Risk Factors For Nonalcoholic Fatty Liver Disease Research Articles

P0427 Nutritional factors associated with the presence of non-alcoholic fatty liver disease (NAFLD) in patients with inflammatory bowel disease (IBD)

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is increasingly prevalent in patients with inflammatory bowel disease (IBD), not only due to the presence of chronic inflammation, but also due to the presence of dysbiosis and risk factors for metabolic disease. Due to the complications of NAFLD, evaluation of at-risk patients is recommended. Therefore, the objective of the study is to evaluate the nutritional status and body composition in IBD patients, comparing groups with and without NAFLD, and identifying the factors associated with NAFLD. Methods A cross-sectional study was conducted, assessing clinical data, metabolic syndrome presence, nutritional status, and biochemical markers. Patients were categorized into IBD+NAFLD and IBD-only groups based on hepatic ultrasound findings. Statistical analysis included descriptive statistics and logistic regression. Results In total, 129 IBD patients were included, 67 (51.94%) UC and 62 (48.06%) CD, 89 (68.99%) female, 31 (24.03%) with high blood pressure, 18 (13.95%) with dyslipidemia, and 16 (12.40%) with diabetes. Biological therapy was indicated in 65 (50.39%) patients. Clinical activity was observed in 60 (46.51%) of the patients. Presence of NAFLD was observed in 57 (44.19%) patients, being mild (43.86%), moderate (43.86%) or severe (12.28%). Factors associated with the presence of NAFLD were BMI (p<0.0001), overweight or obesity (p<0.0001), waist circumference (p<0.0001), arm circumference (p=0.0002), arm muscle area (p= 0.0136), waist-hip ratio (p=0.0215), calf circumference (p=0.0003), triceps skinfold (p=0.0086), fat mass (p=0.0001), visceral fat (p<0.0001), and hang- grip (p=0.0071). Regarding biochemical tests, patients with NAFLD presented alterations in creatinine (p=0.0343), AST (p=0.0018), ALT (p<0.0001), gammaGT (p<0.0001), ferritin (p=0.0107), glycemia (p=0.0017), glycated hemoglobin (p=0.0064), triglycerides (p<0.0001), basal insulin (p=0.0012). The presence of NAFLD was not associated with IBD activity (p=0.59) or with the use of medications (p>0,05). Conclusion The prevalence of NAFLD was high in the IBD population. Risk factors for NAFLD are related to metabolic syndrome. Patients should be investigated for the presence of NAFLD with the aim of controlling risk factors to avoid progression to complications such as liver cirrhosis.

Association between SPISE and NAFLD in patients with type 2 diabetes.

Non-alcoholic fatty liver disease (NAFLD) is closely related to type 2 diabetes (T2D), with reduced insulin sensitivity being a key factor in their disrupted metabolic processes. The single point insulin sensitivity estimator (SPISE) is a novel index. This study aims to explore the association between SPISE and NAFLD in T2D population. This study included a total of 2,459 patients with T2D. SPISE was calculated based on high density lipoprotein-cholesterol (HDL-c), triglycerides (TG), and body mass index (BMI). Participants were categorized into NAFLD and non-NAFLD groups based on the results of ultrasonographic diagnosis. The relationship between SPISE and NAFLD was analyzed separately for each gender. The overall prevalence of NAFLD is 38.5%. In females and males, the SPISE was significantly reduced in the NAFLD group compared to the non-NAFLD group (both P < 0.05). The prevalence of NAFLD showed a significant reduction across quartiles of the SPISE in both genders (both P < 0.05).Additionally, univariate correlation analysis showed a negative correlation between SPISE and NAFLD (both P < 0.05). In multivariate regression analysis, a reduced SPISE was identified as an independent risk factor for NAFLD (odds ratios of 0.572 and 0.737, 95% CI of 0.477-0.687 and 0.587-0.926, respectively).Moreover, the area under the receiver operating characteristic (ROC) curve for SPISE was 0.209 in females and 0.268 in males (95% CI of 0.175-0.244 and 0.216-0.320, respectively). These results are more meaningful than those of other variables. SPISE is significantly reduced in NAFLD patients with T2D. Compared to other indicators, SPISE demonstrates superior predictive value in diagnosing NAFLD, and it is independent of gender.

The association between working hours and working type with non-alcoholic fatty liver disease: results from the NHANES 1999-2014.

