Serum metabolomic profile and potential biomarkers for severity of fibrosis in nonalcoholic fatty liver disease

Background Biomarker for usefulness in diagnosing advanced fibrosis in nonalcoholic fatty liver disease (NAFLD) is expected. In order to discover novel biomarkers for NAFLD and its pathogenesis, we performed matabolomics screening. Methods (1) The initial cohort was 44 NAFLD patients. (2) This valid...

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Veröffentlicht in:Journal of gastroenterology 2013-12, Vol.48 (12), p.1392-1400
Hauptverfasser: Tokushige, Katsutoshi, Hashimoto, Etsuko, Kodama, Kazuhisa, Tobari, Maki, Matsushita, Noriko, Kogiso, Tomomi, Taniai, Makiko, Torii, Nobuyuki, Shiratori, Keiko, Nishizaki, Yasuhiro, Ohga, Takushi, Ohashi, Yoshiaki, Sato, Takaya
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container_end_page 1400
container_issue 12
container_start_page 1392
container_title Journal of gastroenterology
container_volume 48
creator Tokushige, Katsutoshi
Hashimoto, Etsuko
Kodama, Kazuhisa
Tobari, Maki
Matsushita, Noriko
Kogiso, Tomomi
Taniai, Makiko
Torii, Nobuyuki
Shiratori, Keiko
Nishizaki, Yasuhiro
Ohga, Takushi
Ohashi, Yoshiaki
Sato, Takaya
description Background Biomarker for usefulness in diagnosing advanced fibrosis in nonalcoholic fatty liver disease (NAFLD) is expected. In order to discover novel biomarkers for NAFLD and its pathogenesis, we performed matabolomics screening. Methods (1) The initial cohort was 44 NAFLD patients. (2) This validation cohort was 105 NAFLD patients, 26 primary biliary cirrhosis (PBC) patients, and 48 healthy controls. Using capillary electrophoresis and liquid chromatography with mass spectrometry, we analyzed low molecular weight metabolites in these groups. Results 1. In the initial cohort, we found 28 metabolites associated with advanced fibrosis. Among them, 4 sulfated steroids showed the greatest difference. A decrease of dehydroepiandrosterone sulfate (DHEA-S) and 5α-androstan-3β ol-17-one sulfate (etiocholanolone-S) was observed with the progression of fibrosis. Furthermore, 16 hydroxydehydroepiandrosterone sulfate (16-OH-DHEA-S) increased with the progression of fibrosis. 2. In the validation cohort, the decrease of DHEA-S and etiocholanolone-S, as well as the increase of 16-OH-DHEA-S, with the progression of fibrosis was confirmed. The 16-OH-DHEA-S/DHEA-S ratio and 16-OH-DHEA-S/etiocholanolone-S ratio were even more strongly associated with the grade of fibrosis. Among PBC patients, 16-OH-DHEA-S tended to be higher in stages 3 and 4 than in stages 1 and 2. However, levels of DHEA-S, etiocholanolone-S, and the two ratios were not associated with the stage of PBC. Conclusion Several metabolic products were found to be biomarkers of fibrosis in NAFLD and could also be useful for diagnosis of this condition. Our findings suggested disturbance of hormone metabolism in NAFLD and might lead to the development of new therapy.
