but rose in the Americas and Southeast Asia. HBV remained the dominant cause of global incident liver cancer cases and deaths. MASLD (metabolic dysfunction-associated steatotic liver disease) was the only etiology of liver cancer with rising ASIRs and ASDRs. By contrast, ASIRs and ASDRs remained stable for alcohol-related liver cancer, and declined for HBV- and HCV-related liver cancer., Conclusions: While age-adjusted incidence and deaths from liver cancer have started to decline, the absolute number of incident cases and deaths continues to increase. Population growth and aging contribute to the observed disconnect in the temporal trends of absolute cases and rates. Disparities remain, and MASLD-related liver cancer continues to surge., Impact and Implications: Liver cancer remains a major cause of death globally, but its causes and burden in various regions are changing. This study highlights that new diagnoses and deaths related to liver cancer continue to rise. Age-adjusted death rates of liver cancer related to viral hepatitis are declining but remain high. By contrast, age-adjusted death rates of liver cancer related to MASLD (metabolic dysfunction-associated steatotic liver disease) are rising. Sustained efforts and resources are needed to eliminate viral hepatitis, reverse current trends in heavy alcohol use, and tackle the metabolic risk factors of MASLD., Competing Interests: Conflict of interest Daniel Q Huang has served as an advisory board member for Gilead and Roche. Yao-Chun Hsu has received research support from Gilead Sciences and Sysmex has served as an advisory board member for Gilead Sciences and has received payments for lectures from Abbvie, Bristol-Myers Squibb, Gilead Sciences, Merck Sharp & Dohme, and Novartis. Ju Dong Yang consults for AstraZeneca, Eisai, Exact Sciences, and FujiFilm Medical Sciences. Hirokazu Takahashi has received research grants from Astellas Pharma, AbbVie GK, and Sysmex. Ming-Hua Zheng has received honoraria for lectures from AstraZeneca, Hisky Medical Technologies, and Novo Nordisk and consulting fees from Boehringer Ingelheim and serves as a consultant for Eieling Technology; He also serves as an unpaid editorial board member of Hepatobiliary Surgery and Nutrition and Liver International. Amit Singal has served as a consultant or on advisory boards for Genentech, AstraZeneca, Eisai, Exelixis, Bayer, Elevar, Boston Scientific, Sirtex, Histosonics, FujiFilm Medical Sciences, Exact Sciences, Roche, Abbott, Glycotest, Freenome, and GRAIL. His research effort is supported by the National Cancer Institute R01 CA256977 and R01 CA222900. Cheng Han Ng has served as a consultant to Boxer Capital. Mark Muthiah has consulted for Roche, Astellas, Gilead, served on an advisory board for LernaBio and has received paid speaking engagements from Boston Scientific, Olympus Medical, Roche and Astellas. He is supported by the Singapore Ministry of Health through the National Medical Research Council (NMRC) Office, MOH Holdings Pte Ltd under the NMRC Clinician Scientist-Individual Research Grant (MOH-001228) and NMRC Clinician Scientist Award (MOH-001631), as well as the National Research Foundation, Singapore (NRF) under the NMRC Open Fund – Large Collaborative Grant (MOH-001325) and administered by the Singapore Ministry of Health through the NMRC Office, MOH Holdings Pte Ltd. All other authors do not have any conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Introduction: The 2023 nomenclature defined criteria for steatotic liver disease (SLD), including metabolic dysfunction-associated SLD (MASLD), alcohol-associated liver disease (ALD), and the overlapping MASLD/ALD (MetALD). We aimed to assess racial and ethnic disparities in the SLD prevalence among United States (US) adults based on this new nomenclature., Methods: We undertook a cross-sectional study employing the 2017-2018 National Health and Nutrition Examination Survey (NHANES) database. We identified SLD according to a controlled attenuation parameter ≥288 dB/m, liver stiffness ≥7.2 kPa, or elevated aminotransferase levels. Alcohol use thresholds were established according to the updated SLD definition. We estimated prevalences using the complex design of the NHANES survey. Multivariable logistic regressions with complex design weights were employed., Results: A total of 5532 individuals are included. The mean age is 45.4 years, and 50.9% are women. The adjusted estimated prevalence of MASLD is 42.4% (95% CI: 41.1-43.8%), MetALD 1.7% (95% CI: 1.3-2.0%), and ALD 0.6% (95% CI: 0.3-0.8%). Hispanics exhibit a higher prevalence of SLD, but there are no significant differences in advanced fibrosis prevalence due to SLD among racial/ethnic groups. In MASLD, men, individuals aged 40-64 and ≥65 years, Hispanics, those with health insurance, higher BMI, diabetes, hypertension, hypertriglyceridemia, and low high-density lipoprotein (HDL) cholesterol or use of lipid-lowering agents are independently associated with a higher risk, while Blacks have the lowest risk. In MetALD, men and higher BMI are independently associated with a higher risk of MetALD in adjusted multivariable analysis. In ALD, the adjusted multivariable analysis shows that only health insurance is independently associated with a lower ALD risk., Conclusions: MASLD prevalence is high in the US, especially in men, older individuals, and Hispanics. MetALD and ALD prevalence was substantial but could be underestimated., (© 2024. The Author(s).)

