Nonalcoholic fatty liver disease and hepatic cirrhosis: Comparison with viral hepatitis-associated steatosis.
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SUBMITTER: Haga Y
PROVIDER: S-EPMC4674717 | biostudies-literature | 2015 Dec
REPOSITORIES: biostudies-literature
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Nonalcoholic fatty liver disease and hepatic cirrhosis: Comparison with viral hepatitis-associated steatosis.
Haga Yuki Y Kanda Tatsuo T Sasaki Reina R Nakamura Masato M Nakamoto Shingo S Yokosuka Osamu O
World journal of gastroenterology 20151201 46
Nonalcoholic fatty liver disease (NAFLD) including nonalcoholic steatohepatitis (NASH) is globally increasing and has become a world-wide health problem. Chronic infection with hepatitis B virus or hepatitis C virus (HCV) is associated with hepatic steatosis. Viral hepatitis-associated hepatic steatosis is often caused by metabolic syndrome including obesity, type 2 diabetes mellitus and/or dyslipidemia. It has been reported that HCV genotype 3 exerts direct metabolic effects that lead to hepati ...[more]
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Project description:Background & aimsMany individuals presumed to have nonalcoholic fatty liver disease (NAFLD) consume moderate amounts of alcohol. Little is known about patterns of alcohol use in patients with NAFLD or how drinking behaviors affect liver fat.MethodsWe conducted a cross-sectional study of 2475 participants of the Framingham Heart Study with hepatic steatosis, as determined by computed tomography. We performed multivariable-adjusted logistic regression models to evaluate the association between alcohol drinking patterns and hepatic steatosis. Models were adjusted for sociodemographic factors, diet, and the components of the metabolic syndrome. We excluded heavy alcohol users, defined as women who consume more than 14 alcohol drinks per week and men who consume more than 21 alcohol drinks per week.ResultsIn our sample (mean age, 49.8 ± 10.2 y; 50.3% women), the prevalence of hepatic steatosis was 17.5%. The total number of alcohol drinks per week and the maximum drinks consumed per drinking day each were associated with hepatic steatosis (adjusted odds ratio [aOR], 1.15; 95% CI, 1.02-1.29 and aOR 1.15; 95% CI, 1.02-1.30). Binge drinking occurred in 25.4% of individuals with presumed NAFLD and was associated with an increased odds of hepatic steatosis (aOR, 1.45; 95% CI, 1.06-1.98) among alcohol users. In a beverage-specific analysis, alcohol use patterns were associated with hepatic steatosis among beer drinkers, but not among wine drinkers.ConclusionsIn a cross-sectional study of participants of the Framingham Heart Study with hepatic steatosis, we observed an association between alcohol use and liver fat, even after excluding heavy alcohol users from our analysis. Alcohol use therefore appears to be a risk factor for NAFLD. Prospective studies are needed to validate these findings and determine if alcohol use should be a focus for research, prevention, and treatment of presumed NAFLD.
| S-EPMC7569606 | biostudies-literature
Project description:BACKGROUND/AIMS:A number of clinical trials reported varying effects of cholesterol lowering agents in nonalcoholic fatty liver disease (NAFLD) patients. We, therefore, assessed the changes in hepatic steatosis and NAFLD activity score (NAS) after treatment with cholesterol lowering agents in NAFLD patients by metaanalysis. METHODS:The Cochrane Library, the MEDLINE, and the Embase databases were searched until May 2015, without any language restrictions, for randomized controlled trials (RCTs) and nonrandomized studies (NRSs). Additional references were obtained from review of bibliography of relevant articles. The quality of evidence was assessed using the grading of recommendations assessment, development and evaluation guidelines. RESULTS:Three RCTs (n = 98) and two NRSs (n = 101) met our study inclusion criteria (adult, NAFLD, liver biopsy). Liver biopsy was performed in all five studies, but only the three studies reported NAS. Ezetimibe significantly decreased NAS (standardized mean difference [SMD], -0.30; 95% confidence interval [CI], -0.57 to -0.03) but not hepatic steatosis in RCT (SMD, -0.1; 95% CI, -0.53 to 0.32), while the effect was significant for both NAS and intrahepatic content in NRSs (SMD, -3.0; 95% CI, -6.9 to 0.91). CONCLUSION:Ezetimibe decreased NAS without improving hepatic steatosis.
