Health and economic burden of insufficient physical activity in Saudi Arabia.

BACKGROUND: Insufficient physical activity (PA) was estimated to cause 4.8% of deaths and 2.6% of disability-adjusted life-years (DALYs) due to noncommunicable diseases in Saudi Arabia in 2019. While Saudi Arabia is already achieving great improvements, we predict the health and economic burden of insufficient PA up to 2040 to present a case for policy makers to invest more in the uptake of PA. METHODS: Using a population health model to estimate avoidable health loss, we identified four causes of health loss related to low PA (cardiovascular diseases, diabetes, breast cancer, and colorectal cancer) and estimated the deaths and DALYs from these causes. We projected the expected disease burden until 2040 under alternative assumptions about future PA levels and trends by using three health scenarios: baseline (no change in 2019 PA levels), intervention (81% of the population achieving sufficient PA levels), and ideal (65% of population: moderate PA, 30%: high PA, and 5%: inactive). We applied an "intrinsic value" approach to estimate the economic impact of each scenario. RESULTS: Overall, we estimate that between 2023 and 2040, about 80,000 to 110,000 deaths from all causes and 2.0 million to 2.9 million DALYs could be avoided by increasing PA levels in Saudi Arabia. The average annual economic loss from insufficient PA is valued at 0.49% to 0.68% of the current gross domestic product, with an average of US$5.4 billion to US$7.6 billion annually till 2040. The most avoidable disease burden and economic losses are expected among males and because of ischemic heart disease. CONCLUSIONS: This study highlights that low PA levels will have considerable health and economic impacts in Saudi Arabia if people remain inactive and do not start following interventions. There is an urgent need to develop innovative programs and policies to encourage PA among all age and sex groups.

Clinical and patient-reported outcomes in patients with chronic hepatitis B and C and non-alcoholic fatty liver disease from real-world practices in Saudi Arabia, Turkey and Egypt.

Patients with chronic liver disease (CLD) experience health-related quality of life (HRQoL) and patient-reported outcomes (PROs) impairments. We assessed and identified predictors of HRQoL and PROs in CLD patients from Saudi Arabia (SA), Turkey and Egypt. Patients enrolled in Global Liver Registry™ with chronic hepatitis B (CHB), chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) were included. Clinical data and PRO questionnaires (FACIT-F, CLDQ and WPAI) were compared across countries. Linear regression identified PRO predictors. Of the 4014 included patients, 26.9% had CHB, 26.9% CHC and 46.1% NAFLD/NASH; 19.2% advanced fibrosis. Compared across countries, CHB patients were younger in Egypt (mean age [years] 41.2 ± 11.4 vs. 45.0 ± 10.3 SA, 46.1 ± 12.0 Turkey), most often employed in SA (64.8% vs. 53.2% Turkey) and had the lowest prevalence of obesity in Turkey (26.7% vs. 37.8% SA, 38.5% Egypt). In SA, CHB patients had lowest prevalence of fibrosis and comorbidities (all p < .01). There was a higher frequency of males with NAFLD/NASH in SA (70.0% vs. 49.6% Turkey, and 35.5% Egypt). Among NAFLD/NASH patients, CLDQ-NAFLD/NASH scores were highest in SA (mean total score: 5.3 ± 1.2 vs. 4.8 ± 1.2 Turkey, 4.1 ± 0.9 Egypt, p < .01). Independent predictors of worse PROs included younger age, female sex, advanced fibrosis, non-hepatic comorbidities and lack of regular exercise (all p < .05). Clinical presentation and PRO scores of CLD patients vary across SA, Turkey and Egypt. Impairment of HRQoL is associated with demographic factors, lack of regular exercise, advanced fibrosis and non-hepatic comorbidities.

Inhibition of MERTK reduces organ fibrosis in mouse models of fibrotic disease.

