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Acute liver failure (ALF) is a rare, acute, potentially reversible condition resulting in severe liver impairment and rapid clinical deterioration in patients without preexisting liver disease. Due to the rarity of this condition, published studies are limited by the use of retrospective or prospective cohorts and lack of randomized controlled trials. Current guidelines represent the suggested approach to the identification, treatment, and management of ALF and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence was reviewed using the Grading of Recommendations, Assessment, Development and Evaluation process to develop recommendations. When no robust evidence was available, expert opinions were summarized using Key Concepts. Considering the variety of clinical presentations of ALF, individualization of care should be applied in specific clinical scenarios.

Cirrhosis is the fifth leading cause of death in adults. Advanced cirrhosis can cause significant portal hypertension (PH), which is responsible for many of the complications observed in patients with cirrhosis, such as varices. If portal pressure exceeds a certain threshold, the patient is at risk of developing life-threatening bleeding from varices. Variceal bleeding has a high incidence among patients with liver cirrhosis and carries a high risk of mortality and morbidity. The management of variceal bleeding is complex, often requiring a multidisciplinary approach involving pharmacological, endoscopic, and radiologic interventions. In terms of management, three stages can be considered: primary prophylaxis, active bleeding, and secondary prophylaxis. The main goal of primary and secondary prophylaxis is to prevent variceal bleeding. However, active variceal bleeding is a medical emergency that requires swift intervention to stop the bleeding and achieve durable hemostasis. We describe the pathophysiology of cirrhosis and PH to contextualize the formation of gastric and esophageal varices. We also discuss the currently available treatments and compare how they fare in each stage of clinical management, with a special focus on drugs that can prevent bleeding or assist in achieving hemostasis.

Obesity and type 2 diabetes (T2DM) are increasing in Saudi Arabia (SA). Among other conditions, these risk factors increase the likelihood of non-alcoholic fatty liver disease (NAFLD), which in turn increases risks for advanced liver diseases, such as non-alcoholic steatohepatitis (NASH), cirrhosis and cancer. The goal of this study was to quantify the health and economic burden of obesity-attributable T2DM and liver disease in SA. We developed a microsimulation of the SA population to quantify the future incidence and direct health care costs of obesity-attributable T2DM and liver disease, including liver cancer. Model inputs included population demographics, body mass index, incidence, mortality and direct health care costs of T2DM and liver disease and relative risks of each condition as a function of BMI category. Model outputs included age- and sex-disaggregated incidence of obesity-attributable T2DM and liver disease and their direct health care costs for SA's working-age population (20-59 years) between 2020 and 2040. Between 2020 and 2040, the available data predicts 1,976,593 [± 1834] new cases of T2DM, 285,346 [±874] new cases of chronic liver diseases, and 2,101 [± 150] new cases of liver cancer attributable to obesity, amongst working-age people. By 2040, the direct health care costs of these obesity-attributable diseases are predicted to be 127,956,508,540 [± 51,882,446] USD. The increase in obesity-associated T2DM and liver disease emphasises the urgent need for obesity interventions and strategies to meaningfully reduce the future health and economic burden of T2DM, chronic liver diseases and liver cancer in SA.

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. Graphical Abstract

Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent disease globally. Current estimates are that 24% of the adult population, thus, one billion individuals worldwide, are affected. Interestingly, the prevalence of fatty liver seems to peak between 40-50 years of age in males and 60-69 years in females, often slightly decreasing in older (>70 years) cohorts. Furthermore, several risk factors for NAFLD development, such as hypertension, diabetes, hyperlipidemia, and obesity are higher in older adults. The diagnosis and management strategies in older adults are sometimes challenging, and certain age- specific factors have to be taken into account by healthcare professionals. In this review, we provide an overview of considerations relevant to the management and diagnosis of NAFLD in older adults (age >65 years) and discuss the types of pharmacological interventions available for the management of non-alcoholic steatohepatitis (NASH) in the aging population. Keywords: liver disease, aging, fatty liver, NASH, senescence, regeneration

Artificial intelligence (AI)-powered chatbots, such as Chat Generative Pretrained Transformer (ChatGPT), have shown promising results in healthcare settings. These tools can help patients obtain real-time responses to queries, ensuring immediate access to relevant information. The study aimed to explore the potential use of ChatGPT-generated medical Arabic responses for patients with metabolic dysfunction-associated steatotic liver disease (MASLD). An English patient questionnaire on MASLD was translated to Arabic. The Arabic questions were then entered into ChatGPT 3.5 on November 12, 2023. The responses were evaluated for accuracy, completeness, and comprehensibility by 10 Saudi MASLD experts who were native Arabic speakers. Likert scales were used to evaluate: 1) Accuracy, 2) Completeness, and 3) Comprehensibility. The questions were grouped into 3 domains: (1) Specialist referral, (2) Lifestyle, and (3) Physical activity. Accuracy mean score was 4.9 ± 0.94 on a 6-point Likert scale corresponding to \"Nearly all correct.\" Kendall's coefficient of concordance (KCC) ranged from 0.025 to 0.649, with a mean of 0.28, indicating moderate agreement between all 10 experts. Mean completeness score was 2.4 ± 0.53 on a 3-point Likert scale corresponding to \"Comprehensive\" (KCC: 0.03-0.553; mean: 0.22). Comprehensibility mean score was 2.74 ± 0.52 on a 3-point Likert scale, which indicates the responses were \"Easy to understand\" (KCC: 0.00-0.447; mean: 0.25). MASLD experts found that ChatGPT responses were accurate, complete, and comprehensible. The results support the increasing trend of leveraging the power of AI chatbots to revolutionize the dissemination of information for patients with MASLD. However, many AI-powered chatbots require further enhancement of scientific content to avoid the risks of circulating medical misinformation.