| S-EPMC6406097 | biostudies-literature
Project description:Background Advanced confounder-corrected chemical shift-encoded MRI-derived proton density fat fraction (PDFF) is a leading parameter for fat fraction quantification in nonalcoholic fatty liver disease (NAFLD). Because of the limited availability of this MRI technique, there is a need to develop and validate alternative parameters to assess liver fat. Purpose To assess relationship of quantitative US parameters to MRI PDFF and to develop multivariable quantitative US models to detect hepatic steatosis and quantify hepatic fat. Materials and Methods Adults with known NAFLD or who were suspected of having NAFLD were prospectively recruited between August 2015 and February 2019. Participants underwent quantitative US and chemical shift-encoded MRI liver examinations. Liver biopsies were performed if clinically indicated. The correlation between seven quantitative US parameters and MRI PDFF was evaluated. By using leave-one-out cross validation, two quantitative US multivariable models were evaluated: a classifier to differentiate participants with NAFLD versus participants without NAFLD and a fat fraction estimator. Classifier performance was summarized by area under the receiver operating characteristic curve and area under the precision-recall curve. Fat fraction estimator performance was evaluated by correlation, linearity, and bias. Results Included were 102 participants (mean age, 52 years ± 13 [standard deviation]; 53 women), 78 with NAFLD (MRI PDFF ≥ 5%). A two-variable classifier yielded a cross-validated area under the receiver operating characteristic curve of 0.89 (95% confidence interval: 0.82, 0.96) and an area under the precision-recall curve of 0.96 (95% confidence interval: 0.93, 0.99). The cross-validated fat fraction predicted by a two-variable fat fraction estimator was correlated with MRI PDFF (Spearman ρ = 0.82 [P < .001]; Pearson r = 0.76 [P < .001]). The mean bias was 0.02% (P = .97), and 95% limits of agreement were ±12.0%. The predicted fat fraction was linear with MRI PDFF (R 2 = 0.63; slope, 0.69; intercept, 4.3%) for MRI PDFF of 34% or less. Conclusion A multivariable quantitative US approach yielded excellent correlation with MRI proton density fat fraction for hepatic steatosis assessment in nonalcoholic fatty liver disease. © RSNA, 2020 Online supplemental material is available for this article.
| S-EPMC7104700 | biostudies-literature
Project description:Weight loss by ketogenic diet (KD) has gained popularity in management of nonalcoholic fatty liver disease (NAFLD). KD rapidly reverses NAFLD and insulin resistance despite increasing circulating nonesterified fatty acids (NEFA), the main substrate for synthesis of intrahepatic triglycerides (IHTG). To explore the underlying mechanism, we quantified hepatic mitochondrial fluxes and their regulators in humans by using positional isotopomer NMR tracer analysis. Ten overweight/obese subjects received stable isotope infusions of: [D7]glucose, [13C4]β-hydroxybutyrate and [3-13C]lactate before and after a 6-d KD. IHTG was determined by proton magnetic resonance spectroscopy (1H-MRS). The KD diet decreased IHTG by 31% in the face of a 3% decrease in body weight and decreased hepatic insulin resistance (-58%) despite an increase in NEFA concentrations (+35%). These changes were attributed to increased net hydrolysis of IHTG and partitioning of the resulting fatty acids toward ketogenesis (+232%) due to reductions in serum insulin concentrations (-53%) and hepatic citrate synthase flux (-38%), respectively. The former was attributed to decreased hepatic insulin resistance and the latter to increased hepatic mitochondrial redox state (+167%) and decreased plasma leptin (-45%) and triiodothyronine (-21%) concentrations. These data demonstrate heretofore undescribed adaptations underlying the reversal of NAFLD by KD: That is, markedly altered hepatic mitochondrial fluxes and redox state to promote ketogenesis rather than synthesis of IHTG.
| S-EPMC7132133 | biostudies-literature
Project description:Nonalcoholic fatty liver disease (NAFLD) usually takes decades to develop into cirrhosis, which limits the longitudinal study of NAFLD. This work aims at developing a NAFLD-caused cirrhosis model in gerbil and examining the dynamic relationship between hepatic lipid metabolism and cirrhosis. We fed gerbil a high-fat and high-cholesterol diet (HFHCD) for 24 weeks, and recorded the gerbil's phenotype at 3, 6, 9, 12, 15, 18, 21, 24 weeks. The model's pathological process, lipid metabolism, oxidative stress, liver collagen deposition and presence of relevant cytokines were tested and evaluated during the full-time frame of disease onset. The gerbil model can induce non-alcoholic steatohepatitis (NASH) within 9 weeks, and can develop cirrhosis after 21 weeks induction. The model's lipids metabolism disorder is accompanied with the liver damage development. During the NAFLD progression, triglycerides (TG) and free fatty acids (FFA) have presented distinct rise and fall tendency, and the turning points are at the fibrosis stage. Besides that, the ratios of total cholesterol (CHO) to high-density lipoprotein cholesterol (HDL-C) exhibited constant growth tendency, and have a good linear relationship with hepatic stellate cells (HSC) (R2 = 0.802, P < 0.001). The gerbil NAFLD cirrhosis model has been developed and possesses positive correlation between lipids metabolism and cirrhosis. The compelling rise and fall tendency of TG and FFA indicated that the fibrosis progression can lead to impairment in lipoprotein synthesis and engender decreased TG level. CHO/HDL-C ratios can imply the fibrosis progress and be used as a blood indicator for disease prediction and prevention.
