Aim: Previous studies have suggested that metabolic diseases are gene- and heritability-related and there are potential cross-genetic correlations. We aim to elucidate the causal relationships among specific metabolic diseases.

Methods: We investigated seven metabolic diseases by analyzing summary statistics from Genome-Wide Association Studies (GWAS). Genetic correlations and pleiotropic associations were identified, and biological functions were determined. In addition, two-sample bidirectional Mendelian randomization (MR) analysis was performed to establish causal inferences.

Results: Most metabolic diseases shared common genetic components, and more than sixty percent of paired disorders presented significant positive genetic correlations. The primary MR analysis revealed that obesity causally induced a higher risk of type 2 diabetes (T2D). Both obesity and T2D increased the risk of hypertension, gout, and high triglyceride (TG) levels, whereas gout and TG could pose direct risks for hypertension. Significant differential expression of pleiotropic genes was found in the adrenal gland and brain, and the most enriched tissues were the pancreas, liver, and heart.

Conclusion: This study identified causal relationships among a set of metabolic diseases and indicated potential mechanisms of disease comorbidities. These findings underscore the need for integrative strategies for metabolic disease management and provide insights for future development of targeted medical therapy.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) involve a complex interplay of genetics, metabolism, and the gut-liver axis. In a new study, Zhang et al. assess a previously unrecognized role of the intestinal epithelium in protecting against MASH by focusing on Transmembrane 6 Superfamily Member 2 (TM6SF2), a gene highly expressed in both the liver and intestine, whose common loss-of-function variant (E167K) is a well-established genetic risk factor for MASLD/MASH in humans. Herein, we provide an overview of Zhang et al.’s study and highlight the clinical significance of these new findings by focusing on two specific areas: the gut-liver axis in MASLD and the modification of the intestinal microbiota.

Wilson disease, a well-established genetic disorder characterized by impaired copper excretion and toxic copper accumulation in the liver, has clear clinical presentations and diagnostic criteria. However, the metabolic and molecular pathways leading to liver injury - a critical hallmark of the disease - remain largely cryptic and require new analytical approaches to elucidate underlying mechanisms. In Wilson disease, supraphysiological and toxic amounts of hepatic copper arise due to genetically reduced biliary excretion. Interestingly, hepatic iron accumulation of unknown etiology is also observed. Both metals contribute to the production of reactive oxygen species (ROS), including singlet oxygen, superoxide anions, and highly disruptive hydroxyl radicals generated via the Haber-Weiss and Fenton reactions. Historically, liver injury has been attributed to copper-induced toxicity (cuproptosis) without sufficient consideration of ROS involvement, neglecting the significant ROS burden in hepatic tissue. A revised concept of cuproptosis incorporates ROS, particularly hydroxyl radicals, which convert copper ions into reactive intermediates such as copper peroxyl, copper hydroperoxyl, and copper superoxyl species. These intermediates induce mitochondrial oxidative stress by covalently binding to mitochondrial constituents including lipoylated dihydrolipoamide S-acetyltransferase (DLAT), leading to its aggregation and triggering regulated cell death via cuproptosis. Thus, copper ions must first be converted into reactive intermediates to initiate cuproptosis effectively. Furthermore, singlet oxygen and superoxide anion hydroxyl radicals generated by hepatic iron ions may promote regulated cell death via ferroptosis. This process involves the accumulation of lipid peroxides derived from polyunsaturated fatty acids in mitochondrial membranes, with malondialdehyde (MDA) serving as a diagnostic marker. Consequences include enhanced mitochondrial membrane rigidity, disruption of plasma membrane integrity, and ultimately cell death. This mechanistic pathway requires the activity of iron-dependent enzymes such as lipoxygenases, ferroptosis suppressor protein 1, glutathione peroxidase 4, dihydroorotate dehydrogenase, and lysosomal iron release from ferritin stores. To sum up, the definition of cuproptosis requires refinement to incorporate its mechanistic dependence on ROS, and its quantitative contribution to liver injury should be reassessed alongside hepatic iron and ferroptosis.

Aim: A new definition of metabolic dysfunction-associated steatotic liver disease (MASLD) was proposed in 2023; however, its impact on adverse pregnancy outcomes (APOs) remains undetermined. This study aimed to comprehensively analyze the association between MASLD and the risk of APOs, and to evaluate the relative contributions of its components - steatotic liver disease (SLD) and cardiometabolic risk factors (CMRF).