Background: Major society guidelines recommend the fibrosis-4 index (FIB-4) as the initial step to risk stratifying people with metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to evaluate the proportion of people with MASLD-related hepatocellular carcinoma (HCC) and a low FIB-4., Methods: This cohort study included 613 consecutive adults (33% female) diagnosed with MASLD-related HCC from January 2008 to August 2023 at seven international centres in Australia, India, Japan, South Korea, Singapore and the United States. The primary objective was to determine the proportion of participants with a low FIB-4, defined as FIB-4 < 1.3, or < 2 if age > 65 years, in people without cirrhosis., Results: The mean (±SD) age and body mass index were 71 (±11) years and 27 (±7) kg/m 2 , respectively. Overall, 235 participants (38%) did not have known cirrhosis. The median FIB-4 was 3.90 (IQR 2.42-6.42). A total of 78 participants (13%) had a low FIB-4. Among participants without known cirrhosis (n = 235), 62 participants (26%) had a low FIB-4. Participants with a low FIB-4 had larger median total tumour diameter (p < 0.001) and lower median serum alpha-fetoprotein (p = 0.005), compared to participants without a low FIB-4. Cirrhosis was associated with lower odds of low FIB-4, but not other factors such as male sex, type 2 diabetes, or obesity., Conclusion: More than a quarter of those with MASLD-related HCC without cirrhosis have a low FIB-4. The proposed clinical care pathways may not identify these people for further evaluation., (© 2024 John Wiley & Sons Ltd.)

Background and Aims: Chronic liver disease is a known risk factor for cholangiocarcinoma (CCA), but the proportion of people with CCA who have concurrent chronic liver disease is unclear. We aimed to evaluate the prevalence of chronic liver diseases in people with CCA., Methods: In this single-arm meta-analysis, we searched MEDLINE and EMBASE from inception to August 10, 2024, for articles in English containing data for CCA with and without chronic liver diseases. Data were pooled to obtain the prevalence of different chronic liver diseases, with further stratification by geographical location and tumor location., Results: In total, 118,068 individuals diagnosed with CCA were included, of whom 16,771 had chronic liver diseases. A pooled analysis of 109 studies determined that the prevalence of chronic liver disease was 25.23% (95% confidence interval [CI], 20.82%-30.23%; I 2  = 99.0%), and 10.21% (7.75%-13.35%; I 2  = 98.6%) of CCA patients had cirrhosis. Chronic liver diseases were associated more with intrahepatic CCAs, compared with extrahepatic CCAs (relative risk, 2.46; 95% CI, 2.37-2.55; P < .0001). This was observed across all etiologies of liver disease, except for primary sclerosing cholangitis, which was associated with extrahepatic CCAs (relative risk, 0.49; 95% CI, 0.43-0.57; P < .0001)., Conclusions: Around 1 in 4 people with CCA have chronic liver diseases, and 1 in 10 have cirrhosis., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

One-third of adults across the globe exhibit metabolic dysfunction-associated steatotic liver disease (MASLD) - formerly known as nonalcoholic fatty liver disease (NAFLD). To date, MASLD is the fastest-growing etiology of chronic liver disease and hepatocellular carcinoma (HCC). Besides the population with obesity, MASLD can also be found in lean populations, accounting for 13% of the global population, especially Asians. Notably, individuals with lean MASLD face equal or higher overall mortality rates compared to their non-lean counterparts. Risk modifiers encompass advanced age, hepatic fibrosis, and type 2 diabetes mellitus (T2DM). Moreover, the population with lean MASLD is associated with an increased risk of HCC, while their non-lean counterparts are more prone to cardiovascular outcomes and T2DM. Existing evidence indicates a similar risk of liver-related events and extrahepatic cancer between the two groups. However, MASLD-related genetic variants, such as PNPLA3 and TM6SF2, did not significantly affect mortality between the two populations. Still, underreporting alcohol consumption and regional representation limits the study's comprehensiveness. Longitudinal studies and mechanistic explorations are needed to understand differences in lean versus non-lean MASLD populations. This review highlights the need for awareness and tailored interventions in managing MASLD, considering lean individuals' unique risks.

