Nonalcoholic fatty liver disease in children: A follow-up study for up to 16 years

The association between white blood cell (WBC) and nonalcoholic fatty liver disease (NAFLD) has been studied before, but whether different WBC subtypes were related to NAFLD was not detailed. The aim of our study was to investigate the relationship between WBC subtypes and NAFLD cross-sectionally and prospectively. The detailed research design has been described previously. At baseline, there were 9930 participants who had complete information, in the end a total of 8079 participants (2588 men and 5491 women) were eventually included in this study. Hepatic ultrasound examination was performed on each participant at baseline and at the end of follow-up. Alcohol abuse and hepatitis were excluded. WBC subtypes and other serum indices were measured at baseline. We found that the total WBC, neutrophil, and lymphocyte counts were independently associated with the prevalence and incidence of NAFLD. After multiple adjustments for age, gender, body mass index (BMI), insulin, HOMA-IR, TG, TC, LDL, and HDL, increased odds ratios (ORs) for new onset NAFLD were observed from the 1st to the 4th quartiles of WBC, neutrophil, and lymphocyte (all P < 0.001 for trend). In conclusion, total WBC counts, neutrophils, and lymphocytes were all independent risk factors for NAFLD in the rural Chinese population. The association was independent of insulin resistance.

Download Full-text

Afamin predicts the prevalence and incidence of nonalcoholic fatty liver disease

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2021-0837 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Niina Pitkänen ◽

Armin Finkenstedt ◽

Claudia Lamina ◽

Markus Juonala ◽

Mika Kähönen ◽

...

Keyword(s):

Metabolic Syndrome ◽

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Population Based ◽

Healthy Controls ◽

Nonalcoholic Fatty Liver ◽

Age And Sex

Abstract Objectives In the general population, increased afamin concentrations are associated with the prevalence and incidence of metabolic syndrome as well as type 2 diabetes. Although metabolic syndrome is commonly associated with nonalcoholic fatty liver disease (NAFLD), there exist no information on afamin and NAFLD. Methods Afamin concentrations were cross-sectionally measured in 146 Austrian patients with NAFLD, in 45 patients without NAFLD, and in 292 age- and sex-matched healthy controls. Furthermore, the feasibility of afamin to predict incident NAFLD was evaluated in 1,434 adult participants in the population-based Cardiovascular Risk in Young Finns Study during a 10-year follow-up. Results Median afamin concentrations were significantly higher in NAFLD patients (83.6 mg/L) than in patients without NAFLD (61.6 mg/L, p<0.0001) or in healthy controls (63.9 mg/L, p<0.0001). In age- and sex-adjusted logistic regression analyses a 10 mg/L increase of afamin was associated with a 1.5-fold increase of having NAFLD as compared with patients without NAFLD and the risk was even two-fold when compared with healthy controls. In the population-based cohort, afamin concentrations at baseline were significantly lower in participants without NAFLD (n=1,195) than in 239 participants who developed NAFLD (56.5 vs. 66.9 mg/L, p<0.0001) during the 10-year follow up, with highest afamin values observed in individuals developing severe forms of NAFLD. After adjustment for several potentially confounding parameters, afamin remained an independent predictor for the development of NAFLD (OR=1.37 [95% CI 1.23–1.54] per 10 mg/L increase, p<0.0001). Conclusions Afamin concentrations are increased in patients with NAFLD and independently predict the development of NAFLD in a population-based cohort.

Download Full-text

Utility of ALT Concentration in Men and Women with Nonalcoholic Fatty Liver Disease: Cohort Study

Journal of Clinical Medicine ◽

10.3390/jcm8040445 ◽

2019 ◽

Vol 8 (4) ◽

pp. 445 ◽

Cited By ~ 3

Author(s):