Previous research has indicated that long working hours are connected to a variety of health conditions, including nonalcoholic fatty liver disease (NAFLD). However, this association which has been observed in more population is limited. Our research is designed to evaluate the association between working hours, working type, and NAFLD. The study comprised adults with complete details on working hours, working type, and NAFLD from the NHANES 1999-2014. We employed the hepatic steatosis index (HSI) to evaluate NAFLD and examined the relationship between working hours or working type and hepatic steatosis using weighted multiple-variable regression models and restricted cubic spline (RCS) analysis. In addition, further subgroup analysis was performed based on sex, age, ratio of family income to poverty (PIR), education, and diabetes. Long working hours were significantly linked to an elevated risk of NAFLD (OR: 1.57, 95%CI: 1.21-2.05), even after controlling for confounding factors. RCS analysis suggested that there was no nonlinear relationship between them. When weekly working hours > 50, the likelihood of NAFLD among the population heightened to 57% and this risk increased to 99% in the female population. As for working type, increasing physical intensity of work was associated with higher NAFLD risk, but only heavy manual labor continued to show significance after adjustment (OR:1.39, 95%CI: 1.06-1.81). We observed that the relationship between heavy manual labor and NAFLD was more significant in the older and male populations. Our results indicate that long working hours and engaging in heavy physical labor are independent risk factors for NAFLD. As working hours increase and individuals engage in heavy physical labor for extended periods, the risk of developing NAFLD significantly rises.

Correlation Among Psoriasis, Iridocyclitis, and Non-alcoholic Fatty Liver Disease: Insights from Mendelian Randomization and Mediation Analysis.

Purpose: The aim of this study is to utilize two-sample Mendelian randomization (MR) to investigate the potential causal relationship among psoriasis, iridocyclitis, and non-alcoholic fatty liver disease (NAFLD), and to explore any potential mediation effects. Methods: Pooled data were derived from the public genome-wide association study (GWAS) in NAFLD (finn-b-NAFLD), iridocyclitis (finn-b-H7_IRIDOCYCLITIS) and psoriasis (finn-b-L12_PSORI_VULG). Univariable MR (UVMR) analysis was implemented to explore the causal relationship among psoriasis, iridocyclitis, and NAFLD, and inverse variance weighting (IVW) was used as the primary analytical method. Additionally, Cochran's Q and MR-Egger tests were utilized to evaluate the heterogeneity and horizontal pleiotropy, respectively. Simultaneously, the reliability of MR results was evaluated by leave-one-out (LOO) method. Finally, multivariable MR (MVMR) analysis and mediation analysis were performed to further reveal the mechanism of mediation effect among the three diseases. Results: With regard to the results of IVW method, both iridocyclitis (P=0.0185, OR=1.0757) and psoriasis (P=0.0115, OR=1.1246) had significant causal relationships with the occurrence of NAFLD, and both were risk factors for NAFLD. Besides, it was observed that there was significant causal effect of iridocyclitis (P= 0.0181, OR=1.1729) on psoriasis and iridocyclitis was a risk factor. Additionally, there was a lack of heterogeneity (P>0.05) among the selected SNPs when MR analysis was conducted with NAFLD as the outcome. Horizontal pleiotropy was not detected by the MR-Egger test. The LOO analysis demonstrated that the instrumental variables were appropriately chosen, suggesting the reliability of the MR results. Ultimately, MVMR and mediation analysis revealed iridocyclitis affected the development of NAFLD, 20.81% of which was caused by the pathway of iridocyclitis induced psoriasis leading to NAFLD. Conclusion: This study highlighted that iridocyclitis was significantly associated with an increased risk of NAFLD and that psoriasis was involved in the mechanism by which iridocyclitis triggered NAFLD, which might offer potential preventive strategies for NAFLD.

Added value of Dixon MRI in quantification of liver fat in nonalcoholic fatty liver disease

Background The Dixon method for fat/water separation employs a technique for achieving consistent fat suppression by utilizing water-only reconstruction. The fat-only Dixon technique is a tool for identifying microscopic fat and assessing pathological lesions of concern. Aim To investigate the MRI Dixon fat fraction role in assessing fat deposition among nonalcoholic fatty liver disease (NAFLD) cases and correlation with ultrasonography (USG). Patients and methods This study included 30 cases, with an age range falling between 19 and 80 years, both sexes. We included those with one or more risk factors for NAFLD in which diffuse hepatic steatosis or normal liver was identified utilizing USG of the abdomen. Participants were examined using USG examination and MRI. Results Good agreement (k=0.615) between two imagining methods (MRI T1 Dixon and USG) in detecting fatty liver with significant difference between diagnostic confidence (accuracy) of MRI T1 Dixon and USG in detection of fatty liver (P=0.005). A significant variance was observed among the grading of fatty liver by MRI T1 Dixon and the presence of METs criteria and alanine aminotransferase level (P&lt;0.05). By USG, a moderate agreement between fatty liver grading utilizing MRI T1 Dixon and fatty liver grading utilizing USG (k=0.526). Conclusions Dixon MRI was a noninvasive method for quantifying fat fraction in NAFLD. When comparing the fatty liver grading on USG with the assessment of liver fat with MRI T1 Dixon of the liver, there was a significant overlap in the fat percentage within each grade.