Methods: This retrospective cohort study enrolled 4,118 pregnant women admitted to the hospital between March 2020 and December 2022. Participants were categorized into MASLD and non-MASLD groups based on MASLD status. The non-MASLD group was further divided into three subgroups according to the presence of SLD and CMRF. Adjusted relative risks (aRRs) for APOs were estimated using modified Poisson regression analysis, adjusting for relevant covariates.

Results: The prevalence of MASLD among pregnant women was 7.3%. MASLD was associated with elevated risks of cesarean section (aRR = 1.459, 95%CI: 1.253-1.700, P < 0.001), gestational diabetes mellitus(aRR = 2.081, 95%CI: 1.711-2.530, P < 0.001), pregnancy-associated hypertension (aRR = 2.192, 95%CI: 1.541-3.118, P < 0.001), preterm birth (aRR = 1.826, 95%CI: 1.181-2.823, P = 0.007), and large-for gestational-age neonates (aRR = 2.024, 95%CI: 1.488-2.754, P < 0.001). Compared with the CMRF-only group, the MASLD group showed higher risks of cesarean section (aRR = 1.387, 95%CI: 1.177-1.634, P < 0.001), gestational diabetes mellitus (aRR = 1.734, 95%CI: 1.405-2.139, P < 0.001), pregnancy-associated hypertension (aRR = 1.606, 95%CI: 1.105-2.333, P = 0.013), and large-for-gestational-age neonates (aRR = 1.845, 95%CI: 1.318-2.581, P < 0.001). No significant differences in risk were observed between the MASLD and SLD-only groups.

Conclusion: MASLD during pregnancy is associated with an increased risk of several APOs, with SLD appearing to play a more critical role than CMRF.

Obesity has become a global epidemic, posing significant health challenges for individuals and straining healthcare systems worldwide. Endoscopic bariatric and metabolic therapies have emerged as an evolving field, characterized by their minimally invasive, reversible, and organ-preserving nature. This modality offers a promising alternative to traditional bariatric surgery. Various endoscopic therapies targeting the stomach and small bowel have been developed. Among these, endoscopic gastric remodeling interventions have demonstrated superior effectiveness and durability. These procedures utilize endoscopic tissue approximation devices to perform full-thickness suturing or plication of the gastric wall, thereby restricting the stomach volume and altering gastric motility to induce early satiety. This review aims to provide a comprehensive summary of the different endoscopic gastric remodeling interventions and discuss potential future developments in this rapidly evolving field, which holds the promise of offering an alternative therapeutic approach to the management of the global obesity epidemic.

Aim: Although the weight-loss efficacy of the latest anti-obesity medications is widely recognized and evidence-supported, bariatric surgery remains the most effective treatment for obesity and type 2 diabetes mellitus (T2DM). While laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (RYGB) - the most extensively adopted procedures - demonstrate proven weight-reduction effects, suboptimal outcomes still occur in some patients. This highlights the critical importance of effectively evaluating postoperative weight achievement. Our study, therefore, investigates the influence of social factors and minimum medical insurance coverage on surgical weight-loss outcomes.

Methods: A retrospective cohort study was conducted on 260 patients with obesity who underwent bariatric surgery between 2021 and 2023. Continuous variables with normal distribution were expressed as mean ± standard deviation (SD) and analyzed using Student’s t-test, whereas non-normally distributed variables were presented as median with interquartile range (IQR) [M (Q1, Q3)] and compared with the Mann-Whitney U test. Categorical variables were presented as frequency (n) and percentage (%), with intergroup comparisons conducted through x² tests. Linear regression and logistic regression models were employed to identify independent influencing factors, and P-value < 0.05 considered statistically significant.

Results: The study included 260 patients (102 males, 158 females), with 196 (75.4%) receiving LSG and 64 (24.6%) RYGB. Patients achieving target weight loss were younger (31.8 ± 9.13 years vs. 35.0 ± 10.4 years, P < 0.05), had higher baseline BMI (39.6 ± 7.86 kg/m² vs. 36.0 ± 6.46 kg/m², P < 0.05), and higher smoking rates (23.8% vs. 12.0%, P < 0.05), but lower family support (83.2% vs. 97.3%, P < 0.05) and reduced hypertension/T2DM incidence (P < 0.05). Multivariate analysis identified five independent predictors: family support (OR = 0.11, 95%CI: 0.02-0.42; β: -3.52, 95%CI: 1.45, -2.43), smoking (OR = 3.27, 95%CI: 1.36-8.73; β: 3.06, 95%CI: 1.20, 2.55), RYGB procedure (vs. LSG, OR = 0.18, 95%CI: 0.07-0.43; β: -4.41, 95%CI: 1.35, -3.26), baseline BMI (OR = 1.15 per unit, 95%CI: 1.08-1.22, β: 0.45, 95%CI: 0.07, 6.31), and HbA1c (OR = 0.77 per %, 95%CI: 0.62-0.96). Insurance coverage and education level showed no significant association (P > 0.05).

