Incidence and risk factors of anti‐tuberculosis drug induced liver injury (DILI): Large cohort study involving 4652 Chinese adult tuberculosis patients
Background and Aims Anti‐tuberculosis drugs remain as an important cause of drug‐induced liver injury (DILI) worldwide. Adverse drug reactions reduce the effectiveness of treatment. We aimed to determine the incidence and risk factors associated with anti‐tuberculosis DILI (ATDILI). Methods Using es...
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| Veröffentlicht in: | Liver international 2021-07, Vol.41 (7), p.1565-1575 |
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| creator | Jiang, Fanrong Yan, Huadong Liang, Lili Du, Jingyuan Jin, Susu Yang, Shiqing Wang, Hongxia Hu, Ting Zhu, Yuying Wang, Guangming Hu, Yaoren Cai, Ting Aithal, Guruprasad P. |
| description | Background and Aims
Anti‐tuberculosis drugs remain as an important cause of drug‐induced liver injury (DILI) worldwide. Adverse drug reactions reduce the effectiveness of treatment. We aimed to determine the incidence and risk factors associated with anti‐tuberculosis DILI (ATDILI).
Methods
Using established criteria and causality assessment methods, risk factors for ATDILI were identified in a contemporary cohort and validated in another cohort prospectively. Independent determinants of ATDILI were identified using Cox regression analysis.
Results
In the derivation cohort (n = 3155), 170 (5.4%) developed ATDILI of which 27 (15.9%) developed jaundice; 9(5.3%) developed acute liver failure (ALF) and 3 died. Among HBsAg positive patients, 11/27 (40.7%) of ATDILI developed after 3 months of starting treatment. In addition, of 218 (6.9%) who developed raised alanine transferase (ALT) levels ≥3 times upper limit normal, 193 (88.5%) resolved and 25 (11.4%) progressed to DILI. Age (HR = 1.014, 95% CI: 1.005‐1.023), baseline ALT (HR = 1.014, 95% CI: 1.003‐1.024), haemoglobin (HR = 1.011, 95% CI: 1.002‐1.020) and HBsAg positivity (HR = 1.516, 95% CI: 1.004‐2.290) were independent risk factors for DILI. In the second cohort (n = 1497) of which 85 (5.7%) developed ATDILI. Age (HR = 1.029, 95% CI: 1.003‐1.056), baseline AST (HR = 1.036, 95% CI: 1.010‐1.062), previous TB treatment (HR = 3.894, 95% CI: 1.304‐11.625) and active drinking (HR = 3.624, 95% CI: 1.147‐11.454) were risk factors for developing jaundice.
Conclusion
Elevation of ALT of ≥3 × ULN during anti‐TB treatment resolves in the vast majority without developing serious consequences. In two cohorts involving 4652 patients, incidence of ALF and death because of ATDILI are low. Age, baseline ALT, haemoglobin and HBsAg positivity are risk factors for the development of DILI and these inform monitoring and management of these patients. |