Transforming growth factor-ß (TGFß) drives fibrosis and disease progression in a number of chronic disorders, but targeting this ubiquitously expressed cytokine may not yield a viable and safe antifibrotic therapy. Here, we sought to identify alternative ways to inhibit TGFß signaling using human hepatic stellate cells and macrophages from humans and mice in vitro, as well as mouse models of liver, kidney, and lung fibrosis. We identified Mer tyrosine kinase (MERTK) as a TGFß-inducible effector of fibrosis that was up-regulated during fibrosis in multiple organs in three mouse models. We confirmed these findings in liver biopsy samples from patients with metabolic dysfunction-associated fatty liver disease (MAFLD). MERTK also induced TGFß expression and drove TGFß signaling resulting in a positive feedback loop that promoted fibrosis in cultured cells. MERTK regulated both canonical and noncanonical TGFß signaling in both mouse and human cells in vitro. MERTK increased transcription of genes regulating fibrosis by modulating chromatin accessibility and RNA polymerase II activity. In each of the three mouse models, disrupting the fibrosis-promoting signaling loop by reducing MERTK expression reduced organ fibrosis. Pharmacological inhibition of MERTK reduced fibrosis in these mouse models either when initiated immediately after injury or when initiated after fibrosis was established. Together, these data suggest that MERTK plays a role in modulating organ fibrosis and may be a potential target for treating fibrotic diseases.

Gut microbiota in MAFLD: therapeutic and diagnostic implications.

Metabolic dysfunction-associated fatty liver disease (MAFLD), formerly known as nonalcoholic fatty liver disease, is becoming a significant contributor to chronic liver disease globally, surpassing other etiologies, such as viral hepatitis. Prevention and early treatment strategies to curb its growing prevalence are urgently required. Recent evidence suggests that targeting the gut microbiota may help treat and alleviate disease progression in patients with MAFLD. This review aims to explore the complex relationship between MAFLD and the gut microbiota in relation to disease pathogenesis. Additionally, it delves into the therapeutic strategies targeting the gut microbiota, such as diet, exercise, antibiotics, probiotics, synbiotics, glucagon-like peptide-1 receptor agonists, and fecal microbiota transplantation, and discusses novel biomarkers, such as microbiota-derived testing and liquid biopsy, for their diagnostic and staging potential. Overall, the review emphasizes the urgent need for preventive and therapeutic strategies to address the devastating consequences of MAFLD at both individual and societal levels and recognizes that further exploration of the gut microbiota may open avenues for managing MAFLD effectively in the future.

Mapping the landscape of medical research in the Arab world countries: A comprehensive bibliometric analysis.

OBJECTIVES: To describe the productivity, performance, and impact of medical research in the Arab world countries. METHODS: We carried out a bibliometric analysis using Clarivate Analytics databases from January 2017 to March 2023. We reported research productivity, national and international research collaboration patterns, impact of Arab medical research output compared to the global average, top medical journals publishing Arab-affiliated research, and performance of the most productive Arab institutions. RESULTS: The Arab world contributed 2.72% to global medical research publication, with a citation impact of 11.98 compared to the global impact of 12.02. Qatar, Lebanon, and Saudi Arabia led medical research publications per million population among Arab countries, ranking 26th, 36th, and 37th globally. Medical research publications increased by 87% annually from 2017-2022, with 70% of research originating from Saudi Arabia and Egypt. National collaborations accounted for 15% of Arab world publications, while international collaborations represented 66%. The median impact factor across the top 20 medical journals with Arab-affiliated authors was 5.14, with 50% being quartile one journals. The top 10 Arab-origin medical journals had a median impact factor of 3.13. Approximately 80% of the top 20 Arab institutions were academic, with a median publication count of 3,162.5 and a median citation impact of 14.5. CONCLUSION: The study provides insights into the state of medical research in the Arab countries, indicating room for improvement in the region's medical research.

The Use of Mobile Technologies to Promote Physical Activity and Reduce Sedentary Behaviors in the Middle East and North Africa Region: Systematic Review and Meta-Analysis.