Lipoprotein(a) as a Predictor of Nonalcoholic Fatty Liver After Pancreatectomy.

Lipoprotein(a) (Lp(a)) is a complex protein involved in the transport of insoluble lipids in plasma. Its expression is predominantly genetically determined, with 70% to over 90% influenced by the number of Kringle IV type 2 domains. This study investigated the association between preoperative serum Lp(a) level and development of post-pancreatectomy nonalcoholic fatty liver disease (NAFLD) in patients who underwent pancreatectomy. Serum Lp(a) level was measured preoperatively and retrospectively evaluated together with other known risk factors for NAFLD, which was defined using a computed tomography-based Hounsfield unit (HU) value for liver parenchyma below 40 HU at the anteroposterior midpoint. NAFLD developed after pancreatectomy in 40 patients (17.5%) in the high Lp(a)-group, which was significantly lower compared to the 30 patients (53%) in the low Lp(a)-group (p=0.01). There were no other significant background factors related to preoperative Lp (a) level. Multivariate analysis indicated that low Lp(a) level is an independent risk factor for postoperative NAFLD, as well as pancreatic head resection, a small residual pancreatic volume, poor intake of pancrelipase, and postoperative diarrhea. NAFLD after pancreatectomy could be predicted preoperatively to a certain extent by examining serum Lp(a) level.

Insulin Resistance Mediates the Association Between Vitamin D and Non-Alcoholic Fatty Liver Disease.

Vitamin D (VD) deficiency and insulin resistance (IR) increase the risk of non-alcoholic fatty liver disease (NAFLD), but few studies have explored the potential mechanisms by which IR mediates the association between VD and the pathogenesis of NAFLD at the genetic level using publicly available databases. This is a cross-sectional study, and we utilized the National Health and Nutrition Examination Survey (NHANES) dataset, as well as data from GSE200765 obtained from the Gene Expression Omnibus (GEO) website. A total of 723 individuals who had completed liver ultrasound examination and the detection of VD levels were included in the final analysis. A gene expression dataset, GSE200765, was also downloaded from the GEO website, to explore the potential mechanism of VD and NAFLD. In the NHANES data, covariates significantly differed in four VD categories, and the controlled attenuation parameter (CAP), vibration-controlled transient elastography-liver stiffness measurement (VCTE-LSM), and IR were reduced with an increase in VD levels. Mediation analysis revealed that IR mediated the association between VD and both CAP and LSM, and the estimated mediation effects were 29.0% and 39.8%, respectively. Bioinformatics analysis showed that seven differentially expressed genes (DEGs) (solute carrier family 2 member 2 [SLC2A2], protein phosphatase 1 regulatory subunit 3E [PPP1R3E], CAMP responsive element binding protein 3-like 3 [CREB3L3], Interleukin-6 [IL-6], peroxisome proliferator-activated receptor gamma coactivator 1-alpha [PPARGC1A], nuclear factor kappa B inhibitor alpha [NFKBIA], and phosphoenolpyruvate carboxykinase 2 [PCK2]) were enriched in the IR pathway in comparison groups (VD group vs. lipid group), suggesting that VD improved NAFLD via changed IR. VD deficiency and IR were the risk factors for NAFLD, and increased VD levels improved the status of NAFLD. The underlying mechanism may be that elevated VD levels reduced IR, which improved the expression of DEGs involved in the IR pathway.

Relationship of the Degree of Sarcopenia with the Severity of Nonalcoholic Fatty Liver Disease and Cardiometabolic Risk in Adolescents.

The association between nonalcoholic fatty liver disease (NAFLD) and sarcopenia has been suggested. We investigated sarcopenia's impact on NAFLD severity and its relationship with cardiometabolic risk in adolescents. We conducted a retrospective study on 122 patients aged 13-18 years and diagnosed with both NAFLD and sarcopenia by laboratory tests, abdominal ultrasound (US), and multifrequency bioelectrical impedance analysis. Sarcopenia was stratified into tertiles based on the skeletal muscle-to-fat ratio (MFR), NAFLD severity was established by the US, and cardiometabolic risk was assessed by the triglyceride-glucose (TyG) index and the atherogenic index of plasma (AIP). Compared with the other patients, those in the lower MFR tertiles exhibited a greater severity of NAFLD (p < 0.001) and significantly higher TyG index and AIP. The independent effect of MFR was observed to have a negative correlation with the severity of NAFLD (p < 0.001). Based on the aforementioned results, the degree of sarcopenia can be considered as one of the risk factors of severe NAFLD and might be an indicator of cardiometabolic risk in adolescents. Weight training to reach the amount of muscle mass could be included in the treatment strategies to improve or prevent NAFLD in adolescents with sarcopenia.

