Accuracy of proton magnetic resonance for diagnosing non-alcoholic steatohepatitis: a meta-analysis.
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SUBMITTER: Kim TH
PROVIDER: S-EPMC6802098 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundMagnetic resonance imaging-derived measures of liver fat and volume are emerging as accurate, non-invasive imaging biomarkers in non-alcoholic steatohepatitis (NASH). Little is known about these measures in relation to histology longitudinally.AimTo examine any relationship between MRI-derived proton-density fat-fraction (PDFF), total liver volume (TLV), total liver fat index (TLFI), vs. histology in a NASH trial.MethodsThis is a secondary analysis of a 24-week randomised, double-blind, placebo-controlled trial of 50 patients with biopsy-proven NASH randomised to oral ezetimibe 10 mg daily (n = 25) vs. placebo (n = 25). Baseline and post-treatment anthropometrics, biochemical profiling, MRI and biopsies were obtained.ResultsBaseline mean PDFF correlated strongly with TLFI (Spearman's ρ = 0.94, n = 45, P < 0.0001) and had good correlation with TLV (ρ = 0.57, n = 45, P < 0.0001). Mean TLV correlated strongly with TLFI (ρ = 0.78, n = 45, P < 0.0001). After 24 weeks, PDFF remained strongly correlated with TLFI (ρ = 0.94, n = 45, P < 0.0001), maintaining good correlation with TLV (ρ = 0.51, n = 45, P = 0.0004). TLV remained strongly correlated with TLFI (ρ = 0.74, n = 45, P < 0.0001). Patients with Grade 1 vs. 3 steatosis had lower PDFF, TLV, and TLFI (P < 0.0001, P = 0.0003, P < 0.0001 respectively). Regression analysis of changes in MRI-PDFF vs. TLV indicates that 10% reduction in MRI-PDFF predicts 257 mL reduction in TLV.ConclusionsThe MRI-PDFF and TLV strongly correlated with TLFI. Decreases in steatosis were associated with an improvement in hepatomegaly. Lower values of these measures reflect lower histologic steatosis grades. MRI-derived measures of liver fat and volume may be used as dynamic and more responsive imaging biomarkers in a NASH trial, than histology.
| S-EPMC5346270 | biostudies-literature
Project description:IntroductionAssociation between elevated cytokeratin 18 (CK-18) levels and hepatocyte death has made circulating CK-18 a candidate biomarker to differentiate non-alcoholic fatty liver from non-alcoholic steatohepatitis (NASH). Yet studies produced variable diagnostic performance. We aimed to provide summary estimates with increased precision for the accuracy of CK-18 (M30, M65) in detecting NASH and fibrosis among non-alcoholic fatty liver disease (NAFLD) adults.MethodsWe searched five databases to retrieve studies evaluating CK-18 against a liver biopsy in NAFLD adults. Reference screening, data extraction and quality assessment (QUADAS-2) were independently conducted by two authors. Meta-analyses were performed for five groups based on the CK-18 antigens and target conditions, using one of two methods: linear mixed-effects multiple thresholds model or bivariate logit-normal random-effects model.ResultsWe included 41 studies, with data on 5,815 participants. A wide range of disease prevalence was observed. No study reported a pre-defined cut-off. Thirty of 41 studies provided sufficient data for inclusion in any of the meta-analyses. Summary AUC [95% CI] were: 0.75 [0.69-0.82] (M30) and 0.82 [0.69-0.91] (M65) for NASH; 0.73 [0.57-0.85] (M30) for fibrotic NASH; 0.68 (M30) for significant (F2-4) fibrosis; and 0.75 (M30) for advanced (F3-4) fibrosis. Thirteen studies used CK-18 as a component of a multimarker model.ConclusionsFor M30 we found lower diagnostic accuracy to detect NASH compared to previous meta-analyses, indicating a limited ability to act as a stand-alone test, with better performance for M65. Additional external validation studies are needed to obtain credible estimates of the diagnostic accuracy of multimarker models.