BACKGROUND: The Middle East and North Africa (MENA) region faces unique challenges in promoting physical activity and reducing sedentary behaviors, as the prevalence of insufficient physical activity is higher than the global average. Mobile technologies present a promising approach to delivering behavioral interventions; however, little is known about the effectiveness and user perspectives on these technologies in the MENA region. OBJECTIVE: This study aims to evaluate the effectiveness of mobile interventions targeting physical activity and sedentary behaviors in the MENA region and explore users' perspectives on these interventions as well as any other outcomes that might influence users' adoption and use of mobile technologies (eg, appropriateness and cultural fit). METHODS: A systematic search of 5 databases (MEDLINE, Embase, CINAHL, Scopus, and Global Index Medicus) was performed. Any primary studies (participants of all ages regardless of medical condition) conducted in the MENA region that investigated the use of mobile technologies and reported any measures of physical activity, sedentary behaviors, or user perceptions were included. We conducted a narrative synthesis of all studies and a meta-analysis of randomized controlled trials (RCTs). The Cochrane risk-of-bias tool was used to assess the quality of the included RCTs; quality assessment of the rest of the included studies was completed using the relevant Joanna Briggs Institute critical appraisal tools. RESULTS: In total, 27 articles describing 22 interventions (n=10, 37% RCTs) and 4 (15%) nonexperimental studies were included (n=6141, 46% women). Half (11/22, 50%) of the interventions included mobile apps, whereas the other half examined SMS. The main app functions were goal setting and self-monitoring of activity, whereas SMS interventions were primarily used to deliver educational content. Users in experimental studies described several benefits of the interventions (eg, gaining knowledge and receiving reminders to be active). Engagement with the interventions was poorly reported; few studies (8/27, 30%) examined users' perspectives on the appropriateness or cultural fit of the interventions. Nonexperimental studies examined users' perspectives on mobile apps and fitness trackers, reporting several barriers to their use, such as perceived lack of usefulness, loss of interest, and technical issues. The meta-analysis of RCTs showed a positive effect of mobile interventions on physical activity outcomes (standardized mean difference=0.45, 95% CI 0.17-0.73); several sensitivity analyses showed similar results. The trim-and-fill method showed possible publication bias. Only 20% (2/10) of the RCTs measured sedentary behaviors; both reported positive changes. CONCLUSIONS: The use of mobile interventions for physical activity and sedentary behaviors in the MENA region is in its early stages, with preliminary evidence of effectiveness. Policy makers and researchers should invest in high-quality studies to evaluate long-term effectiveness, intervention engagement, and implementation outcomes, which can inform the design of culturally and socially appropriate interventions for countries in the MENA region. TRIAL REGISTRATION: PROSPERO CRD42023392699; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=392699.

Prevalence of metabolic dysfunction-associated steatotic liver disease in the Middle East and North Africa.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is common and closely associated with type 2 diabetes (T2D). We assessed the prevalence of NAFLD/MASLD in the general population and among patients with T2D in the Middle East and North Africa (MENA) region. METHODS: We searched PubMed and Embase for English-language articles published between 1990 and 2023 according to PRISMA. Each country's NAFLD/MASLD prevalence in the general population and in T2D patients was predicted by using a multivariable meta regression model. Input data were extracted from our systematic review, GBD and NCD Risk Factor Collaboration. Confidence intervals were constructed by using prediction intervals with the delta method. RESULTS: Meta-analytic pooling estimated the prevalence of NAFLD/MASLD as 39.43% in the general population and 68.71% among T2D patients. NAFLD/MASLD prevalence has increased from 35.42% (2008-2016) to 46.20% (2017-2020). Using GBD-2019 dataset, it was predicted that there are 141.51 million cases of NAFLD/MASLD in the MENA region. The highest number of NAFLD/MASLD cases were expected in Egypt (25.71 million), followed by Türkiye (23.33 million) and Iran (19.85 million). Estimated NAFLD prevalence exceeded 40% in 10 of 21 countries with the top countries being Kuwait (45.37%), Egypt (45.0%), Qatar (44.4%), and Jordan (43.3%). Furthermore, it was predicted that there are 24.96 million cases of NAFLD/MASLD with T2D in the MENA region. CONCLUSIONS: In the MENA region, prevalence of NAFLD/MASLD is very high and growing, necessitating an urgent need for regional public policy to deal with this growing burden.