Conclusion: One-year postoperative weight loss outcomes were significantly associated with preoperative factors including lack of family support, LSG procedure (vs. RYGB), smoking status, and higher baseline BMI (all P < 0.05), but showed no significant correlation with educational attainment or insurance coverage (P > 0.05).

Metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease are leading contributors to chronic liver disease globally, with incidence rates escalating in parallel with the worldwide increase in metabolic dysfunction and harmful alcohol use. A recent Delphi Consensus statement introduced the term metabolic and alcohol-associated liver disease (MetALD) to emphasize the synergistic contributions of metabolic and alcohol-related factors to liver injury. While this conceptual framework advances our understanding of heterogeneous liver disease etiologies, it also presents new diagnostic and therapeutic challenges. This review presents current evidence on the prevalence of MetALD, as well as its heterogeneous disease risk profiles, underlying pathogenesis, clinical diagnostic biomarkers, and evolving treatment strategies. Particular emphasis is placed on the necessity for robust preclinical models that accurately replicate the multifactorial pathogenesis of MetALD. Emerging therapies, including fecal microbiota transplantation and dietary supplementation, are critically evaluated, alongside perspectives on future pharmacological innovations for MetALD management.

Type 1 Diabetes Mellitus (T1DM) is a chronic autoimmune disease characterized by the destruction of pancreatic β-cells, leading to insulin deficiency. While insulin remains the cornerstone of treatment, achieving optimal disease control and preventing long-term complications remain significant challenges. This review synthesizes recent findings on the epidemiology, pathophysiology, and management of T1DM, with a particular focus on sex-based differences in disease presentation and outcomes, the role of the liver, and the emerging significance of C-peptide in understanding disease complications. Additionally, the involvement of T cells and B cells in the immune response and the potential of disease-modifying therapies, such as TNF-alpha inhibitors, anti-CD3 antibodies, abatacept, and cell-based therapies, are explored. The article highlights the need for further research into personalized and gender-specific treatment approaches and the development of novel therapeutic strategies. Addressing these critical areas may lead to improved disease management and quality of life for individuals with T1DM, paving the way for more effective and individualized therapeutic interventions.

Cardiovascular diseases (CVD) remain the leading global cause of mortality with a complex etiology involving both genetic and environmental factors. Despite the identification of numerous genetic loci associated with CVD, the mechanisms underlying disease variability are incompletely understood. Recent advances in multi-omics technologies, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, and microbiomics, offer a more comprehensive view of the molecular networks involved in disease progression and recovery. This commentary explores how multi-omics data could enhance cardiac rehabilitation (CR) by identifying novel biomarkers, revealing individualized responses to exercise, and informing personalized therapeutic strategies. We present specific use cases for omics technology in CR, highlight barriers such as cost and implementation feasibility, and propose future research directions, including the need for pilot studies and standardization protocols. Integrating omics technologies into CR has the potential to improve patient outcomes and promote precision cardiovascular care, provided that practical and ethical challenges are adequately addressed.

Aim: The post-COVID-19 pandemic era has witnessed changes in psychological states and lifestyles. This study aims to explore the associations between depression, obesity, and hypertension, and further assess the mediating effects of lifestyle factors such as sleep duration, working hours, and physical activity on these disease relationships.

Methods: Using data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2023, we calculated long-term trends in depression, sleep duration, working hours, metabolic equivalent of exercise, obesity, and blood pressure. Data from 42,395 (sleep duration), 23,101 (working hours), and 20,435 participants (physical activity) were used to evaluate the relationships between lifestyle factors, depression, obesity, and blood pressure.