Gallstones increase the risk of nonalcoholic fatty liver: A case-control study.

Nonalcoholic fatty liver disease (NAFLD) and gallstones are generally seen together, and many of the risk factors for fatty liver and gallstones are common and similar. Therefore, this study aims to investigate the relationship between NAFLD and gallstones. This case-control study was conducted in patients referred to Imam Khomeini and Golestan hospitals of Ahvaz University of Medical Sciences in 2023, whose ultrasound showed fatty liver. Patients who were diagnosed with NAFLD by ultrasound were considered as the case group, and patients who did not have diagnostic findings of fatty liver in ultrasound were considered as the control group. Finally, the information recorded in the checklists was statistically analyzed using SPSS version 26 (SPSS Inc.). Three hundred patients were included in our study, 150 as cases and 150 as controls. There was no significant difference between the groups in terms of gender and age (gender P-value: 0.817/age P-value: 0.102). A statistically significant relationship was found between obesity, diabetes mellitus (DM), the presence of gallstones, and NAFLD (weight p-value < 0.001/DM p-value < 0.001/gallstones P-value: 0.03). In addition, based on binary logistic regression analysis, the presence of gallstones increases the odds of NAFLD by 2.33 times (P-value: 0.035). Furthermore, having DM and increasing each BMI unit increases the odds of NAFLD by 16 times and 30%, respectively (BMI p-value < 0.001/DM p-value < 0.001). Based on the results of our study, gallstones are an important risk factor for NAFLD. The possible mechanisms are the existence of common risk factors between gallstones and NAFLD and the reduction of motility and flow of bile in the bile ducts with the presence of gallstones.

Research Progress on Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease worldwide. With the prevalence of overweight and obesity in the Chinese population, NAFLD is no longer a disease exclusive to Western developed countries, and has become one of the most common metabolic diseases in the world. The global prevalence of NAFLD is as high as 37.8%, and the prevalence of NAFLD in the Chinese population is 23.3%. In recent years, with the global epidemic of obesity and metabolic syndrome, the prevalence of NAFLD has gradually increased. The risk factors of NAFLD are closely related to obesity, diabetes, hypercholesterolemia, hypertriglyceridemia, hyperuricemia and other diseases. When NAFLD co-exists with these metabolic diseases, it often increases the risk of cirrhosis, liver cancer, and even death. At the same time, it can aggravate other chronic liver diseases, promote disease progression, and is closely related to the occurrence and development of atherosclerosis and type 2 diabetes. With the progression of NAFLD disease, the related clinical burden and economic burden of NAFLD and its impact on patients' quality of life are becoming more and more serious. Therefore, early identification, early diagnosis, early prevention, early treatment and standardized management of NAFLD are conducive to the control of the risk of cirrhosis, liver cancer and cardiovascular diseases. This article will review the epidemiology, hazards, and related risk factors of NAFLD.

The association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and non-alcoholic fatty liver disease in US adults: a cross-sectional study

The ratio of non-high-density lipoprotein cholesterol (non-HDL-C) to HDL-C (NHHR) is a novel lipid parameter used to assess the risk of cardiovascular disease. Previous studies have demonstrated an association between the NHHR and risk of non-alcoholic fatty liver disease (NAFLD). Owing to the lack of research exploring this relationship in specific populations, this study aimed to determine the potential link between the NHHR and risk of NAFLD among American adults in the United States. Data were retrieved from the National Health and Nutrition Examination Survey (NHANES) spanning 2017–2020. After excluding individuals with other liver diseases, alcohol abuse, and missing lipid data, a total of 6809 eligible adults were included for analysis. The NHHR was calculated as the ratio of (non-HDL-C) to HDL-C, while NAFLD was identified by liver steatosis detected by transient elastography. Multivariable weighted logistic regression models and restricted cubic spline (RCS) models were employed to investigate the relationship between the NHHR and risk of NAFLD. Subgroup and sensitivity analyses were also conducted to test the robustness of the results. As the NHHR increased, the prevalence of NAFLD rose progressively (5.88% vs. 8.75% vs. 12.24% vs. 15.77%, p < 0.001). In the overall population, after adjusting for confounding factors, each unit increase in the NHHR was associated with a 25% increase in NAFLD risk (OR = 1.25, 95% CI: 1.03–1.53, p = 0.0372). When the NHHR was analyzed as a categorical variable (quartiles), participants in the highest quartile had a significantly higher risk of NAFLD than those in the lowest quartile (OR = 2.6, 95% CI: 1.75–3.85, p = 0.009). RCS analysis further indicated a nonlinear dose–response relationship between the NHHR and risk of NAFLD (p non-linearity < 0.0001). This association remained significant in both subgroup and sensitivity analyses. This study confirmed that the NHHR, particularly at higher levels, was an independent risk factor for NAFLD. As a comprehensive lipid indicator, the NHHR had the potential to predict NAFLD risk. These findings provided new insights for the prevention and clinical management of NAFLD.