doi_str_mv 10.1007/s00535-013-0766-5
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In order to discover novel biomarkers for NAFLD and its pathogenesis, we performed matabolomics screening. Methods (1) The initial cohort was 44 NAFLD patients. (2) This validation cohort was 105 NAFLD patients, 26 primary biliary cirrhosis (PBC) patients, and 48 healthy controls. Using capillary electrophoresis and liquid chromatography with mass spectrometry, we analyzed low molecular weight metabolites in these groups. Results 1. In the initial cohort, we found 28 metabolites associated with advanced fibrosis. Among them, 4 sulfated steroids showed the greatest difference. A decrease of dehydroepiandrosterone sulfate (DHEA-S) and 5α-androstan-3β ol-17-one sulfate (etiocholanolone-S) was observed with the progression of fibrosis. Furthermore, 16 hydroxydehydroepiandrosterone sulfate (16-OH-DHEA-S) increased with the progression of fibrosis. 2. In the validation cohort, the decrease of DHEA-S and etiocholanolone-S, as well as the increase of 16-OH-DHEA-S, with the progression of fibrosis was confirmed. The 16-OH-DHEA-S/DHEA-S ratio and 16-OH-DHEA-S/etiocholanolone-S ratio were even more strongly associated with the grade of fibrosis. Among PBC patients, 16-OH-DHEA-S tended to be higher in stages 3 and 4 than in stages 1 and 2. However, levels of DHEA-S, etiocholanolone-S, and the two ratios were not associated with the stage of PBC. Conclusion Several metabolic products were found to be biomarkers of fibrosis in NAFLD and could also be useful for diagnosis of this condition. Our findings suggested disturbance of hormone metabolism in NAFLD and might lead to the development of new therapy.</description><identifier>ISSN: 0944-1174</identifier><identifier>EISSN: 1435-5922</identifier><identifier>DOI: 10.1007/s00535-013-0766-5</identifier><identifier>PMID: 23478936</identifier><language>eng</language><publisher>Tokyo: Springer Japan</publisher><subject>Abdominal Surgery ; Adult ; Aged ; Aged, 80 and over ; Biliary Tract ; Biological markers ; Biomarkers - metabolism ; Case-Control Studies ; Chromatography, Liquid - methods ; Cohort Studies ; Colorectal Surgery ; Dehydroepiandrosterone ; Disease Progression ; Electrophoresis, Capillary - methods ; Fatty liver ; Fatty Liver - diagnosis ; Fatty Liver - metabolism ; Fatty Liver - physiopathology ; Female ; Fibrosis ; Gastroenterology ; Hepatology ; Hormones, Sex ; Humans ; Liquid chromatography ; Liver cirrhosis ; Liver Cirrhosis - diagnosis ; Liver Cirrhosis - metabolism ; Liver Cirrhosis - physiopathology ; Liver Cirrhosis, Biliary - diagnosis ; Liver Cirrhosis, Biliary - metabolism ; Liver Cirrhosis, Biliary - physiopathology ; Male ; Mass spectrometry ; Mass Spectrometry - methods ; Medicine ; Medicine &amp; Public Health ; Metabolites ; Metabolomics - methods ; Middle Aged ; Non-alcoholic Fatty Liver Disease ; Original Article—Liver ; Original —Liver, Pancreas, and Biliary Tract ; Pancreas ; Severity of Illness Index ; Sulfates ; Surgical Oncology ; Type 2 diabetes</subject><ispartof>Journal of gastroenterology, 2013-12, Vol.48 (12), p.1392-1400</ispartof><rights>The Author(s) 2013</rights><rights>COPYRIGHT 2013 Springer</rights><rights>Springer Japan 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c627t-ebacb68fb32fc0ba28b22b454a1809868bf90f39efd51c0dc609ea0e3c2d302c3</citedby><cites>FETCH-LOGICAL-c627t-ebacb68fb32fc0ba28b22b454a1809868bf90f39efd51c0dc609ea0e3c2d302c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00535-013-0766-5$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00535-013-0766-5$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,315,781,785,886,27928,27929,41492,42561,51323</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23478936$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tokushige, Katsutoshi</creatorcontrib><creatorcontrib>Hashimoto, Etsuko</creatorcontrib><creatorcontrib>Kodama, Kazuhisa</creatorcontrib><creatorcontrib>Tobari, Maki</creatorcontrib><creatorcontrib>Matsushita, Noriko</creatorcontrib><creatorcontrib>Kogiso, Tomomi</creatorcontrib><creatorcontrib>Taniai, Makiko</creatorcontrib><creatorcontrib>Torii, Nobuyuki</creatorcontrib><creatorcontrib>Shiratori, Keiko</creatorcontrib><creatorcontrib>Nishizaki, Yasuhiro</creatorcontrib><creatorcontrib>Ohga, Takushi</creatorcontrib><creatorcontrib>Ohashi, Yoshiaki</creatorcontrib><creatorcontrib>Sato, Takaya</creatorcontrib><title>Serum