Ki-Chul Sung ◽

Mi-Yeon Lee ◽

Jong-Young Lee ◽

Sung-Ho Lee ◽

Seong-Hwan Kim ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Full Range ◽

Men And Women ◽

Nonalcoholic Fatty Liver ◽

Prevalence Of Obesity ◽

Metabolic Variables

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of elevated alanine aminotransferase (ALT), but the clinical utility of ALT in detecting and following individuals with NAFLD remains unclear. We conducted a retrospective analysis of 30,988 men and 5204 women with NAFLD diagnosed by ultrasound and stratified them according to sex-specific ALT quartiles. We compared metabolic variables at baseline and repeated ultrasound after at least 6 months among ALT quartiles (Q) in men (Q1 5–24, Q2 25–33, Q3 34–48, Q4 ≥ 49 IU/L) and women (Q1 5–14, Q2 15–20, Q3 21–28, Q4 ≥ 29 IU/L). Prevalence of obesity (BMI ≥ 25 kg/m2) and metabolic abnormalities (glucose intolerance, hypertension) significantly (p < 0.001) increased from ALT Q1 to Q4 in both men and women at baseline. After a mean follow-up of 4.93 years, 17.6% of men and 31.1% of women resolved their NAFLD. The odds ratio (OR) of resolving significantly (p < 0.001) decreased by quartiles even after multiple adjustments. The adjusted OR for resolution in Q4 was 0.20 (0.18–0.23) in men and 0.35 (0.26–0.47) in women compared with Q1. Individuals with NAFLD span the full range of ALT concentrations, but those with the highest ALT have the worst metabolic profile and persistent NAFLD.

Download Full-text

Identification of key target genes and pathway analysis in nonalcoholic fatty liver disease via integrated bioinformatics analysis

10.21203/rs.3.rs-49190/v1 ◽

2020 ◽

Author(s):

Xi Chen ◽

Lian Zhang ◽

Yanyan Wang ◽

Ruien Li ◽

Ming Yang ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Regulatory Network ◽

Fatty Liver Disease ◽

Target Genes ◽

Point Group ◽

Nonalcoholic Fatty Liver ◽

Time Point

Abstract Background This study aimed to explore the mechanisms underlying nonalcoholic fatty liver disease (NAFLD) and develop new diagnostic biomarkers for nonalcoholic steatohepatitis (NASH). Methods The microarray dataset GES83452 was downloaded from the NCBI-GEO database, and the differentially expressed RNAs (DERs) were screened between the NAFLD and non-NAFLD samples of the baseline and 1-year follow-up time point group based on the Limma package. Subsequently, the lncRNA–miRNA–mRNA regulation network was constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on the regulated target genes in the ceRNA regulatory network were performed based on DAVID. Finally, PharmGKB database was used to search for the gene-related drug molecules, and the gene–drug connection network was constructed. Results A total of 561 DERs (268 downregulated and 293 upregulated) were screened in the baseline time point group, and 1163 DERs (522 downregulated and 641 upregulated) were screened in the 1-year follow-up time point group. A total of 74 lncRNA–miRNA pairs and 523 miRNA–mRNA pairs were obtained to construct lncRNA–miRNA–mRNA regulatory network. Subsequently, functional enrichment analysis revealed 28 GO and 9 KEGG pathways in the ceRNA regulatory network. LEPR and CXCL10 are involved in the Cytokine–cytokine receptor interaction (P = 1.86E-02), and the FOXO1 is involved in both the Insulin signaling pathway (P = 1.79E-02) and the pathways in cancer (P = 2.87E-02). Conclusion LEPR, CXCL10, and FOXO1 were the characteristic target genes for NAFLD.

Download Full-text

The Effect of Weight Loss on Pediatric Nonalcoholic Fatty Liver Disease

ISRN Gastroenterology ◽

10.1155/2013/398297 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8

Author(s):

David E. St-Jules ◽

Corilee A. Watters ◽

Ken Nagamori ◽

Jeremy King

Keyword(s):

Weight Loss ◽

Body Weight ◽

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Alanine Aminotransferase ◽

Fatty Liver Disease ◽

Nonalcoholic Fatty Liver ◽

One Year

This study evaluated the effect of weight loss on pediatric nonalcoholic fatty liver disease (NAFLD). Subjects included 81 overweight NAFLD patients referred to two pediatric gastroenterologists from 2000 to 2010. Data on subjects were obtained from review of medical charts. The effect of weight loss was assessed at 1–4 months, 5–8 months, 9–12 months, and beyond one year as the change in weight, BMI -score (for age-and-sex), and alanine aminotransferase and the relationship between the change in body weight and BMI -score, and the change in alanine aminotransferase. Subjects were mostly obese (99%), male (86%), and Asian (63%) and had median age of 14.1 (11.2–16.2) years and alanine aminotransferase of 105 (78–153) U/L at referral. Alanine aminotransferase decreased 32 ± 66 (), 30 ± 65 (), 37 ± 75 (), and 45 ± 69 () for subjects with follow-up data at 1–4 months (), 5–8 months (), 9–12 months (), and beyond one year (), respectively. During these time periods, neither was body weight (−0.2 to +7.1 kg) or BMI -score (−0.12 to −0.05) significantly reduced, nor were changes in these variables associated with the change in alanine aminotransferase. These findings suggest that weight and BMI -score may not be sufficient indicators of treatment response in pediatric NAFLD patients.

