Nonalcoholic Fatty Liver Severity Research Articles

Association between severity of Nonalcoholic fatty liver and left ventricular diastolic dysfunction assessed by tissue Doppler echocardiography

Association between severity of Nonalcoholic fatty liver and left ventricular diastolic dysfunction assessed by tissue Doppler echocardiography

Dietary intake of whole king oyster mushroom (Pleurotus eryngii) attenuated obesity via ameliorating lipid metabolism and alleviating gut microbiota dysbiosis

There is a growing interest in employing whole food-based strategies to prevent chronic diseases, owing to the potential synergistic interactions among various bioactive components found within whole foods. The current research aimed to determine inhibitory effects of the whole edible mushroom Pleurotus eryngii (WPE) on high-fat diet (HFD)-induced obesity in mice. Our results showed that dietary intake of WPE significantly inhibited the abnormal gain of body weight and adipose tissue weight, improved glucose tolerance, and ameliorated the serum biochemical parameters in HFD-fed mice. The histological analysis illustrated that the severity of non-alcoholic fatty liver induced by HFD was significantly reduced by WPE. Oral intake of WPE profoundly modulated the mRNA levels of hepatic genes involved in lipid metabolism and also increased the level of short-chain fatty acids in the mouse cecum. Moreover, WPE alleviated the HFD-induced gut microbiota dysbiosis, increasing the abundance of beneficial bacteria (Akkermansia, Lactobacillus, Bifidobacterium, and Sutteralla), and decreasing the harmful ones (rc4-4, Dorea, Coprococcus, Oscillospira, and Ruminococcus). These findings presented new evidence supporting that WPE could be used as a whole food-based strategy to protect against obesity and obesity-driven health problems.

Ultrasound-based artificial intelligence in gastroenterology and hepatology.

Artificial intelligence (AI), especially deep learning, is gaining extensive attention for its excellent performance in medical image analysis. It can automatically make a quantitative assessment of complex medical images and help doctors to make more accurate diagnoses. In recent years, AI based on ultrasound has been shown to be very helpful in diffuse liver diseases and focal liver lesions, such as analyzing the severity of nonalcoholic fatty liver and the stage of liver fibrosis, identifying benign and malignant liver lesions, predicting the microvascular invasion of hepatocellular carcinoma, curative transarterial chemoembolization effect, and prognoses after thermal ablation. Moreover, AI based on endoscopic ultrasonography has been applied in some gastrointestinal diseases, such as distinguishing gastric mesenchymal tumors, detection of pancreatic cancer and intraductal papillary mucinous neoplasms, and predicting the preoperative tumor deposits in rectal cancer. This review focused on the basic technical knowledge about AI and the clinical application of AI in ultrasound of liver and gastroenterology diseases. Lastly, we discuss the challenges and future perspectives of AI.

Evaluation of novel marker for predicting non-alcoholic fatty liver: Uric acid to high density lipoprotein ratio

Introduction: The aim of this study was to evaluate the association between the existence of nonalcoholic fatty liver (NAFL) with uric acid–high-density lipoprotein (HDL) ratio (UHR) and vitamin B12 levels and the effectiveness of these markers in predicting the severity of NAFL. Methods: This retrospective observational study was conducted in a university hospital between November 2021 and April 2022. The patients who had hepatobiliary ultrasonography examinations with the suspicion of fatty liver were enrolled. Patients who had fatty liver were divided into three groups after an ultrasonographic examination. Results: Of the 575 patients enrolled in the study, NAFL was found in 314 (54.6%) participants. Fatty liver was evalu-ated as grade 1 in 158 (27.5%), grade 2 in 123 (21.4%), and grade 3 in 33 (5.7%). UHR was higher in patients who had NAFL than in those who did not have NAFL. In addition, UHR levels increased as the severity of NAFL increased. Receiv-er operating characteristic (ROC) curve analysis revealed that, among parameters inspected in the study, the most ef-fective parameter to predict NAFL was UHR. A UHR value of 9.47 revealed a sensitivity of 78% and a specificity of 53%. Discussion and Conclusion: According to the results of this study, UHR can be used to predict the existence and se-verity of NAFL. There was no association between vitamin B12 levels and NAFL. UHR may be a noninvasive, available, and very simple inflammatory marker that may predict the existence of NAFL in suspected individuals.

What the New Definition of Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) Left Behind: Genetically Acquired Fatty Liver Disease (GAFLD).

What the New Definition of Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) Left Behind: Genetically Acquired Fatty Liver Disease (GAFLD).

Visceral adiposity as a risk factor for lean non-alcoholic fatty liver disease in potential living liver donors.