Cotinine exposure enhances the association of blood manganese and non-alcoholic fatty liver disease in American children: a cross-sectional study

This cross-sectional survey aims to determine whether cotinine exposure would enhance the relationship between blood manganese (Mn) and non-alcoholic fatty liver disease (NAFLD) in children using the NHANES database. Restricted cubic spline (RCS) and logistic regression analyses were adopted to determine the potential relationship. Besides, we tested the robustness of the results by performing trend tests and subgroup analyses. The study finally enrolled 866 children aged 18 years and below. Blood Mn was linearly linked to NAFLD and the risk of NAFLD was increased with the blood Mn elevation (P < 0.05). There was a notable relationship between blood Mn and NAFLD in crude model 1, which was still significant upon adjustment of all the identified covariates (all P < 0.05). Under Mn exposure, the cotinine-exposed group had a higher risk of NAFLD than the cotinine-unexposed group. In conclusion, blood Mn level is an independent risk factor for pediatric NAFLD, and cotinine exposure can enhance this relationship to some degree. Therefore, reducing cotinine exposure may alleviate detrimental consequences related to exposure to heavy metals in children.

Biochemical and nutritional determinants of non-alcoholic fatty liver disease in Omani adult patients: a case-control study

Background: Non-Alcoholic Fatty Liver Disease (NAFLD) is a risk factor for atherosclerosis, diabetes, kidney disease, and liver cirrhosis. Limited research exists on the biochemical and nutritional elements influencing NAFLD among adult patients in Oman. Objective: This study aimed to characterize the biochemical parameters and nutritional factors of Omani adults diagnosed with NAFLD at the Diwan Polyclinic in Muscat, Oman. Methods: This retrospective case–control study included 104 participants (52 cases and 52 controls) who have 2 or more risk factors for NAFLD and were referred to the Radiology department from January 2021 to January 2022 for abdominal ultrasound after Internal Medicine consultations. A validated scale, incorporating a semi-quantitative food frequency questionnaire, was employed. Results: The study revealed a significantly higher risk of NAFLD among men (69%) compared to women (31%). A common characteristic among participants was a prior diabetes diagnosis, 61.5% of the case group and 65% of the control group. While average liver enzyme levels were within the normal range for both groups, alanine transaminase levels were notably elevated in the case group. The case group exhibited a significantly higher average caloric intake than the control group. Conclusion: NAFLD is significantly more common among men. Alanine transaminase is significantly high in NAFLD group, which might be considered as a biochemical marker for NAFLD, but further investigations are needed. Moreover, high daily caloric intake is directly related to NAFLD.

Relationship between Parathyroid Hormone Level and Degree of Hepatic Steatosis by Fibroscan among Prevalent Hemodialysis Patients

