Association between urinary polycyclic aromatic hydrocarbons and risk of metabolic associated fatty liver disease.

OBJECTIVE: To investigate the effect of urinary PAHs on MAFLD. METHODS: The study included 3,136 adults from the National Health and Nutrition Examination Survey (NHANES) conducted between 2009 and 2016. Among them, 1,056 participants were diagnosed with MAFLD and were designated as the case group. The analysis of the relationship between monohydroxy metabolites of seven PAHs in urine and MAFLD was carried out using logistic regression and Bayesian kernel regression (BKMR) models. RESULTS: In single-pollutant models, the concentration of 2-hydroxynaphthalene (2-OHNAP) was positively correlated with MAFLD (OR = 1.47, 95% CI 1.18, 1.84), whereas 3-hydroxyfluorene (3-OHFLU) and 1-hydroxypyrene (1-OHPYR) demonstrated a negative correlation with MAFLD (OR = 0.59, 95% CI 0.48 0.73; OR = 0.70, 95% CI 0.55, 0.89). Conversely, in multi-pollutant models, 2-OHNAP, 2-hydroxyfluorene (2-OHFLU), 2-hydroxyphenanthrene, and 3-hydroxyphenanthrene (2&3-OHPHE) displayed positive correlations with MAFLD (OR = 6.17, 95% CI 3.15, 12.07; OR = 2.59, 95% CI 1.37, 4.89). However, 3-OHFLU and 1-OHPYR continued to exhibit negative correlations with MAFLD (OR = 0.09, 95% CI 0.05, 0.15; OR = 0.62, 95% CI 0.43, 0.88). Notably, the BKMR analysis mixtures approach did not indicate a significant joint effect of multiple PAHs on MAFLD, but identified interactions between 3-OHFLU and 2-OHFLU, 1-OHPYR and 2-OHFLU, and 1-OHPYR and 3-OHFLU. CONCLUSION: No significant association was found between mixed PAHs exposure and the risk of MAFLD. However, interactions were observed between 3-OHFLU and 2-OHFLU. Both 2-OHFLU and 2&3-OHPHE exposure are significant risk factors for MAFLD, whereas 3-OHFLU is a key protective factor for the disease.

Relationship Between PNPLA3 rs738409 Polymorphism and Decreased Kidney Function in Children With NAFLD.

Emerging evidence suggests that patatin-like phospholipase domain-containing protein-3 (PNPLA3) rs738409 genotype (the major genetic variant associated with susceptibility to nonalcoholic fatty liver disease [NAFLD]) is associated with decreased kidney function in adults. Currently, it is uncertain whether this association also occurs in children/adolescents and whether any association is independent of liver disease severity. We enrolled a sample of 142 Caucasian children and adolescents with biopsy-proven NAFLD, presenting to the Liver Unit of the "Bambino Gesù" Children's Hospital. The glomerular filtration rate (e-GFR) was estimated using the Bedside Schwartz equation, whereas 24-hour proteinuria was measured using a radioimmunoassay method. Genotyping for the PNPLA3 rs738409 genotype was undertaken using the single-nucleotide polymorphism genotyping allelic discrimination method. Overall, 45 children had G/G, 56 had G/C, and 41 had C/C PNPLA3 rs738409 genotype, respectively. Children with G/G genotype had significantly lower e-GFR (107.5 ± 20 versus 112.8 ± 18 versus 125.3 ± 23 mL/min/1.73 m2 , P = 0.002) and higher 24-hour proteinuria (58.5 ± 21 versus 53.9 ± 22 versus 42.9 ± 20 mg/day, P = 0.012) compared with those with either G/C or C/C genotypes. After adjustment for age, sex, systolic blood pressure, measures of adiposity, homeostasis model assessment-estimated insulin resistance and biopsy-confirmed nonalcoholic steatohepatitis and stage of liver fibrosis, the presence of rs738409 G/G genotype was independently associated with both lower e-GFR (ß coefficient: -23.6; 95% confidence interval [CI]: -36.3 to -10.8; P < 0.001) and higher 24-hour proteinuria (ß coefficient: 15.3; 95% CI: 1.12 to 30.5; P = 0.046). Conclusion: Regardless of established renal risk factors and the histological severity of NAFLD, the PNPLA3 G/G genotype was strongly associated with decreasing kidney function and increasing 24-hour proteinuria in children/adolescents with histologically confirmed NAFLD.