Background: Prevalence estimates for overweight and obesity in the Gulf Cooperation Council countries, including Saudi Arabia, have increased over the last 4 decades. Although the World Health Organization encourages countries to implement initiatives aimed at controlling obesity, limited research has been published on the impact of such initiatives in Saudi Arabia. Aims: To assess the epidemiology of overweight and obesity in Saudi Arabia, describe and evaluate the effectiveness of past and current interventions, and recommend actions for prevention and control. Methods: A narrative review of data from the Global Health Observatory was used to determine yearly estimates of prevalence of overweight and obesity in Saudi Arabia from 1975 to 2016. Large-scale interventions aimed at controlling obesity and its risk factors in Saudi Arabia were identified and summarized. Results: Prevalence estimates of overweight and obesity among men and women in Saudi Arabia continued to increase from 1990 to 2019. Prevalence among adults was more than 60% and among children and adolescents it was 20–60%, suggesting a continuing trend. Interventions were identified but their impact on the prevention and control of obesity and its risk factors was unclear. Conclusion: Prevalence estimates of overweight and obesity have been steadily increasing in Saudi Arabia since 1975. Integrated, “whole-of-community” approach, with continuous evaluation, is needed to achieve sustainable prevention and control of obesity in the country.

Liver transplantation (LT) represents the life-saving treatment for advanced liver disease. We aim to investigate LT indication trends and outcomes in Saudi Arabia, following the evolution of effective therapies for hepatitis C virus (HCV) and the rising fatty liver disease prevalence. We retrospectively analyzed data from adult patients who underwent LT from 2011 to 2023 at a tertiary referral center in Saudi Arabia. We assessed demographics, LT indication trends, Model for End-stage Liver Disease (MELD) scores, donor type, and survival outcomes. A total of 1,419 patients were included. The median age was 56.9 years, with 37.4% female. Living donor LT (LDLT) represented 79.8% of all transplants, and 22.0% of recipients had hepatocellular carcinoma (HCC). Metabolic dysfunction-associated steatohepatitis (MASH) was the predominant indication for LT (33.2%), followed by HCV (18.0%) and hepatitis B virus (HBV) (17.1%). Overall survival rates at 1-, 2-, 3-, 5-, and 10-years post-transplantation were 87.9%, 85.0%, 82.4%, 77.7%, and 71.3%, respectively. Hazard ratios (HR) for mortality were lower in patients with HBV compared to MASH (HR: 0.44, 95% CI: 0.28-0.69, p < 0.001), and higher in patients aged ≥65 years (HR: 1.37, 95% CI: 1.02-1.84, p = 0.036), those with diabetes (HR: 1.33, 95% CI: 1.03-1.73, p = 0.029), and those with increased MELD score (HR: 1.02, 95% CI: 1.00-1.04, p = 0.022). LDLT was associated with reduced mortality risk (HR: 0.68, 95% CI: 0.51-0.92, p = 0.013). MASH represents the leading indication for LT in this large cohort, necessitating preventive strategies and early detection efforts.

Cancer is emerging as a leading cause of morbidity and mortality in Saudi Arabia, with the incidence projected to double in the next 20 years. The health-care system in the country has witnessed considerable reforms over the past four decades, resulting in better control of communicable and non-communicable diseases and, subsequently, longer life expectancies. The Health Sector Transformation Program, a part of the Saudi Vision 2030, aims to strengthen the prevention and control of non-communicable diseases including cancer, improve access to care, deliver high-quality care services, improve patients' quality of life, and increase support for research and innovation. This Series paper highlights the considerable progress of the national cancer control programme, identifying remaining challenges and future opportunities. We envision that this paper will inform the development of the next National Cancer Control Plan to be sustainable, evidence-based, integrated, patient-centred, and value-driven for society.

Background: Fatty liver disease in the absence of excessive alcohol consumption is an increasingly common condition with a global prevalence of ~ 25-30% and is also associated with cardiovascular disease (CVD). Since systemic metabolic dysfunction underlies its pathogenesis, the term metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been proposed for this condition. MAFLD is closely intertwined with obesity, type 2 diabetes mellitus and atherogenic dyslipidemia, which are established cardiovascular risk factors. Unlike CVD, which has received attention in the literature on fatty liver disease, the CVD risk associated with MAFLD is often underestimated, especially among Cardiologists. Methods and results: A multidisciplinary panel of fifty-two international experts comprising Hepatologists, Endocrinologists, Diabetologists, Cardiologists and Family Physicians from six continents (Asia, Europe, North America, South America, Africa and Oceania) participated in a formal Delphi survey and developed consensus statements on the association between MAFLD and the risk of CVD. Statements were developed on different aspects of CVD risk, ranging from epidemiology to mechanisms, screening, and management. Conculsions: The expert panel identified important clinical associations between MAFLD and the risk of CVD that could serve to increase awareness of the adverse metabolic and cardiovascular outcomes of MAFLD. Finally, the expert panel also suggests potential areas for future research.