Cancer Research Challenges and Potential Solutions in Saudi Arabia: A Qualitative Discussion Group Study.

PURPOSE: Cancer incidence in Saudi Arabia has recently shown an upward trend. Research efforts within the different cancer continuum are pivotal to strengthening control measures. Since cancer research is evolving in the country, it is crucial to understand the current challenges and implement defined interventions to overcome them. The present qualitative study aimed to assess cancer research barriers among researchers and identify potential solutions from their perspectives. METHODS: We conducted a focus group discussion among 17 Saudi-based cancer researchers from diverse research backgrounds, provinces, and institutions. We used descriptive-interpretive thematic analysis following an open-ended approach to investigate the challenges in conducting cancer research. We also captured the solutions suggested based on the researchers' experiences. RESULTS: Six major themes emerged from the analysis: requirements of the data landscape, organizational support, national research roadmap, sustainable funding, clearer policies and regulations, and capacity building. To address challenges in these areas, researchers stressed the need for improved interinstitutional collaborations, immediate availability of research materials, and unlimited and easy access to research data. CONCLUSION: Improving health research is one of the primary goals of Saudi Vision 2030. It is, therefore, essential to overcome the current challenges in cancer research, enabling research findings to inform policies related to cancer control and care provision.

Global survey of stigma among physicians and patients with nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Patients with fatty liver disease may experience stigma from the disease or comorbidities. In this cross-sectional study, we aimed to understand stigma among patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) and healthcare providers. METHODS: Members of the Global NASH Council created two surveys about experiences/attitudes toward NAFLD and related diagnostic terms: a 68-item patient and a 41-item provider survey. RESULTS: Surveys were completed by 1,976 patients with NAFLD across 23 countries (51% Middle East/North Africa [MENA], 19% Europe, 17% USA, 8% Southeast Asia, 5% South Asia) and 825 healthcare providers (67% gastroenterologists/hepatologists) across 25 countries (39% MENA, 28% Southeast Asia, 22% USA, 6% South Asia, 3% Europe). Of all patients, 48% ever disclosed having NAFLD/NASH to family/friends; the most commonly used term was "fatty liver" (88% at least sometimes); "metabolic disease" or "MAFLD" were rarely used (never by >84%). Regarding various perceptions of diagnostic terms by patients, there were no substantial differences between "NAFLD", "fatty liver disease (FLD)", "NASH", or "MAFLD". The most popular response was being neither comfortable nor uncomfortable with either term (56%-71%), with slightly greater discomfort with "FLD" among the US and South Asian patients (47-52% uncomfortable). Although 26% of patients reported stigma related to overweight/obesity, only 8% reported a history of stigmatization or discrimination due to NAFLD. Among providers, 38% believed that the term "fatty" was stigmatizing, while 34% believed that "nonalcoholic" was stigmatizing, more commonly in MENA (43%); 42% providers (gastroenterologists/hepatologists 45% vs. 37% other specialties, p = 0.03) believed that the name change to metabolic dysfunction-associated steatotic liver disease (or MASLD) might reduce stigma. Regarding the new nomenclature, the percentage of providers reporting "steatotic liver disease" as stigmatizing was low (14%). CONCLUSIONS: The perception of NAFLD stigma varies among patients, providers, geographic locations and sub-specialties. IMPACT AND IMPLICATIONS: Over the past decades, efforts have been made to change the nomenclature of nonalcoholic fatty liver disease (NAFLD) to better align with its underlying pathogenetic pathways and remove any potential stigma associated with the name. Given the paucity of data related to stigma in NAFLD, we undertook this global comprehensive survey to assess stigma in NAFLD among patients and providers from around the world. We found there is a disconnect between physicians and patients related to stigma and related nomenclature. With this knowledge, educational programs can be developed to better target stigma in NAFLD among all stakeholders and to provide a better opportunity for the new nomenclature to address the issues of stigma.

A global action agenda for turning the tide on fatty liver disease.