| doi_str_mv | 10.1111/liv.14896 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2515069268</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2541861891</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3886-484e1da434afe841f114897170ca2acf5d270f02c1891e77068a2efb588c95583</originalsourceid><addsrcrecordid>eNp1kc9uEzEQxi1ERUvhwAsgS1zaQ1rb6931ckOh0JVW4gJcV449Th02dvCfoNx4hF55PZ4Ep2krgcRcZmz99H2j-RB6RckFLXU52e0F5aJrnqATylsxq1hFnz7OrDpGz2NcEUK7rqbP0HFViaYUPUG_eqesBqcAS6dxsPEbNlIlHyL2pvwl-_vnbcoLCCpPPtqIdchLbJ3OCjQu1hDKa5XDDp-974f-_C0eZFgCVv7Gh4RjynpXiK2fttYtMW9qhuc31kEsnjpPCf8lv5HJgkvxBToycorw8r6foi8frj7Pr2fDp4_9_N0wU5UQzYwLDlRLXnFpQHBq6P4SLW2JkkwqU2vWEkOYoqKj0LakEZKBWdRCqK6uRXWKzg66m-C_Z4hpXNuoYJqkA5_jyGpak6ZjzR598w-68jm4sl2hOBXN3qNQ5wdKBR9jADNugl3LsBspGfd5jeVo411ehX19r5gXa9CP5ENABbg8AD_sBLv_K41D__Ug-QcDbKDg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2541861891</pqid></control><display><type>article</type><title>Incidence and risk factors of anti‐tuberculosis drug induced liver injury (DILI): Large cohort study involving 4652 Chinese adult tuberculosis patients</title><source>Wiley Journals</source><creator>Jiang, Fanrong ; Yan, Huadong ; Liang, Lili ; Du, Jingyuan ; Jin, Susu ; Yang, Shiqing ; Wang, Hongxia ; Hu, Ting ; Zhu, Yuying ; Wang, Guangming ; Hu, Yaoren ; Cai, Ting ; Aithal, Guruprasad P.</creator><creatorcontrib>Jiang, Fanrong ; Yan, Huadong ; Liang, Lili ; Du, Jingyuan ; Jin, Susu ; Yang, Shiqing ; Wang, Hongxia ; Hu, Ting ; Zhu, Yuying ; Wang, Guangming ; Hu, Yaoren ; Cai, Ting ; Aithal, Guruprasad P.</creatorcontrib><description>Background and Aims
Anti‐tuberculosis drugs remain as an important cause of drug‐induced liver injury (DILI) worldwide. Adverse drug reactions reduce the effectiveness of treatment. We aimed to determine the incidence and risk factors associated with anti‐tuberculosis DILI (ATDILI).
Methods
Using established criteria and causality assessment methods, risk factors for ATDILI were identified in a contemporary cohort and validated in another cohort prospectively. Independent determinants of ATDILI were identified using Cox regression analysis.
Results
In the derivation cohort (n = 3155), 170 (5.4%) developed ATDILI of which 27 (15.9%) developed jaundice; 9(5.3%) developed acute liver failure (ALF) and 3 died. Among HBsAg positive patients, 11/27 (40.7%) of ATDILI developed after 3 months of starting treatment. In addition, of 218 (6.9%) who developed raised alanine transferase (ALT) levels ≥3 times upper limit normal, 193 (88.5%) resolved and 25 (11.4%) progressed to DILI. Age (HR = 1.014, 95% CI: 1.005‐1.023), baseline ALT (HR = 1.014, 95% CI: 1.003‐1.024), haemoglobin (HR = 1.011, 95% CI: 1.002‐1.020) and HBsAg positivity (HR = 1.516, 95% CI: 1.004‐2.290) were independent risk factors for DILI. In the second cohort (n = 1497) of which 85 (5.7%) developed ATDILI. Age (HR = 1.029, 95% CI: 1.003‐1.056), baseline AST (HR = 1.036, 95% CI: 1.010‐1.062), previous TB treatment (HR = 3.894, 95% CI: 1.304‐11.625) and active drinking (HR = 3.624, 95% CI: 1.147‐11.454) were risk factors for developing jaundice.
