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.

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.

Robotic living donor hepatectomy is associated with superior outcomes for both the donor and the recipient compared with laparoscopic or open - A single-center prospective registry study of 3448 cases.

Minimally invasive donor hepatectomy is an emerging surgical technique in living donor liver transplantation (LDLT). We examined outcomes across open, laparoscopic, and robotic LDLT using a prospective registry. We analyzed 3448 cases (1724 donor-recipient pairs) from January 2011 to March 2023 (NCT06062706). Among donors, 520 (30%) were female. Adult-to-adult LDLT comprised 1061 (62%) cases. A total of 646 (37%) of the donors underwent open, 165 (10%) laparoscopic, and 913 (53%) robotic hepatectomies. Primary outcomes: donor overall morbidity was 4% (35/903) for robotic, 8% (13/165) laparoscopic, and 16% (106/646) open (P < .001) procedures. Pediatric and adult recipient mortality was similar among the 3 donor hepatectomy approaches: robotic 1.5% and 7.0%, compared with 2.3% and 8.3% laparoscopic, and 1.6% and 5.5% for open donor surgery, respectively (P = .802, P = .564). Secondary outcomes: pediatric and adult recipients major morbidity after robotic hepatectomy was 15% and 23%, compared with 25% and 44% for laparoscopic surgery and 19% and 31% for open surgery, respectively (P = .033, P < .001). Graft and recipient 5-year survival were 90% and 93% for pediatrics and 79% and 80% for adults, respectively. In conclusion, robotic LDLT was associated with superior outcomes when compared with the laparoscopic and open approaches. Both donors and, for the first time reported, recipients benefitted from lower morbidity rates in robotic surgery, emphasizing its potential for further advancing this field.

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.

Environmental risk factors for gallbladder cancer: field-wide systematic review and meta-analysis.

BACKGROUND AND AIMS: Cholelithiasis is the most well-recognized risk factor for gallbladder cancer (GBC), the predominant biliary-tract malignancy; however, credibility on other modifiable exposures remains uncertain. We performed a field-wide systematic review and meta-analysis on environmental factors associated with GBC. METHODS: We systematically searched Medline/PubMed and Embase up to May 8, 2023, to identify randomized and non-randomized studies examining environmental factors for GBC. We conducted random-effects meta-analyses focusing on longitudinal studies. Evidence from case-control studies was considered complementary. Evidence credibility was graded by prespecified criteria including the random-effects estimate, 95% confidence interval, P-value, statistical heterogeneity, small-study effects, and robustness to unmeasured confounding. RESULTS: We identified 215 eligible primary studies and performed 350 meta-analyses across seven domains: lifestyle; reproductive; metabolic; dietary; infections; interventions; contaminants, and occupational exposures. Based on longitudinal evidence, body-mass index (RR per 5-unit increase 1.27; 95% CI, 1.21‒1.33), hip circumference (RR per 5-cm increase 1.16; 1.11‒1.22), infection of bile ducts (RR 31.7; 24.8-40.6), high parity (RR 1.48, 1.30‒1.68), obesity (RR 1.70; 1.44‒2.01), overweight (RR 1.28; 1.14‒1.43), waist circumference (RR per 5-cm increase 1.14; 1.10‒1.18), and waist-to-height ratio (RR per 0.1 increase 1.49; 1.36‒1.64) were robustly associated with increased GBC risk, while high education (RR 0.63; 0.49‒0.82) was associated with reduced risk (moderate-to-high credibility). Another 39 significant associations showed lower credibility, including different exposure scenarios of tobacco smoking, alcohol consumption and insufficient physical activity. CONCLUSIONS: This study offers a detailed appraisal and mapping of the evidence on modifiable factors for GBC. Further high-quality prospective studies are essential to validate emerging associations and inform preventive strategies in high-incidence areas.

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.

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.

The global fatty liver disease Sustainable Development Goal country score for 195 countries and territories.

