Association of Serum Bilirubin Level with Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study of 1672 Obese Children.
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SUBMITTER: Bellarosa C
PROVIDER: S-EPMC8268762 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveMetabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD) are the leading chronic diseases worldwide. There are still many controversies about the association between serum bilirubin and MetS or NAFLD. This study aims to evaluate the association of serum total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL) with MetS and NAFLD.MethodsMultiple databases were searched for relevant studies until November 2021. Randomized controlled trials, cross-sectional and cohort studies evaluating the association between serum bilirubin levels and MetS or NAFLD were included.ResultsTwenty-four cross-sectional and cohort studies with 101, 517 participants were finally analyzed. Fifteen studies and 6 studies evaluated the association between bilirubin and MetS or NAFLD in health screening population, respectively, while 3 studies evaluated the association between bilirubin and non-alcoholic steatohepatitis (NASH) in NAFLD patients. Random effect model analysis showed the inverse association between TBIL and MetS in male (95%CI=0.71-0.96) and gender-neutral (95%CI=0.61-0.91) group. However, no significant association was found in females. Notably, the inverse association between DBIL and MetS was noticed in male (95%CI=0.36-0.75), female (95%CI=0.16-0.58) and gender-neutral population (95%CI=0.67-0.92). IBIL level was inversely associated with MetS in females (95%CI=0.52-0.96), whereas no statistical correlation presented in males. TBIL was not statistically correlated with NAFLD in gender-neutral or male subgroup. Similarly, there were no association between DBIL or IBIL and NAFLD in gender-neutral subgroup. However, the negative correlation between DBIL and NAFLD existed in males (95%CI=0.76-0.96). In NAFLD patients, IBIL analysis showed an inverse association with NASH (95%CI=0.01-0.12).ConclusionSerum TBIL and DBIL levels, especially DBIL levels, assume an inverse correlation with MetS in healthy population. Serum IBIL is inversely associated with the onset and degree of NASH in NAFLD patients. Exogenous bilirubin supplement may be a potential strategy to assist in lowering the risk of developing MetS and NAFLD.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42021293349.
| S-EPMC9346511 | biostudies-literature
Project description:BackgroundSerum bilirubin may play a role in preventing antioxidant and cytoprotective effects in physiological conditions. Serum bilirubin levels are inversely correlated with insulin resistance and the prevalence of cardiovascular diseases and diabetes mellitus. However, the correlation between serum bilirubin and nonalcoholic fatty liver disease (NAFLD) is unclear. NAFLD in non-obese participants may lead to serious health problems, calling for prompt recognition and early management. This study aimed at investigating the relationship between the serum bilirubin levels and NAFLD in non-obese Chinese adults.MethodsWe evaluated 4,900 non-obese subjects (body mass index <25 kg/m2) residing in Wuwei, China. The subjects received a baseline questionnaire, physical examination, abdominal ultrasonography, and laboratory check-ups. Fasting serum bilirubin was measured with an automated biochemical analyzer. NAFLD was diagnosed based on imaging findings of fatty liver disease on ultrasonography, without excessive alcohol intake and other known causes for chronic liver disease. A logistic regression model was applied to calculate the association between serum bilirubin level and NAFLD in non-obese subjects.ResultsNAFLD was diagnosed in 408 (203 men) of the subjects, and they had a mean age of 51-year-old. Non-obese NAFLD patients had lower serum direct bilirubin (DBIL) levels than control group did [2.50 (1.80-3.25) vs. 2.60 (1.90-3.50), P=0.004], but no significant differences in indirect bilirubin (IBIL) and total bilirubin (TBIL) levels of the two groups was seen (both P>0.05). After adjusting confounding factors such as age, gender, body mass index, blood glucose, and blood lipids, multivariate analysis showed serum DBIL (OR: 0.96, 95% CI: 0.83-1.11, P trend =0.6022), IBIL (OR: 1.02, 95% CI: 0.89-1.17, P trend =0.7756), and TBIL (OR: 1.00, 95% CI: 0.87-1.15, P trend =0.991) levels were not associated with NAFLD in the non-obese population. In addition, subgroup analyses (stratified according to age, gender, and medical histories of hypertension, and diabetes mellitus) suggested no independent association between NAFLD and DBIL, IBIL, or TBIL.ConclusionsOur data suggest that serum bilirubin levels are unlikely to be associated with NAFLD in non-obese subjects.
