The value of serum aspartate aminotransferase and gamma-glutamyl transpetidase as biomarkers in hepatotoxicity
Background & Aims The current definition of the pattern of liver injury in hepatotoxicity (DILI) is given by the R (ratio) value, dividing alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in upper limits of normal at DILI onset. We aimed to explore the validity of using aspartate am...
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| Veröffentlicht in: | Liver international 2015-11, Vol.35 (11), p.2474-2482 |
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| creator | Robles-Diaz, Mercedes Garcia-Cortes, Miren Medina-Caliz, Inmaculada Gonzalez-Jimenez, Andres Gonzalez-Grande, Rocio Navarro, Jose M. Castiella, Agustin Zapata, Eva M. Romero-Gomez, Manuel Blanco, Sonia Soriano, German Hidalgo, Ramon Ortega-Torres, Maria Clavijo, Encarnacion Bermudez-Ruiz, Pilar M. Lucena, M. Isabel Andrade, Raúl J. |
| description | Background & Aims
The current definition of the pattern of liver injury in hepatotoxicity (DILI) is given by the R (ratio) value, dividing alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in upper limits of normal at DILI onset. We aimed to explore the validity of using aspartate aminotransferase (AST) and gamma‐glutamyl transpeptidase (GGT) as biomarkers of hepatocelullar and cholestatic damage, respectively, when calculating the R value.
Methods
Clinical, laboratory and histological data from 588 DILI episodes included in the Spanish DILI Registry were analyzed. Linear regression analysis was performed to establish the most appropriate cut‐off points for hepatocellular and cholestatic patterns when calculating R with AST and GGT.
Results
The overall agreement between ALT/ALP and AST/ALP was 76%, with 96%, 61% and 41% agreement in the hepatocellular (R ≥ 5), cholestatic (R ≤ 2) and mixed groups respectively (P |
| doi_str_mv | 10.1111/liv.12834 |
| format | Article |
| fullrecord | <record><control><sourceid>istex_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1111_liv_12834</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>ark_67375_WNG_K7N0BVJN_F</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4994-465142e88efbc9409caf0c63efabe64f3b922bdd2ec0bc11946ba4066cba77343</originalsourceid><addsrcrecordid>eNp1kMtOAyEUhonReF_4Aoati2lhoDPDUo33pm68LMmBOaPo3AJU7ds7ttqdbCDnfP8f8hFyxNmID2dcu48RTwshN8gul3mRiFTwzfU7FTtkL4Q3xrhSE75NdtJJwZTkape0D69IP6CeI-0qGtDPGwqhBx8hIoXGtV300IYKPYRh0Jb0BZoGkpd6HqFZ1HS57jG6cgkEalzXgH9HH6hr6Sv2ELvYfTnr4uKAbFVQBzz8vffJ4-XFw_l1Mr2_ujk_nSZWKiUTmU24TLEosDJWSaYsVMxmAiswmMlKGJWmpixTtMxYzpXMDEiWZdZAngsp9snJqtf6LgSPle69G3610JzpH2d6cKaXzgb2eMX2c9NguSb_JA3AeAV8uhoX_zfp6c3TX2WySrgQ8WudGKzoLBf5RD_PrvRdPmNnT7czfSm-AYlriKk</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>The value of serum aspartate aminotransferase and gamma-glutamyl transpetidase as biomarkers in hepatotoxicity</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Robles-Diaz, Mercedes ; Garcia-Cortes, Miren ; Medina-Caliz, Inmaculada ; Gonzalez-Jimenez, Andres ; Gonzalez-Grande, Rocio ; Navarro, Jose M. ; Castiella, Agustin ; Zapata, Eva M. ; Romero-Gomez, Manuel ; Blanco, Sonia ; Soriano, German ; Hidalgo, Ramon ; Ortega-Torres, Maria ; Clavijo, Encarnacion ; Bermudez-Ruiz, Pilar M. ; Lucena, M. Isabel ; Andrade, Raúl J.</creator><creatorcontrib>Robles-Diaz, Mercedes ; Garcia-Cortes, Miren ; Medina-Caliz, Inmaculada ; Gonzalez-Jimenez, Andres ; Gonzalez-Grande, Rocio ; Navarro, Jose M. ; Castiella, Agustin ; Zapata, Eva M. ; Romero-Gomez, Manuel ; Blanco, Sonia ; Soriano, German ; Hidalgo, Ramon ; Ortega-Torres, Maria ; Clavijo, Encarnacion ; Bermudez-Ruiz, Pilar M. ; Lucena, M. Isabel ; Andrade, Raúl J. ; Spanish DILI Registry ; Faster Evidence-based Translation (SAFE-T) Consortium</creatorcontrib><description>Background & Aims
The current definition of the pattern of liver injury in hepatotoxicity (DILI) is given by the R (ratio) value, dividing alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in upper limits of normal at DILI onset. We aimed to explore the validity of using aspartate aminotransferase (AST) and gamma‐glutamyl transpeptidase (GGT) as biomarkers of hepatocelullar and cholestatic damage, respectively, when calculating the R value.