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome (MS) which may be related to cardiovascular mortality among hemodialysis (HD) patients. Hepatic steatosis contributed to many factors related to MS, atherogenic dyslipidemia, insulinresistance, and adipose tissue hormones. Elevated parathyroid hormone is associated with insulin resistance and atherosclerosis and may be considered an independent predictor of metabolic syndrome. some studies reported an association between elevated PTH and non-alcoholic steatohepatitis. However, the relationship between hyperparathyroidism and NAFLD in HD patients is not well defined. Aims of the Study To test the hypothesis of a possible association between hyperparathyroidism and the presence of hepatic steatosis and fibrosis by transient elastography and to evaluate the possible risk factors of NAFLD among hemodialysis patients. Patients and Methods This is a Case-control study included: Group I: (30) chronic HD patients with NAFLD, Group II: (25) chronic HD patients without NAFLD, and Group III: 30 healthy volunteers as a control group. Infection with a hepatotropic virus, Diabetes mellitus (DM), patients with a history of recent hepatobiliary surgery, Abdominal Ascites, Active infection, fever, Active malignancy, drugs induce hepatic steatosis, or Alcohol abuse were excluded. All subjects were subjected to full history and clinical examination. Laboratory tests: Complete blood count (CBC), Iron profile, Serum creatinine, Urea, Calcium (Ca), phosphorus, Intact parathyroid hormone (iPTH), Serum Alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), Serum Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Albumin, Total bilirubin, Total cholesterol, High-density lipoprotein cholesterol (HDL), Low-density Lipoprotein cholesterol (LDL), Triglycerides (TG), C -reactive protein (CRP) Titre, HBsAg, HCV Ab and Urea reduction ratio (URR). Transient elastography Fibroscan® for assessment of Controlled attenuation parameter (CAP) to detect liver steatosis grades and liver stiffness measurement to quantitate liver fibrosis was done. Results The mean ±SD values of CAP of liver steatosis (263.7 ± 52.7, 181.3 ± 23, 210.8 ± 33.7) (dB/m) in group I, II and control group respectively (P &amp;lt; 0.001). There were significant differences between the studied group as regard body mass index (BMI), serum Ca, phosphorus, ALP and GGT and CRP titer, PTH and liver function tests, and lipid profile (P &amp;lt; 0.001). Post Hoc analysis revealed a significant statistical difference between group I and II groups as regard ALT, AST, Bilirubin level and serum albumin, CRP titer, and lipid profile (P &amp;lt; 0.5). In HD patients studied groups, the CAP value of liver steatosis was statistically significantly correlated to BMI ALT (r = 0.387, P=0.004), AST (r = 0.365, P = 0.006), Cholesterol (r = 0.785, P &amp;lt; 0.001), LDL (r = 0.692, P &amp;lt; 0.001), TG (r = 0.668, P &amp;lt;0.001), CRP Titre (r=0.384, P=0.004), but not correlated to PTH or other studied parameters (P &amp;gt; 0.05). In control group III, there was a significant correlation between the measured CAP Value of liver steatosis and BMI, PTH, CRP titer, ALT, AST, cholesterol, LDL, and a negative correlation between HDL and CAP value (P &amp;lt; 0.05). liver stiffness /fibrosis was observed in 18 (60.0%) of HD patients in group I versus 8 (32%) patients in group II (P &amp;lt; 0.05). The mean value of liver stiffness (Kpa) was (6.73 ± 6.08, 6.39 ± 5.65, 4.57 ± 0.75) in groups I, II, and the control group respectively (P &amp;lt; 0.001) and post hoc analysis showed a significant difference between Group I and Group II (P = 0.04) and between group I and control group p (&amp;lt;0.001). There was a significant difference between group I and group II and between group I and the control group regarding mean values of liver stiffness (Kpa) (P &amp;lt; 0.05) Conclusions Non-alcoholic liver disease (NAFLD) in prevalent hemodialysis patients is significantly correlated to high cholesterol, LDL, triglycerides, low HDL, increased body mass index, and CRP titer as a marker of inflammation, but not significantly correlated to elevated parathyroid hormone level. NAFLD is a risk for liver stiffness /fibrosis among chronic hemodialysis patients.

Association between phthalates exposure and non-alcoholic fatty liver disease under different diagnostic criteria: a cross-sectional study based on NHANES 2017 to 2018.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease. Phthalates have been suggested to influence the development of NAFLD due to their endocrine-disrupting properties, but studies based on nationally representative populations are insufficient, and existing studies seem to have reached conflicting conclusions. Due to changes in legislation, the use of traditional phthalates has gradually decreased, and the phthalates substitutes is getting more attention. This study aims to delve deeper into how the choice of diagnostic approach influences observed correlations and concern about more alternatives of phthalates, thereby offering more precise references for the prevention and treatment of NAFLD. A cohort of 641 participants, sourced from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 database, was evaluated for NAFLD using three diagnostic methods: the Hepatic Steatosis Index (HSI), the US Fatty Liver Indicator (US.FLI), and Vibration Controlled Transient Elastography (VCTE). The urinary metabolite concentrations of Di-2-ethylhexyl phthalate (DEHP), Di-isodecyl phthalate (DIDP), Di-isononyl phthalate (DINP), Di-n-butyl phthalate (DnBP), Di-isobutyl phthalate (DIBP), Di-ethyl phthalate (DEP) and Di-n-octyl phthalate (DnOP) were detected. The association between NAFLD and urinary phthalate metabolites was evaluated through univariate and multivariate logistic regression analyses, considering different concentration gradients of urinary phthalates. Univariate logistic regression analysis found significant correlations between NAFLD and specific urinary phthalate metabolites, such as Mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), Mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), Mono-2-ethyl-5-carboxypentyl phthalate (MECPP), and Mono-(carboxyisoctyl) phthalate (MCiOP), across different diagnostic criteria. In a multivariate logistic regression analysis adjusting only for demographic data, MEOHP (OR = 3.26, 95% CI = 1.19-8.94, p = 0.029), MEHHP (OR = 3.98, 95% CI = 1.43-11.1, p = 0.016), MECPP (OR = 3.52, 95% CI = 1.01-12.2, p = 0.049), and MCiOP (OR = 4.55, 95% CI = 1.93-10.7, p = 0.005) were positively related to NAFLD defined by HSI and VCTE. The correlation strength varied with the concentration of phthalates, indicating a potential dose-response relationship. Adjusting for all covariates in multivariate logistic regression, only MCiOP (OR = 4.22, 95% CI = 1.10-16.2, p = 0.044), as an oxidative metabolite of DINP, remained significantly associated with NAFLD under the VCTE criterion, suggesting its potential role as a risk factor for NAFLD. This research highlights a significant association between DINP and NAFLD. These findings underscore the need for further investigation into the role of the phthalates substitutes in the pathogenesis of NAFLD and the importance of considering different diagnostic criteria in research.