BACKGROUND AND AIMS: Fatty liver disease is highly prevalent, resulting in overarching wellbeing and economic costs. Addressing it requires comprehensive and coordinated multisectoral action. We developed a fatty liver disease Sustainable Development Goal (SDG) country score to provide insights into country-level preparedness to address fatty liver disease through a whole-of-society lens. APPROACH AND RESULTS: We developed 2 fatty liver disease-SDG score sets. The first included 6 indicators (child wasting, child overweight, noncommunicable disease mortality, a universal health coverage service coverage index, health worker density, and education attainment), covering 195 countries and territories between 1990 and 2017. The second included the aforementioned indicators plus an urban green space indicator, covering 60 countries and territories for which 2017 data were available. To develop the fatty liver disease-SDG score, indicators were categorized as "positive" or "negative" and scaled from 0 to 100. Higher scores indicate better preparedness levels. Fatty liver disease-SDG scores varied between countries and territories (n = 195), from 14.6 (95% uncertainty interval: 8.9 to 19.4) in Niger to 93.5 (91.6 to 95.3) in Japan; 18 countries and territories scored > 85. Regionally, the high-income super-region had the highest score at 88.8 (87.3 to 90.1) in 2017, whereas south Asia had the lowest score at 44.1 (42.4 to 45.8). Between 1990 and 2017, the fatty liver disease-SDG score increased in all super-regions, with the greatest increase in south Asia, but decreased in 8 countries and territories. CONCLUSIONS: The fatty liver disease-SDG score provides a strategic advocacy tool at the national and global levels for the liver health field and noncommunicable disease advocates, highlighting the multisectoral collaborations needed to address fatty liver disease, and noncommunicable diseases overall.

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.

A systematic review on the associations between the built environment and adult's physical activity in global tropical and subtropical climate regions.

BACKGROUND: Physical inactivity is a major public health concern, exacerbated in countries with a (sub)tropical climate. The built environment can facilitate physical activity; however, current evidence is mainly from North American and European countries with activity-friendly climate conditions. This study explored associations between built environment features and physical activity in global tropical or subtropical dry or desert climate regions. METHODS: A systematic review of four major databases (Web of Science, Scopus, PubMed, and SportDISCUS) was performed. To be included, studies had to investigate associations between perceived or objective built environment characteristics and adult's physical activity and had to be conducted in a location with (sub)tropical climate. Each investigated association was reported as one case and results were synthesized based upon perceived and objectively assessed environment characteristics as well as Western and non-Western countries. Study quality was evaluated using a tool designed for assessing studies on built environment and physical activity. RESULTS: Eighty-four articles from 50 studies in 13 countries with a total of 2546 built environment-physical activity associations were included. Design (connectivity, walking/cycling infrastructure), desirability (aesthetics, safety), and destination accessibility were the built environment characteristics most frequently associated with physical activity across the domains active transport, recreational physical activity, total walking and cycling, and moderate-to-vigorous physical activity, particularly if multiple attributes were present at the same time. Very few studies assessed built environment attributes specifically relevant to physical activity in (sub)tropical climates. Most studies were conducted in Western countries, with results being largely comparable with non-Western countries. Findings were largely generalizable across gender and age groups. Results from natural experiments indicated that relocating to an activity-friendly neighborhood impacted sub-groups differently. CONCLUSIONS: Built environment attributes, including destination accessibility, connectivity, walking and cycling infrastructure, safety, and aesthetics, are positively associated with physical activity in locations with (sub)tropical climate. However, few studies focus on built environment attributes specifically relevant in a hot climate, such as shade or indoor recreation options. Further, there is limited evidence from non-Western countries, where most of the urban population lives in (sub)tropical climates. Policy makers should focus on implementing activity-friendly environment attributes to create sustainable and climate-resilient cities.

Interplay of Donor-Recipient Relationship and Donor Race in Living Liver Donation in the United States.