Methods
Clinical, laboratory and histological data from 588 DILI episodes included in the Spanish DILI Registry were analyzed. Linear regression analysis was performed to establish the most appropriate cut‐off points for hepatocellular and cholestatic patterns when calculating R with AST and GGT.
Results
The overall agreement between ALT/ALP and AST/ALP was 76%, with 96%, 61% and 41% agreement in the hepatocellular (R ≥ 5), cholestatic (R ≤ 2) and mixed groups respectively (P < 0.001). Classified by the causative drug, the agreement was higher (87–95%) among drug classes that mainly present with hepatocellular damage and lower (48–58%) for those in which cholestatic‐mixed injury predominate (P < 0.001)). The overall agreement between ALT/ALP and ALT/GGT was weak (59%), except for in hepatocellular cases that showed a good agreement (94%) (P = 0.001). Pattern of injury according to liver histology demonstrated 65%, 68% and 47% agreement for ALT/ALP, AST/ALP and ALT/GGT ratios respectively.
Conclusions
AST can reliably replace ALT when calculating pattern of liver injury in DILI, while GGT can only substitute ALP when the R value scores as hepatocellular. The biochemical signature of causative drugs does influence the validity of the ratios with AST or GGT.</description><identifier>ISSN: 1478-3223</identifier><identifier>EISSN: 1478-3231</identifier><identifier>DOI: 10.1111/liv.12834</identifier><identifier>PMID: 25809419</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alanine Transaminase - blood ; Alkaline Phosphatase - blood ; aspartate aminotransferase ; Aspartate Aminotransferases - blood ; Biomarkers - blood ; Chemical and Drug Induced Liver Injury - blood ; Chemical and Drug Induced Liver Injury - diagnosis ; Child ; drug-induced liver injury ; Female ; gamma-glutamyl transpeptidase ; gamma-Glutamyltransferase - blood ; hepatotoxicity ; Humans ; Linear Models ; Liver - pathology ; Male ; Middle Aged ; pattern of injury ; Prospective Studies ; R ratio value ; Young Adult</subject><ispartof>Liver international, 2015-11, Vol.35 (11), p.2474-2482</ispartof><rights>2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd</rights><rights>2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4994-465142e88efbc9409caf0c63efabe64f3b922bdd2ec0bc11946ba4066cba77343</citedby><cites>FETCH-LOGICAL-c4994-465142e88efbc9409caf0c63efabe64f3b922bdd2ec0bc11946ba4066cba77343</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fliv.12834$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fliv.12834$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25809419$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Robles-Diaz, Mercedes</creatorcontrib><creatorcontrib>Garcia-Cortes, Miren</creatorcontrib><creatorcontrib>Medina-Caliz, Inmaculada</creatorcontrib><creatorcontrib>Gonzalez-Jimenez, Andres</creatorcontrib><creatorcontrib>Gonzalez-Grande, Rocio</creatorcontrib><creatorcontrib>Navarro, Jose M.</creatorcontrib><creatorcontrib>Castiella, Agustin</creatorcontrib><creatorcontrib>Zapata, Eva M.</creatorcontrib><creatorcontrib>Romero-Gomez, Manuel</creatorcontrib><creatorcontrib>Blanco, Sonia</creatorcontrib><creatorcontrib>Soriano, German</creatorcontrib><creatorcontrib>Hidalgo, Ramon</creatorcontrib><creatorcontrib>Ortega-Torres, Maria</creatorcontrib><creatorcontrib>Clavijo, Encarnacion</creatorcontrib><creatorcontrib>Bermudez-Ruiz, Pilar M.</creatorcontrib><creatorcontrib>Lucena, M. Isabel</creatorcontrib><creatorcontrib>Andrade, Raúl J.</creatorcontrib><creatorcontrib>Spanish DILI Registry</creatorcontrib><creatorcontrib>Faster Evidence-based Translation (SAFE-T) Consortium</creatorcontrib><title>The value of serum aspartate aminotransferase and gamma-glutamyl transpetidase as biomarkers in hepatotoxicity</title><title>Liver international</title><addtitle>Liver Int</addtitle><description>Background & Aims