Download Full-text

Relative fat mass at baseline and its early change may be a predictor of incident nonalcoholic fatty liver disease

Scientific Reports ◽

10.1038/s41598-020-74659-9 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Hwi Young Kim ◽

Su Jung Baik ◽

Hye Ah Lee ◽

Byoung Kwon Lee ◽

Hye Sun Lee ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Muscle Mass ◽

Fatty Liver Disease ◽

Normal Weight ◽

Fat Percentage ◽

Nonalcoholic Fatty Liver ◽

Body Components

Abstract The relationship between changes in body components and the risk of nonalcoholic fatty liver disease (NAFLD) is not fully understood. We investigated the effects of body components and subsequent changes on incident NAFLD at follow-up ultrasound scanning in a longitudinal cohort. We included 9967 participants without NAFLD at baseline who underwent serial health examinations. Sex-specific, weight-adjusted skeletal muscle index (SMI_Wt) was used. Mean follow-up duration was 48.5 ± 33.5 months. NAFLD developed in 2395 participants (24.0%). Body composition was measured using bioelectrical impedance analysis. The following baseline body components were significantly associated with incident NAFLD: the lowest and middle SMI_Wt tertiles in the normal-weight group (adjusted hazard ratio [aHR] = 2.20 and 1.54, respectively), and fat percentage in the normal-weight (aHR = 1.12), overweight (aHR = 1.05), and obese groups (aHR = 1.03) (all P < 0.05). Among 5,033 participants who underwent ≥ 3 health examinations, SMI_Wt increase between the first and second examinations was an independent protective factor against incident NAFLD in non-obese groups (P < 0.05). Increased fat percentage was an independent risk factor for incident NAFLD in all weight categories (P < 0.05). High fat mass at baseline may be a better predictor of incident NAFLD than muscle mass. Reciprocal changes in fat and muscle mass during the first year of follow-up predicted incident NAFLD in non-obese groups.

Download Full-text

Depressive symptoms and liver fat in subjects with nonalcoholic fatty liver disease after 6-month weight loss intervention: The FLiO study

Proceedings of The Nutrition Society ◽

10.1017/s0029665120003213 ◽

2020 ◽

Vol 79 (OCE2) ◽

Author(s):

Bertha Araceli Marin-Alejandre ◽

Itziar Abete ◽

Irene Cantero ◽

Cristina Galarregui ◽

Mariana Elorz ◽

...

Keyword(s):

Body Weight ◽

Depressive Symptoms ◽

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Controlled Trial ◽

Liver Fat ◽

Nonalcoholic Fatty Liver

AbstractIntroduction:Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in Western countries and is strongly associated with obesity and insulin resistance-related comorbidities. Moreover, there is some evidence of a relationship between NAFLD and depression. The aim of this study was to compare the effect of two personalized energy-restricted diets on liver fat and depressive symptoms in overweight or obese subjects with NAFLD after a 6-month follow-up.Materials and methods:Ninety-eight overweight or obese adults with NAFLD were enrolled and randomized to follow one of two different personalized energy-restricted diets (American Heart Association vs. FLiO diet) accompanied by healthy lifestyle advice. Study registered as FLiO: Fatty Liver in Obesity; NCT03183193. Anthropometry, body composition, biochemical features and liver status were assessed at baseline and after a 6-month follow-up. Liver fat was evaluated by Magnetic Resonance Imaging and depressive symptoms using the Beck's Depression Inventory-II (BDI-II).Results:Participants of both groups showed significant reductions in body weight, total fat mass, glucose, insulin and alanine aminotransferase (p < 0.001 for all these parameters in both groups). A significant decrease in liver fat (p < 0.001 in both groups) and depressive symptoms (p < 0.01 in both groups) was observed after the follow-up. The effects of the intervention in the evaluated variables did not differ when both diets were compared. Consequently, the two groups were considered together as one sample for the further analyses. Correlation analyses evidenced a positive association between the decrease in depressive symptoms and the reduction in body weight (r = 0.241; p = 0.044) and liver fat (r = 0.251; p = 0.046).Discussion:Previous studies have reported that the prevalence of depression in patients with chronic liver disease (including NAFLD) is higher than in the general population and that major depressive disorder is associated with more severe hepatic steatosis and with worse outcomes in the treatment of NAFLD subjects. In our study, both healthy personalized energy-restricted diets were able to improve metabolic parameters, liver fat content and depressive symptoms in overweight and obese participants with NAFLD. To our knowledge, this is the first study to report an association between the changes in depressive symptoms and the decrease in liver fat after a dietary randomized controlled trial. Further investigation is needed to clarify the relationship between depression and the development and treatment of NAFLD.

