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Journal ArticleDOI

Metabolic Phenotyping for Enhanced Mechanistic Stratification of Chronic Hepatitis C-Induced Liver Fibrosis

TL;DR: The findings suggest that modeling against a continuous ELF-derived score of fibrosis provides a more robust assessment of the metabolic changes associated with fibrosis than modeling against the categorical METAVIR score.
About: This article is published in The American Journal of Gastroenterology.The article was published on 2015-01-01. It has received 31 citations till now.
Citations
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Journal ArticleDOI
TL;DR: In this article, the compositional and functional changes in the gut microbiota in early stage chronic hepatitis B (CHB) patients suggest the potential contributions of gut microbiota to the progression of CHB, and thus provide new insight into gut microbiota-targeted interventions to improve the prognosis of this disease.
Abstract: Chronic hepatitis B (CHB) is a global epidemic disease that results from hepatitis B virus (HBV) infection and may progress to severe liver failure, including liver fibrosis, cirrhosis and hepatocellular carcinoma. Previous evidence has indicated that the dysbiosis of gut microbiota occurs after liver virus infection and is associated with severe liver disease. The aim of this study is to elucidate the compositional and functional characteristics of the gut microbiota in early-stage CHB and to understand their influence on disease progression. We investigated the gut microbial composition of stool samples from 85 CHB patients with low Child-Pugh scores and 22 healthy controls using the Illumina MiSeq sequencing platform. Furthermore, the serum metabolome of 40 subjects was measured by gas chromatography mass spectrometry. Compared with the controls, significant alteration in the gut microbiota was observed in the CHB patients; 5 operational taxonomic units (OTUs) belonging to Actinomyces, Clostridium sensu stricto, unclassified Lachnospiraceae and Megamonas were increased, and 27 belonging to Alistipes, Asaccharobacter, Bacteroides, Butyricimonas, Clostridium IV, Escherichia/Shigella, Parabacteroides, Ruminococcus, unclassified Bacteria, unclassified Clostridiales, Unclassified Coriobacteriaceae, unclassified Enterobacteriaceae, unclassified Lachnospiraceae and unclassified Ruminococcaceae were decreased. The inferred metagenomic information of gut microbiota in CHB showed 21 enriched and 17 depleted KEGG level-2 pathways. Four OTUs, OTU38 (Streptococcus), OTU124 (Veillonella), OTU224 (Streptococcus), and OTU55 (Haemophilus), had high correlations with hosts' hepatic function indices and 10 serum metabolites, including phenylalanine and tyrosine, which are aromatic amino acids that play pathogenic roles in liver disease. In particular, these 4 OTUs were significantly higher in patients with higher Child-Pugh scores, who also showed diminished phenylalanine and tryptophan metabolisms in the inferred gut metagenomic functions. These compositional and functional changes in the gut microbiota in early-stage CHB patients suggest the potential contributions of gut microbiota to the progression of CHB, and thus provide new insight into gut microbiota-targeted interventions to improve the prognosis of this disease.

119 citations


Cites background from "Metabolic Phenotyping for Enhanced ..."

  • ...…associated with both the clinical indices and the accumulation of 10 serum metabolites, especially L-phenylalanine and L-tyrosine, which are AAAs that play a pathogenic role in liver disease (Morgan et al., 1978; Heberer et al., 1980; Dejong et al., 2007; Gao et al., 2015; Sands et al., 2015)....

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  • ...Using high-throughput sequencing and multi-omics strategies, we further emphasized the potential role of the gut-liver axis in the progression of liver disease through the abnormal accumulation of AAAs in the serum (Morgan et al., 1978; Heberer et al., 1980; Dejong et al., 2007; Gao et al., 2015; Sands et al., 2015)....

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  • ...Particularly, four OTUs, OTU38 (Streptococcus), OTU124 (Veillonella), OTU224 (Streptococcus) and OTU55 (Haemophilus), were closely associated with both the clinical indices and the accumulation of 10 serum metabolites, especially L-phenylalanine and L-tyrosine, which are AAAs that play a pathogenic role in liver disease (Morgan et al., 1978; Heberer et al., 1980; Dejong et al., 2007; Gao et al., 2015; Sands et al., 2015)....