| S-EPMC7485872 | biostudies-literature
Project description:The mechanisms underlying the progression of non-alcoholic steatohepatitis (NASH) are not completely elucidated. In this study we have integrated gene expression profiling of liver biopsies of NASH patients with translational studies in a mouse model of steatohepatitis and with pharmacological interventions in isolated hepatocytes to identify a novel mechanism implicated in the pathogenesis of NASH. By using high-density oligonucleotide microarray analysis we identified a significant enrichment of known genes involved in the multi-step catalysis of long chain polyunsaturated fatty acids, including delta-5 and 6 desaturases. A combined inhibitor of delta-5 and delta-6 desaturases significantly reduced intracellular lipid accumulation and inflammatory gene expression in isolated hepatocytes. Gas chromatography analysis revealed impaired delta-5 desaturase activity toward the omega-3 pathway in livers from mice with high-fat diet (HFD)-induced NASH. Consistently, restoration of omega-3 index in transgenic fat-1 mice expressing an omega-3 desaturase, which allows the endogenous conversion of omega-6 into omega-3 fatty acids, produced a significant reduction in hepatic insulin resistance, hepatic steatosis, macrophage infiltration and necroinflammatory liver injury, accompanied by attenuated expression of genes involved in inflammation, fatty acid uptake and lipogenesis. These results were comparable to those obtained in a group of mice receiving a HFD supplemented with EPA/DHA. Of interest, hepatocytes from fat-1 mice or supplemented with EPA exhibited synergistic anti-steatotic and anti-inflammatory actions with the delta-5/ delta-6 inhibitor. Conclusion: These findings indicate that both endogenous and exogenous restoration of the hepatic balance between omega-6 and omega-3 fatty acids and/or modulation of desaturase activities exert preventive actions in NASH. The complete database comprised the expression measurements of 18185 genes for liver sample groups: 8 non-alcoholic steatohepatitis (NASH ) and 7 control samples. This dataset is part of the TransQST collection.
2013-04-02 | E-GEOD-37031 | biostudies-arrayexpress
Project description:This paper is based upon the "Charles Lieber Satellite Symposia" organized by Manuela G. Neuman at the Research Society on Alcoholism (RSA) Annual Meetings, 2013 and 2014. The present review includes pre-clinical, translational and clinical research that characterize alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH). In addition, a literature search in the discussed area was performed. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD. The liver biopsy can confirm the etiology of NASH or alcoholic steatohepatitis (ASH) and assess structural alterations of cells, their organelles, as well as inflammatory activity. Three histological stages of ALD are simple steatosis, ASH, and chronic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes such as cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Alcohol mediated hepatocarcinogenesis, immune response to alcohol in ASH, as well as the role of other risk factors such as its co-morbidities with chronic viral hepatitis in the presence or absence of human immunodeficiency virus are discussed. Dysregulation of hepatic methylation, as result of ethanol exposure, in hepatocytes transfected with hepatitis C virus (HCV), illustrates an impaired interferon signaling. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota are suggested. The clinical aspects of NASH, as part of metabolic syndrome in the aging population, are offered. The integrative symposia investigate different aspects of alcohol-induced liver damage and possible repair. We aim to (1) determine the immuno-pathology of alcohol-induced liver damage, (2) examine the role of genetics in the development of ASH, (3) propose diagnostic markers of ASH and NASH, (4) examine age differences, (5) develop common research tools to study alcohol-induced effects in clinical and pre-clinical studies, and (6) focus on factors that aggravate severity of organ-damage. The intention of these symposia is to advance the international profile of the biological research on alcoholism. We also wish to further our mission of leading the forum to progress the science and practice of translational research in alcoholism.
| S-EPMC4696068 | biostudies-literature
Project description:We aimed to determine the performance of surveillance abbreviated magnetic resonance imaging (AMRI) for detecting hepatocellular carcinoma (HCC), and to compare the performance of surveillance AMRI according to different protocols. Original research studies reporting the performance of surveillance AMRI for the detection of HCC were identified in MEDLINE, EMBASE, and Cochrane databases. The pooled sensitivity and specificity of surveillance AMRI were calculated using a hierarchical model. The pooled sensitivity and specificity of contrast-enhanced hepatobiliary phase (HBP)-AMRI and non-contrast (NC)-AMRI were calculated and compared using bivariate meta-regression. Ten studies, including 1547 patients, reported the accuracy of surveillance AMRI. The pooled sensitivity and specificity of surveillance AMRI for detecting any-stage HCC were 86% (95% confidence interval (CI), 80-90%; I2 = 0%) and 96% (95% CI, 93-98%; I2 = 80.5%), respectively. HBP-AMRI showed a significantly higher sensitivity for detecting HCC than NC-AMRI (87% vs. 82%), but significantly lower specificity (93% vs. 98%) (p = 0.03). Study quality and MRI magnet field strength were factors significantly associated with study heterogeneity (p ≤ 0.01). In conclusion, surveillance AMRI showed good overall diagnostic performance for detecting HCC. HBP-AMRI had significantly higher sensitivity for detecting HCC than NC-AMRI, but lower specificity.