Identification of novel targets associated with cholesterol metabolism in nonalcoholic fatty liver disease: a comprehensive study using Mendelian randomization combined with transcriptome analysis.

There is limited research on cholesterol metabolism-related genes (CM-RGs) in non-alcoholic fatty liver disease (NAFLD), despite hypercholesterolemia being a recognized risk factor. The role of CM-RGs in NAFLD remains unclear. The differentially expressed genes (DEGs) between NAFLD and control were acquired by differential expression analysis. The differentially expressed genes associated with cholesterol metabolism (DE-CM-RGs) were identified and functional enrichment analyses were performed. Protein-protein interaction network analysis and a two-sample Mendelian randomization study were utilized for identifying hub genes. Nomogram model, competing endogenous RNA and messenger RNA-drug networks were established. In addition, immunoinfiltration analysis was performed. We identified four hub genes (MVK, HMGCS1, TM7SF2, and FDPS) linked to NAFLD risk. MVK and TM7SF2 were protective factors, HMGCS1 and FDPS were risk factors for NAFLD. The area under the curve values of nomograms in GSE135251 and GSE126848 were 0.79 and 0.848, respectively. The gene set enrichment analysis indicated that hub genes participated in calcium signaling pathways and biosynthesis of unsaturated fatty acids. NAFLD patients showed increased CD56dim NK cells and Th17. Tretinoin, alendronate, zoledronic acid, and quercetin are potential target agents in NAFLD. Our study has linked cholesterol metabolism genes (MVK, HMGCS1, TM7SF2, and FDPS) to NAFLD, providing a promising diagnostic framework, identifying treatment targets, and offering novel perspectives into its mechanisms.

Association between heavy metal exposure and biomarkers for non-alcoholic fatty liver disease in Korean adolescents

The global prevalence of non-alcoholic fatty liver disease (NAFLD) in adolescents has increased. In addition to childhood obesity, environmental risk factors, such as heavy metals that are known to be involved in hepatotoxicity, play role in NAFLD occurrence. However, their association with NAFLD remains unclear. This study aimed to investigate the association between heavy metal exposure and NAFLD biomarkers in adolescents. In this cross-sectional study, we used the data of a total of 1505 adolescents aged 12-17 years who participated in the Korean National Environmental Health Survey III (2015-2017) and IV (2018-2020). The presence of blood lead (BPb), blood mercury (BHg), urinary mercury (UHg), and urinary cadmium (UCd) were measured. Liver enzymes including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT) were evaluated. For NAFLD biomarkers, the hepatic steatosis index (HSI) was calculated. Multivariate linear regression models, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) model were used to investigate the association between heavy metals and NAFLD biomarkers. Among heavy metals, mercury presence showed a significant association with NAFLD biomarkers. Two-fold increases in BHg and UHg were associated with 0.21 points (95% confidence interval [CI]: 0.08-0.35) and 0.19 points (95% CI: 0.09-0.30) higher HSI, respectively. In the WQS model, heavy metal mixture was significantly associated with increased HSI (β=0.06, 95% CI: 0.01-0.11). Similarly, in the BKMR model, heavy metal mixture was positively associated with NAFLD biomarkers, and BHg was the most important contributor in the association. BHg and UHg were significantly associated with NAFLD biomarkers in adolescents, indicating that organic and inorganic mercury exposure could potentially be a risk factor for NAFLD. To mitigate and address the risk of NAFLD associated with heavy metal exposure, it is imperative to take measure to reduce avoidable mercury exposure is necessary.

HYPERCHOLESTEROLEMIA AS A CAUSATIVE RISK FACTOR FOR NON-ALCOHOLIC FATTY LIVER DISEASE.