Objective: To update the global burden of Inflammatory Bowel Disease (IBD) using data from the Global Burden of Disease (GBD) 2021., Methods: Data from GBD 2021 were analyzed to assess the IBD burden., Results: In 2021, there were 375,140 new cases and 3.83 million total cases of IBD. Elderly-onset IBD accounted for 11% of incidences. 167 countries increased IBD incidence rate, with rates rising in females (APC:+0.06%) and the elderly (APC:+0.14%) but stable in males and the overall population., Conclusion: While the global burden of IBD has decreased overall, it has increased in females and the elderly., (Copyright © 2024 by The American College of Gastroenterology.)

Background and Aim: The global burden of gallbladder and biliary tract cancer (GBTC) has been on the rise, making it a major public health concern. We aim to comprehensively analyze sex disparities in the temporal trends of GBTC incidence, mortality, and disability-adjusted life years (DALYs) regionally and globally from 2010 to 2019., Methods: Age-standardized rates of GBTC incidence, death, and DALYs were analyzed utilizing the Global Burden of Disease study 2019., Results: From 2010 to 2019, the estimated annual percent change (APC) of the age-standardized incidence rates (ASIRs) and age-standardized disability-adjusted life years (ASDALYs) due to GBTC globally decreased in both sexes (males, APC: -0.80%; APC: -1.00%) and (females, APC: -0.89%; APC: -0.96%). At the same time, age-standardized death rates (ASDRs) decreased only in males (APC: -0.82%) and remained stable in females. By regions, ASIRs and ASDR increased in both sexes only in Southeast Asia (SEA) but decreased in the other regions. All regions had decreased ASDALYs except for an increase in ASDALYs for females only in the SEA region (APC: 0.41%), and males have a stable trend., Conclusions: Our study reveals substantial geographic variance in the burden of GBTC, specifically in the SEA region. Therefore, localized interventional methodologies must be undertaken to effectively address this global burden from GBTC., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Backgrounds/aims: The trends in mortality of hepatocellular carcinoma (HCC) and biliary tract cancers stratified by sex and race/ethnicity in the US continue to evolve. We estimated the sex- and race/ethnicity-based trends in HCC and biliary tract cancers-related mortality in US adults with a focus on disease burden., Methods: We performed a population-based analysis using the US national mortality records from 2018 to 2023. We identified HCC and biliary tract cancer using appropriate ICD-10 codes. Temporal trends in mortality were calculated by joinpoint analysis with annual percentage change (APC)., Results: Annual age-standardized mortality from HCC decreased steadily with an APC of -1.4% (95% confidence interval [CI]: -2.0% to -0.7%). While there was a linear increase in intrahepatic cholangiocarcinoma-related mortality (APC: 3.1%, 95% CI: 1.2-4.9%) and ampulla of Vater cancer-related mortality (APC: 4.1%, 95% CI: 0.5-7.9%), gallbladder cancer-related mortality decreased (APC: -1.9%, 95% CI: -3.8% to -0.0%). Decreasing trends in mortality from HCC were noted in males, not females. HCC-related mortality decreased more steeply in racial and ethnic minority individuals compared with non-Hispanic White individuals. Racial and ethnic differences in trends in mortality for biliary tract cancers depended on the malignancy's anatomical site., Conclusion: While the annual mortality for HCC and gallbladder cancer demonstrated declining trends, ICC- and AVC-related mortality continued to increase from 2018 to 2023. Although racial and ethnic minority individuals in the US experienced disproportionately higher HCC and biliary tract cancer, recent declines in HCC may be primarily due to declines among racial and ethnic minority individuals and males.