| S-EPMC8231787 | biostudies-literature
Project description:BACKGROUND:This study was performed to systematically evaluate the accuracy of magnetic resonance elastography (MRE) in staging of liver fibrosis in non-alcoholic fatty liver disease (NAFLD). METHODS:PUBMED, EMBASE, Web of Science, CNKI, Cochrane Library database were searched from January 2008 to December 2018 for studies related to MRE in the diagnosis of NAFLD liver fibrosis. The quality of the included literature was assessed by Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The pooled sensitivity, the pooled specificity, and area under the receiver operating characteristic curve (AUROC) value was performed by STATA 14.0 software. RESULTS:A total of 12 studies were included, involving 910 patients. The pooled sensitivity and specificity of each group were 0.77 (95%CI 0.69-0.83) and 0.90 (95%CI 0.83-0.94) for F???1 (mild liver fibrosis), 0.87 (95%CI 0.74-0.94) and 0.86 (95%CI 0.71-0.94) for F???2 (significant liver fibrosis), 0.89 (95%CI 0.81-0.94) and 0.84 (95%CI 0.63-0.94) for F???3(severe liver fibrosis), 0.94 (95%CI 0.85-0.98) and 0.75 (95%CI 0.35-0.94) for F???4 (early cirrhosis), respectively. The area under the summary receiver operating characteristic (SROC) curve was 0.89, 0.93, 0.93, and 0.95, respectively. CONCLUSIONS:MRE has high accuracy in the diagnosis of hepatic fibrosis staging in patients with NAFLD.
| S-EPMC7137512 | biostudies-literature
Project description:While metabolic syndrome and alcohol consumption are the two main causes of chronic liver disease, one of the two conditions is often predominant, with the other acting as a cofactor of morbimortality. It has been shown that obesity and alcohol act synergistically to increase the risk of fibrosis progression, hepatic carcinogenesis and mortality, while genetic polymorphisms can strongly influence disease progression. Based on common pathogenic pathways, there are several potential targets that could be used to treat both diseases; based on the prevalence and incidence of these diseases, new therapies and clinical trials are needed urgently.
| S-EPMC7267467 | biostudies-literature
Project description:BACKGROUND & AIMS:With the rising prevalence of non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) non-invasive tools obtaining pathomechanistic insights to improve risk stratification are urgently needed. We therefore explored high- and ultra-high-field magnetic resonance spectroscopy (MRS) to obtain novel mechanistic and diagnostic insights into alterations of hepatic lipid, cell membrane and energy metabolism across the spectrum of NAFLD. METHODS:MRS and liver biopsy were performed in 30 NAFLD patients with NAFL (n=8) or NASH (n=22). Hepatic lipid content and composition were measured using 3-Tesla proton (1 H)-MRS. 7-Tesla phosphorus (31 P)-MRS was applied to determine phosphomonoester (PME) including phosphoethanolamine (PE), phosphodiester (PDE) including glycerophosphocholine (GPC), phosphocreatine (PCr), nicotinamide adenine dinucleotide phosphate (NADPH), inorganic phosphate (Pi), ?-ATP and total phosphorus (TP). Saturation transfer technique was used to quantify hepatic ATP flux. RESULTS:Hepatic steatosis in 1 H-MRS highly correlated with histology (P<.001) showing higher values in NASH than NAFL (P<.001) without differences in saturated or unsaturated fatty acid indices. PE/TP ratio increased with advanced fibrosis (F3/4) (P=.002) whereas GPC/PME+PDE decreased (P=.05) compared to no/mild fibrosis (F0-2). ?-ATP/TP was lower in advanced fibrosis (P=.049), while PCr/TP increased (P=.01). NADPH/TP increased with higher grades of ballooning (P=.02). Pi-to-ATP exchange rate constant (P=.003) and ATP flux (P=.001) were lower in NASH than NAFL. CONCLUSIONS:Ultra-high-field MRS, especially saturation transfer technique uncovers changes in energy metabolism including dynamic ATP flux in inflammation and fibrosis in NASH. Non-invasive profiling by MRS appears feasible and may assist further mechanistic and therapeutic studies in NAFLD/NASH.
