Elevated Hemoglobin Level Is Associated With Advanced Fibrosis in Pediatric Nonalcoholic Fatty Liver Disease

Giorgio, Valentina; Mosca, Antonella; Alterio, Arianna; Alisi, Anna; Greco, Antonio; Miele, Luca

doi:10.1097/mpg.0000000000001614

Cited by 19 publications

(13 citation statements)

References 31 publications

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“…hematocrit and hemoglobin, were significantly higher in DD pigs over almost the whole time-course, making the finding more robust. High levels of hematocrit and hemoglobin are associated with obesity and metabolic syndrome 36,37 , respectively, and both metrics are related to insulin resistance, NAFLD and NASH in humans [38][39][40] . Mean corpuscular volume was also higher in DD pigs; however, even though this parameter is increased in some liver pathologies, it does not seem to be linked to NAFLD 41 .…”

Section: Discussionmentioning

confidence: 99%

Integrative analysis of blood and gut microbiota data suggests a non-alcoholic fatty liver disease (NAFLD)-related disorder in French SLAdd minipigs

Moroldo

Munyaka

Lecardonnel

et al. 2020

Sci Rep

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Minipigs are a group of small-sized swine lines, which show a broad range of phenotype variation and which often tend to be obese. the SLA dd (DD) minipig line was created by the niH and selected as homozygous at the SLA locus. It was brought to France more than 30 years ago and maintained inbred ever since. in this report, we characterized the physiological status of a herd of french DD pigs by measuring intermediate phenotypes from blood and faeces and by using Large White (LW) pigs as controls. three datasets were produced, i.e. complete blood counts (cBcs), microarray-based blood transcriptome, and faecal microbiota obtained by 16S rRNA sequencing. CBCs and expression profiles suggested a non-alcoholic fatty liver disease (nAfLD)-related pathology associated to comorbid cardiac diseases. The characterization of 16S sequencing data was less straightforward, suggesting only a potential weak link to obesity. The integration of the datasets identified several fine-scale associations between CBCs, gene expression, and faecal microbiota composition. NAFLD is a common cause of chronic liver disease in Western countries and is linked to obesity, type 2 diabetes mellitus and cardiac pathologies. Here we show that the French DD herd is potentially affected by this syndrome. Minipigs are a group of small-sized swine lines, which started to be developed in the 1940s for biomedical research. They present many advantages over conventional pigs, like size, ease of handling and decreased feed requirements 1. Today, a large variety of breeds is available for very different applications. Minipig lines are maintained using specific breeding strategies, which minimize inbreeding while keeping the genetic integrity of the population 2. Examples of minipigs include the MeLiM line, a model to study an inheritable form of melanoma undergoing spontaneous regression 3 and the Yucatan strain, used for research on cardiovascular pathologies and diabetes 1. Minipig lines homozygous at the major histocompatibility locus (MHC, also known as Swine Leukocyte Antigen or SLA in pigs) were also produced by the NIH, mostly for immunology studies and transplantation programs 4. Non-alcoholic fatty liver disease is the most common cause of chronic liver disease in developed countries 5,6. It spans a spectrum of pathologies ranging from hepatic steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis 6-8. While NAFLD was traditionally seen as a pathology affecting mainly the liver, it has recently been shown that its burden is not limited to this organ. There is increasing evidence that NAFLD is multisystemic, involving extra-hepatic organs and pathways. It is associated with obesity 9 , type 2 diabetes mellitus, insulin resistance, metabolic syndrome and cardiovascular diseases 5-7,10-12. Despite the complexity of this pathology, many NAFLD-related molecular pathways are known 13-15 , and its development is usually modelled using the "two-hit hypothesis" 12,13. The "first hit" corresponds to insulin resistance-mediated fat accumulation in h...

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Section: Discussionmentioning

confidence: 99%

Integrative analysis of blood and gut microbiota data suggests a non-alcoholic fatty liver disease (NAFLD)-related disorder in French SLAdd minipigs

Moroldo

Munyaka

Lecardonnel

et al. 2020

Sci Rep

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“…Therefore, the study may not have included the most ill youth with the highest degree of inflammation. In addition, hemoglobin was higher in the HS group, which has also been reported to be associated with the presence of hepatic inflammation (NASH) and fibrosis in youth [ 27 ]. Future work with more specific markers, or tissue measured samples of inflammatory markers is needed.…”