BACKGROUND AND AIMS: Fatty liver disease is a major public health threat due to its very high prevalence and related morbidity and mortality. Focused and dedicated interventions are urgently needed to target disease prevention, treatment, and care. APPROACH AND RESULTS: We developed an aligned, prioritized action agenda for the global fatty liver disease community of practice. Following a Delphi methodology over 2 rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the action priorities using Qualtrics XM, indicating agreement using a 4-point Likert-scale and providing written feedback. Priorities were revised between rounds, and in R2, panelists also ranked the priorities within 6 domains: epidemiology, treatment and care, models of care, education and awareness, patient and community perspectives, and leadership and public health policy. The consensus fatty liver disease action agenda encompasses 29 priorities. In R2, the mean percentage of "agree" responses was 82.4%, with all individual priorities having at least a super-majority of agreement (> 66.7% "agree"). The highest-ranked action priorities included collaboration between liver specialists and primary care doctors on early diagnosis, action to address the needs of people living with multiple morbidities, and the incorporation of fatty liver disease into relevant non-communicable disease strategies and guidance. CONCLUSIONS: This consensus-driven multidisciplinary fatty liver disease action agenda developed by care providers, clinical researchers, and public health and policy experts provides a path to reduce the prevalence of fatty liver disease and improve health outcomes. To implement this agenda, concerted efforts will be needed at the global, regional, and national levels.

The impact of hepatitis B and C positive serologies on the outcomes of non-hepatic solid organ transplantation in the United States.

Chronic viral hepatitis B (HBV) and C (HCV) infection could negatively affect outcomes of non-hepatic solid organ transplantations due to the risk of viral reactivation in the presence of immunosuppression. This study aimed to determine post-transplant outcomes in patients with HBV or HCV positivity receiving non-hepatic solid-state organ transplant. Data was collected from the Scientific Registry of Transplant Recipients (SRTR) 2006-2021 for patients (≥18) who received a lung, heart, or kidney single organ transplant in the U.S. Hepatitis C positivity (HCV+) was determined as positive HCV Ab and hepatitis B positivity (HBV+) as positive HBsAg. We included N = 30,872 lung, N = 36,990 heart and N = 280,162 kidney transplant recipients. The prevalence of HBV+ was 1.3% in lung, 1.5% in heart and 1.7% in kidney patients, HCV+ was 2.2%, 2.2% and 5.0%, respectively. Post-transplant survival of patients with vs. without HBV+ was similar in all solid organ transplants (all p > .05). Similarly, there was no difference in post-transplant survival between lung transplant recipients with vs. without anti-HCV (all p > .05). Heart transplant recipients with HCV+ had higher crude post-transplant mortality (all p < .01). Similarly, there was higher post-transplant mortality in kidney transplant recipients with HCV+ (1-year: 6% vs. 3%; 5-year: 21% vs. 13%; 10-year: 47% vs. 31%; all p < .0001). In multivariate analysis controlling for confounders, only the association of HCV+ with higher post-kidney transplant mortality remained significant: adjusted hazard ratio (aHR) (95% CI) = 1.16 (1.12-1.20), p < .0001. There was no association of viral hepatitis seropositivity with the risk of graft failure in all groups (p > .05). In most cases, the presence of HBV or HCV serologies is not associated with adverse post-transplant outcomes in non-hepatic solid organ transplants. However, kidney transplant recipients who are positive for HCV serology have an increased risk for post-transplant mortality.

The changing epidemiology of adult liver transplantation in the United States in 2013-2022: The dominance of metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease.