Elevated urinary bisphenol A levels are associated with non-alcoholic fatty liver disease among adults in the United States.

BACKGROUND AND AIMS: The relationship between bisphenol A (BPA) and non-alcoholic fatty liver disease (NAFLD) is undefined. We studied the impact of BPA on NAFLD. METHODS: We performed a cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) 2005-2014 among adults in the United States (US). NAFLD was diagnosed using the hepatic steatosis index (HSI) and the US fatty liver index (USFLI) in the absence of other causes of chronic liver diseases. The first sample using HSI consisted of 7605 adults. The second sample using USFLI consisted of 3631 participants with availability of fasting data. RESULTS: Of the first 7605 participants (mean age 47 years, 48.4% male), the prevalence of NAFLD and abnormally elevated alanine aminotransferase (ALT) levels was correlated with urinary BPA levels (P < 0.05). Compared to the reference group with lowest quartile of urinary BPA levels, those with the third and fourth quartiles were 81% and 53% more likely to develop NAFLD defined by HSI. In a multivariate model, the ORs for NAFLD in the third and fourth quartiles were 1.69 (95% CI 1.39-2.04) and 1.44 (95% CI 1.19-1.76) respectively (P for trend <0.001). In the second sample using USFLI, high BPA levels (fourth quartile) remained an independent predictor of NAFLD (OR 1.44, 95% CI 1.05-1.98, P for trend = 0.012). CONCLUSIONS: High levels of urinary BPA were associated with NAFLD in a nationally representative sample of adults in the US. The pathophysiology remains unclear and warrants further investigation.

Non-alcoholic fatty liver disease is associated with low-grade albuminuria in men without diabetes mellitus.

Background: Non-alcoholic fatty liver disease (NAFLD) is associated with the dysregulation of multiple metabolic and inflammatory pathways. These can lead to extrahepatic disorders involving the kidney, a vulnerable organ responsible for extra-renal complications. Evaluating the association between NAFLD and low-grade albuminuria as a renal complication would be helpful to better understand the pathophysiology and extra-hepatic complications of NAFLD. Patients and Methods: Our study extracted data from database obtained a representative population sample. Overall, 3867 men were included in this survey. Our study included only men without diabetes mellitus, with a urinary albumin/creatinine ratio < 30 mg/g (n = 1390). Low-grade albuminuria was defined by a urinary albumin/creatinine ratio within the highest quartile. The fatty liver index was calculated in accordance with Bedogni's equation. We defined the NAFLD group as patients with a fatty liver index of ≥ 60. Results: In the multivariate analysis, the urinary albumin/creatinine ratio in the non-NAFLD and NAFLD groups was 3.05 ± 0.14 and 5.19 ± 0.42, respectively (P < 0.001). The correlation coefficients between the fatty liver index and urinary albumin/creatinine ratio were 0.124 in the Pearson's correlation test and 0.084 in the partial correlation test (P < 0.001 and P = 0.002, respectively). Linear regression analysis showed a positive association between the fatty liver index and the urinary albumin/creatinine ratio on multivariate analysis. Logistic regression analysis showed that the odds ratio for low-grade albuminuria with NAFLD was 2.31 (95% confidence interval, 1.47-3.61; P < 0.001) on the multivariate analysis. Subgroup analyses according to the presence of metabolic syndrome or age (< 50 or ≥ 50 years) showed that the association between NAFLD and the urinary albumin/creatinine ratio was stronger for participants without metabolic syndrome and in those aged < 50 years. Conclusion: NAFLD was associated with low-grade albuminuria in men without diabetes mellitus in this study. Therefore, men with a relatively high fatty liver index or NAFLD should be closely monitored for low-grade albuminuria, especially in absence of metabolic syndrome.