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., (Copyright © 2024 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background and Aims: The worldwide burden of cancer is increasing in younger populations. However, the epidemiology of primary liver cancer remains understudied in young adults compared to other cancer forms., Approach and Results: This study analyzed data from the Global Burden of Disease study between 2010 and 2019 to assess the age-standardized incidence, mortality, and disability-adjusted life years associated with primary liver cancer in the young (15-49 y), stratified by region, nation, sociodemographic index, and sex. The study found a global estimate of 78,299 primary liver cancer cases, 60,602 deaths, and 2.90 million disability-adjusted life years in the young population. The Western Pacific region exhibited the highest burden in 2019, showing the most significant increase compared to other regions between 2010 and 2019. More than half of the countries worldwide have undergone an increase in primary liver cancer incidence rates in young adults. Around 12.51% of deaths due to primary liver cancer occur in young individuals. Throughout the study period, there was a significant decline in primary liver cancer mortality due to most etiologies, except for metabolic dysfunction-associated steatotic liver disease-attributable primary liver cancer (annual percentage change + 0.87%, 95% CI: 0.70%-1.05%) and alcohol-attributable primary liver cancer (annual percentage change + 0.21%, 95% CI: 0.01%-0.42%). The limitations of the Global Burden of Disease database include reliance on the quality of primary data and possible underestimation of alcohol consumption., Conclusions: Over the past decade, there has been a marked increase in the burden of primary liver cancer, especially that originating from steatotic liver disease. This trend calls for the development of urgent and comprehensive strategies to mitigate this rising burden globally., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiometabolic conditions affect populations across economic strata. Nevertheless, there are limited epidemiological studies addressing these diseases in low (LICs) and lower-middle-income countries (lower MICs). Therefore, an analysis of the trend of MASLD and cardiometabolic conditions in these countries is necessary., Methods: From 2000 to 2019, jointpoint regression analysis was employed to calculate the prevalence, mortality, and disability-adjusted life years (DALYs) for cardiometabolic conditions including MASLD, type 2 diabetes mellitus (T2DM), dyslipidemia (DLP), hypertension (HTN), obesity, peripheral artery disease (PAD), atrial fibrillation and flutter (AF/AFL), ischemic heart disease (IHD), stroke, and chronic kidney disease from HTN and T2DM, in LICs and lower MICs (according to the World Bank Classification 2019) using the Global Burden of Disease 2019 data., Results: Among the eleven cardiometabolic conditions, MASLD (533.65 million), T2DM (162.96 million), and IHD (76.81 million) had the highest prevalence in LICs and Lower MICs in 2019. MASLD represented the largest proportion of global prevalence in these countries (43 %). From 2000 to 2019, mortality in LICs and lower MICs increased in all cardiometabolic conditions, with obesity-related mortality having the highest increase (+134 %). During this timeframe, there were increased age-standardized death rates (ASDR) from obesity, PAD, and AF/AFL. From all conditions, the DALYs-to-prevalence ratio was higher in LICs and lower MICs than the global average., Conclusion: The burden of MASLD and cardiometabolic conditions is increasing worldwide, with LICs and lower MICs experiencing higher (DALYs) disability per prevalence. As these conditions are preventable, counteracting these trends requires not only the modification of ongoing actions but also the strategizing of immediate interventions., Competing Interests: Declaration of competing interest Mazen Noureddin has been on the advisory board for 89BIO, Gilead, Intercept, Pfizer, Novo Nordisk, Blade, EchoSens, Fractyl, Terns, Siemens, and Roche diagnostic; has received research support from Allergan, BMS, Gilead, Galmed, Galectin, Genfit, Conatus, Enanta, Madrigal, Novartis, Pfizer, Shire, Viking and Zydus; and is a minor shareholder or has stocks in Anaetos, Rivus Pharma and Viking. Vincent Chen's institution has received research grants from KOWA and AstraZeneca. Christos S. Mantzoros: reports grants through his institution from Merck, Massachusetts Life Sciences Center, and Boehringer Ingelheim; he reports personal consulting fees and support through his institution from Ansh Inc., collaborative research support from LabCorp Inc., reports personal consulting fees from Nestle, Olympus, Genfit, Lumos, Novo Nordisk, Amgen, Corcept, Intercept, 89 Bio, Madrigal, Aligos, Esperion, Biodexa and Regeneron, reports educational activity meals through his institution or