metabolomic profile and potential biomarkers for severity of fibrosis in nonalcoholic fatty liver disease</title><title>Journal of gastroenterology</title><addtitle>J Gastroenterol</addtitle><addtitle>J Gastroenterol</addtitle><description>Background Biomarker for usefulness in diagnosing advanced fibrosis in nonalcoholic fatty liver disease (NAFLD) is expected. In order to discover novel biomarkers for NAFLD and its pathogenesis, we performed matabolomics screening. Methods (1) The initial cohort was 44 NAFLD patients. (2) This validation cohort was 105 NAFLD patients, 26 primary biliary cirrhosis (PBC) patients, and 48 healthy controls. Using capillary electrophoresis and liquid chromatography with mass spectrometry, we analyzed low molecular weight metabolites in these groups. Results 1. In the initial cohort, we found 28 metabolites associated with advanced fibrosis. Among them, 4 sulfated steroids showed the greatest difference. A decrease of dehydroepiandrosterone sulfate (DHEA-S) and 5α-androstan-3β ol-17-one sulfate (etiocholanolone-S) was observed with the progression of fibrosis. Furthermore, 16 hydroxydehydroepiandrosterone sulfate (16-OH-DHEA-S) increased with the progression of fibrosis. 2. In the validation cohort, the decrease of DHEA-S and etiocholanolone-S, as well as the increase of 16-OH-DHEA-S, with the progression of fibrosis was confirmed. The 16-OH-DHEA-S/DHEA-S ratio and 16-OH-DHEA-S/etiocholanolone-S ratio were even more strongly associated with the grade of fibrosis. Among PBC patients, 16-OH-DHEA-S tended to be higher in stages 3 and 4 than in stages 1 and 2. However, levels of DHEA-S, etiocholanolone-S, and the two ratios were not associated with the stage of PBC. Conclusion Several metabolic products were found to be biomarkers of fibrosis in NAFLD and could also be useful for diagnosis of this condition. Our findings suggested disturbance of hormone metabolism in NAFLD and might lead to the development of new therapy.</description><subject>Abdominal Surgery</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biliary Tract</subject><subject>Biological markers</subject><subject>Biomarkers - metabolism</subject><subject>Case-Control Studies</subject><subject>Chromatography, Liquid - methods</subject><subject>Cohort Studies</subject><subject>Colorectal Surgery</subject><subject>Dehydroepiandrosterone</subject><subject>Disease Progression</subject><subject>Electrophoresis, Capillary - methods</subject><subject>Fatty liver</subject><subject>Fatty Liver - diagnosis</subject><subject>Fatty Liver - metabolism</subject><subject>Fatty Liver - physiopathology</subject><subject>Female</subject><subject>Fibrosis</subject><subject>Gastroenterology</subject><subject>Hepatology</subject><subject>Hormones, Sex</subject><subject>Humans</subject><subject>Liquid chromatography</subject><subject>Liver cirrhosis</subject><subject>Liver Cirrhosis - diagnosis</subject><subject>Liver Cirrhosis - metabolism</subject><subject>Liver Cirrhosis - physiopathology</subject><subject>Liver Cirrhosis, Biliary - diagnosis</subject><subject>Liver Cirrhosis, Biliary - metabolism</subject><subject>Liver Cirrhosis, Biliary - physiopathology</subject><subject>Male</subject><subject>Mass spectrometry</subject><subject>Mass Spectrometry - methods</subject><subject>Medicine</subject><subject>Medicine &amp; Public