This study aimed to investigate the relationship between hepatic steatosis (HS) evaluated by biopsy and visceral adiposity assessed by computed tomography in lean living liver donor candidates and to determine the risk factors for lean non-alcoholic fatty liver disease (NAFLD). This retrospective study included 250 lean (body mass index, <23kg/m2 ) potential living liver donors (mean age, 31.1±8.6years; 141 men) who had undergone liver biopsy and abdominal computed tomography between 2017 and 2018. Anthropometry, laboratory parameters, body composition, and the degree of HS were evaluated. Logistic regression was used to identify independent predictors of lean NAFLD. The visceral fat area (VFA) was significantly correlated with the degree of HS in men (r=0.408; P<0.001) and women (r=0.360; P<0.001). The subcutaneous fat area was significantly correlated with the degree of HS in men (r=0.398; P<0.001), but not in women. The skeletal muscle area did not correlate with the degree of HS in either men or women. In the multivariable logistic regression analysis, the VFA (odds ratio [OR], 1.028; 95% confidence interval [CI], 1.013-1.044; P<0.001) and subcutaneous fat area (OR, 1.016; 95% CI, 1.004-1.028; P=0.009) were independent risk factors for lean NAFLD in men, and the VFA (OR, 1.036; 95% CI, 1.013-1.059; P=0.002) was an independent risk factor for lean NAFLD in women. The severity of non-alcoholic fatty liver was positively correlated with visceral fat accumulation in a lean Asian population. Visceral adiposity may be a risk factor for lean NAFLD in potential living liver donors.

Association of Skeletal Muscle and Adipose Tissue Distribution with Histologic Severity of Non-Alcoholic Fatty Liver.

Adipose tissue and skeletal muscle is associated with non-alcoholic fatty liver disease (NAFLD). This study evaluates the association between body composition and histologic severity in patients with NAFLD. Using the cross-sectional CT images at the level of L3 vertebra and the histologic findings of 178 patients with biopsy-proven NAFLD, we analyzed the correlation of the histologic findings to the skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI), and visceral adipose tissue index (VATI), which is defined as the body composition area (cm2) by height squared (m2). The clinical and laboratory features with body composition were analyzed to determine the risk factors for advanced fibrosis. The VATI significantly increased in severe non-alcoholic steatohepatitis (NASH) or advanced fibrosis. In addition, the VATI was correlated with the NAFLD activity score (NAS) and the fibrosis stage. In multivariate analyses, age (odds ratio (OR), 1.09; 95% confidence interval (CI), 1.02–1.19; p = 0.025), severe NASH (OR, 8.66; 95% CI, 2.13–46.40; p = 0.005), and visceral adiposity (OR, 6.77; 95% CI, 1.81–29.90; p = 0.007) were independently associated with advanced fibrosis in patients with NAFLD. Visceral adiposity is correlated with the histologic severity of NAFLD, which is independently associated with advanced fibrosis.

Perfluoroalkyl substances and severity of nonalcoholic fatty liver in Children: An untargeted metabolomics approach

BackgroundToxicant-associated steatohepatitis has been described in adults but less is known regarding the role of toxicants in liver disease of children. Perfluoroalkyl substances (PFAS) cause hepatic steatosis in rodents, but few previous studies have examined PFAS effects on severity of liver injury in children. ObjectivesWe aimed to examine the relationship of PFAS to histologic severity of nonalcoholic fatty liver disease (NAFLD) in children. MethodsSeventy-four children with physician-diagnosed NAFLD were recruited from Children’s Healthcare of Atlanta between 2007 and 2015. Biopsy-based liver histological features were scored for steatosis, lobular and portal inflammation, ballooning, and fibrosis. Plasma concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonic acid (PFHxS), and untargeted plasma metabolomic profiling, were determined using liquid chromatography with high-resolution mass spectrometry. A metabolome-wide association study coupled with pathway enrichment analysis was performed to evaluate metabolic dysregulation associated with PFAS. A structural integrated analysis was applied to identify latent clusters of children with more severe form of NAFLD based on their PFAS levels and metabolite pattern. ResultsPatients were 7–19 years old, mostly boys (71%), Hispanic (51%), and obese (85%). The odds of having nonalcoholic steatohepatitis (NASH), compared to children with steatosis alone, was significantly increased with each interquartile range (IQR) increase of PFOS (OR: 3.32, 95% CI: 1.40–7.87) and PFHxS (OR: 4.18, 95% CI: 1.64–10.7). Each IQR increase of PFHxS was associated with increased odds for liver fibrosis (OR: 4.44, 95% CI: 1.34–14.8), lobular inflammation (OR: 2.87, 95% CI: 1.12–7.31), and higher NAFLD activity score (β coefficient 0.46; 95% CI: 0.03, 0.89). A novel integrative analysis identified a cluster of children with NASH, characterized by increased PFAS levels and altered metabolite patterns including higher plasma levels of phosphoethanolamine, tyrosine, phenylalanine, aspartate and creatine, and decreased plasma levels of betaine. ConclusionsΗigher PFAS exposure was associated with more severe disease in children with NAFLD. PFAS may be an important toxicant contributing to NAFLD progression; however larger, longitudinal studies are warranted to confirm these findings.