Nonalcoholic Fatty Liver Disease (NAFLD), But not Its Susceptibility Gene Variants, Influences the Decrease of Kidney Function in Overweight/Obese Children.

: Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of kidney disease in adults and children. However, it is uncertain whether this association is influenced by major NAFLD susceptibility genes. In a sample of 230 overweight/obese children, 105 with NAFLD (hepatic fat fraction ≥5% by magnetic resonance imaging) and 125 without NAFLD, rs738409 in PNPLA3, rs58542926 in TM6SF2, rs1260326 in GCKR, and rs641738 in MBOAT7 were genotyped. Abnormal kidney function was defined as estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2 and/or the presence of microalbuminuria (24 h urinary albumin excretion between 30 and 300 mg). In comparison with children without NAFLD, those with NAFLD showed increased prevalence of reduced eGFR (13.3% vs. 1.6%; p < 0.001) and microalbuminuria (8.6% vs. 3.4%, p = 0.025). TM6SF2, GCKR, and MBOAT7 risk alleles did not show any impact on kidney function, while the PNPLA3 G allele was associated with lower eGFR, but only in children with NAFLD (p = 0.003). After adjustment for confounders, NAFLD (OR, 4.7; 95% CI, 1.5-14.8; padj = 0.007), but not the PNPLA3 gene variant, emerged as the main independent predictor of renal dysfunction. Overall, our findings suggest that NAFLD remains the main determinant of decline in kidney function in overweight/obese children, while the PNPLA3 rs738409 prosteatogenic variant has a small impact, if any.

Association between cotinine-verified smoking status and risk of nonalcoholic fatty liver disease.

BACKGROUND & AIMS: The relationship between cigarette smoking and nonalcoholic fatty liver disease (NAFLD) has been controversial. Most relevant studies have relied on self-reported questionnaires. We aimed to elucidate the association between smoking status and NAFLD using an objective biomarker of tobacco exposure (urinary cotinine) and self-reported questionnaire. METHODS: A cross-sectional study was conducted on 160 862 asymptomatic examinees who underwent abdominal ultrasonography and urinary cotinine measurements between April 2011 and December 2015. Cotinine-verified current smokers were defined as participants with urinary cotinine levels ≥50 ng/mL. RESULTS: The mean age of the study population was 36.1 years, and the proportion of men was 51.7%. The proportions of self-reported and cotinine-verified current smokers were 17.6% and 17.7% respectively. After adjusting for confounding factors, self-reported current smoking was associated with an increased risk of NAFLD (adjusted odds ratio [AOR], 1.10; 95% confidence interval [CI], 1.06-1.14). Moreover, among the current smokers, the risk of NAFLD increased with an increase in the amount of cigarette smoking (<10 and ≥10 pack-years vs never smokers; AOR, 1.04 and 1.11; 95% CI, 1.01-1.08 and 1.05-1.16 respectively). Cotinine-verified current smoking was also associated with an increased risk of NAFLD (AOR, 1.10; 95% CI, 1.06-1.14). CONCLUSIONS: Cotinine-verified current smoking and self-reported current smoking were independent risk factors for NAFLD. Further longitudinal studies are needed to more clearly elucidate the impact of smoking on the development of NAFLD.