BACKGROUND: The high prevalence of obesity in the United States drives the burden of NASH, recently renamed as metabolic dysfunction-associated steatohepatitis (MASH). We assessed the most recent trends in liver transplantation in the United States. METHODS: The Scientific Registry of Transplant Recipients (SRTR 2013-2022) was used to select adult (18 years or above) candidates who underwent liver transplant. RESULTS: There were 116,292 candidates who underwent liver transplant with known etiology of chronic liver disease. In candidates without HCC, the most common etiology was alcohol-associated liver disease (ALD), increasing from 23% (2013) to 48% (2022), followed by NASH/MASH, which increased from 19% to 27%; the rates of viral hepatitis decreased (chronic hepatitis C: 28%-4%; chronic hepatitis B: 1.8%-1.1%) (all trend p<0.01). The proportion of HCC decreased from 25% (2013-2016) to 17% (2021-2022). Among HCC cohort, the proportion of chronic hepatitis C decreased from 60% (2013) to 27% (2022), NASH/MASH increased from 10% to 31%, alcohol-associated liver disease increased from 9% to 24% (trend p<0.0001), and chronic hepatitis B remained stable between 5% and 7% (trend p=0.62). The rapid increase in the proportion of NASH/MASH in HCC continued during the most recent study years [20% (2018), 28% (2020), 31% (2022)]; the trend remained significant after adjustment for age, sex, ethnicity, obesity, and type 2 diabetes. CONCLUSIONS: Liver transplant etiologies in the United States have changed over the last decade. Alcohol-associated liver disease and NASH/MASH remain the 2 most common indications for transplantation among those without HCC, and NASH/MASH is the most common in patients with HCC.

Implementation of a liver health check in people with type 2 diabetes.

As morbidity and mortality related to potentially preventable liver diseases are on the rise globally, early detection of liver fibrosis offers a window of opportunity to prevent disease progression. Early detection of non-alcoholic fatty liver disease allows for initiation and reinforcement of guidance on bodyweight management, risk stratification for advanced liver fibrosis, and treatment optimisation of diabetes and other metabolic complications. Identification of alcohol-related liver disease provides the opportunity to support patients with detoxification and abstinence programmes. In all patient groups, identification of cirrhosis ensures that patients are enrolled in surveillance programmes for hepatocellular carcinoma and portal hypertension. When considering early detection strategies, success can be achieved from applying ad-hoc screening for liver fibrosis in established frameworks of care. Patients with type 2 diabetes are an important group to consider case findings of advanced liver fibrosis and cirrhosis, as up to 19% have advanced fibrosis (which is ten times higher than the general population) and almost 70% have non-alcoholic fatty liver disease. Additionally, patients with type 2 diabetes with alcohol use disorders have the highest proportion of liver-related morbidity of people with type 2 diabetes generally. Patients with type 2 diabetes receive an annual diabetes review as part of their routine clinical care, in which the health of many organs are considered. Yet, liver health is seldom included in this review. This Viewpoint argues that augmenting the existing risk stratification strategy with an additional liver health check provides the opportunity to detect advanced liver fibrosis, thereby opening a window for early interventions to prevent end-stage liver disease and its complications, including hepatocellular carcinoma.

Cardiovascular and mortality outcomes with GLP-1 receptor agonists vs other glucose-lowering drugs in individuals with NAFLD and type 2 diabetes: a large population-based matched cohort study.

AIMS/HYPOTHESIS: We aimed to determine whether the use of glucagon-like peptide-1 receptor agonists (GLP-1RA) in individuals with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus decreases the risk of new-onset adverse cardiovascular events (CVEs) and mortality rate compared with other glucose-lowering drugs in a real setting at a population level. METHODS: We conducted a population-based propensity-matched retrospective cohort study using TriNetX. The cohort comprised patients over 20 years old who were newly treated with glucose-lowering drugs between 1 January 2013 and 31 December 2021, and followed until 30 September 2022. New users of GLP-1RAs were matched based on age, demographics, comorbidities and medication use by using 1:1 propensity matching with other glucose-lowering drugs. The primary outcome was the new onset of adverse CVEs, including heart failure, composite incidence of major adverse cardiovascular events (MACE; defined as unstable angina, myocardial infarction, or coronary artery procedures or surgeries) and composite cerebrovascular events (defined as the first occurrence of stroke, transient ischaemic attack, cerebral infarction, carotid intervention or surgery), and the secondary outcome was all-cause mortality. Cox proportional hazards models were used to estimate HRs. RESULTS: The study involved 2,835,398 patients with both NAFLD and type 2 diabetes. When compared with the sodium-glucose cotransporter 2 (SGLT2) inhibitors group, the GLP-1RAs group showed no evidence of a difference in terms of new-onset heart failure (HR 0.97; 95% CI 0.93, 1.01), MACE (HR 0.95; 95% CI 0.90, 1.01) and cerebrovascular events (HR 0.99; 95% CI 0.94, 1.03). Furthermore, the two groups had no evidence of a difference in mortality rate (HR 1.06; 95% CI 0.97, 1.15). Similar results were observed across sensitivity analyses. Compared with other second- or third-line glucose-lowering medications, the GLP-1RAs demonstrated a lower rate of adverse CVEs, including heart failure (HR 0.88; 95% CI 0.85, 0.92), MACE (HR 0.89; 95% CI 0.85, 0.94), cerebrovascular events (HR 0.93; 95% CI 0.89, 0.96) and all-cause mortality rate (HR 0.70; 95% CI 0.66, 0.75). CONCLUSIONS/INTERPRETATION: In individuals with NAFLD and type 2 diabetes, GLP-1RAs are associated with lower incidences of adverse CVEs and all-cause mortality compared with metformin or other second- and third-line glucose-lowering medications. However, there was no significant difference in adverse CVEs or all-cause mortality when compared with those taking SGLT2 inhibitors.