Section: Discussionmentioning

confidence: 99%

Nonalcoholic fatty liver disease in obese adolescent females is associated with multi-tissue insulin resistance and visceral adiposity markers

et al. 2019

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Objective Nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance (IR) and visceral adiposity in adults and boys, but girls with NAFLD are understudied. We sought to evaluate adipose, liver, and skeletal muscle insulin sensitivity in obese adolescent females with or without hepatic steatosis (HS) (intrahepatic triglyceride (IHTG) content >5.5%) along with cardiometabolic components typically associated with IR. Study design 73 obese adolescent girls at high risk for NAFLD were enrolled. Participants underwent fasting labs, an MRI to measure IHTG and visceral fat, 31 phosphorous MR spectroscopy for muscle mitochondrial function, 1 H MR spectroscopy for intramyocellular lipid (IMCL), bicycle ergometry to assess VO 2 peak and a 4-phase hyperinsulinemic euglycemic clamp with isotope tracers to measure hepatic and peripheral IR. 29 participants had HS [age 15 yrs(13,16), BMI%ile 98.7(97.4,99.0), IHTG 10.4%(8.0,13.5)] and 44 did not [age 15 yrs(13,17), BMI%ile 98.5(96.2,99.0), IHTG 2.0%(1.1,3.0)]. Results During hyperinsulinemia, participants with HS vs. non-HS had failure to suppress free fatty acids (p = 0.008), endogenous glucose release (p = 0.002), and a lower glucose metabolic rate of disappearance (Rd) (p = 0.012). Girls with NALFD also had higher visceral fat (p < 0.001), systolic blood pressure (p = 0.026), triglycerides (p = 0.02), ALT (p < 0.01) and white blood cell count (p < 0.01), and lower adiponectin (p = 0.02). There was no difference between girls with and without HS in systemic glycerol turnover measured with glycerol release, or in IMCL, mitochondrial function or VO 2 peak. Conclusions Obese adolescent girls with HS have evidence of multi-tissue IR, visceral adiposity, inflammation and multiple components of the metabolic syndrome, arguing for close cardiometabolic surveillance over time of girls with HS.

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“…High-fat diet induced dysfunction of erythrocytes by increasing their oxidative stress levels and reducing their survival in a rat model of high fat diet-induced obesity [14]. Also, patients with non-alcoholic fatty liver disease were more likely to have a high red cell distribution width (RDW) and elevated hemoglobin (Hb) levels [15,16]. In addition, indicators for fat content in blood, such as serum cholesterol (TC) and triglycerides (TG), were also associated with hematological diseases [17].…”

Section: Introductionmentioning

confidence: 99%

Influence of benzene exposure, fat content, and their interactions on erythroid-related hematologic parameters in petrochemical workers: a cross-sectional study

Zhang

Deng

et al. 2020

BMC Public Health

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Background: Ubiquitously distributed benzene is a known hematotoxin. Increasing evidence has suggested that erythroid-related hematologic parameters may be sensitive to benzene exposure. Fat content, which is also closely associated with erythroid-related hematologic parameters, may affect the distribution and/or metabolism of benzene, and eventually benzene-induced toxicity. Methods: To explore the influence of benzene exposure, fat content, and their interactions on erythroid-related hematologic parameters, we recruited 1669 petrochemical workers and measured their urinary S-phenylmercapturic acid (SPMA) concentration and erythroid-related hematological parameters. Indices for fat content included body fat percentage (BF%), plasma total cholesterol (TC) and triglycerides (TG), and occurrence of fatty liver. Results: The dose-response curve revealed U-shaped nonlinear relationships of SPMA with hematocrit (HCT) and mean corpuscular hemoglobin concentration (MCHC) (P-overall < 0.001, and P-nonlinear < 0.015), as well as positive linear associations and r-shaped nonlinear relationships of continuous fat content indices with erythroid-related hematological parameters (P-overall ≤0.005). We also observed modification effects of fat content on the associations between benzene exposure and erythroid-related hematological parameters, with workers of lower or higher BF% and TG more sensitive to benzene-induced elevation of MCHC (P interaction = 0.021) and benzene-induced decrease of HCT (P interaction = 0.050), respectively. We also found that some erythroid-related hematologic parameters differed between subgroups of workers with different SPMA levels and fat content combination.

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Elevated Hemoglobin Level Is Associated With Advanced Fibrosis in Pediatric Nonalcoholic Fatty Liver Disease

Cited by 19 publications

References 31 publications

Integrative analysis of blood and gut microbiota data suggests a non-alcoholic fatty liver disease (NAFLD)-related disorder in French SLAdd minipigs

Integrative analysis of blood and gut microbiota data suggests a non-alcoholic fatty liver disease (NAFLD)-related disorder in French SLAdd minipigs

Nonalcoholic fatty liver disease in obese adolescent females is associated with multi-tissue insulin resistance and visceral adiposity markers

Influence of benzene exposure, fat content, and their interactions on erythroid-related hematologic parameters in petrochemical workers: a cross-sectional study

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