INTRODUCTION: Living liver donation improves survival of end-stage liver disease (ESLD) patients. Yet, it continues to represent a small proportion of United States (U.S.) liver transplantation with existing racial disparities. We investigated the interplay of donor-recipient relationship and donor race to understand donor subgroups with no significant increase. METHODS: We studied 4407 living liver donors in the U.S. from January 1, 2012, to December 31, 2022 (median age = 36 years, and 59% were biologically related to the recipient). We quantified the change in the number of donors per 3-year increment using negative binomial regression (incidence rate ratio [IRR]), stratified by donor-recipient relationship and race/ethnicity. RESULTS: Among biologically related donors, the observed annual number of White donors increased from 146 to 253, Hispanic donors from 18 to 53, and Black donors decreased from 11 to 10. Among unrelated donors, White donors increased from 65 to 221, Hispanic donors from 4 to 25, and Black donors from 3 to 11. For the IRR of biologically related donors aged <40 and ≥40 years, White donors increased by 18% and 22%; Hispanic donors increased by 25% and 54%; and Black donors did not change. Likewise, the IRR of unrelated donors aged <40 and ≥40 years, White donors increased by 48% and 55%; Hispanic donors increased by 52% and 65%; and Black donors did not change. CONCLUSIONS: While biologically related donors represent the majority of donors, unrelated donors have substantially risen in recent years, primarily driven by White donors. Although the rate of unrelated donations increased among Hispanic donors, the absolute number remains very small (≤25 donors/year). Interventions are needed to increase education among Hispanic and Black communities to grow unrelated living liver donations across race/ethnicity.

Knowledge about metabolic dysfunction-associated steatotic liver disease among the medical professionals from countries in the MENA region.

INTRODUCTION AND OBJECTIVES: Given the substantial burden of metabolic dysfunction-associated steatotic liver disease (MASLD), there is an urgent need to assess knowledge and awareness levels among physicians. We assessed MASLD knowledge among healthcare providers from Saudi Arabia, Egypt, and Türkiye. MATERIALS AND METHODS: Two global surveys containing 54-59 items assessed awareness and knowledge of MASLD/NAFLD- one was for hepatologists and gastroenterologists, and the second was for non-specialists (e.g. endocrinologists, primary care providers [PCPs], and other healthcare professionals). Data were collected using an electronic data collection form. Knowledge scores and variables associated with higher knowledge scores were compared across all specialties. RESULTS: A total of 584 physicians completed the survey (126 hepatologists, 178 gastroenterologists (GEs), 38 endocrinologists, 242 PCPs/others). Practice guidelines were the primary source for knowledge across all specialties (43-51%), then conferences (24-31%) except PCPs/others who selected the internet as the second common source (25%). Adherence to societal guidelines varied by specialty (81-84% of specialists vs 38-51% of non-specialists). Hepatologists and GEs showed similar mean knowledge scores (51-72% correct answers across three knowledge domains, p > 0.05); endocrinologists outperformed PCPs/others in knowledge scores in all knowledge domains, including Epidemiology/Pathogenesis (72% vs. 60%), Diagnostics (73% vs. 67%), and Treatment (78% vs. 67%) (all p < 0.01). Hospital-based practice and seeing a greater number of patients with MASLD/NAFLD were identified as independent predictors of higher knowledge scores among specialists (both p < 0.05). CONCLUSIONS: A knowledge gap in the identification, diagnosis, and management of MASLD/NAFLD was found despite the growing burden of MASLD/NAFLD in Saudi Arabia, Egypt, and Türkiye. Education to increase awareness is needed.

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.

A global research priority agenda to advance public health responses to fatty liver disease.

BACKGROUND & AIMS: An estimated 38% of adults worldwide have non-alcoholic fatty liver disease (NAFLD). From individual impacts to widespread public health and economic consequences, the implications of this disease are profound. This study aimed to develop an aligned, prioritised fatty liver disease research agenda for the global health community. METHODS: Nine co-chairs drafted initial research priorities, subsequently reviewed by 40 core authors and debated during a three-day in-person meeting. Following a Delphi methodology, over two rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the priorities, via Qualtrics XM, indicating agreement using a four-point Likert-scale and providing written feedback. The core group revised the draft priorities between rounds. In R2, panellists also ranked the priorities within six domains: epidemiology, models of care, treatment and care, education and awareness, patient and community perspectives, and leadership and public health policy. RESULTS: The consensus-built fatty liver disease research agenda encompasses 28 priorities. The mean percentage of 'agree' responses increased from 78.3 in R1 to 81.1 in R2. Five priorities received unanimous combined agreement ('agree' + 'somewhat agree'); the remaining 23 priorities had >90% combined agreement. While all but one of the priorities exhibited at least a super-majority of agreement (>66.7% 'agree'), 13 priorities had <80% 'agree', with greater reliance on 'somewhat agree' to achieve >90% combined agreement. CONCLUSIONS: Adopting this multidisciplinary consensus-built research priorities agenda can deliver a step-change in addressing fatty liver disease, mitigating against its individual and societal harms and proactively altering its natural history through prevention, identification, treatment, and care. This agenda should catalyse the global health community's efforts to advance and accelerate responses to this widespread and fast-growing public health threat. IMPACT AND IMPLICATIONS: An estimated 38% of adults and 13% of children and adolescents worldwide have fatty liver disease, making it the most prevalent liver disease in history. Despite substantial scientific progress in the past three decades, the burden continues to grow, with an urgent need to advance understanding of how to prevent, manage, and treat the disease. Through a global consensus process, a multidisciplinary group agreed on 28 research priorities covering a broad range of themes, from disease burden, treatment, and health system responses to awareness and policy. The findings have relevance for clinical and non-clinical researchers as well as funders working on fatty liver disease and non-communicable diseases more broadly, setting out a prioritised, ranked research agenda for turning the tide on this fast-growing public health threat.