| S-EPMC6957964 | biostudies-literature
Project description:BACKGROUND & AIMS:De novo lipogenesis is increased in livers of patients with nonalcoholic steatohepatitis (NASH). Acetyl-coenzyme carboxylase catalyzes the rate-limiting step in this process. We evaluated the safety and efficacy of GS-0976, an inhibitor of acetyl-coenzyme A carboxylase in liver, in a phase 2 randomized placebo-controlled trial of patients with NASH. METHODS:We analyzed data from 126 patients with hepatic steatosis of at least 8%, based on the magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF), and liver stiffness of at least 2.5 kPa, based on magnetic resonance elastography measurement or historical biopsy result consistent with NASH and F1-F3 fibrosis. Patients were randomly assigned (2:2:1) to groups given GS-0976 20 mg, GS-0976 5 mg, or placebo daily for 12 weeks, from August 8, 2016 through July 18, 2017. Measures of hepatic steatosis, stiffness, serum markers of fibrosis, and plasma metabolomics were evaluated. The primary aims were to confirm previous findings and evaluate the relation between dose and efficacy. RESULTS:A relative decrease of at least 30% from baseline in MRI-PDFF (PDFF response) occurred in 48% of patients given GS-0976 20 mg (P = .004 vs placebo), 23% given GS-0976 5 mg (P = .43 vs placebo), and 15% given placebo. Median relative decreases in MRI-PDFF were greater in patients given GS-0976 20 mg (decrease of 29%) than those given placebo (decrease of 8%; P = .002). Changes in magnetic resonance elastography-measured stiffness did not differ among groups, but a dose-dependent decrease in the fibrosis marker tissue inhibitor of metalloproteinase 1 was observed in patients given GS-0976 20 mg. Plasma levels of acylcarnitine species also decreased in patients with a PDFF response given GS-0976 20 mg. GS-0976 was safe, but median relative increases of 11% and 13% in serum levels of triglycerides were observed in patients given GS-0976. CONCLUSIONS:In a randomized placebo-controlled trial of patients with NASH, we found 12-week administration of GS-0976 20 mg decreased hepatic steatosis, selected markers of fibrosis, and liver biochemistry. ClinicalTrials.gov ID NCT02856555.
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Project description:Mitochondria produce the majority of cellular ATP through oxidative phosphorylation, and their capacity to do so is influenced by many factors. Mitochondrial morphology is recently suggested as an important contributor in controlling mitochondrial bioenergetics. Mitochondria divide and fuse continuously, which is affected by environmental factors, including metabolic alterations. Underscoring its bioenergetic influence, altered mitochondrial morphology is reported in tissues of patients and in animal models of metabolic dysfunction. In this study, we found that mitochondrial fission plays a vital role in the progression of nonalcoholic fatty liver disease (NAFLD). The development of hepatic steatosis, oxidative/nitrative stress, and hepatic tissue damage, induced by a high-fat diet, were alleviated in genetically manipulated mice suppressing mitochondrial fission. The alleviation of steatosis was recapitulated in primary hepatocytes with the inhibition of mitochondrial fission. Mechanistically, our study indicates that fission inhibition enhances proton leak under conditions of free fatty acid incubation, implicating bioenergetic change through manipulating mitochondrial fission. Taken together, our results suggest a mechanistic role for mitochondrial fission in the etiology of NAFLD. The efficacy of decreasing mitochondrial fission in the suppression of NAFLD suggests that mitochondrial fission represents a novel target for therapeutic treatment of NAFLD.