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  • ...Unbalanced amino acid metabolism, especially high serum levels of aromatic amino acids (AAAs), including phenylalanine, tyrosine and tryptophan, is a major phenomenon indicating functional disorder in liver tissue and is critical in the pathogenesis of chronic liver diseases, including liver fibrosis, cirrhosis and HCC (Morgan et al., 1978; Heberer et al., 1980; Dejong et al., 2007; Gao et al., 2015; Sands et al., 2015)....

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  • ...…and tryptophan, is a major phenomenon indicating functional disorder in liver tissue and is critical in the pathogenesis of chronic liver diseases, including liver fibrosis, cirrhosis and HCC (Morgan et al., 1978; Heberer et al., 1980; Dejong et al., 2007; Gao et al., 2015; Sands et al., 2015)....

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Journal ArticleDOI
TL;DR: The background physics the busy clinician needs to know before considering using the technique as an investigative tool is discussed.
Abstract: Magnetic resonance spectroscopy (MRS) provides a non-invasive ‘window’ on biochemical processes within the body. Its use is no longer restricted to the field of research, with applications in clinical practice increasingly common. MRS can be conducted at high magnetic field strengths (typically 11–14 T) on body fluids, cell extracts and tissue samples, with new developments in whole-body magnetic resonance imaging (MRI) allowing clinical MRS at the end of a standard MRI examination, obtaining functional information in addition to anatomical information. We discuss the background physics the busy clinician needs to know before considering using the technique as an investigative tool. Some potential applications of hepatic and cerebral MRS in chronic liver disease are also discussed.

71 citations

Journal ArticleDOI
TL;DR: The applications reviewed here demonstrated that GlycA was potentially a key biomarker in a wide range of diseases such as cancer, metabolic diseases, cardiovascular risk, and chronic inflammatory diseases among others and launches an encouraging new paradigm for its future incorporation in clinical diagnosis.
Abstract: Several studies suggest that variations in the concentration of plasma glycoproteins can influence cellular changes in a large number of diseases. In recent years, proton nuclear magnetic resonance (1H-NMR) has played a major role as an analytical tool for serum and plasma samples. In recent years, there is an increasing interest in the characterization of glycoproteins through 1H-NMR in order to search for reliable and robust biomarkers of disease. The objective of this review was to examine the existing studies in the literature related to the study of glycoproteins from an analytical and clinical point of view. There are currently several techniques to characterize circulating glycoproteins in serum or plasma, but in this review, we focus on 1H-NMR due to its great robustness and recent interest in its translation to the clinical setting. In fact, there is already a marker in H-NMR representing the acetyl groups of the glycoproteins, GlycA, which has been increasingly studied in clinical studies. A broad search of the literature was performed showing a general consensus that GlycA is a robust marker of systemic inflammation. The results also suggested that GlycA better captures systemic inflammation even more than C-reactive protein (CRP), a widely used classical inflammatory marker. The applications reviewed here demonstrated that GlycA was potentially a key biomarker in a wide range of diseases such as cancer, metabolic diseases, cardiovascular risk, and chronic inflammatory diseases among others. The profiling of glycoproteins through 1H-NMR launches an encouraging new paradigm for its future incorporation in clinical diagnosis.

49 citations

Journal ArticleDOI
TL;DR: A rapid decrease in non-invasive fibrosis markers measured by ELF-scores and FibroScan in hepatitis C-infected patients receiving sofosbuvir treatment is observed, indicating improvement of the dynamics of liver fibrosis.