The current definition of the pattern of liver injury in hepatotoxicity (DILI) is given by the R (ratio) value, dividing alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in upper limits of normal at DILI onset. We aimed to explore the validity of using aspartate aminotransferase (AST) and gamma‐glutamyl transpeptidase (GGT) as biomarkers of hepatocelullar and cholestatic damage, respectively, when calculating the R value.
Methods
Clinical, laboratory and histological data from 588 DILI episodes included in the Spanish DILI Registry were analyzed. Linear regression analysis was performed to establish the most appropriate cut‐off points for hepatocellular and cholestatic patterns when calculating R with AST and GGT.
Results
The overall agreement between ALT/ALP and AST/ALP was 76%, with 96%, 61% and 41% agreement in the hepatocellular (R ≥ 5), cholestatic (R ≤ 2) and mixed groups respectively (P < 0.001). Classified by the causative drug, the agreement was higher (87–95%) among drug classes that mainly present with hepatocellular damage and lower (48–58%) for those in which cholestatic‐mixed injury predominate (P < 0.001)). The overall agreement between ALT/ALP and ALT/GGT was weak (59%), except for in hepatocellular cases that showed a good agreement (94%) (P = 0.001). Pattern of injury according to liver histology demonstrated 65%, 68% and 47% agreement for ALT/ALP, AST/ALP and ALT/GGT ratios respectively.
Conclusions
AST can reliably replace ALT when calculating pattern of liver injury in DILI, while GGT can only substitute ALP when the R value scores as hepatocellular. The biochemical signature of causative drugs does influence the validity of the ratios with AST or GGT.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alanine Transaminase - blood</subject><subject>Alkaline Phosphatase - blood</subject><subject>aspartate aminotransferase</subject><subject>Aspartate Aminotransferases - blood</subject><subject>Biomarkers - blood</subject><subject>Chemical and Drug Induced Liver Injury - blood</subject><subject>Chemical and Drug Induced Liver Injury - diagnosis</subject><subject>Child</subject><subject>drug-induced liver injury</subject><subject>Female</subject><subject>gamma-glutamyl transpeptidase</subject><subject>gamma-Glutamyltransferase - blood</subject><subject>hepatotoxicity</subject><subject>Humans</subject><subject>Linear Models</subject><subject>Liver - pathology</subject><subject>Male</subject><subject>Middle Aged</subject><subject>pattern of injury</subject><subject>Prospective Studies</subject><subject>R ratio value</subject><subject>Young Adult</subject><issn>1478-3223</issn><issn>1478-3231</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMtOAyEUhonReF_4Aoati2lhoDPDUo33pm68LMmBOaPo3AJU7ds7ttqdbCDnfP8f8hFyxNmID2dcu48RTwshN8gul3mRiFTwzfU7FTtkL4Q3xrhSE75NdtJJwZTkape0D69IP6CeI-0qGtDPGwqhBx8hIoXGtV300IYKPYRh0Jb0BZoGkpd6HqFZ1HS57jG6cgkEalzXgH9HH6hr6Sv2ELvYfTnr4uKAbFVQBzz8vffJ4-XFw_l1Mr2_ujk_nSZWKiUTmU24TLEosDJWSaYsVMxmAiswmMlKGJWmpixTtMxYzpXMDEiWZdZAngsp9snJqtf6LgSPle69G3610JzpH2d6cKaXzgb2eMX2c9NguSb_JA3AeAV8uhoX_zfp6c3TX2WySrgQ8WudGKzoLBf5RD_PrvRdPmNnT7czfSm-AYlriKk</recordid><startdate>201511</startdate><enddate>201511</enddate><creator>Robles-Diaz, Mercedes</creator><creator>Garcia-Cortes, Miren</creator><creator>Medina-Caliz, Inmaculada</creator><creator>Gonzalez-Jimenez, Andres</creator><creator>Gonzalez-Grande, Rocio</creator><creator>Navarro, Jose M.