| S-EPMC4166723 | biostudies-literature
Project description:UnlabelledNonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children. In order to advance the field of NAFLD, noninvasive imaging methods for measuring liver fat are needed. Advanced magnetic resonance imaging (MRI) has shown great promise for the quantitative assessment of hepatic steatosis but has not been validated in children. Therefore, this study was designed to evaluate the correlation and diagnostic accuracy of MRI-estimated liver proton density fat fraction (PDFF), a biomarker for hepatic steatosis, compared to histologic steatosis grade in children. The study included 174 children with a mean age of 14.0 years. Liver PDFF estimated by MRI was significantly (P < 0.01) correlated (0.725) with steatosis grade. The correlation of MRI-estimated liver PDFF and steatosis grade was influenced by both sex and fibrosis stage. The correlation was significantly (P < 0.01) stronger in girls (0.86) than in boys (0.70). The correlation was significantly (P < 0.01) weaker in children with stage 2-4 fibrosis (0.61) than children with no fibrosis (0.76) or stage 1 fibrosis (0.78). The diagnostic accuracy of commonly used threshold values to distinguish between no steatosis and mild steatosis ranged from 0.69 to 0.82. The overall accuracy of predicting the histologic steatosis grade from MRI-estimated liver PDFF was 56%. No single threshold had sufficient sensitivity and specificity to be considered diagnostic for an individual child.ConclusionsAdvanced magnitude-based MRI can be used to estimate liver PDFF in children, and those PDFF values correlate well with steatosis grade by liver histology. Thus, magnitude-based MRI has the potential for clinical utility in the evaluation of NAFLD, but at this time no single threshold value has sufficient accuracy to be considered diagnostic for an individual child.
| S-EPMC4670559 | biostudies-literature
Project description:During the progression from hepatitis to fibrosis, cirrhosis, and liver failure, the accumulation of stressed/damaged hepatocyte elements associated with liver inflammation is critical. The causes of hepatocyte injuries include viral hepatitis infections, alcoholic hepatitis, and non-alcoholic fatty liver disease. Hepatocyte-derived extracellular vesicles (Hep-EVs) released from stressed/damaged hepatocytes are partly responsible for liver disease progression and liver damage because they activate non-parenchymal cells and infiltrate inflammatory cells within the liver, which are in turn are an important source of EVs. This cell-to-cell signaling is prevalent during inflammation in many liver diseases. Accordingly, special emphasis should be placed on liquid biopsy methods for the long-term monitoring of chronic liver diseases. In the present review, we have highlighted various aspects of current liquid biopsy research into chronic liver diseases. We have also reviewed recent progress on liquid biopsies that focus on cell-free DNA (cfDNA), long non-coding RNA (lncRNA), and the proteins in EVs as potential diagnostic tools and novel therapeutic targets in patients with viral hepatitis, fatty liver steatosis, and alcoholic liver diseases.
| S-EPMC7279404 | biostudies-literature
Project description:Background and Aims The redefinition of metabolic-associated fatty liver disease (MAFLD) from nonalcoholic fatty liver disease (NAFLD) has caused a revolution in clinical practice, and the characteristics of patients with steatosis but not MAFLD remain unclear. The aims were to compare the diagnosis rate of MAFLD in NAFLD using different steatosis methods and explore the features of non-MAFLD–NAFLD and MAFLD–non-NAFLD. Methods A cross-sectional study enrolling consecutive individuals was conducted at three medical centers in southern China from January 2015 to September 2020. Steatosis was evaluated by liver biopsy or magnetic resonance imaging-based proton density fat fraction (MRI-PDFF), ultrasound, controlled attenuation parameter (CAP), and fatty liver index (FLI). Fibrosis was assessed by the NAFLD fibrosis score, transient elastography, or shear wave elastography. Results The study enrolled 14,985 Chinese adults. The agreement of MAFLD and NAFLD diagnoses were 83% for FLI, 95% for ultrasound, 94% for both CAP and MRI-PDFF, and 95% for liver biopsy. The body mass index, blood pressure and lipid levels among non-MAFLD–NAFLD patients were similar metabolic parameters (p>0.05 for all), but not the alanine aminotransferase and the proportion of patients with insulin resistance, which were significantly higher in non-MAFLD–NAFLD with significant fibrosis. Conclusions The new MAFLD definition ruled out 5–17% of NAFLD cases. NAFLD and MAFLD–NAFLD involved more severe metabolic abnormalities than MAFLD and MAFLD–non-NAFLD. Non-MAFLD–NAFLD patients with significant fibrosis had more severe liver injury and increased glycemic dysregulation within the normal range. Attention should be paid to its progression. Graphical abstract
| S-EPMC9634785 | biostudies-literature