The Severity of Non-Alcoholic Fatty Liver in Type II Diabetes

Abstract Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease that affects up to one third of the adult population of industrialized countries. The pathophysiological spectrum includes the following entities that are clinically and histologically distinct: hepatic steatosis and steatohepatitis; their subsequent evolution can lead to cirrhosis and hepatocellular carcinoma.The increase of the prevalence of NAFLD during the last decade is caused by the epidemiological and pathophysiological association with type II diabetes and obesity, NAFLD being present in about 70-80% of patients with type II diabetes mellitus. It has long been thought that the relationship between type II diabetes mellitus and NAFLD is unidirectional, fatty liver being secondary to insulin resistance and type II diabetes mellitus, but recent studies show that hepatic steatosis may precede insulin resistance and diabetes mellitus, thus demonstrating abidirectional causal relationship between these two disorders. Weight loss through diet andexercise is effective in preventing and treating NAFLD in diabetic patients; also, drugs that causeweight loss need to be evaluated. Both anti-diabetic medication and statins play an important vrole in the prevention and treatment of NAFLD.

Relationship of sarcopenia with steatohepatitis and advanced liver fibrosis in non-alcoholic fatty liver disease: a meta-analysis

BackgroundSeveral studies have emerged indicating that sarcopenia is associated with nonalcoholic fatty liver disease, we aimed to systematically review and quantify the association between sacropenia and the histological severity of nonalcoholic fatty liver disease.MethodsPubmed, the Cochrane Library and EMBASE were searched (until August 2017) for studies examining the relationship of sarcopenia with steatohepatitis and advanced liver fibrosis in nonalcoholic fatty liver disease. Pooled odds ratios were estimated by fixed effects models.ResultsThree articles met our inclusion criteria, with a total of 3226 individuals. Two of the studies examined the association between sacropenia and steatohepatitis, a significant association was documented between sarcopenia and steatohepatitis (OR = 2.35, 95%CI 1.45, 3.81). All of the three studies assessed the association between sacropenia and advanced liver fibrosis, a significant association between sarcopenia and advanced liver fibrosis (OR = 2.41, 95%CI 1.94, 2.98). No significant heterogeneity was detected among studies in all comparisons. These results remained essentially unchanged after excluding any of the studies in the sensitivity analysis.ConclusionsSarcopenia in patients with nonalcoholic fatty liver disease is associated with a higher likelihood of having steatohepatitis or advanced liver fibrosis. Demonstration of the role of sarcopenia in nonalcoholic fatty liver disease development in future studies could have important therapeutic implications.

FRI-318 - The FTO rs1421085 T > C Polymorphism is Associated with the Severity of Non-Alcoholic Fatty Liver

FRI-318 - The FTO rs1421085 T > C Polymorphism is Associated with the Severity of Non-Alcoholic Fatty Liver

Serum adipokines might predict liver histology findings in non-alcoholic fatty liver disease.

To assess significance of serum adipokines to determine the histological severity of non-alcoholic fatty liver disease. Patients with persistent elevation in serum aminotransferase levels and well-defined characteristics of fatty liver at ultrasound were enrolled. Individuals with a history of alcohol consumption, hepatotoxic medication, viral hepatitis or known liver disease were excluded. Liver biopsy was performed to confirm non-alcoholic liver disease (NAFLD). The degrees of liver steatosis, lobular inflammation and fibrosis were determined based on the non-alcoholic fatty liver activity score (NAS) by a single expert pathologist. Patients with a NAS of five or higher were considered to have steatohepatitis. Those with a NAS of two or lower were defined as simple fatty liver. Binary logistic regression was used to determine the independent association of adipokines with histological findings. Receiver operating characteristic (ROC) analysis was employed to determine cut-off values of serum adipokines to discriminate the grades of liver steatosis, lobular inflammation and fibrosis. Fifty-four participants aged 37.02 ± 9.82 were enrolled in the study. Higher serum levels of visfatin, IL-8, TNF-α levels were associated independently with steatosis grade of more than 33% [β = 1.08 (95%CI: 1.03-1.14), 1.04 (95%CI: 1.008-1.07), 1.04 (95%CI: 1.004-1.08), P < 0.05]. Elevated serum IL-6 and IL-8 levels were associated independently with advanced lobular inflammation [β = 1.4 (95%CI: 1.09-1.8), 1.07 (95%CI: 1.003-1.15), P < 0.05]. Similarly, higher TNF-α, resistin, and hepcidin levels were associated independently with advanced fibrosis stage [β = 1.06 (95%CI: 1.002-1.12), 19.86 (95%CI: 2.79-141.19), 560.72 (95%CI: 5.98-5255.33), P < 0.05]. Serum IL-8 and TNF-α values were associated independently with the NAS score, considering a NAS score of 5 as the reference value [β = 1.05 (95%CI: 1.01-1.1), 1.13 (95%CI: 1.04-1.22), P < 0.05]. Certain adipokines may determine the severity of NAFLD histology accurately.

