ABSTRACT
Objectives: To synthesize data on circulating ferritin between patients with histologically confirmed nonalcoholic fatty liver disease (NAFLD) and non-NAFLD controls. Methods: A systematic literature search was conducted in PubMed, Scopus, and the Cochrane Library. Thirty-one studies comprising data on 5631 individuals (2929 biopsy-proven NAFLD patients and 2702 controls) were included in the meta-analysis. Results: Higher circulating ferritin levels were observed in NAFLD patients than in controls [standardized mean difference (SMD) 1.14; 95% confidence interval (95% CI) 0.73-1.55], in patients with simple nonalcoholic fatty liver (NAFL) than in controls (SMD 0.57; 95% CI 0.34-0.80), in patients with nonalcoholic steatohepatitis (NASH) than in controls (SMD 0.95; 95% CI 0.69-1.22), and in NASH than in NAFL patients (SMD 0.62; 95% CI 0.25-0.99). There was moderate-to-high heterogeneity among studies in the above pairs of comparisons (I2 = 68-97%); no risk of publication bias was observed by Egger's test (P = 0.81, P = 0.72, P = 0.59, P = 0.42, respectively). The heterogeneity was reduced in the subgroup of biopsy-proven controls in all pairs of comparisons (I2 = 0-65%). The heterogeneity was also reduced after excluding studies with the Newcastle-Ottawa Scale (NOS) score <7 (n = 10) for the comparison of NAFLD patients vs. controls (I2 = 54%, P = 0.02). The meta-regression analysis revealed that the male ratio was positively associated with ferritin SMD in the comparison between NAFLD patients and controls and accounted for 32.7% (P = 0.002) of the heterogeneity in this pair of comparison. Conclusions: Circulating ferritin was higher in NAFLD (or NAFL or NASH) patients compared with controls. Higher levels of circulating ferritin were also associated with the severity of the disease, which, however, should be cautiously interpreted.PROSPERO registration ID: CRD42022354025.
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Background: This systematic review and meta-analysis aimed to summarize and compare data on retinal vascular lesions between patients with nonalcoholic fatty liver disease (NAFLD) and individuals without the disease. Methods: Search was performed in PubMed, Scopus and Cochrane Library, complemented by handsearching (PROSPERO ID: CRD42022345558). Thirty-six studies comprising 24,985 individuals (12,387 NAFLD patients and 12,598 controls) were selected for the meta-analysis. Results: Apart from retinopathy, no study with a different type of retinal vascular lesion was retrieved. Overall, there was no significant difference in the presence of retinopathy in NAFLD patients compared to controls (Odds Ratio (OR) = 1.20; 95% Confidence Interval (CI): 0.91-1.59). Heterogeneity among studies was high (I2 = 93%; p < 0.00001), while Egger's test revealed no publication bias (p = 0.60). However, subgroup analysis showed positive association between retinopathy and NAFLD in type 1 diabetes mellitus (T1DM) (OR = 2.35; 95% CI: 1.53-3.60), but not in type 2 diabetes mellitus patients. Meta-regression analysis exploring potential confounders revealed no significant association. Conclusions: The presence of retinopathy was not overall different between individuals with and without NAFLD; however, T1DM patients with NAFLD had higher rates of retinopathy compared to T1DM patients without NAFLD, a finding warranting further research to show whether NAFLD may predict retinopathy in T1DM patients.
ABSTRACT
INTRODUCTION: Keratoconus (KC) is a complex, genetically heterogeneous, multifactorial degenerative disorder that is accompanied by corneal ectasia which usually progresses asymmetrically. With an incidence of approximately 1 per 2000 and 2 cases per 100,000 population presenting annually, KC follows an autosomal recessive or dominant pattern of inheritance and is, apparently, associated with genes that interact with environmental, genetic, and/or other factors. This is an important consideration in refractive surgery in the case of familial KC, given the association of KC with other genetic disorders and the imbalance between dizygotic twins. The present review attempts to identify the genetic loci contributing to the different KC clinical presentations and relate them to the common genetically determined comorbidities associated with KC. METHODS: The PubMed, MEDLINE, Google Scholar, and GeneCards databases were screened for KC-related articles published in English between January 2006 and November 2017. Keyword combinations of "keratoconus," "risk factor(s)," "genetics," "genes," "genetic association(s)," and "cornea" were used. In total, 217 articles were retrieved and analyzed, with greater weight placed on the more recent literature. Further bibliographic research based on the 217 articles revealed another 124 relevant articles that were included in this review. Using the reviewed literature, an attempt was made to correlate genes and genetic risk factors with KC characteristics and genetically related comorbidities associated with KC based on genome-wide association studies, family-based linkage analysis, and candidate-gene approaches. RESULTS: An association matrix between known KC-related genes and KC symptoms and/or clinical signs together with an association matrix between identified KC genes and genetically related KC comorbidities/syndromes were constructed. CONCLUSION: Twenty-four genes were identified as potential contributors to KC and 49 KC-related comorbidities/syndromes were found. More than 85% of the known KC-related genes are involved in glaucoma, Down syndrome, connective tissue disorders, endothelial dystrophy, posterior polymorphous corneal dystrophy, and cataract.