</creator><creator>Castiella, Agustin</creator><creator>Zapata, Eva M.</creator><creator>Romero-Gomez, Manuel</creator><creator>Blanco, Sonia</creator><creator>Soriano, German</creator><creator>Hidalgo, Ramon</creator><creator>Ortega-Torres, Maria</creator><creator>Clavijo, Encarnacion</creator><creator>Bermudez-Ruiz, Pilar M.</creator><creator>Lucena, M. Isabel</creator><creator>Andrade, Raúl J.</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</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></search><sort><creationdate>201511</creationdate><title>The value of serum aspartate aminotransferase and gamma-glutamyl transpetidase as biomarkers in hepatotoxicity</title><author>Robles-Diaz, Mercedes ; Garcia-Cortes, Miren ; Medina-Caliz, Inmaculada ; Gonzalez-Jimenez, Andres ; Gonzalez-Grande, Rocio ; Navarro, Jose M. ; Castiella, Agustin ; Zapata, Eva M. ; Romero-Gomez, Manuel ; Blanco, Sonia ; Soriano, German ; Hidalgo, Ramon ; Ortega-Torres, Maria ; Clavijo, Encarnacion ; Bermudez-Ruiz, Pilar M. ; Lucena, M. Isabel ; Andrade, Raúl J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4994-465142e88efbc9409caf0c63efabe64f3b922bdd2ec0bc11946ba4066cba77343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alanine Transaminase - blood</topic><topic>Alkaline Phosphatase - blood</topic><topic>aspartate aminotransferase</topic><topic>Aspartate Aminotransferases - blood</topic><topic>Biomarkers - blood</topic><topic>Chemical and Drug Induced Liver Injury - blood</topic><topic>Chemical and Drug Induced Liver Injury - diagnosis</topic><topic>Child</topic><topic>drug-induced liver injury</topic><topic>Female</topic><topic>gamma-glutamyl transpeptidase</topic><topic>gamma-Glutamyltransferase - blood</topic><topic>hepatotoxicity</topic><topic>Humans</topic><topic>Linear Models</topic><topic>Liver - pathology</topic><topic>Male</topic><topic>Middle Aged</topic><topic>pattern of injury</topic><topic>Prospective Studies</topic><topic>R ratio value</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Robles-Diaz, Mercedes</creatorcontrib><creatorcontrib>Garcia-Cortes, Miren</creatorcontrib><creatorcontrib>Medina-Caliz, Inmaculada</creatorcontrib><creatorcontrib>Gonzalez-Jimenez, Andres</creatorcontrib><creatorcontrib>Gonzalez-Grande, Rocio</creatorcontrib><creatorcontrib>Navarro, Jose M.</creatorcontrib><creatorcontrib>Castiella, Agustin</creatorcontrib><creatorcontrib>Zapata, Eva M.</creatorcontrib><creatorcontrib>Romero-Gomez, Manuel</creatorcontrib><creatorcontrib>Blanco, Sonia</creatorcontrib><creatorcontrib>Soriano, German</creatorcontrib><creatorcontrib>Hidalgo, Ramon</creatorcontrib><creatorcontrib>Ortega-Torres, Maria</creatorcontrib><creatorcontrib>Clavijo, Encarnacion</creatorcontrib><creatorcontrib>Bermudez-Ruiz, Pilar M.</creatorcontrib><creatorcontrib>Lucena, M. Isabel</creatorcontrib><creatorcontrib>Andrade, Raúl J.</creatorcontrib><creatorcontrib>Spanish DILI Registry</creatorcontrib><creatorcontrib>Faster Evidence-based Translation (SAFE-T) Consortium</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Liver international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Robles-Diaz, Mercedes</au><au>Garcia-Cortes, Miren</au><au>Medina-Caliz, Inmaculada</au><au>Gonzalez-Jimenez, Andres</au><au>Gonzalez-Grande, Rocio</au><au>Navarro, Jose M.