Racial Disparities in Candidates for Hepatocellular Carcinoma Liver Transplant After 6-Month Wait Policy Change.

Importance: Racial disparities in liver transplant (LT) for hepatocellular carcinoma (HCC) may be associated with unequal access to life-saving treatment. Objective: To quantify racial disparities in LT for HCC and mortality after LT, adjusting for demographic, clinical, and socioeconomic factors. Design, Setting, and Participants: This cohort study was a retrospective analysis of United Network Organ Sharing/Organ Procurement Transplant Network (OPTN) data from 2003 to 2021. Participants were adult patients with HCC on the LT waiting list and those who received LT. Data were analyzed from March 2022 to September 2023. Exposures: Race and time before and after the 2015 OPTN policy change. Main Outcomes and Measures: Proportion of LT from wait-listed candidates, the proportion of waiting list removals, and mortality after LT. Results: Among 12 031 patients wait-listed for LT with HCC (mean [SD] age, 60.8 [7.4] years; 9054 [75.3%] male; 7234 [60.1%] White, 2590 [21.5%] Latinx/o/a, and 1172 [9.7%] Black or African American), this study found that after the 2015 model of end-stage liver disease (MELD) exception policy changes for HCC (era 2), the overall proportion of LT for HCC across all races decreased while the proportion of dropouts on the LT waiting list remained steady compared with patients who did not have HCC. In Kaplan-Meier analysis, Asian patients demonstrated the lowest dropout rates in both era 1 and era 2 (1-year dropout, 16% and 17%, respectively; P < .001). In contrast, Black or African American patients had the highest dropout rates in era 1 (1-year dropout, 24%), but comparable dropout rates (23%) with White patients (23%) and Latinx/o/a patients in era 2 (23%). In both eras, Asian patients had the highest survival after LT (5-year survival, 82% for era 1 and 86% for era 2), while Black or African American patients had the worst survival after LT (5-year survival, 71% for era 1 and 79% for era 2). In the multivariable analysis for HCC LT recipients, Black or African American race was associated with increased risk of mortality in both eras, compared with White race (HR for era 1, 1.17; 95% CI, 1.05-1.35; and HR for era 2, 1.31; 95% CI, 1.10-1.56). Conclusions and Relevance: This cohort study of LT candidates in the US found that after the 2015 MELD exception policy change for HCC, the proportion of LT for HCC had decreased for all races. Black or African American patients had worse outcomes after LT than other races. Further research is needed to identify the underlying causes of this disparity and develop strategies to improve outcomes for HCC LT candidates.

Corrigendum: Prevalence of overweight and obesity among saudi children: a comparison of two widely used international standards and the national growth references.

[This corrects the article DOI: 10.3389/fendo.2022.954755.].

Fatty acid composition but not quantity is an important indicator of non-alcoholic fatty liver disease: a systematic review.