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.

Risk of severe disease and mortality of COVID-19 in patients with Budd-Chiari syndrome: A population-based matched cohort study.

BACKGROUND & AIMS: Budd-Chiari syndrome (BCS) is a rare and potentially life-threatening disorder characterized by obstruction of the hepatic outflow tract. It is unknown whether patients with BCS represent a high risk for severe disease and mortality from coronavirus disease 2019 (COVID-19). Thus, we aimed to assess hospitalization rates, severe disease, all-cause mortality, intensive care unit (ICU) requirement and acute kidney injury (AKI) from COVID-19 diagnoses. METHODS & RESULTS: We identified 467 patients with BCS with COVID-19, 96 427 non-chronic liver disease (CLD) and 9652 non-BCS CLD. The BCS and non-CLD cohorts (n = 467 each) and BCS and non-BCS CLD (n = 440 each) were well balanced after propensity matching. When compared to the non-CLD cohort, the BCS group had a higher risk of all-cause mortality (5.1% vs. 2.4%, HR 2.18; 95% CI, 1.08-4.40), severe disease (6.0% vs. 2.4%, HR 2.20; 95% CI, 1.09-4.43), hospitalization (24.6% vs. 13.1%, HR 1.77; 95% CI, 1.30-2.42) and AKI (7.9% vs. 2.8%, HR 2.57; 95% CI, 1.37-4.85), but no significant differences in ICU requirements (2.4% vs. 2.1%, HR 0.75; 95% CI, 0.27-2.08) at 60-days time points. When compared to the non-BCS CLD cohort, the BCS group had a higher risk of all-cause mortality (3.6% vs. 2.5%, HR 3.94; 95% CI, 1.31-11.79), hospitalization (29.8% vs. 21.6%, HR 1.43; 95% CI, 1.09-1.86), but differences in ICU requirements (HR 0.90 (0.38-2.12)), AKI (HR 1.41 (0.86-2.30)) or severe disease (HR 1.92 (0.99-3.71)) did not reach statistical significance at 60-day follow up. CONCLUSION: In conclusion, COVID-19 infection in patients with BCS is associated with poor outcomes. Patients with BCS infected with COVID-19 carry a significantly higher risk of hospitalization and all-cause mortality and a possible effect on severe disease and AKI compared with COVID-19 patients without CLD or with non-BCS-CLD.

Hepatitis delta virus infection prevalence, diagnosis and treatment in the Middle East: A scoping review.

Hepatitis D virus (HDV) infection is a global public health concern, especially because of its unique existence in the presence of hepatitis B virus infection. HDV infection is estimated to affect 12 million people globally. Having a clearer understanding of its prevalence in all regions of the world is essential for helping direct preventive and early interventional treatment. This mini-review assessed the literature over the last 10 years to determine the prevalence, diagnostic means and treatment guidelines available for HDV in the Middle East. The search found limited data available in 21 articles, of which 18 were studies focused on Iran. Prevalence rates ranged dramatically among the countries, and none of the 12 countries included in the search had specific HDV guidelines. This review highlights the urgent need for more precise data for the Middle East region to help establish early diagnosis and treatment options for HDV.

Significant liver fibrosis is a predictor of poor health-related quality of life in people living with HIV.