Association between Serum Fibroblast Growth Factor-21 Levels and Nonalcoholic Fatty Liver in Korean Men with Type 2 Diabetes

목적: 혈청 FGF-21의 증가는 비만, 대사증후군, 제2형 당뇨병을 가진 환자에서 관찰되었으나 현재까지 제2형 당뇨병환자에서 NAFL과 FGF-21의 연관성은 확실하게 정립되어 있지 않다. 이에 저자들은 제2형 당뇨병을 가진 한국인 남성환자에서 혈중 FGF-21 수치와 NAFL의 연관성을 확인하고 혈중 FGF-21 수치에 영향을 미치는 독립적 위험인자를 알아보고자 하였다. 방법: 제2형 당뇨병으로 진단 받은 한국인 성인 남자 135명 (평균 56.2 ± 9.2세)을 대상으로 하였다. 임상 및 생화학적 대사 지표를 측정했고 혈청 FGF-21은 ELISA를 이용하여 측정했다. NAFL의 정도는 복부 초음파 검사를 통해 진단했으며 간 내 혈관 경계와 횡격막이 희미하게 보이거나 또는 보이지 않으면서 간 실질의 초음파 음영이 두드러지게 증가한 경우를 중등도 이상의 지방간으로 판정하였다. 결과: 정상간을 가진 환자에 비해 중등도 이상 지방간을 가진 환자에서 BMI, 허리둘레, HOMA-IR, TG, 간효소 및 혈청 FGF-21 수치가 유의하게 증가되어 있었다. 혈청 FGF-21은 BMI, 혈청 Cr, TG, 간효소 수치, 그리고, hsCRP와 양의 상관관계를 갖고, HDL 콜레스테롤과 음의 상관관계가 관찰되었다. 다변량 선형 회귀분석에서 TG, 중증도 이상의 지방간 그리고 혈청 Cr만이 FGF-21 농도와 통계학적으로 유의한 양의상관관계를 보였다. 로지스틱 회귀분석에서도 중등도 이상지방간 동반의 위험도는 혈청 Cr, TG, BMI 그리고 HOMA-IR을 보정하고 난 이후에도 혈청 FGF-21과 통계적으로 유의했다. 결론: 본 연구는 제2형 당뇨병을 가진 한국 남자 환자에서 NAFL과 혈중 FGF-21 농도가 독립적인 연관성이 있음을 확인했다.

Nitrosative stress predicts the presence and severity of nonalcoholic fatty liver at different stages of the development of insulin resistance and metabolic syndrome: possible role of vitamin A intake

Background:Although nonalcoholic fatty liver disease (NAFLD) is associated with the metabolic syndrome, the mechanisms responsible for the development of NAFLD at different stages of the development of insulin resistance are unknown. Diet, adipokines, and nitrosative stress have been linked to both NAFLD and insulin resistance.Objective:We aimed to identify the factors that are specifically associated with NAFLD at different stages in the development of insulin resistance and the metabolic syndrome.Design:Circulating concentrations of adipokines (ie, tumor necrosis factor-α, adiponectin, resistin, leptin, and interleukin-6), markers of nitrosative stress (nitrotyrosine), dietary habits, and MTP −493G/T polymorphism were cross-sectionally related to the presence and severity of insulin resistance (homeostasis model assessment index for insulin resistance: ≥2), the metabolic syndrome, and fatty liver in 64 nonobese nondiabetic patients with NAFLD (33 insulin-sensitive and 31 insulin-resistant subjects) and 74 control subjects without liver disease who were matched for sex, BMI, homeostasis model assessment index for insulin resistance status, and the various features of the metabolic syndrome.Results:Persons with NAFLD had greater systemic nitrosative stress and a lower intake of vitamins A and E than did control subjects, but the 2 groups did not differ significantly in any other features. Nitrotyrosine and adiponectin concentrations and vitamin A intakes independently predicted alanine aminotransferase concentrations in NAFLD patients and liver histology in a subgroup of 29 subjects with biopsy-proven nonalcoholic steatohepatitis.Conclusions:Oxidative stress is operating in NAFLD and nonalcoholic steatohepatitis, even in the absence of insulin resistance, the metabolic syndrome, and hypoadiponectinemia, which aggravate liver histology at more severe stages of metabolic disease. The possible pathogenetic role of reduced vitamin A intake in NAFLD warrants further investigation.