Study on the Correlation Between Urinary Transferrin and Nonalcoholic Fatty Liver Disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) can cause renal injury, and urinary transferrin (UTRF) is extremely sensitive to renal injury. We aimed to investigate the correlation between UTRF and NAFLD and to observe the distribution of NAFLD at different levels of UTRF. METHODS: A total of 711 subjects fulfilled the diagnostic criteria of NAFLD and 1,396 healthy control participants were enrolled in this study. UTRF levels and other clinical and laboratory parameters were measured. RESULTS: The UTRF level was higher in NAFLD than in non-NAFLD patients. Unit and multiple regression analysis showed that UTRF was an independent risk factor for NAFLD, with OR values of 1.474 (1.328 - 1.635, p < 0.001) and 1.435 (1.267 - 1.625, p < 0.001), respectively. The prevalence of UTRF (groups 1, 2, 3, 4) was 25.61%, 26.56%, 38.14%, and 44.59%, respectively (p < 0.001), and the prevalence of NAFLD in the high UTRF group was significantly higher than in the low UTRF group. CONCLUSIONS: UTRF is an independent risk factor for NAFLD.

Association Between Urinary Alpha1-Microglobulin Levels and Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study.

BACKGROUND: We aimed to explore the association between urinary alpha1-microglobulin (A1M) levels and nonalcoholic fatty liver disease (NAFLD) in a Chinese population. STUDY: We performed a cross-sectional study among 2,215 Chinese who attended their annual health examination at First Affiliated Hospital, College of Medicine, Zhejiang University. Urinary A1M-creatinine ratio and other clinical and laboratory parameters were measured. RESULTS: A total of 20.9% of subjects fulfilled the diagnostic criteria of NAFLD. NAFLD subjects had significantly higher urinary A1M-creatinine ratios. These levels were positively associated with NAFLD prevalence. The association between A1M-creatinine ratio and NAFLD was independent of hyperglycemia status. Stepwise regression showed that urinary A1M-creatinine ratio was significantly associated with the risk for NAFLD. Urinary A1M-creatinine ratio was an independent factor predicting advanced fibrosis (FIB-4 ≥1.3) in NAFLD patients. CONCLUSIONS: Our results showed a significant association between urinary A1M-creatinine ratio and NAFLD.

Association between urine retinol-binding protein levels and nonalcoholic fatty liver disease: A cross-sectional study in Chinese population.

OBJECTIVE: The prevalence of nonalcoholic fatty liver disease (NAFLD) has been rapidly increased, becoming a public health problem worldwide. Our objective was to investigate the association between urine retinol-binding protein (RBP) and NAFLD in a Chinese population and develop a multivariate logistic regression model for NAFLD prediction. METHODS: A total of 317 NAFLD patients and 391 healthy controls were enrolled in this cross-sectional study based on inclusion and exclusion criteria, from whom fasting urine and blood were collected for further study. Urine RBP level and other parameters were measured and compared between NAFLD subjects and controls. RESULTS: Urine RBP levels (expressed by RBP/creatinine ratio) in NAFLD patients were significantly higher than controls (median 133.1 mg/g vs 110.7 mg/g; P < .001). Urine RBP/creatinine ratio was verified as an independent factor for NAFLD prediction after adjustment in multivariate logistic regression. The area under curve (AUC) of receiver operating characteristic (ROC) was 0.889 with the 95% confidence interval from 0.867 to 0.912.With a cutoff point of 0.215, the sensitivity and specificity of urine RBP/creatinine ratio in NAFLD prediction were 81.1% and 84.5%, respectively. CONCLUSION: Our results demonstrated that urine RBP/creatinine ratio was an independent risk factor for NAFLD while the predictive model for NAFLD diagnosis is noninvasive with high sensitivity and specificity.

FEATURES OF EXCRETION OF MELATONIN IN URINE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND NON-ALCOHOLIC FATTY LIVER DISEASE WITH MANIFESTATIONS OF FIBROSIS AND ITS RELATIONSHIP WITH CERTAIN METABOLIC AND IMMUNOLOGICAL INDICATORS.