| S-EPMC9347058 | biostudies-literature
Project description:Serum uric acid (SUA) and heavy metals are closely related to non-alcoholic fatty liver disease (NAFLD). Yet, the conjunctional relationship between SUA and serum nickel (Ni) concentrations with the risk of NAFLD in men has not yet been investigated. Therefore, we designed this cross-sectional study to investigate the association of SUA or serum Ni with NAFLD in men. The cross-sectional study was based on data obtained from a prospective cohort study of common chronic non-communicable diseases in Central China, conducted in Xinxiang city, Central China's Henan Province, between April and June 2017. A total of 1709 male participants completed the physical examination. B-ultrasound was used to examine the liver and to diagnose NAFLD. Binary logistic regression models and restricted cubic splines were performed to estimate the association of the SUA and serum Ni with NAFLD. The prevalence of NAFLD among 1709 male participants was 46.6%. After adjusting for potential confounders, with the highest quartile compared to those with the lowest quartile, SUA (OR = 1.579, 95% CI: 1.140-2.189) and serum Ni (OR = 1.896, 95% CI: 1.372-2.625) were associated with NAFLD, respectively. At the same time, the associations for the second and third SUA quartiles were null. Restricted cubic splines showed a positive linear relationship between serum Ni (ln-transformed) and NAFLD risk. Intriguingly, high SUA and high Ni (OR = 2.370, 95% CI: 1.577-3.597) increased the risk of NAFLD, compared with those with low SUA and low Ni. Our findings demonstrate a positive linear trend between serum Ni concentrations and NAFLD risk. Men with elevated serum Ni had a higher risk of developing NAFLD when compared to those with high SUA. Furthermore, the conjunctional relationship of SUA and serum Ni with NAFLD risk was observed in men.
| S-EPMC9180290 | biostudies-literature
Project description:Microsomal triglyceride transfer protein (MTP) works to lipidate and assemble the apoB-containing lipoproteins in liver. It closely links up the hepatic secretion of lipid to regulate serum lipid and atherosclerosis. Cases of MTTP gene mutation is characterized by abetalipoproteinemia and remarkable hepatic steatosis or cirrhosis. Several MTTP polymorphisms have been reported relating to metabolic syndrome, hyperlipidemia and steatohepatitis. We supposed the regulation of serum lipids and risk of non-alcoholic fatty liver disease (NAFLD) formation may be modified by individual susceptibility related to the MTTP polymorphisms.A cross-sectional population of 1193 subjects, 1087 males and 106 females mean aged 45.9 ± 8.9 years, were enrolled without recognized secondary hyperlipidemia. Fasting serum lipid, insulin, and non-esterified fatty acid were assessed and transformed to insulin resistance index, HOMA-IR and Adipo-IR. After ruling out alcohol abuser, non-alcoholic fatty liver disease (NAFLD) was diagnosed by abdominal ultrasound. Five common MTTP polymorphisms (promoter -493 G/T, E98D, I128T, N166S, and Q297H) were conducted by TaqMan assay. Multivariate regression analysis was used to estimate their impact on serum lipid and NAFLD risk. Assessment revealed a differential impact on LDL-C and non-HDL-C, which were sequentially determined by the Q297H polymorphism, insulin resistance, body mass index and age. Carriers of homozygous minor allele (297 H) had significantly lower LDL-C and non-HDL-C but higher risk for NAFLD. Molecular modeling of the 297 H variant demonstrated higher free energy, potentially referring to an unstable structure and functional sequence.These results evidenced the MTTP polymorphisms could modulate the lipid homeostasis to determine the serum lipids and risk of NAFLD. The MTTP 297 H polymorphism interacted with age, insulin resistance and BMI to decrease serum apoB containing lipoproteins (LDL-C and non-HDL-C) but increase the risk of NAFLD formation.