national conferences from Esperion, Merck, Boehringer Ingelheim and travel support and fees from UptoDate, TMIOA, Elsevier, and the Cardio Metabolic Health Conference. None is related to this manuscript. Peer review of this manuscript was handled by an associate editor independently of the EIC and their research groups. As EIC recused himself from handling this manuscript. Naim Alkhouri reports grant/research support from 89Bio, Akero, Arbutus, AstraZeneca, Better Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Corcept, Cymabay, DSM, Galectin, Genentech, Genfit, Gilead, Hepagene, Healio, Intercept, Inventiva, Ionis, Ipsen, Madrigal, Merck, NGM, Noom, NorthSea, Novo Nordisk, Perspectum, Pfizer, Poxel, Viking, and Zydus; speaker's fees from AbbVie, Alexion, Echosens, Eisai, Gilead, Intercept, Ipsen, Madrigal, Perspectum, Salix, and Theratechnologies; Consultant for 89Bio, Boehringer Ingelheim, Echosens, Fibronostics, Gilead, Intercept, Madrigal, NorthSea, Novo Nordisk, Perspectum, Pfizer, and Zydus. Cheng Han Ng: CHN has served as a consultant to Boxer Capital. Jeffrey V. Lazarus: acknowledges grants to ISGlobal from AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Madrigal, MSD, Novo Nordisk, Pfizer, and Roche Diagnostics, consulting fees from Echosens, NovoVax, GSK, Novo Nordisk and Pfizer and payment or honoraria for lectures from AbbVie, Echosens, Gilead Sciences, Janssen, Moderna, MSD, Novo Nordisk and Pfizer, outside of the submitted work. The other authors declares there are no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Aim: In recent years, there has been a growing incidence of gastrointestinal cancer in young individuals. Despite its significant morbidity and mortality, research on upper gastrointestinal (UGI) cancer in young populations has been relatively limited. Therefore, studies on the epidemiological changes of this cancer are needed., Methods: Using data from the Global Burden of Disease Study 2019, we examined the incidence, death, and disability-adjusted life years (DALYs) from UGI cancers in the young, namely, early-onset esophageal cancer (EOEC) and early-onset gastric cancer (EOGC). These results were stratified by sex, geographical region, country, and sociodemographic index., Results: There was a total of 185 140 cases, 120 289 deaths, and 5.70 million DALYs attributable to early-onset UGI cancers globally. From 2010 to 2019, the global incidence, death, and DALYs rates of early-onset UGI cancers decreased. In contrast, the incidence rates increased in both EOEC (+1.15%) and EOGC (+0.21%) in the Eastern Mediterranean region., Conclusions: Over the past decade, the burden of UGI cancer in the young has decreased. However, it has increased in the Eastern Mediterranean region. Further research to elucidate the attributable risk factors in this population is warranted., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

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., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

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., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Primary liver cancer is the third leading cause of cancer-related mortality. The increasing prevalence of metabolic syndrome and alcohol consumption, along with the existing burden of viral hepatitis, could significantly heighten the impact of primary liver cancer. However, the specific effects of these factors in the Asia-Pacific region, which comprises more than half of the global population, remain largely unexplored. This study aims to analyze the epidemiology of primary liver cancer in the Asia-Pacific region. We evaluated regional and national data from the Global Burden of Disease study spanning 2010 to 2019 to assess the age-standardized incidence, mortality, and disability-adjusted life years associated with primary liver cancer in the Asia-Pacific region. During the study period, there were an estimated 364,700 new cases of primary liver cancer and 324,100 deaths, accounting for 68 and 67% of the global totals, respectively. Upward trends were observed in the age-standardized incidence rates of primary liver cancer due to metabolic dysfunction-associated fatty liver disease (MASLD) and alcohol-associated liver disease (ALD) in the Asia-Pacific region, as well as an increase in primary liver cancer from Hepatitis B virus infection in the Western Pacific region. Notably, approximately 17% of new cases occurred in individuals aged 15-49 years. Despite an overall decline in the burden of primary liver cancer in the Asia-Pacific region over the past decade, increases in incidence were noted for several etiologies, including MASLD and ALD. However, viral hepatitis remains the leading cause, responsible for over 60% of the total burden. These findings underscore the urgent need for comprehensive strategies to address the rising burden of primary liver cancer in the Asia-Pacific region., (© 2024. The Author(s).)