| S-EPMC5638103 | biostudies-literature
Project description:ObjectiveTo establish the diagnostic accuracy of magnetic resonance imaging (MRI) as an auxiliary means for the diagnosis of oral cancer through a systematic review and meta-analysis.MethodsAn exhaustive search of publications from 1986 to 2016 was performed of Medline, Embase and Cochrane (and related databases), including grey literature. Primary diagnostic accuracy studies that assessed oral cancer (target condition) using MRI (index test) were included. Diagnostic threshold, sensitivity and meta-regression analyses were performed. A meta-analysis was performed using Meta-DiSc® v. 1.4 software.ResultsA total of 24 primary studies were assessed, comprising 1,403 oral cancer lesions. Nine studies used diffusion-weighted MRI, with a diagnostic odds ratio (DOR) of 30.7 (95% confidence interval [CI]: 12.7-74.3) and area under the curve (AUC) of 0.917 (95% CI: 0.915-0.918); seven studies used dynamic contrast-enhanced MRI, with a DOR of 48.1 (95%CI: 22.4-103.2) and AUC of 0.936 (95% CI: 0.934-0.937); and 13 studies used traditional MRI, with a DOR of 23.9 (95%CI: 13.2-43.3) and AUC of 0.894 (95% CI: 0.894-0.895). Meta-regression analysis indicated that the magnetic field strength may have influenced the heterogeneity of the results obtained (p = 0.0233) using traditional MRI. Sensitivity analysis revealed a discrete reduction of inconsistency in some subgroups.ConclusionThe three types of MRI assessed exhibited satisfactory accuracy compared to biopsy. Considering the relevance of early treatment and screening and that better health care results in improved survival rates and quality of life for oral cancer patients, we suggest the use of MRI as a part of the pre-treatment and monitoring protocol at public health services.
| S-EPMC5443513 | biostudies-literature
Project description:Thiazolidinediones (TZDs) have been used in the treatment of non-alcoholic steatohepatitis (NASH). However, the magnitude of treatment response associated with TZDs in improving liver histology in NASH has not been quantified systematically.To conduct a meta-analysis of randomised, placebo-controlled clinical trials (RPCTs) using pioglitazone and rosiglitazone in the treatment of NASH.Pubmed/MEDLINE and Cochrane Central Register of Controlled Trials 2010 were searched until September 2010 and four RPCTs were identified. Peto odds ratios (ORs) and their respective 95% confidence intervals (CIs) were used to assess the efficacy of TZDs in improving liver histological parameters.Four good quality RPCTs derived from three continents were included. The meta-analysis showed that TZDs (n = 169) were significantly better than placebo (n = 165) in improving ballooning degeneration, lobular inflammation and steatosis with combined ORs of 2.11 (95% CI, 1.33-3.36), 2.58 (95% CI, 1.68-3.97) and 3.39 (95% CI, 2.19-5.25) respectively. The improvement in combined necroinflammation with TZD (n = 58) vs. placebo (n = 52) was also statistically significant (combined OR 6.52[95% CI, 3.03-14.06]), but improvement in fibrosis was not. When pioglitazone (n = 137) was analysed alone, the improvement in fibrosis with pioglitazone (n = 137) vs. placebo (n = 134) (combined OR 1.68 [95% CI, 1.02-2.77]) was statistically significant. The total body fat slightly decreased in the control, while it markedly and highly significantly increased with TZD treatment.Thiazolidinediones significantly improve ballooning degeneration, lobular inflammation, steatosis and combined necroinflammation in patients with NASH. Pioglitazone may improve fibrosis. Larger randomised, placebo-controlled clinical trials are needed to examine the efficacy of thiazolidinediones in improving NASH fibrosis.
| S-EPMC3488596 | biostudies-literature