</au><au>Castiella, Agustin</au><au>Zapata, Eva M.</au><au>Romero-Gomez, Manuel</au><au>Blanco, Sonia</au><au>Soriano, German</au><au>Hidalgo, Ramon</au><au>Ortega-Torres, Maria</au><au>Clavijo, Encarnacion</au><au>Bermudez-Ruiz, Pilar M.</au><au>Lucena, M. Isabel</au><au>Andrade, Raúl J.</au><aucorp>Spanish DILI Registry</aucorp><aucorp>Faster Evidence-based Translation (SAFE-T) Consortium</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The value of serum aspartate aminotransferase and gamma-glutamyl transpetidase as biomarkers in hepatotoxicity</atitle><jtitle>Liver international</jtitle><addtitle>Liver Int</addtitle><date>2015-11</date><risdate>2015</risdate><volume>35</volume><issue>11</issue><spage>2474</spage><epage>2482</epage><pages>2474-2482</pages><issn>1478-3223</issn><eissn>1478-3231</eissn><abstract>Background & Aims
The current definition of the pattern of liver injury in hepatotoxicity (DILI) is given by the R (ratio) value, dividing alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in upper limits of normal at DILI onset. We aimed to explore the validity of using aspartate aminotransferase (AST) and gamma‐glutamyl transpeptidase (GGT) as biomarkers of hepatocelullar and cholestatic damage, respectively, when calculating the R value.
Methods
Clinical, laboratory and histological data from 588 DILI episodes included in the Spanish DILI Registry were analyzed. Linear regression analysis was performed to establish the most appropriate cut‐off points for hepatocellular and cholestatic patterns when calculating R with AST and GGT.
Results
The overall agreement between ALT/ALP and AST/ALP was 76%, with 96%, 61% and 41% agreement in the hepatocellular (R ≥ 5), cholestatic (R ≤ 2) and mixed groups respectively (P < 0.001). Classified by the causative drug, the agreement was higher (87–95%) among drug classes that mainly present with hepatocellular damage and lower (48–58%) for those in which cholestatic‐mixed injury predominate (P < 0.001)). The overall agreement between ALT/ALP and ALT/GGT was weak (59%), except for in hepatocellular cases that showed a good agreement (94%) (P = 0.001). Pattern of injury according to liver histology demonstrated 65%, 68% and 47% agreement for ALT/ALP, AST/ALP and ALT/GGT ratios respectively.
Conclusions
AST can reliably replace ALT when calculating pattern of liver injury in DILI, while GGT can only substitute ALP when the R value scores as hepatocellular. The biochemical signature of causative drugs does influence the validity of the ratios with AST or GGT.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>25809419</pmid><doi>10.1111/liv.12834</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Liver international, 2015-11, Vol.35 (11), p.2474-2482 |
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| language | eng |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adolescent Adult Aged Aged, 80 and over Alanine Transaminase - blood Alkaline Phosphatase - blood aspartate aminotransferase Aspartate Aminotransferases - blood Biomarkers - blood Chemical and Drug Induced Liver Injury - blood Chemical and Drug Induced Liver Injury - diagnosis Child drug-induced liver injury Female gamma-glutamyl transpeptidase gamma-Glutamyltransferase - blood hepatotoxicity Humans Linear Models Liver - pathology Male Middle Aged pattern of injury Prospective Studies R ratio value Young Adult |
| title | The value of serum aspartate aminotransferase and gamma-glutamyl transpetidase as biomarkers in hepatotoxicity |
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