Health</subject><subject>Metabolites</subject><subject>Metabolomics - methods</subject><subject>Middle Aged</subject><subject>Non-alcoholic Fatty Liver Disease</subject><subject>Original Article—Liver</subject><subject>Original —Liver, Pancreas, and Biliary Tract</subject><subject>Pancreas</subject><subject>Severity of Illness Index</subject><subject>Sulfates</subject><subject>Surgical Oncology</subject><subject>Type 2 diabetes</subject><issn>0944-1174</issn><issn>1435-5922</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1kk1rFTEUhoMo9lr9AW4k4MbN1HzNTLIRSvELCi7UdUgyJ7epmeSazC303zfjrbUVJYtAzvO-4ZzzIvSSkhNKyPi2EtLzviOUd2Qchq5_hDZUtJdeMfYYbYgSoqN0FEfoWa2XpIGkl0_REeNilIoPG5S_QtnPeIbF2BzzHBzelexDBGzShHd5gbQEE7ENeTblB5SKfS64whWUsFzj7LEPtuQaKg4Jp5xMdPkix-bkzdKIGBqKp1DBVHiOnngTK7y4vY_R9w_vv5196s6_fPx8dnreuYGNSwfWODtIbznzjljDpGXMil4YKomSg7ReEc8V-KmnjkxuIAoMAe7YxAlz_Bi9O_ju9naGybUuiol6V0Lr4lpnE_TDSgoXepuvNJdSMSmawZtbg5J_7qEueg7VQYwmQd5XTcWgBqEElw19_Rd6mfelzeEXJSUllPZ_qK2JoEPyuf3rVlN9OlLRS0HHlTr5B9XOBG03OcG6mocCehC4toNawN_1SIleU6IPKdFt-XpNiV41r-4P507xOxYNYAegtlLaQrnX0X9dbwDXxsmg</recordid><startdate>20131201</startdate><enddate>20131201</enddate><creator>Tokushige, Katsutoshi</creator><creator>Hashimoto, Etsuko</creator><creator>Kodama, Kazuhisa</creator><creator>Tobari, Maki</creator><creator>Matsushita, Noriko</creator><creator>Kogiso, Tomomi</creator><creator>Taniai, Makiko</creator><creator>Torii, Nobuyuki</creator><creator>Shiratori, Keiko</creator><creator>Nishizaki, Yasuhiro</creator><creator>Ohga, Takushi</creator><creator>Ohashi, Yoshiaki</creator><creator>Sato, Takaya</creator><general>Springer Japan</general><general>Springer</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20131201</creationdate><title>Serum metabolomic profile and potential biomarkers for severity of fibrosis in nonalcoholic fatty liver disease</title><author>Tokushige, Katsutoshi ; Hashimoto, Etsuko ; Kodama, Kazuhisa ; Tobari, Maki ; Matsushita, Noriko ; Kogiso, Tomomi ; Taniai, Makiko ; Torii, Nobuyuki ; Shiratori, Keiko ; Nishizaki, Yasuhiro ; Ohga, Takushi ; Ohashi, Yoshiaki ; Sato, Takaya</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c627t-ebacb68fb32fc0ba28b22b454a1809868bf90f39efd51c0dc609ea0e3c2d302c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Abdominal Surgery</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biliary Tract</topic><topic>Biological markers</topic><topic>Biomarkers - metabolism</topic><topic>Case-Control Studies</topic><topic>Chromatography, Liquid - methods</topic><topic>Cohort Studies</topic><topic>Colorectal Surgery</topic><topic>Dehydroepiandrosterone</topic><topic>Disease Progression</topic><topic>Electrophoresis, Capillary - methods</topic><topic>Fatty liver</topic><topic>Fatty Liver - diagnosis</topic><topic>Fatty Liver - metabolism</topic><topic>Fatty Liver - physiopathology</topic><topic>Female</topic><topic>Fibrosis</topic><topic>Gastroenterology</topic><topic>Hepatology</topic><topic>Hormones, Sex</topic><topic>Humans</topic><topic>Liquid chromatography</topic><topic>Liver cirrhosis</topic><topic>Liver Cirrhosis - diagnosis</topic><topic>Liver Cirrhosis - metabolism</topic><topic>Liver Cirrhosis - physiopathology</topic><topic>Liver Cirrhosis, Biliary - diagnosis</topic><topic>Liver Cirrhosis, Biliary - metabolism</topic><topic>Liver Cirrhosis, Biliary - physiopathology</topic><topic>Male</topic><topic>Mass spectrometry</topic><topic>Mass Spectrometry - methods</topic><topic>Medicine</topic><topic>Medicine &amp; Public Health</topic><topic>Metabolites</topic><topic>Metabolomics - methods</topic><topic>Middle Aged</topic><topic>Non-alcoholic Fatty Liver Disease</topic><topic>Original Article—Liver</topic><topic>Original —Liver, Pancreas, and Biliary Tract</topic><topic>Pancreas</topic><topic>Severity of Illness Index</topic><topic>Sulfates</topic><topic>Surgical Oncology</topic><topic>Type 2 