Results: Between 2021 and 2023, the average depression score in the U.S. increased to 4.13 (4.74), with prevalence rising to 13.2%. Over the past 18 years, national body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), and sleep duration increased (P < 0.001), while working hours decreased (P < 0.001) and physical activity declined post-pandemic (P < 0.001). Depression was positively correlated with BMI, WC, WHtR, and diastolic blood pressure (DBP) (P < 0.0001), and negatively correlated with systolic blood pressure, sleep duration, and physical activity (P < 0.0001). Sleep duration and physical activity mediated 1.72%-4.52% and 9.28%-14.79%, respectively, of the positive correlation between depression and obesity. Physical activity mediated 5.49%-9.96% of the positive correlation between depression and DBP. No mediating effect of working hours was found between depression and obesity or blood pressure (P = 0.500-0.936).

Conclusion: In the post-COVID-19 pandemic era, this study advocates for increased attention to lifestyle factors. Moderate extensions in sleep duration, reductions in working hours, and increased physical activity may help alleviate the burdens of depression, obesity, and blood pressure.

Aim: This study aimed to explore the relationship between visceral fat and obesity-related metabolic diseases, validate the obesity criteria from the European Association for the Study of Obesity (EASO) in the Chinese population, and propose new standards for identifying visceral fat using simple anthropometric indicators.

Methods: This cross-sectional study involved 3,371 participants aged 26-76 years in Pinggu District, Beijing. Anthropometric measurements and metabolic indicators were assessed, and visceral fat area (VFA) was calculated from non-contrast abdominal computed tomography scans. The McNemar test was used to compare the diagnostic accuracy of the EASO criteria and body mass index (BMI) for identifying visceral obesity. The correlation between anthropometric indicators and VFA was analysed using Spearman’s correlation coefficient. Receiver operating characteristic curves were used to compare the diagnostic efficacy and thresholds of anthropometric indicators with the EASO criteria.

Results: Among 3,371 participants, 61.2% were diagnosed with visceral obesity. Metabolic disease prevalence was higher in individuals with visceral obesity, suggesting that visceral fat accumulation is a sensitive marker for identifying metabolic diseases. The EASO criteria showed higher sensitivity and lower specificity than BMI alone for diagnosing visceral obesity. Waist circumference (WC) and waist-to-height ratio correlated strongly with VFA. BMI combined with WC was the most effective tool for diagnosing visceral obesity in the Chinese population.

Conclusion: Visceral fat accumulation is associated with metabolic diseases, and the EASO criteria are superior to BMI in identifying visceral obesity. BMI combined with WC is effective for diagnosing visceral obesity in the Chinese population.

Aim: Diabetes-related chronic kidney disease (CKD) is a major cause of both CKD and end-stage renal disease. This study aimed to examine updated global trends in the burden of diabetes-related CKD from 1990 to 2021, stratified by location, age, and sex.

Methods: Using data from the Global Burden of Disease (GBD) 2021 dataset, we quantified the burden of CKD worldwide, including prevalence, incidence, mortality, and disability-adjusted life years (DALYs).

Results: From 1990 to 2021, global surveillance revealed a persistent increase in the burden of diabetes-related CKD, with age-standardized incidence rates (ASIRs) rising significantly across socio-demographic index (SDI) quintiles. Forecasted ASIR for type 2 diabetes-related CKD (T2D-CKD) shows a consistent pattern of escalation, whereas type 1 diabetes-related CKD (T1D-CKD) is expected to decrease from 2021 to 2036. Across all SDI quintiles, ASIR for diabetes-related CKD increased progressively, with high-SDI regions showing the highest rates. Moreover, the global DALY burden peaked in the 50-54 age group for T1D-CKD and in the 65-69 age group for T2D-CKD in the Southeast Asia, East Asia, and Oceania super-region. Overall, the burden of diabetes-related CKD was higher in males, while the prevalence of T1D-CKD was higher in females.

Conclusion: The global burden of diabetes-related CKD increased substantially between 1990 and 2021 across diverse geographic regions. Target strategies are urgently needed to reduce the burden of diabetes-related CKD and address this growing public health challenge.

Aim: This study aimed to explore the cumulative effects of metabolic, behavioral, and early-life risk factors on metabolic dysfunction-associated steatotic liver disease (MASLD).

Methods: Data were obtained from a school-based longitudinal survey conducted in Beijing in 2023. Logistic regression models were used to examine independent associations, construct a risk score, and assess the cumulative effects of risk factors on pediatric MASLD. The risk score was further validated using data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020 cycles.

Results: The prevalence of MASLD among Chinese children was 4.4% at baseline and 7.6% at follow-up. Baseline MASLD was significantly associated with exposure to second-hand smoke (OR = 2.36) and sedentary behavior (SB, OR = 3.21). Each one-unit increase in the risk score was associated with a 73% higher risk of MASLD at baseline, with similar cumulative effects observed in the NHANES cohort. At follow-up, each unit increase in the score corresponded to a 263% higher risk of MASLD. Furthermore, the risk of incident MASLD and persistent MASLD increased by 150% and 111%, respectively, for each unit increase in the score.