Conclusion
Elevation of ALT of ≥3 × ULN during anti‐TB treatment resolves in the vast majority without developing serious consequences. In two cohorts involving 4652 patients, incidence of ALF and death because of ATDILI are low. Age, baseline ALT, haemoglobin and HBsAg positivity are risk factors for the development of DILI and these inform monitoring and management of these patients.</description><identifier>ISSN: 1478-3223</identifier><identifier>EISSN: 1478-3231</identifier><identifier>DOI: 10.1111/liv.14896</identifier><identifier>PMID: 33866661</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Age ; Alanine ; anti‐tuberculosis drug ; Cohort analysis ; Drug induced liver injury ; Hemoglobin ; Hepatitis B surface antigen ; incidence ; Injury prevention ; Jaundice ; Liver ; Liver diseases ; Regression analysis ; Risk analysis ; risk factor ; Risk factors ; Side effects ; Tuberculosis</subject><ispartof>Liver international, 2021-07, Vol.41 (7), p.1565-1575</ispartof><rights>2021 The Authors. Liver International published by John Wiley & Sons Ltd.</rights><rights>2021. This article is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3886-484e1da434afe841f114897170ca2acf5d270f02c1891e77068a2efb588c95583</citedby><cites>FETCH-LOGICAL-c3886-484e1da434afe841f114897170ca2acf5d270f02c1891e77068a2efb588c95583</cites><orcidid>0000-0003-3924-4830 ; 0000-0003-2792-7490</orcidid></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.14896$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fliv.14896$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33866661$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jiang, Fanrong</creatorcontrib><creatorcontrib>Yan, Huadong</creatorcontrib><creatorcontrib>Liang, Lili</creatorcontrib><creatorcontrib>Du, Jingyuan</creatorcontrib><creatorcontrib>Jin, Susu</creatorcontrib><creatorcontrib>Yang, Shiqing</creatorcontrib><creatorcontrib>Wang, Hongxia</creatorcontrib><creatorcontrib>Hu, Ting</creatorcontrib><creatorcontrib>Zhu, Yuying</creatorcontrib><creatorcontrib>Wang, Guangming</creatorcontrib><creatorcontrib>Hu, Yaoren</creatorcontrib><creatorcontrib>Cai, Ting</creatorcontrib><creatorcontrib>Aithal, Guruprasad P.</creatorcontrib><title>Incidence and risk factors of anti‐tuberculosis drug induced liver injury (DILI): Large cohort study involving 4652 Chinese adult tuberculosis patients</title><title>Liver international</title><addtitle>Liver Int</addtitle><description>Background and Aims
Anti‐tuberculosis drugs remain as an important cause of drug‐induced liver injury (DILI) worldwide. Adverse drug reactions reduce the effectiveness of treatment. We aimed to determine the incidence and risk factors associated with anti‐tuberculosis DILI (ATDILI).
Methods
Using established criteria and causality assessment methods, risk factors for ATDILI were identified in a contemporary cohort and validated in another cohort prospectively. Independent determinants of ATDILI were identified using Cox regression analysis.
Results
In the derivation cohort (n = 3155), 170 (5.4%) developed ATDILI of which 27 (15.9%) developed jaundice; 9(5.3%) developed acute liver failure (ALF) and 3 died. Among HBsAg positive patients, 11/27 (40.7%) of ATDILI developed after 3 months of starting treatment. In addition, of 218 (6.9%) who developed raised alanine transferase (ALT) levels ≥3 times upper limit normal, 193 (88.5%) resolved and 25 (11.4%) progressed to DILI. Age (HR = 1.014, 95% CI: 1.005‐1.023), baseline ALT (HR = 1.014, 95% CI: 1.003‐1.024), haemoglobin (HR = 1.011, 95% CI: 1.002‐1.020) and HBsAg positivity (HR = 1.516, 95% CI: 1.004‐2.290) were independent risk factors for DILI. In the second cohort (n = 1497) of which 85 (5.7%) developed ATDILI. Age (HR = 1.029, 95% CI: 1.003‐1.056), baseline AST (HR = 1.036, 95% CI: 1.010‐1.062), previous TB treatment (HR = 3.894, 95% CI: 1.304‐11.625) and active drinking (HR = 3.624, 95% CI: 1.147‐11.454) were risk factors for developing jaundice.