diabetes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tokushige, Katsutoshi</creatorcontrib><creatorcontrib>Hashimoto, Etsuko</creatorcontrib><creatorcontrib>Kodama, Kazuhisa</creatorcontrib><creatorcontrib>Tobari, Maki</creatorcontrib><creatorcontrib>Matsushita, Noriko</creatorcontrib><creatorcontrib>Kogiso, Tomomi</creatorcontrib><creatorcontrib>Taniai, Makiko</creatorcontrib><creatorcontrib>Torii, Nobuyuki</creatorcontrib><creatorcontrib>Shiratori, Keiko</creatorcontrib><creatorcontrib>Nishizaki, Yasuhiro</creatorcontrib><creatorcontrib>Ohga, Takushi</creatorcontrib><creatorcontrib>Ohashi, Yoshiaki</creatorcontrib><creatorcontrib>Sato, Takaya</creatorcontrib><collection>Springer Nature OA/Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing &amp; 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In order to discover novel biomarkers for NAFLD and its pathogenesis, we performed matabolomics screening. Methods (1) The initial cohort was 44 NAFLD patients. (2) This validation cohort was 105 NAFLD patients, 26 primary biliary cirrhosis (PBC) patients, and 48 healthy controls. Using capillary electrophoresis and liquid chromatography with mass spectrometry, we analyzed low molecular weight metabolites in these groups. Results 1. In the initial cohort, we found 28 metabolites associated with advanced fibrosis. Among them, 4 sulfated steroids showed the greatest difference. A decrease of dehydroepiandrosterone sulfate (DHEA-S) and 5α-androstan-3β ol-17-one sulfate (etiocholanolone-S) was observed with the progression of fibrosis. Furthermore, 16 hydroxydehydroepiandrosterone sulfate (16-OH-DHEA-S) increased with the progression of fibrosis. 2. In the validation cohort, the decrease of DHEA-S and etiocholanolone-S, as well as the increase of 16-OH-DHEA-S, with the progression of fibrosis was confirmed. The 16-OH-DHEA-S/DHEA-S ratio and 16-OH-DHEA-S/etiocholanolone-S ratio were even more strongly associated with the grade of fibrosis. Among PBC patients, 16-OH-DHEA-S tended to be higher in stages 3 and 4 than in stages 1 and 2. However, levels of DHEA-S, etiocholanolone-S, and the two ratios were not associated with the stage of PBC. Conclusion Several metabolic products were found to be biomarkers of fibrosis in NAFLD and could also be useful for diagnosis of this condition. Our findings suggested disturbance of hormone metabolism in NAFLD and might lead to the development of new therapy.</abstract><cop>Tokyo</cop><pub>Springer Japan</pub><pmid>23478936</pmid><doi>10.1007/s00535-013-0766-5</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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language eng
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source MEDLINE; SpringerNature Journals
subjects Abdominal Surgery
Adult
Aged
Aged, 80 and over
Biliary Tract
Biological markers
Biomarkers - metabolism
Case-Control Studies
Chromatography, Liquid - methods
Cohort Studies
Colorectal Surgery
Dehydroepiandrosterone
Disease Progression
Electrophoresis, Capillary - methods
Fatty liver
Fatty Liver - diagnosis
Fatty Liver - metabolism
Fatty Liver - physiopathology
Female
Fibrosis
Gastroenterology
Hepatology
Hormones, Sex
Humans
Liquid chromatography
Liver cirrhosis
Liver Cirrhosis - diagnosis
Liver Cirrhosis - metabolism
Liver Cirrhosis - physiopathology
Liver Cirrhosis, Biliary - diagnosis
Liver Cirrhosis, Biliary - metabolism
Liver Cirrhosis, Biliary - physiopathology
Male
Mass spectrometry
Mass Spectrometry - methods
Medicine
Medicine & Public Health
Metabolites
Metabolomics - methods
Middle Aged
Non-alcoholic Fatty Liver Disease
Original Article—Liver
Original —Liver, Pancreas, and Biliary Tract
Pancreas
Severity of Illness Index
Sulfates
Surgical Oncology
Type 2 diabetes
title Serum metabolomic profile and potential biomarkers for severity of fibrosis in nonalcoholic fatty liver disease
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