BACKGROUND: There is still paucity on the effects of dietary and supplemental fatty acid on non-alcoholic fatty liver disease (NAFLD). The aim of this review is to systematically review and summarise the effect of fatty acids intake on liver-related outcomes in adult patients with NAFLD. METHODS: The review was conducted using Cochrane CENTRAL Library, Scopus, Embase, MEDLINE, PubMed, and Web of Science. A total of 2786 records were identified, and of these, 36 studies (31 were randomised control trials (RCTs), and 5 were case-control studies) were included. Quality assessment was conducted using the Revised Cochrane Risk of Bias tool and Joanna Briggs Institute checklists. RESULTS: Of 36 articles, 79% of RCTs and 66% of case-control studies had a low risk of bias. Potential heterogeneity has been observed in assessment of liver-related outcomes. According to the RCTs, there was moderate evidence (3/6 studies) that a diet characterised by a high MUFA, PUFA and low SFA showed reduced liver fat and stiffness. The using of culinary fats that are high in MUFA (4/6 studies) reduces liver steatosis. n-3 PUFA supplementation in combination with a hypocaloric or heart healthy diet with a low SFA improved liver enzyme level (5/14 studies) and steatosis score (3/14 studies). CONCLUSIONS: Effects on NAFLD parameters, including liver fat content (assessed via magnetic resonance imaging/spectroscopy), stiffness and steatosis score (assessed by ultrasonography), were primarily related to fatty acid composition independent of energy intake. Further investigation is needed to determine the mechanism of specific fatty acid on the accumulation of liver fat.

Surveillance and treatment of primary hepatocellular carcinoma (aka. STOP HCC): protocol for a prospective cohort study of high-risk patients for HCC using GALAD-score.

BACKGROUND: Vietnam and Saudi Arabia have high disease burden of primary hepatocellular carcinoma (HCC). Early detection in asymptomatic patients at risk for HCC is a strategy to improve survival outcomes in HCC management. GALAD score, a serum-based panel, has demonstrated promising clinical utility in HCC management. However, in order to ascertain its potential role in the surveillance of the early detection of HCC, GALAD needs to be validated prospectively for clinical surveillance of HCC (i.e., phase IV biomarker validation study). Thus, we propose to conduct a phase IV biomarker validation study to prospectively survey a cohort of patients with advanced fibrosis or compensated cirrhosis, irrespective of etiologies, using semi-annual abdominal ultrasound and GALAD score for five years. METHODS: We plan to recruit a cohort of 1,600 patients, male or female, with advanced fibrosis or cirrhosis (i.e., F3 or F4) and MELD ≤ 15, in Vietnam and Saudi Arabia (n = 800 each). Individuals with a liver mass ≥ 1 cm in diameter, elevated alpha-fetoprotein (AFP) (≥ 9 ng/mL), and/or elevated GALAD score (≥ -0.63) will be scanned with dynamic contrast-enhanced magnetic resonance imaging (MRI), and a diagnosis of HCC will be made by Liver Imaging Reporting and Data System (LiRADS) assessment (LiRADS-5). Additionally, those who do not exhibit abnormal imaging findings, elevated AFP titer, and/or elevated GALAD score will obtain a dynamic contrast-enhanced MRI annually for five years to assess for HCC. Only MRI nearest to the time of GALAD score measurement, ultrasound and/or AFP evaluation will be included in the diagnostic validation analysis. MRI will be replaced with an abdominal computed tomography scan when MRI results are poor due to patient conditions such as movement etc. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced MRI will not be carried out in study sites in both countries. Bootstrap resampling technique will be used to account for repeated measures to estimate standard errors and confidence intervals. Additionally, we will use the Cox proportional hazards regression model with covariates tailored to the hypothesis under investigation for time-to-HCC data as predicted by time-varying biomarker data. DISCUSSION: The present work will evaluate the performance of GALAD score in early detection of liver cancer. Furthermore, by leveraging the prospective cohort, we will establish a biorepository of longitudinally collected biospecimens from patients with advanced fibrosis or cirrhosis to be used as a reference set for future research in early detection of HCC in the two countries. TRIAL REGISTRATION: Name of the registry: ClinicalTrials.gov Registration date: 22 April 2022 Trial registration number: NCT05342350 URL of trial registry record.