Conclusion
Elevation of ALT of ≥3 × ULN during anti‐TB treatment resolves in the vast majority without developing serious consequences. In two cohorts involving 4652 patients, incidence of ALF and death because of ATDILI are low. Age, baseline ALT, haemoglobin and HBsAg positivity are risk factors for the development of DILI and these inform monitoring and management of these patients.</description><subject>Age</subject><subject>Alanine</subject><subject>anti‐tuberculosis drug</subject><subject>Cohort analysis</subject><subject>Drug induced liver injury</subject><subject>Hemoglobin</subject><subject>Hepatitis B surface antigen</subject><subject>incidence</subject><subject>Injury prevention</subject><subject>Jaundice</subject><subject>Liver</subject><subject>Liver diseases</subject><subject>Regression analysis</subject><subject>Risk analysis</subject><subject>risk factor</subject><subject>Risk factors</subject><subject>Side effects</subject><subject>Tuberculosis</subject><issn>1478-3223</issn><issn>1478-3231</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><recordid>eNp1kc9uEzEQxi1ERUvhwAsgS1zaQ1rb6931ckOh0JVW4gJcV449Th02dvCfoNx4hF55PZ4Ep2krgcRcZmz99H2j-RB6RckFLXU52e0F5aJrnqATylsxq1hFnz7OrDpGz2NcEUK7rqbP0HFViaYUPUG_eqesBqcAS6dxsPEbNlIlHyL2pvwl-_vnbcoLCCpPPtqIdchLbJ3OCjQu1hDKa5XDDp-974f-_C0eZFgCVv7Gh4RjynpXiK2fttYtMW9qhuc31kEsnjpPCf8lv5HJgkvxBToycorw8r6foi8frj7Pr2fDp4_9_N0wU5UQzYwLDlRLXnFpQHBq6P4SLW2JkkwqU2vWEkOYoqKj0LakEZKBWdRCqK6uRXWKzg66m-C_Z4hpXNuoYJqkA5_jyGpak6ZjzR598w-68jm4sl2hOBXN3qNQ5wdKBR9jADNugl3LsBspGfd5jeVo411ehX19r5gXa9CP5ENABbg8AD_sBLv_K41D__Ug-QcDbKDg</recordid><startdate>202107</startdate><enddate>202107</enddate><creator>Jiang, Fanrong</creator><creator>Yan, Huadong</creator><creator>Liang, Lili</creator><creator>Du, Jingyuan</creator><creator>Jin, Susu</creator><creator>Yang, Shiqing</creator><creator>Wang, Hongxia</creator><creator>Hu, Ting</creator><creator>Zhu, Yuying</creator><creator>Wang, Guangming</creator><creator>Hu, Yaoren</creator><creator>Cai, Ting</creator><creator>Aithal, Guruprasad P.</creator><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>WIN</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7T5</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-3924-4830</orcidid><orcidid>https://orcid.org/0000-0003-2792-7490</orcidid></search><sort><creationdate>202107</creationdate><title>Incidence and risk factors of anti‐tuberculosis drug induced liver injury (DILI): Large cohort study involving 4652 Chinese adult tuberculosis patients</title><author>Jiang, Fanrong ; Yan, Huadong ; Liang, Lili ; Du, Jingyuan ; Jin, Susu ; Yang, Shiqing ; Wang, Hongxia ; Hu, Ting ; Zhu, Yuying ; Wang, Guangming ; Hu, Yaoren ; Cai, Ting ; Aithal, Guruprasad P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3886-484e1da434afe841f114897170ca2acf5d270f02c1891e77068a2efb588c95583</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Age</topic><topic>Alanine</topic><topic>anti‐tuberculosis drug</topic><topic>Cohort analysis</topic><topic>Drug induced liver injury</topic><topic>Hemoglobin</topic><topic>Hepatitis B surface antigen</topic><topic>incidence</topic><topic>Injury prevention</topic><topic>Jaundice</topic><topic>Liver</topic><topic>Liver diseases</topic><topic>Regression analysis</topic><topic>Risk analysis</topic><topic>risk factor</topic><topic>Risk factors</topic><topic>Side effects</topic><topic>Tuberculosis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jiang, Fanrong</creatorcontrib><creatorcontrib>Yan, Huadong</creatorcontrib><creatorcontrib>Liang, Lili</creatorcontrib><creatorcontrib>Du, Jingyuan</creatorcontrib><creatorcontrib>Jin, Susu</creatorcontrib><creatorcontrib>Yang, Shiqing</creatorcontrib><creatorcontrib>Wang, Hongxia</creatorcontrib><creatorcontrib>Hu, Ting</creatorcontrib><creatorcontrib>Zhu, Yuying</creatorcontrib><creatorcontrib>Wang, Guangming</creatorcontrib><creatorcontrib>Hu, Yaoren</creatorcontrib><creatorcontrib>Cai, Ting</creatorcontrib><creatorcontrib>Aithal, Guruprasad P.