Download Full-text

The association of genetic polymorphisms with nonalcoholic fatty liver disease in a longitudinal study

BMC Gastroenterology ◽

10.1186/s12876-020-01469-8 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Goh Eun Chung ◽

Eunsoon Shin ◽

Min-Sun Kwak ◽

Jong In Yang ◽

Jong-Eun Lee ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Genetic Variants ◽

Fatty Liver Disease ◽

Nonalcoholic Fatty Liver ◽

Genome Wide ◽

A Genome ◽

Validation Set

Abstract Background Several genetic variants are known to be associated with nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the longitudinal associations between genetic variants and NAFLD. Methods We performed a genome-wide association study (GWAS) in Korean individuals who underwent repeated health check-ups. NAFLD was defined by ultrasonography and exclusion of secondary causes. Results The subjects had a median age of 50.0 years, and 54.8% were male. The median follow-up duration was 39 months. Among the 3905 subjects without NAFLD at baseline, 874 (22.4%) subjects developed NAFLD, and among the 1818 subjects with NAFLD at baseline, NAFLD regressed in 336 (18.5%) subjects during the follow-up period. After adjusting for age, sex and body mass index, no single-nucleotide polymorphism (SNP) passed Bonferroni correction for genome-wide significance in the development or regression of NAFLD. Among the SNPs that passed the genome-wide suggestiveness threshold (p = 1E-04) in the discovery set in the GWAS, only 1 SNP (rs4906353) showed an association with the development of NAFLD, with marginal significance in the validation set (p-value, discovery set = 9.68E-5 and validation set = 0.00531). Conclusions This exploratory study suggests that longitudinal changes in NAFLD are not associated with genetic variants in the Korean population. These findings provide new insight into genetic mechanisms in the pathogenesis of NAFLD.

Download Full-text

Nonalcoholic fatty liver disease is associated with the development of obstructive sleep apnea

Scientific Reports ◽

10.1038/s41598-021-92703-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Goh Eun Chung ◽

Eun Ju Cho ◽

Jeong-Ju Yoo ◽

Young Chang ◽

Yuri Cho ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Liver Disease ◽

Sleep Apnea ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

National Health Insurance System ◽

Nonalcoholic Fatty Liver ◽

Obstructive Sleep

AbstractIncreasing evidence suggests that obstructive sleep apnea (OSA) is a metabolic syndrome-related disease; however, the association between nonalcoholic fatty liver disease (NAFLD) and OSA is not firmly established. In this study, we investigated the relationship between NAFLD and OSA in a general population drawn from a nationwide population-based cohort. Data from the Korean National Health Insurance System between January 2009 and December 2009 were analyzed using Cox proportional hazards model. NAFLD was defined as a fatty liver index (FLI) ≥ 60 in patients without excessive alcohol consumption (who were excluded from the study). Newly diagnosed OSA during follow-up was identified using claims data. Among the 8,116,524 participants, 22.6% had an FLI score of 30–60 and 11.5% had an FLI ≥ 60. During median follow-up of 6.3 years, 45,143 cases of incident OSA occurred. In multivariable analysis, the risk of OSA was significantly higher in the higher FLI groups (adjusted hazard ratio [aHR] 1.15, 95% confidence interval [CI] 1.12–1.18 for FLI 30–60 and aHR 1.21, 95% CI 1.17–1.26 for FLI ≥ 60). These findings were consistent regardless of body mass index and presence of abdominal obesity. In conclusion, a high FLI score may help identify individuals with a high risk of OSA. Understanding the association between NAFLD and OSA may have clinical implications for risk-stratification of individuals with NAFLD.

Download Full-text