Background and Aims: The objective of the study was to analyse the prevalence, incidence, and death of alcohol-associated liver disease (ALD) among adolescents and young adults globally, continentally, and nationally, focusing on trends over time., Methods: The study analysed data from the Global Burden of Disease (GBD) study between 2000 and 2019. It examined ALD's prevalence, incidence, and death in adolescents and young adults aged 15-29, segmented by region, nation, and sociodemographic index. The analysis utilised Joinpoint regression modelling to calculate the annual per cent change (APC) in the rate of these parameters over time., Results: In 2019, there were 281,450 ALD prevalences, 18,930 incidences, and 3190 deaths among adolescents and young adults globally. From 2000 to 2019, the age-adjusted prevalence rate per 100,000 increased in the 25-29 age group (APC: +0.6%, p = 0.003), remained stable among ages 20-24 (p = 0.302) and ages 15-19 (p = 0.160). Prevalence increased significantly from age 15-19 to 20-24 (19-fold increase) and from age 20-24 to 25-29 (2.5-fold increase). ALD prevalence rates increased in all age groups in adolescents and young adults in Africa and the Eastern Mediterranean region. Around three-quarters of countries and territories experienced an increase in ALD incidence rates in young adults., Conclusion: Over two decades, the burden of ALD among adolescents and young adults has increased globally. The study emphasises the importance of public health policies aimed at reducing alcohol consumption and preventing ALD among younger populations., (© 2024 John Wiley & Sons Ltd.)

Background: Economic hardship associated with chronic liver disease (CLD) may delay timely access to healthcare., Aim: To estimate the national burden of financial hardship across the spectrum of CLD in the United States (US) during the coronavirus disease 2019 (COVID-19) pandemic., Methods: A cross-sectional analysis was performed using the 2020-2021 US National Health Interview Survey database. The questionnaire defined financial hardship from medical bills and cost-related nonadherence to medications in patients with CLD. We used weighted survey analysis to obtain the national estimates., Results: While 6.9% (95% confidence interval [CI]: 6.7%-7.2%) out of 60,689 US adults (weighted sample: 251 million) reported financial hardship and inability to pay medical bills; 10.6% (95% CI: 8.3%-13.4%), 18.2% (95% CI: 14.5%-22.6%), 22.6% (95% CI: 11.0%-41.0%) with hepatitis, CLD/cirrhosis, and liver cancer experienced an inability to pay their medical bills due to financial hardship, respectively. 19.8% (95% CI: 15.9%-24.5%) and 23.3% (95% CI: 12.5%-39.3%) with CLD/cirrhosis and liver cancer, respectively experienced cost-related nonadherence to medications, compared to a tenth of US adults (10.7%, 95% CI: 10.3%-11.2%). CLD/cirrhosis demonstrated an independent association with financial hardship from medical bills and cost-related nonadherence to medications. Overall, these disparities were more pronounced in individuals aged <65 years old. In addition, over 40% of individuals with CLD/cirrhosis reported difficulties accessing medical care during the COVID-19 pandemic. CLD/cirrhosis showed an independent association with difficulties accessing medical care due to COVID-19., Conclusions: Financial hardship from medical bills and cost-related nonadherence to medication can negatively impact individuals with CLD and need further evaluation., (© 2024 John Wiley & Sons Ltd.)