Conclusion: Within a conceptual framework addressing multiple levels of risk, we found that metabolic, behavioral, and early-life factors exert cumulative effects on pediatric MASLD. These effects were evident despite the substantial differences between the Chinese and U.S. populations. Targeted intervention strategies informed by this framework - such as improving the early-life environment, promoting healthier lifestyle behaviors, and maintaining favorable metabolic profiles - are essential for the management of pediatric MASLD.

Aim: To explore the relationship between the hemoglobin glycation index (HGI) and the hypoglycemia risk, and the potential effect of glycosylated hemoglobin (HbA1c) and body mass index (BMI) on this relationship.

Methods: This is a prospective observational study. A total of 1,203 type 2 diabetes mellitus (T2DM) patients were included. Linear regression was used to establish an equation for calculating the HGI. Logistic regression models were employed to explore the association between the HGI and hypoglycemia. A moderated mediation approach was taken to detect the effect of BMI and HbA1c on the association between HGI and hypoglycemia.

Results: During the follow-up period (median 34.73 months), 344 patients developed hypoglycemia. The relationship between the HGI and hypoglycemia was significant [odds ratio (OR), 95% confidence interval (CI): 1.255 (1.089-1.446), P = 0.001] after adjusting for potential confounders. Compared to the low-HGI group, the risk of hypoglycemia in the high-HGI group was significantly elevated [OR (95%CI) = 1.603 (1.167-2.201), P = 0.006]. Trend tests suggested that the risk of hypoglycemia increased significantly from the low- to the high-HGI groups (P = 0.003). A significant mediation effect of HbA1c was observed along the path HGI → Hypoglycemia (coefficient = 0.128, 95%CI: 0.140-0.247, P = 0.008) and a significant moderation effect of BMI was observed along the path HGI → HGI*BMI → HbA1c (coefficient = 0.019, 95%CI: 0.004-0.040, P = 0.022), suggesting that HbA1c served as a mediator and BMI as a moderator of the relationship between the HGI and hypoglycemia.

Conclusion: The HGI was significantly associated with the risk of hypoglycemia in T2DM subjects. Moderated mediation analysis demonstrated that the association between the HGI and hypoglycemia was mediated by HbA1c and moderated by BMI. Interventions targeting HbA1c and BMI may mitigate the risk of hypoglycemia in T2DM patients.

This commentary discusses the results of a study that assessed the relationship between homocysteine metabolism and histological severity of metabolic dysfunction-associated steatotic liver disease (MASLD), and applied a mathematical model to examine how replacement with different cofactors (pyridoxine, cobalamin, betaine, and folate) may affect homocysteine levels in patients with MASLD. It highlights the clinical implications of the study and examines the pathophysiological support behind the detected associations. It also discusses its limitations, emphasizing the need for further longitudinal and interventional studies to confirm whether modulating homocysteine levels could be a viable therapeutic strategy for MASLD.

Aim: Limited evidence exists on the effects of endocrine-disrupting chemical exposure on metabolic dysfunction-associated steatotic liver disease (MASLD) in adolescents. We aimed to assess the effects of multiple chemicals on the hepatic steatosis index (HSI) and MASLD in adolescents, and to further explore the potential roles of inflammation and lifestyle factors.

Methods: Associations between chemical exposures and HSI/MASLD were examined using generalized linear models, restricted cubic spline analysis, weighted quantile sum regression, and Bayesian kernel machine regression. Mediation analysis was conducted to evaluate whether inflammation mediated these relationships.

Results: Among 2,163 adolescents (median age 15 years), 490 (22.7%) were diagnosed with MASLD. Bisphenol A, mono-ethyl phthalate, mono-(carboxyoctyl) phthalate, and mono-benzyl phthalate (MBzP) were significantly associated with HSI or MASLD. Both weighted quantile sum and Bayesian kernel machine regression consistently indicated a positive correlation between chemical mixtures and MASLD, with MBzP and bisphenol A identified as key contributors. Mediation analysis showed that white blood cells partially mediated the associations of MBzP with HSI and MASLD, and of mono-(carboxynonyl) phthalate with MASLD. Sedentary behavior and physical activity further modulated the combined effects of chemical mixtures on MASLD.