To study the features of secretion of melatonin in the urine in patients with DM type 2 and NAFLD with manifestations of fibrosis and its relationship with some metabolic and immunological parameters, 23 patients with DM type 2 and NAFLD were examined. The degree of fibrosis in patients was diagnosed on the basis of static elastography and the study of indirect fibrosis markers 16 persons (72%) diagnosed with mild fibrosis (F0-F1 on METAVIR), 5 people (18.2%) - with moderate fibrosis (F2-F3 on METAVIR). Only 2 (8.7%) patients did not have any fibrotic disorders, so they were excluded from the further study. All patients underwent determination of melatonin excretion of albumin and in daily urine, as well as the determination of homocysteine in the blood. The level of excretion of melatonin in the urine in patients with DM type 2 and NAFLD did not depend on the degree of fibrosis and on the average was 89.50±16.66 mmol/day, which exceeded the reference values. It has been established that the increase in melatonin level in patients with DM type 2 and NAFLD is associated with the presence of fibrotic changes in the liver and a decrease in the activity of the inflammatory process. In addition, a direct correlation was found between the excretion of melatonin and homocysteine (r=0.43), as well as between melatonin and albumin excretion in the urine (r=0.20). Thus, an increased level of excretion of melatonin in the urine can be not only a marker of liver fibrosis, but also a predictor of cardiovascular disorders in patients with DM type 2 and NAFLD.

[Clinical and metabolic features of nonalcoholic fatty liver disease in men and women]. / Klinicheskie i metabolicheskie osobennosti nealkogol'noi zhirovoi bolezni pecheni u muzhchin i zhenshchin.

AIM: To evaluate clinical features and metabolic disorders in men and women with non-alcoholic fatty liver disease (NAFLD).

Tomato Juice Consumption Modifies the Urinary Peptide Profile in Sprague-Dawley Rats with Induced Hepatic Steatosis.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in Western countries, with a high prevalence, and has been shown to increase the risk of type 2 diabetes, cardiovascular disease (CVD), etc. Tomato products contain several natural antioxidants, including lycopene-which has displayed a preventive effect on the development of steatosis and CVD. Accordingly, the aim of the present work was to evaluate the effect of tomato juice consumption on the urinary peptide profile in rats with NAFLD induced by an atherogenic diet and to identify potential peptide biomarkers for diagnosis. Urine samples, collected weekly for four weeks, were analyzed by capillary electrophoresis (CE) coupled to a mass spectrometer (MS). A partial least squares-discriminant analysis (PLS-DA) was carried out to explore the association between differential peptides and treatments. Among the 888 peptides initially identified, a total of 55 were obtained as potential biomarkers. Rats with steatosis after tomato juice intake showed a profile intermediate between that of healthy rats and that of rats with induced hepatic steatosis. Accordingly, tomato products could be considered as a dietary strategy for the impairment of NAFLD, although further research should be carried out to develop a specific biomarkers panel for NAFLD.

Biomarkers of NAFLD progression: a lipidomics approach to an epidemic.

The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis (NASH), and cirrhosis. Recognition and timely diagnosis of these different stages, particularly NASH, is important for both potential reversibility and limitation of complications. Liver biopsy remains the clinical standard for definitive diagnosis. Diagnostic tools minimizing the need for invasive procedures or that add information to histologic data are important in novel management strategies for the growing epidemic of NAFLD. We describe an "omics" approach to detecting a reproducible signature of lipid metabolites, aqueous intracellular metabolites, SNPs, and mRNA transcripts in a double-blinded study of patients with different stages of NAFLD that involves profiling liver biopsies, plasma, and urine samples. Using linear discriminant analysis, a panel of 20 plasma metabolites that includes glycerophospholipids, sphingolipids, sterols, and various aqueous small molecular weight components involved in cellular metabolic pathways, can be used to differentiate between NASH and steatosis. This identification of differential biomolecular signatures has the potential to improve clinical diagnosis and facilitate therapeutic intervention of NAFLD.

Urinary (1)H-NMR-based metabolic profiling of children with NAFLD undergoing VSL#3 treatment.