Increased serum Cholesterol level is a known risk factor for cardiovascular diseases. Derangements in serum Cholesterol levels will affect normal hepatic Cholesterol homeostasis resulting in hypercholesterolemia. Non-Alcoholic fatty liver disease (NAFLD) initially asymptomatic but can lead to cirrhosis and hepatocellular carcinoma from mild steatosis to non-alcoholic steatohepatitis. The objective of this study is to find out hypercholesterolemia as a causative risk factor in NAFLD patients. This will help to prevent the development and progression of the disease. This cross-sectional study was conducted from 16th August 2021 to 16th August 2022 at Ayub Medical institute Abbottabad. Random sampling technique was used. Sample size was 100, in which 50 were diagnosed cases of liver disease and 50 normal subjects diagnosed on ultrasound. A questionnaire was designed. Subjects between 40-65 years age group were selected after informed consent and confidentiality. Data was collected from the out-patient department of medical and surgical unit and analysed with the help of SPSS-22.00. Chi-square test was used. Enzymatic kit method was used for serum cholesterol and triglycerides estimation. BMI was derived from the mass (weight) and height of the person. It was found that 48% study subjects with NAFLD shows high serum Cholesterol levels while 52% subjects with NAFLD were found within normal limits but 10% individuals with no fatty infiltration had high serum Cholesterol levels while 90% without NAFLD had shown normal serum Cholesterol levels. Significant p-value of <0.001 was found between presence of NAFLD and high serum Cholesterol levels. Significant association was also found among serum Cholesterol and serum Triglyceride levels showing strong association of serum cholesterol levels with NAFLD and raised serum triglycerides levels with p-value 0.001. Similarly, significant association was found between serum cholesterol levels and BMI with p-value ˂0.001. Highly significant association was found between Hypercholesterolemia and non-alcoholic fatty liver disease. It suggests hypercholesterolemia as a causative risk factor for NAFLD.

Causal relationships between neuropsychiatric disorders and nonalcoholic fatty liver disease: A bidirectional Mendelian randomization study

BackgroundIncreasing evidences suggest that nonalcoholic fatty liver disease (NAFLD) is associated with neuropsychiatric disorders. Nevertheless, whether there were causal associations between them remained vague. A causal association between neuropsychiatric disorders and NAFLD was investigated in this study.MethodsWe assessed the published genome-wide association study summary statistics for NAFLD, seven mental disorder-related diseases and six central nervous system dysfunction-related diseases. The causal relationships were first assessed using two-sample and multivariable Mendelian randomization (MR). Then, sensitivity analyses were performed, followed by a reverse MR analysis to determine whether reverse causality is possible. Finally, we performed replication analyses and combined the findings from the above studies.ResultsOur meta-analysis results showed NAFLD significantly increased the risk of anxiety disorders (OR = 1.016, 95% CI = 1.010–1.021, P value < 0.0001). In addition, major depressive disorder was the potential risk factor for NAFLD (OR = 1.233, 95% CI = 1.063–1.430, P value = 0.006). Multivariable MR analysis showed that the causal effect of major depressive disorder on NAFLD remained significant after considering body mass index, but the association disappeared after adjusting for the effect of waist circumference. Furthermore, other neuropsychiatric disorders and NAFLD were not found to be causally related.ConclusionsThese results implied causal relationships of NAFLD with anxiety disorders and Major Depressive Disorder. This study highlighted the need to recognize and understand the connection between neuropsychiatric disorders and NAFLD to prevent the development of related diseases.

Causal effects of female reproductive features on nonalcoholic fatty liver disease: A mendelian randomization study.

Epidemiological evidence on the associations between female reproductive features and nonalcoholic fatty liver disease (NAFLD) is conflicting. To explore their causalities, we conducted a Mendelian randomization (MR) study. Summary-level data were obtained, and univariable MR was performed to explore the causalities between female reproductive features and NAFLD. And we performed multivariable MR and MR mediation analysis to explore the mediation effects of educational attainment (EA) and body mass index (BMI) for these associations. Sensitivity analyses were performed to evaluate pleiotropy and heterogeneity. There were causal effects of age at menarche (AAMA) (odds ratio [OR]: 0.817, 95% confidence interval [CI]: 0.736-0.907, per year-increase), age at first birth (AFB) (OR: 0.851, 95%CI: 0.791-0.926, per year-increase) and age at first sexual intercourse (AFS) (OR: 0.676, 95%CI: 0.511-0.896, per standard deviation-increase) on NAFLD risk. Besides, the causal effects were also observed on NAFLD phenotypes including liver fat content (LFC) and alanine aminotransferase (ALT). Further mediation analysis showed that BMI mediated partial proportion of effects of AAMA and AFS on NAFLD/ALT, AFB on NAFLD/LFC/ALT, while EA mediated partial proportion of effects of AFB on NAFLD/LFC/ALT, and AFS on NAFLD/ALT. This study provided convincing evidence that early AAMA, AFB, and AFS were risk factors for NAFLD. Reproductive health education, obesity management, and education spread might be the beneficial strategies for NAFLD prevention.