Conclusion: Exposure to phenols, pesticides, and phthalates was significantly associated with HSI or MASLD, with white blood cells acting as a mediator. Reducing sedentary behavior and increasing physical activity may mitigate the adverse impacts of chemical mixtures on MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), is a fast-growing global medical concern, affecting approximately one-third of the population, with numbers rising. Recognized as a multisystemic disease, MASLD extends beyond the liver, presenting extrahepatic manifestations such as cardiovascular disease, type 2 diabetes, endocrine disorders such as hypothyroidism and polycystic ovarian syndrome, chronic kidney disease, psoriasis, and extrahepatic malignancies. This review aims to summarize the systemic effects of MASLD/NAFLD and to highlight possible shared pathophysiological pathways, including insulin resistance, lipid metabolism dysregulation, inflammation, oxidative stress, and gut dysbiosis. In addition, we discuss emerging therapeutic strategies for MASLD/NAFLD and its associated comorbidities. By integrating current evidence, this review provides insights into the multisystemic nature of MASLD and underscores the need for comprehensive management approaches.

Aim: This study aimed to evaluate the effect of the intermittent fasting (IF) intervention on metabolism and thyroid hormone sensitivity (THS) in patients with steatotic liver disease (SLD) and to further investigate the association between changes in THS and alterations in metabolic parameters during the intervention.

Methods: A total of 78 patients with SLD underwent a 5:2 IF intervention for 8 weeks. Metabolic outcomes and THS, measured by the thyroid feedback quantile-based index (TFQI), thyrotroph thyroxine resistance index, thyroid-stimulating hormone index (TSHI), and free triiodothyronine to free thyroxine ratio (FT3/FT4), were assessed at baseline and after the intervention. Multiple regression analysis was performed to examine relationships between changes in THS and metabolic parameters during the intervention.

Results: Average hepatic fat content was 15.02% at baseline and decreased by 3.79% after the 8-week IF intervention, accompanied by significant reductions in body weight, blood glucose, serum lipids, fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and adipose tissue insulin resistance index (Adipo-IR). After the intervention, THS improved: TFQI, thyrotroph thyroxine resistance index, and TSHI all decreased, while FT3/FT4 increased. Significant positive correlations were observed between ΔTFQI and ΔTSHI and changes in fasting insulin, HOMA-IR, and Adipo-IR. In multivariate models adjusted for age, sex, and weight loss, ΔTFQI and ΔTSHI remained significantly correlated with Δinsulin, ΔHOMA-IR, and ΔAdipo-IR.

Conclusion: IF-induced improvement in THS was associated with enhanced insulin sensitivity independent of weight loss in patients with SLD. These findings suggest that THS may play a role in metabolic improvements and could inform therapeutic strategies for SLD.

Aim: Gastric leak following foregut surgery remains a major challenge to clinicians. Treatment algorithms may vary between institutions often depending on clinician preference. The objective of this review is to assess the efficacy of different treatment strategies (i.e., endoscopic and surgical) for sleeve gastrectomy leaks across the literature, share our own centre’s experiences and attempt to implement an algorithm in managing sleeve leaks according to their severity as classified by a computed tomography-based staging system.

Methods: A comprehensive search of existing literature over the last decade was conducted using pre-defined criteria in accordance with preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Sleeve gastrectomy leaks in the included studies were further categorized according to severity, prior to analysing the efficacy of treatment methods.

Results: Following review of 1,109 potential articles, 36 studies were included, involving a total of 1,246 sleeve leak patients. The mean age and body mass index of patients ranged from 33 to 46 years of age and 37 to 48 kg/m², respectively. In type 1-2 leaks, surgical or radiological drainage followed by primary endoscopic therapy (i.e., stenting, internal drainage, over the scope clips, fibrin glue and/or E-VAC) was effective (leak resolution rates - 50%-100% between reporting papers). Endoscopic therapy remains a viable treatment option in treating type 3-4 leaks with success rates ranging from 33%-95%, although surgery (i.e., fistulo-jejunostomy, Roux-en-Y gastric bypass or total gastrectomy) may be required in chronic leaks where all other modalities have failed.

Conclusion: Management of sleeve leaks should be driven by the underlying leak pathophysiology. Defining variables such as the size of the defect, size of any abscess/collection and presence of a stenosis can allow differing options to be applied. Patients who fail to respond appropriately can be escalated to alternate therapies with the aim of resuming per oral nutrition and minimizing inpatient stay.