BACKGROUND: Nowadays, non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in children. Our recent clinical trial demonstrated that dietary and VSL#3-based interventions may improve fatty liver by ultrasound and body mass index (BMI) after 4 months. OBJECTIVES: As in this short-term trial, as in others, it is impracticable to monitor response to therapy or treatment by liver biopsy, we aimed to identify a panel of potential non-invasive metabolic biomarkers by a urinary metabolic profiling. METHODS: Urine samples from a group of 31 pediatric NAFLD patients, enrolled in a VSL#3 clinical trial, were analyzed by high-resolution proton nuclear magnetic resonance spectroscopy in combination with analysis of variance-Simultaneous Component Analysis model and multivariate data analyses. Urinary metabolic profiles were interpreted in terms of clinical patient feature, treatment and chronology pattern correlations. RESULTS: VSL#3 treatment induced changes in NAFLD urinary metabolic phenotype mainly at level of host amino-acid metabolism (that is, valine, tyrosine, 3-amino-isobutyrate or ß-aminoisobutyric acid (BAIBA)), nucleic acid degradation (pseudouridine), creatinine metabolism (methylguanidine) and secondarily at the level of gut microbial amino-acid metabolism (that is, 2-hydroxyisobutyrate from valine degradation). Furthermore, some of these metabolites correlated with clinical primary and secondary trial end points after VSL#3 treatment: tyrosine and the organic acid U4 positively with alanine aminotransferase (R=0.399, P=0.026) and BMI (R=0.36, P=0.045); BAIBA and tyrosine negatively with active glucagon-like-peptide 1 (R=-0.51, P=0.003; R=-0.41, P=0.021, respectively). CONCLUSIONS: VSL#3 treatment-dependent urinary metabotypes of NAFLD children may be considered as non-invasive effective biomarkers to evaluate the response to treatment.

Altered regulation of hepatic efflux transporters disrupts acetaminophen disposition in pediatric nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, representing a spectrum of liver pathologies that include simple hepatic steatosis and the more advanced nonalcoholic steatohepatitis (NASH). The current study was conducted to determine whether pediatric NASH also results in altered disposition of acetaminophen (APAP) and its two primary metabolites, APAP-sulfate and APAP-glucuronide. Pediatric patients with hepatic steatosis (n = 9) or NASH (n = 3) and healthy patients (n = 12) were recruited in a small pilot study design. All patients received a single 1000-mg dose of APAP. Blood and urine samples were collected at 1, 2, and 4 hours postdose, and APAP and APAP metabolites were determined by high-performance liquid chromatography. Moreover, human liver tissues from patients diagnosed with various stages of NAFLD were acquired from the Liver Tissue Cell Distribution System to investigate the regulation of the membrane transporters, multidrug resistance-associated protein 2 and 3 (MRP2 and MRP3, respectively). Patients with the more severe disease (i.e., NASH) had increased serum and urinary levels of APAP-glucuronide along with decreased serum levels of APAP-sulfate. Moreover, an induction of hepatic MRP3 and altered canalicular localization of the biliary efflux transporter, MRP2, describes the likely mechanism for the observed increase in plasma retention of APAP-glucuronide, whereas altered regulation of sulfur activation genes may explain decreased sulfonation activity in NASH. APAP-glucuronide and APAP-sulfate disposition is altered in NASH and is likely due to hepatic membrane transporter dysregulation as well as altered intracellular sulfur activation.

[ALLELES C282Y AND H63D HFE GENE, INSULIN RESISTANCE AND SUSCEPTIBILITY TO DISTURBANCE OF PORPHYRIN METABOLISM IN NON-ALCOHOLIC FATTY LIVER DISEASE].