| S-EPMC4603340 | biostudies-literature
Project description:BACKGROUND: Serum bilirubin may have potent antioxidant and cytoprotective effects. Serum bilirubin levels are inversely associated with several cardiovascular and metabolic endpoints, but their association with nonalcoholic fatty liver disease (NAFLD) has not been investigated except for a single cross-sectional study in a pediatric population. We assessed the prospective association between serum bilirubin concentrations (total, direct, and indirect) and the risk for NAFLD. METHODS AND FINDINGS: We performed a cohort study in 5,900 Korean men, 30 to 59 years of age, with no evidence of liver disease and no major risk factors for liver disease at baseline. Study participants were followed in annual or biennial health examinations between 2002 and 2009. The presence of fatty liver was determined at each visit by ultrasonography. We observed 1,938 incident cases of NAFLD during 28,101.8 person-years of follow-up. Increasing levels of serum direct bilirubin were progressively associated with a decreasing incidence of NAFLD. In age-adjusted models, the hazard ratio for NAFLD comparing the highest to the lowest quartile of serum direct bilirubin levels was 0.61 (95% CI 0.54-0.68). The association persisted after adjusting for multiple metabolic parameters (hazard ratio comparing the highest to the lowest quartile 0.86, 95% CI 0.76-0.98; P trend?=?0.039). Neither serum total nor indirect bilirubin levels were significantly associated with the incidence of NAFLD. CONCLUSIONS: In this large prospective study, higher serum direct bilirubin levels were significantly associated with a lower risk of developing NAFLD, even adjusting for a variety of metabolic parameters. Further research is needed to elucidate the mechanisms underlying this association and to establish the role of serum direct bilirubin as a marker for NAFLD risk.
| S-EPMC3352875 | biostudies-literature
Project description:Low serum amylase (LSA) was reported to be associated with obesity, metabolic syndrome (MetS) and diabetes. However, it is unknown as to whether LSA is associated with non-alcoholic fatty liver disease (NAFLD), a hepatic manifestation of MetS and insulin resistance. Therefore, we performed a clinical epidemiological study to investigate this potential association.A cross-sectional observational study with multivariate analysis.Subjects were recruited in a healthcare centre in Saitama, an eastern district of Japan, near Tokyo.A total of 1475 asymptomatic adults aged 30-79 years who underwent detailed medical check-ups and who regularly consumed small amounts of alcohol (<20 g/day).Serum amylase, cardiometabolic risk factors, NAFLD determined by ultrasound, MetS determined by Adult Treatment Panel-III criteria and diabetes were assessed.The prevalence of NAFLD increased significantly from 22.5% to 42.4% (all grades) and from 9.2% to 24.0% (moderate or severe grade) from the highest to the lowest quartile of serum amylase. Multiple logistic regression analysis showed that, compared with the highest quartile of serum amylase, the lowest quartile of serum amylase was significantly associated with any-grade NAFLD and with moderate-to-severe NAFLD, even after adjusting for MetS or diabetes. The association between LSA and any-grade NAFLD disappeared after further adjustment for body mass index or waist circumference, whereas the association between LSA and moderate or severe NAFLD remained statistically significant (ORs (95%CI), 2.01 (1.07 to 3.78) and 2.06 (1.09 to 3.87), respectively, both p=0.01).Our results suggest that LSA may be associated with moderate or severe NAFLD in asymptomatic adults independent of MetS, diabetes and obesity. These results warrant confirmation in further studies.
| S-EPMC3549261 | biostudies-literature
Project description:BackgroundThe effects of sleep quality on the risk of developing non-alcoholic fatty liver disease (NAFLD) remain uncertain. The purpose of this study was to clarify the association between sleep quality and NAFLD.MethodsThe data of 4828 participants who underwent health check-ups at four hospitals were analysed. Sleep quality was evaluated by the Pittsburgh Sleep Quality Index (PSQI), which comprised seven elements scored from 0 to 3. The global PSQI score and the score for each element were compared between NAFLD and non-NAFLD groups separately by sex. Logistic regression analysis was performed to determine the association between NAFLD and each PSQI score.ResultsIn both men and women, the mean PSQI score for sleep medication use was significantly higher in non-NAFLD than in NAFLD. With regard to sleep medication use in men, the OR (95% CI) for NAFLD was lower with a score of 3 (OR 0.60, 95% CI 0.38-0.95) than with a score of 0 on multivariate logistic regression analysis adjusted for age, smoking habits and physical activity. The OR for NAFLD based on daytime dysfunction was also higher with a score of 3 than with a score of 0 in both men (OR 2.82, 95% CI 1.39-5.75) and women (OR 2.08, 95% CI 1.10-3.92). After adjustment for body mass index, the sleep latency scores in men and daytime dysfunction in women were associated with NAFLD.ConclusionSleep quality was associated with NAFLD, and there were sex differences.