</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Free Content</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Liver international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jiang, Fanrong</au><au>Yan, Huadong</au><au>Liang, Lili</au><au>Du, Jingyuan</au><au>Jin, Susu</au><au>Yang, Shiqing</au><au>Wang, Hongxia</au><au>Hu, Ting</au><au>Zhu, Yuying</au><au>Wang, Guangming</au><au>Hu, Yaoren</au><au>Cai, Ting</au><au>Aithal, Guruprasad P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Incidence and risk factors of anti‐tuberculosis drug induced liver injury (DILI): Large cohort study involving 4652 Chinese adult tuberculosis patients</atitle><jtitle>Liver international</jtitle><addtitle>Liver Int</addtitle><date>2021-07</date><risdate>2021</risdate><volume>41</volume><issue>7</issue><spage>1565</spage><epage>1575</epage><pages>1565-1575</pages><issn>1478-3223</issn><eissn>1478-3231</eissn><abstract>Background and Aims
Anti‐tuberculosis drugs remain as an important cause of drug‐induced liver injury (DILI) worldwide. Adverse drug reactions reduce the effectiveness of treatment. We aimed to determine the incidence and risk factors associated with anti‐tuberculosis DILI (ATDILI).
Methods
Using established criteria and causality assessment methods, risk factors for ATDILI were identified in a contemporary cohort and validated in another cohort prospectively. Independent determinants of ATDILI were identified using Cox regression analysis.
Results
In the derivation cohort (n = 3155), 170 (5.4%) developed ATDILI of which 27 (15.9%) developed jaundice; 9(5.3%) developed acute liver failure (ALF) and 3 died. Among HBsAg positive patients, 11/27 (40.7%) of ATDILI developed after 3 months of starting treatment. In addition, of 218 (6.9%) who developed raised alanine transferase (ALT) levels ≥3 times upper limit normal, 193 (88.5%) resolved and 25 (11.4%) progressed to DILI. Age (HR = 1.014, 95% CI: 1.005‐1.023), baseline ALT (HR = 1.014, 95% CI: 1.003‐1.024), haemoglobin (HR = 1.011, 95% CI: 1.002‐1.020) and HBsAg positivity (HR = 1.516, 95% CI: 1.004‐2.290) were independent risk factors for DILI. In the second cohort (n = 1497) of which 85 (5.7%) developed ATDILI. Age (HR = 1.029, 95% CI: 1.003‐1.056), baseline AST (HR = 1.036, 95% CI: 1.010‐1.062), previous TB treatment (HR = 3.894, 95% CI: 1.304‐11.625) and active drinking (HR = 3.624, 95% CI: 1.147‐11.454) were risk factors for developing jaundice.
Conclusion
Elevation of ALT of ≥3 × ULN during anti‐TB treatment resolves in the vast majority without developing serious consequences. In two cohorts involving 4652 patients, incidence of ALF and death because of ATDILI are low. Age, baseline ALT, haemoglobin and HBsAg positivity are risk factors for the development of DILI and these inform monitoring and management of these patients.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>33866661</pmid><doi>10.1111/liv.14896</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-3924-4830</orcidid><orcidid>https://orcid.org/0000-0003-2792-7490</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Age Alanine anti‐tuberculosis drug Cohort analysis Drug induced liver injury Hemoglobin Hepatitis B surface antigen incidence Injury prevention Jaundice Liver Liver diseases Regression analysis Risk analysis risk factor Risk factors Side effects Tuberculosis |
| title | Incidence and risk factors of anti‐tuberculosis drug induced liver injury (DILI): Large cohort study involving 4652 Chinese adult tuberculosis patients |
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