47 citations

Journal ArticleDOI
01 Mar 2019
TL;DR: The selection of standard thresholds for detection and prognosis of liver fibrosis is described and their performance reported and should prove useful in both interpreting and explaining test results and when considering the relationship of ELF score to Ishak stage in the context of monitoring.
Abstract: Introduction: Noninvasive tests are increasingly used to assess liver fibrosis and determine prognosis but suggested test thresholds vary. We describe the selection of standardized thresholds for the Enhanced Liver Fibrosis (ELF) test for the detection of liver fibrosis and for prognostication in chronic liver disease. Methods: A Delphi method was used to identify thresholds for the ELF test to predict histological liver fibrosis stages, including cirrhosis, using data derived from 921 patients in the EUROGOLF cohort. These thresholds were then used to determine the prognostic performance of ELF in a subset of 457 patients followed for a mean of 5 years. Results: The Delphi panel selected sensitivity of 85% for the detection of fibrosis and >95% specificity for cirrhosis. The corresponding thresholds were 7.7, 9.8, and 11.3. Eighty-five percent of patients with mild or worse fibrosis had an ELF score ≥7.7. The sensitivity for cirrhosis of ELF ≥9.8 was 76%. ELF ≥11.3 was 97% specific for cirrhosis. ELF scores show a near-linear relationship with Ishak fibrosis stages. Relative to the Conclusion: The selection of standard thresholds for detection and prognosis of liver fibrosis is described and their performance reported. These thresholds should prove useful in both interpreting and explaining test results and when considering the relationship of ELF score to Ishak stage in the context of monitoring.

43 citations

References
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Journal ArticleDOI
TL;DR: The calculation of the q‐value is discussed, the pFDR analogue of the p‐value, which eliminates the need to set the error rate beforehand as is traditionally done, and can yield an increase of over eight times in power compared with the Benjamini–Hochberg FDR method.
Abstract: Summary. Multiple-hypothesis testing involves guarding against much more complicated errors than single-hypothesis testing. Whereas we typically control the type I error rate for a single-hypothesis test, a compound error rate is controlled for multiple-hypothesis tests. For example, controlling the false discovery rate FDR traditionally involves intricate sequential p-value rejection methods based on the observed data. Whereas a sequential p-value method fixes the error rate and estimates its corresponding rejection region, we propose the opposite approach—we fix the rejection region and then estimate its corresponding error rate. This new approach offers increased applicability, accuracy and power. We apply the methodology to both the positive false discovery rate pFDR and FDR, and provide evidence for its benefits. It is shown that pFDR is probably the quantity of interest over FDR. Also discussed is the calculation of the q-value, the pFDR analogue of the p-value, which eliminates the need to set the error rate beforehand as is traditionally done. Some simple numerical examples are presented that show that this new approach can yield an increase of over eight times in power compared with the Benjamini–Hochberg FDR method.

5,414 citations

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TL;DR: This research presents a meta-analysis of Anatomia e Istologia Patologica, a large quantity of which has never before been published in a peer-reviewed journal, which aims to provide real-time information about the immune system’s response to disease.

4,655 citations

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TL;DR: New database visualization tools and new data content have been added or enhanced to the HMDB, which includes better spectral viewing tools, more powerful chemical substructure searches, an improved chemical taxonomy and better, more interactive pathway maps.
Abstract: The Human Metabolome Database (HMDB) (www.hmdb.ca) is a resource dedicated to providing scientists with the most current and comprehensive coverage of the human metabolome. Since its first release in 2007, the HMDB has been used to facilitate research for nearly 1000 published studies in metabolomics, clinical biochemistry and systems biology. The most recent release of HMDB (version 3.0) has been significantly expanded and enhanced over the 2009 release (version 2.0). In particular, the number of annotated metabolite entries has grown from 6500 to more than 40,000 (a 600% increase). This enormous expansion is a result of the inclusion of both 'detected' metabolites (those with measured concentrations or experimental confirmation of their existence) and 'expected' metabolites (those for which biochemical pathways are known or human intake/exposure is frequent but the compound has yet to be detected in the body). The latest release also has greatly increased the number of metabolites with biofluid or tissue concentration data, the number of compounds with reference spectra and the number of data fields per entry. In addition to this expansion in data quantity, new database visualization tools and new data content have been added or enhanced. These include better spectral viewing tools, more powerful chemical substructure searches, an improved chemical taxonomy and better, more interactive pathway maps. This article describes these enhancements to the HMDB, which was previously featured in the 2009 NAR Database Issue. (Note to referees, HMDB 3.0 will go live on 18 September 2012.).

2,656 citations

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TL;DR: It is revealed that certain features of major importance in assessing disease activity show significant observer variation, including the acceptable degree of concordance of the Knodell index, whereas other numerical items displayed substantial observer variations.

1,887 citations

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TL;DR: Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection is found to be low and consistent with previous studies.

1,839 citations