| S-EPMC7597499 | biostudies-literature
Project description:BackgroundThe incidence of non-alcoholic fatty liver disease (NAFLD) is rapidly increasing worldwide parallel to the global obesity epidemic. NAFLD encompasses a range of liver pathologies and most often originates from metabolically driven accumulation of fat in the liver, or non-alcoholic fatty liver (NAFL). In a subset of NAFL patients, the disease can progress to non-alcoholic steatohepatitis (NASH), which is a more severe form of liver disease characterized by hepatocyte injury, inflammation, and fibrosis. Significant progress has been made over the past decade in our understanding of NASH pathogenesis, but gaps remain in our mechanistic knowledge of the precise metabolic triggers for disease worsening.Scope of reviewThe transition from NAFL to NASH likely involves a complex constellation of multiple factors intrinsic and extrinsic to the liver. This review focuses on early metabolic events in the establishment of NAFL and initial stages of NASH. We discuss the association of NAFL with obesity as well as the role of adipose tissue in disease progression and highlight early metabolic drivers implicated in the pathological transition from hepatic fat accumulation to steatohepatitis.Major conclusionsThe close association of NAFL with features of metabolic syndrome highlight plausible mechanistic roles for adipose tissue health and the release of lipotoxic lipids, hepatic de novo lipogenesis (DNL), and disruption of the intestinal barrier in not only the initial establishment of hepatic steatosis, but also in mediating disease progression. Human genetic variants linked to NASH risk to date are heavily biased toward genes involved in the regulation of lipid metabolism, providing compelling support for the hypothesis that NASH is fundamentally a metabolic disease.
| S-EPMC8324696 | biostudies-literature
Project description:Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disorder worldwide. The aim of our study was to assess the role of bilirubin, and the heme oxygenase 1 (HMOX1) and bilirubin UDP-glucuronosyl transferase (UGT1A1) promoter gene variants, which are involved in bilirubin homeostasis, in the NAFLD development in adult patients. The study was performed on 84 patients with NAFLD and 103 age/sex-matched controls. Routine biochemistry, inflammatory markers, adipokines, and the fibrosis/steatohepatitis stage were determined in the NAFLD patients. The (GT)n/(TA)n dinucleotide variations in HMOX1/UGT1A1 gene promoters, respectively, were analyzed by fragment analysis. Compared to controls, serum bilirubin concentrations in NAFLD patients tended to be decreased, while the prevalence of phenotypic Gilbert syndrome was significantly low. Genetic variations in HMOX1 and UGT1A1 gene promoters did not differ between NAFLD patients and controls, and no relationship was found in the NAFLD patients between these gene variants and any of the laboratory or histological parameters. In conclusion, metabolism of bilirubin is dysregulated in NAFLD patients, most likely due to increased oxidative stress, since frequencies of the major functional variants in the HMOX1 or UGT1A1 gene promoters did not have any effect on development of NAFLD in adult patients.
| S-EPMC8698489 | biostudies-literature
Project description:Dysregulation of several metabolite pathways, including branched-chain amino acids (BCAAs), are associated with Non-Alcoholic Fatty Liver Disease (NAFLD) and insulin resistance in adults, while studies in youth reported conflicting results. We explored whether, independently of obesity and insulin resistance, obese adolescents with NAFLD display a metabolomic signature consistent with disturbances in amino acid and lipid metabolism. A total of 180 plasma metabolites were measured by a targeted metabolomic approach in 78 obese adolescents with (n = 30) or without (n = 48) NAFLD assessed by magnetic resonance imaging (MRI). All subjects underwent an oral glucose tolerance test and subsets of patients underwent a two-step hyperinsulinemic-euglycemic clamp and/or a second MRI after a 2.2 ± 0.8-year follow-up. Adolescents with NAFLD had higher plasma levels of valine (p = 0.02), isoleucine (p = 0.03), tryptophan (p = 0.02), and lysine (p = 0.02) after adjustment for confounding factors. Circulating BCAAs were negatively correlated with peripheral and hepatic insulin sensitivity. Furthermore, higher baseline valine levels predicted an increase in hepatic fat content (HFF) at follow-up (p = 0.01). These results indicate that a dysregulation of BCAA metabolism characterizes obese adolescents with NAFLD independently of obesity and insulin resistance and predict an increase in hepatic fat content over time.
| S-EPMC5537762 | biostudies-literature