Backgrounds and Aims: Alcohol use leads to disabilities and deaths worldwide. It not only harms the liver but also causes alcohol use disorder (AUD) and heart disease. Additionally, alcohol consumption contributes to health disparities among different socio-economic groups., Methods: We estimated global and regional trends in the burden of AUD, liver disease, and cardiovascular disease from alcohol using the methodology of the Global Burden of Disease study., Results: In 2019, the highest disability-adjusted life years rate per 100,000 population was due to AUD (207.31 [95% Uncertainty interval (UI) 163.71-261.66]), followed by alcohol-associated liver disease (ALD) (133.31 [95% UI 112.68-156.17]). The prevalence rate decreased for AUD (APC [annual percentage change] -0.38%) and alcohol-induced cardiomyopathy (APC -1.85%) but increased for ALD (APC 0.44%) and liver cancer (APC 0.53%). Although the mortality rate for liver cancer from alcohol increased (APC 0.30%), mortality rates from other diseases decreased. Between 2010 and 2019, the burden of alcohol-associated complications increased in countries with low and low-middle sociodemographic index (SDI), contributing more significantly to the global burden., Conclusion: The global burden of AUD, liver, and cardiovascular disease has been high and increasing over the past decade, particularly for liver complications. Lower SDI countries are contributing more to this global burden. There is a pressing need for effective strategies to address this escalating burden., (© 2024 John Wiley & Sons Ltd.)

Background and Aims: Inflammatory Bowel Disease (IBD) represents a significant health threat worldwide. However, there are deficiencies in large-scale epidemiological research focusing on these issues, especially among young women. We aim to examine the trend of IBD in young females globally., Methods: We utilized data from the Global Burden of Disease (GBD) study between 2010 and 2019 to conduct a comprehensive analysis of the prevalence, mortality, and disability-adjusted life years (DALYs) from IBD in young females (15-49 years), stratified by region, nation, and sociodemographic index (SDI)., Results: Globally, there were 1.27 million (95 % UI 1.10 to 1.45 million) cases and 314,120 (95 % UI 240,880 to 395,420) DALYs from IBD in young females in 2019. Geographically, Europe had the highest burden of IBD in young females (n = 421,320). From 2010 to 2019, the prevalence rate increased in Africa (APC 0.34 %, 95 % CI 0.25 to 0.44 %), the Eastern Mediterranean (APC 0.77 %, 95 % CI 0.74 to 0.81 %), Europe (APC 0.48 %, 95 % CI 0.44 to 0.51 %) and the Western Pacific region (APC 1.01 %, 95 % CI 0.89 to 1.14 %). Countries with lower SDI exhibited higher DALYs to prevalence ratio. Over the study period, the percentage of young women with IBD compared to young adults increased by 0.24 %. This percentage varies significantly between countries, from 26 % to 62 %., Conclusion: The burden of IBD in young females is high and increasing. Countries with lower SDIs generate higher disability per case. This necessitates immediate and inclusive measures to tackle the rising burden of IBD in this vulnerable group., Lay Summary: From 2010 to 2019, in the largest global epidemiology database, prevalence rates of inflammatory bowel disease in young females increased in many regions. Countries with lower socioeconomic development, as indicated by sociodemographic index, generated a higher burden compared to countries with higher development., Competing Interests: Conflict of interest All authors denied any relevant conflict of interest., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a leading cause of liver disease. Dynamic changes in MRI proton-density-fat fraction (PDFF) are associated with MASH resolution. We aimed to determine the relative efficacy of therapeutic agents for reducing hepatic fat, assessed by MRI-PDFF., Approach and Results: In this systematic review and network meta-analysis, we searched MEDLINE and Embase from inception until December 26, 2023, for published randomized controlled trials comparing pharmacological interventions in patients with MASH that assessed changes in MRI-PDFF. The primary outcome was the absolute change in MRI-PDFF. The secondary outcome was a ≥30% decline in MRI-PDFF. A surface under-the-curve cumulative ranking probabilities (SUCRA) analysis was performed. Of 1550 records, a total of 39 randomized controlled trials (3311 participants) met the inclusion criteria. For MRI-PDFF decline at 24 weeks, aldafermin (SUCRA: 83.65), pegozafermin (SUCRA: 83.46), and pioglitazone (SUCRA: 71.67) were ranked the most effective interventions. At 24 weeks, efinopegdutide (SUCRA: 67.02), semaglutide + firsocostat (SUCRA: 62.43), and pegbelfermin (SUCRA: 61.68) were ranked the most effective interventions for achieving a ≥30% decline in MRI-PDFF., Conclusions: This study provides an updated, relative rank-order efficacy of therapies for MASH in reducing hepatic fat. These data may help inform the design and sample size calculation of future clinical trials and assist in the selection of combination therapy., (Copyright © 2024 American Association for the Study of Liver Diseases.)