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OBJECTIVE: Epidemiological studies have reported an association between primary hypothyroidism and metabolic dysfunction-associated steatotic liver disease (MASLD). However, the magnitude of the risk and whether this risk changes with the severity of MASLD remains uncertain. We performed a meta-analysis of observational studies to quantify the magnitude of the association between primary hypothyroidism and the risk of MASLD. DESIGN: We systematically searched PubMed, Scopus and Web of Science from database inception to 31 January 2024, using predefined keywords to identify observational studies in which MASLD was diagnosed by liver biopsy, imaging or International Classification of Diseases codes. A meta-analysis was performed using random-effects modelling. RESULTS: We identified 24 cross-sectional and 4 longitudinal studies with aggregate data on ~76.5 million individuals. Primary hypothyroidism (defined as levothyroxine replacement treatment, subclinical hypothyroidism or overt hypothyroidism) was associated with an increased risk of prevalent MASLD (n=24 studies; random-effects OR 1.43, 95% CI 1.23 to 1.66; I2=89%). Hypothyroidism was also associated with a substantially higher risk of metabolic dysfunction-associated steatohepatitis or advanced fibrosis (n=5 studies; random-effects OR 2.84, 95% CI 2.07 to 3.90; I2=0%). Meta-analysis of data from four longitudinal studies showed that there was a marginally non-significant association between hypothyroidism and risk of developing MASLD over a median 4.5-year follow-up (random-effects HR 1.39, 95% CI 0.98 to 1.97; I2=85%). Sensitivity analyses did not modify these findings. The funnel plot did not reveal any significant publication bias. CONCLUSION: This large and updated meta-analysis provides evidence that primary hypothyroidism is significantly associated with both an increased presence of and histological severity of MASLD.
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BACKGROUND: Recent observational studies examining the association between Helicobacter pylori infection and the risk of metabolic dysfunction-associated steatotic liver disease (MASLD) have reported conflicting results. We performed a meta-analysis to quantify the magnitude of the association between H. pylori infection and the risk of MASLD. METHODS: We systematically searched three large electronic databases to identify eligible observational studies (published up to 30 November 2023) in which liver biopsy, imaging methods or blood-based biomarkers/scores were used for diagnosing MASLD. Data from selected studies were extracted, and meta-analysis was performed using common and random-effects modelling. Statistical heterogeneity among published studies, subgroup analyses, meta-regression analyses and publication bias were assessed. RESULTS: A total of 28 observational studies (24 cross-sectional and 4 longitudinal studies) were identified, including 231 291 middle-aged individuals of predominantly Asian ethnicity (~95%). Meta-analysis of cross-sectional studies showed that H. pylori infection was significantly associated with a small increase in the risk of prevalent MASLD (n = 24 studies; random-effects odds ratio 1.11, 95% CI 1.05-1.18; I2 = 63%). Meta-analysis of data from longitudinal studies showed that H. pylori infection was significantly associated with an increased risk of developing incident MASLD over a mean 5-year follow-up (n = 4 studies; random-effects odds ratio 1.20, 95%CI 1.08-1.33; I2 = 44%). Sensitivity analyses did not modify these results. The funnel plot did not reveal any significant publication bias. CONCLUSIONS: H. pylori infection is associated with a mildly increased risk of prevalent and incident MASLD. Further well-designed prospective and mechanistic studies are required to better decipher the complex link between H. pylori infection and the risk of MASLD.
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BACKGROUND: High-risk carotid artery plaque (HPR) is associated with a markedly increased risk of ischemic stroke. The aims of this study were: 1) to examine the prevalence of HRP in a cohort of asymptomatic adults with type 2 diabetes (T2D); 2) to investigate the relationship between HRP, established cardiovascular risk factors and computed tomography angiography (CTA) profile; and 3) to assess whether the presence of HRP is associated with an increased risk of major adverse cardiovascular events (MACE). METHODS: This was a retrospective cohort study of T2D asymptomatic patients who underwent carotid endarterectomy (CEA) from January 2018 to July 2021. The carotid atherosclerotic plaque (CAP) was assessed for the presence of ulceration, the presence of lipids, fibrosis, thrombotic deposits, hemorrhage, neovascularization, and inflammation. A CAP presenting at least five of these histological features was defined as a HRP (Group A); in all other cases it was defined as a mild to moderate heterogeneous plaque and no-HRP (Group B). CTA features included the presence of rim sign consisting of thin peripheral adventitial calcification (<2 mm) and internal soft plaque (≥2 mm), NASCET percent diameter stenosis, maximum plaque thickness, ulceration, calcification, and intraluminal thrombus were recorded. Binary logistic regression with Uni- and Multivariate was used to evaluate possible predictors for HRP while multivariable Cox Proportional Hazards was used to assess independent predictors for MACE. RESULTS: One hundred eighty-five asymptomatic patients (mean age 73±8 years, 131 men), undergoing carotid endarterectomy, were included. Of these, 124 (67%) had HRP, and the 61 (33%) did not. Diabetic complications (OR 2.4, 95% CI: 1.1-5.1, P=0.01), NASCET stenosis ≥75% (OR 2.4, 95% CI: 1.2-3.7, P=0.02) and carotid RIM sign (OR 4.3, 95% CI: 3.9-7.3, P<0.001) were independently associated with HRP. However, HRP was not associated with a higher risk of MACE (freedom from MACE at 5 years: HRP 83.4% vs. non HRP 87.8%, P=0.72) or a reduction of survival (5-year survival estimates: HRP 96.4% vs. non HRP: 94.6%, P=0.76). CONCLUSIONS: A high prevalence of HRP (67%) was observed in asymptomatic and elderly T2D patients. Independent predictors of HRP were diabetic complications, NASCET stenosis ≥75% and carotid RIM sign (OR 4.3, 95% CI: 3.9-7.3, P<0.001). HRP was not associated with an increased risk of MACE during a mean follow-up of 39±24 years.