THE PURPOSE OF THE STUDY: The aim of the present work was to study the frequency of genotypes and alleles of C282Y and H63D HFE gene that may be associated with impaired porphyrin metabolism, as well as possible reasons for the formation of dysmetabolism porphyrins with NAFLD. MATERIALS AND METHODS: The study involved 65 patients (52 men and 13 women) aged 21 to 69 years (mean age 48.5±1.5 years). Excretion uroporphyrin, coproporphyrin, 6-aminolevulinic acid of porphobilinogen in urine was determined by chromatography and spectrophotometry calculated total excretion of porphyrins. Allele frequencies C282Y and H63D were determined during the molecular genetic analysis of DNA using the polymerase chain reaction followed by analysis of length polymorphism restraktsionnyh fragments. Condition of carbohydrate metabolism was evaluated by the level of fasting blood glucose and standard glucose tolerance test. Diagnosis of insulin resistance was performed according to the criteria proposed by the European Group for the Study of insulin resistance (EGIR). RESULTS: Skill test for the C282Y mutation carriage and H63D in the HFE gene in 65 patients with non-alcoholic fatty liver disease. Disturbances in the metabolism of porphyrins were recorded in 43 (66.2%) patients. H63D and C282Y mutations were found in 18 (27.7%) patients, of whom 13 (72.2%) people with different options dismetabolism porphyrins and signs of insulin resistance. In 47 (72.3%) patients without mutations studied porphyrin metabolism disorders were detected in 30 (63.8 %), of which insulin resistance is registered only in 16 (34.0 %). CONCLUSION: Detection of mutations C282Y and H63D in the HFE gene in combination with disorders of porphyrin metabolism on the background of insulin resistance is likely to allow such patients considered as candidates for inclusion in the higher risk of formation of diabetes.

The association between serum fructosamine and random spot urine fructose levels with the severity of non-alcoholic fatty liver disease - an analytical cross-sectional study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) in South Africa and Africa at large is considered a hidden threat. Our local population is burdened with increased metabolic risk factors for NAFLD. Our setting requires a reasonable approach to screen for and aid the diagnosis of NAFLD. OBJECTIVES: To investigate serum fructosamine and random spot urine fructose levels as biomarkers for the screening, diagnosis and monitoring of NAFLD. The primary objective of this study was to compare serum fructosamine and random spot urine fructose levels between groups with different levels of NAFLD severity as measured by ultrasound. A secondary objective was to determine the association, if any, between serum transaminases, the aspartate aminotransferase (AST) to platelet ratio index (APRI) score, serum fructosamine and urine fructose in different groups with steatosis. METHODS: Using a cross-sectional study design, 65 patients with three different levels of NAFLD, as detected by imaging, were enrolled. The primary exposures measured were serum fructosamine with random spot urine fructose, and secondary exposures were the serum transaminases (AST and alanine aminotransferase (ALT)) and the APRI score. Patients identified at the departments of gastroenterology, general internal medicine and diagnostic radiology were invited to participate. RESULTS: There were 38, 17 and 10 patients with mild, moderate and severe steatosis, respectively. There was no significant difference between the groups regarding serum fructosamine, measured as median (interquartile range): mild 257 (241 - 286) µmol/L, moderate 239 (230 - 280) µmol/L and severe 260 (221 - 341) µmol/L, p=0.5; or random spot urine fructose: mild 0.86 (0.51 - 1.30) mmol/L, moderate 0.84 (0.51 - 2.62) mmol/L and severe 0.71 (0.58 - 1.09) mmol/L, p = 0.8. ALT (U/L) differed between groups: mild 19 (12 - 27), moderate 27 (22 - 33), severe 27 (21 - 56), p=0.03, but not AST (U/L) (p=0.7) nor APRI (p=0.9). Urine fructose and ALT were correlated in the moderate to severe steatosis group (R=0.490, p<0.05), but not in the mild steatosis group. Serum fructosamine was associated with age in the mild steatosis group but not the moderate-severe steatosis group (R=0.42, p<0.01). CONCLUSION: Serum fructosamine and random spot urine fructose did not vary with the severity of NAFLD, indicating that they would not be useful biomarkers in this condition.

Animal Fat Intake Is Associated with Albuminuria in Patients with Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome.

Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) are associated with chronic kidney disease (CKD). Diet could play a predisposing role in the development of increased albuminuria in patients with NAFLD and MetS; however, published evidence is still limited. The aim of this cross-sectional analysis was to assess whether dietary fats are associated with changes in urinary albumin-to-creatinine ratio (UACR) in 146 patients aged 40-60-years with NAFLD and MetS. Dietary data were collected by food frequency questionnaire; UACR was measured in a single first morning void. Sources and types of dietary fats used in the analysis were total fat, fats from animal and vegetable sources, saturated, monounsaturated, polyunsaturated, and trans fats. One-way analysis of variance was performed to assess differences in dietary fats intakes across stages of UACR. The association between dietary fats and UACR was assessed by Pearson's correlation coefficient and multivariable linear regression. Patients with increased UACR showed a worse cardiometabolic profile and higher intakes of animal fat, as compared to patients with normal levels of albuminuria. Animal fat intake was associated with mean UACR, independent of potential covariates.

Liver fibrosis assessed by transient elastography is independently associated with albuminuria in the general United States population.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) are frequent and progressive conditions that share traditional risk factors: obesity, type 2 diabetes and hypertension. AIMS: To evaluate whether an independent relationship exists between liver steatosis and fibrosis and different CKD phenotypes. METHODS: Cross sectional study based on data from the 2017-18 cycle of the National Health and Nutrition Examination Survey. Vibration controlled transient elastography (VCTE) was performed in a US representative sample allowing the simultaneous assessment of liver steatosis (CAP: controlled attenuation parameter) and fibrosis (LSM: liver stiffness measurement) and their relationships with CKD phenotypes (albuminuria and reduced estimated glomerular filtration rate, eGFR). RESULTS: 4746 adult participants had a complete VCTE exam. Prevalence of liver steatosis and significant fibrosis was 33.7% (95%CI: 30.9-36.6%) and 8.9% (95%CI: 7.5-10.5%), respectively. Logistic regression analysis showed that liver fibrosis, but not steatosis, was associated with albuminuria (OR 2.19, 95%CI: 1.49-3.20) and albuminuria or reduced eGFR (OR 2.18, 95%CI: 1.59-3.00) also when adjusted for age, sex, ethnicity, BMI, diabetes, blood pressure categories, glycated haemoglobin, use of renin-angiotensin-aldosterone system blockers and CAP. CONCLUSIONS: In the general US population liver fibrosis assessed using VCTE is associated with CKD, and in particular with the albuminuric phenotype, regardless of traditional risk factors.

Pharmacokinetic and metabolomic analyses of Mangiferin calcium salt in rat models of type 2 diabetes and non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver is one of the most common comorbidities of diabetes. It can cause disturbance of glucose and lipid metabolism in the body, gradually develop into liver fibrosis, and even cause liver cirrhosis. Mangiferin has a variety of pharmacological activities, especially for the improvement of glycolipid metabolism and liver injury. However, its poor oral absorption and low bioavailability limit its further clinical development and application. The modification of mangiferin derivatives is the current research hotspot to solve this problem. METHODS: The plasma pharmacokinetic of mangiferin calcium salt (MCS) and mangiferin were monitored by HPLC. The urine metabolomics of MCS were conducted by UPLC-Q-TOF-MS. RESULTS: The pharmacokinetic parameters of MCS have been varied, and the oral absorption effect of MCS was better than mangiferin. Also MCS had a good therapeutic effect on type 2 diabetes and NAFLD rats by regulating glucose and lipid metabolism. Sixteen potential biomarkers had been identified based on metabolomics which were related to the corresponding pathways including Pantothenate and CoA biosynthesis, fatty acid biosynthesis, citric acid cycle, arginine biosynthesis, tryptophan metabolism, etc. CONCLUSIONS: The present study validated the favorable pharmacokinetic profiles of MCS and the biochemical mechanisms of MCS in treating type 2 diabetes and NAFLD.