PURPOSE: Liver-related comorbidities can impair the health-related quality of life (HRQL) in people living with human immunodeficiency virus (HIV) (PLWH). However, the role of hepatic steatosis and significant fibrosis in PLWH remains incompletely characterized. Therefore, the aim of this study was to explore the association of hepatic steatosis and significant fibrosis on the HRQL using the medical outcomes study HIV health survey (MOS-HIV) in PLWH. METHODS: A total of 222 PLWH were included in the final analysis of this cohort study. Metabolic comorbidities, socioeconomic factors, and HIV-related parameters were assessed. Hepatic steatosis and fibrosis were measured using vibration-controlled transient elastography (VCTE). The MOS-HIV survey, containing two summary scores (physical health summary (PHS) and mental health summary (MHS)) and ten domains, was used to assess the HRQL. Clinical predictors were identified using multivariable linear regression models. RESULTS: The majority of this cohort was male, and the median age was 52 years, with a high prevalence of hepatic steatosis (n = 81, 36.5%). Significant fibrosis was present in 7.7% (n = 17). The mean PHS and MHS scores were 52.7 ± 9.5 and 51.4 ± 10.5, respectively. The lowest scores were in the general health perception (GHP) and energy/fatigue (EF) domains. A high BMI and waist circumference were associated with a poor PHS score. Lower education, unemployment, arterial hypertension, and significant fibrosis remained independent predictors of an impaired HRQL. CONCLUSION: Metabolic comorbidities, significant fibrosis, and a lower socioeconomic status may negatively affect the HRQL in PLWH. Considering the negative impact of significant fibrosis on the outcome, counseling and preventive measures according to current guidelines are recommended in this subgroup of PLWH.

A scoping review on the impact of the COVID-19 pandemic on physical activity and sedentary behavior in Saudi Arabia.

BACKGROUND: In Saudi Arabia, stay-at-home orders to address the coronavirus disease 2019 (COVID-19) pandemic between March 15 and 23, 2020 and eased on May 28, 2020. We conducted a scoping review to systematically describe physical activity and sedentary behavior in Saudi Arabia associated with the timing of the lockdown. METHODS: We searched six databases on December 13, 2021 for articles published in English or Arabic from 2018 to the search date. Studies must have reported data from Saudi Arabia for any age and measured physical activity or sedentary behavior. RESULTS: Overall, 286 records were found; after excluding duplicates, 209 records were screened, and 19 studies were included in the review. Overall, 15 studies were cross-sectional, and 4 studies were prospective cohorts. Three studies included children and adolescents (age: 2-18 years), and 16 studies included adults (age: 15-99 years). Data collection periods were < = 5 months, with 17 studies collecting data in 2020 only, one study in 2020-2021, and one study in 2021. The median analytic sample size was 363 (interquartile range 262-640). Three studies of children/adolescents collected behaviors online at one time using parental reporting, with one also allowing self-reporting. All three studies found that physical activity was lower during and/or following the lockdown than before the lockdown. Two studies found screen time, television watching, and playing video games were higher during or following the lockdown than before the lockdown. Sixteen adult studies assessed physical activity, with 15 utilizing self-reporting and one using accelerometry. Physical activity, exercise, walking, and park visits were all lower during or following the lockdown than before the lockdown. Six adult studies assessed sedentary behavior using self-report. Sitting time (4 studies) and screen time (2 studies) were higher during or following the lockdown than before the lockdown. CONCLUSIONS: Among children, adolescents, and adults, studies consistently indicated that in the short-term, physical activity decreased and sedentary behavior increased in conjunction with the movement restrictions. Given the widespread impact of the pandemic on other health behaviors, it would be important to continue tracking behaviors post-lockdown and identify subpopulations that may not have returned to their physical activity and sedentary behavior to pre-pandemic levels to focus on intervention efforts.

The Impact of NASH to Liver Transplantations With Hepatocellular Carcinoma in the United States.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease worldwide.1,2 It is believed that about one fourth of the world population may have NAFLD.3 The Global Burden of Disease data suggest that NAFLD and nonalcoholic steatohepatitis (NASH) are the main drivers of liver disease burden in most regions of the world, including that of hepatocellular carcinoma (HCC).4,5.