Drug-induced liver injury
Identifieur interne : 000811 ( Pmc/Checkpoint ); précédent : 000810; suivant : 000812Drug-induced liver injury
Auteurs : Jeong Ill SuhSource :
- Yeungnam University Journal of Medicine [ 2384-0293 ] ; 2019.
Abstract
Drug-induced liver injury (DILI), including herbal and dietary supplement hepatotoxicity, is often passed lightly; however, it can lead to the requirement of a liver transplant or may even cause death because of liver failure. Recently, the American College of Gastroenterology, Chinese Society of Hepatology and European Association for the Study of the Liver guidelines for the diagnosis and treatment of DILI have been established, and they will be helpful for guiding clinical treatment decisions. Roussel Uclaf Causality Assessment Method scoring is the most commonly used method to diagnose DILI; however, it has some limitations, such as poor validity and reproducibility. Recently, studies on new biomarkers have been actively carried out, which will help diagnose DILI and predict the prognosis of DILI. It is expected that the development of new therapies such as autophagy inducers and various other technologies of the fourth industrial revolution will be applicable to DILI research.
Url:
DOI: 10.12701/yujm.2019.00297
PubMed: 31661757
PubMed Central: 6986960
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Drug-induced liver injury</title><author><name sortKey="Suh, Jeong Ill" sort="Suh, Jeong Ill" uniqKey="Suh J" first="Jeong Ill" last="Suh">Jeong Ill Suh</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31661757</idno><idno type="pmc">6986960</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986960</idno><idno type="RBID">PMC:6986960</idno><idno type="doi">10.12701/yujm.2019.00297</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000B20</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000B20</idno><idno type="wicri:Area/Pmc/Curation">000B20</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000B20</idno><idno type="wicri:Area/Pmc/Checkpoint">000811</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000811</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Drug-induced liver injury</title><author><name sortKey="Suh, Jeong Ill" sort="Suh, Jeong Ill" uniqKey="Suh J" first="Jeong Ill" last="Suh">Jeong Ill Suh</name></author></analytic><series><title level="j">Yeungnam University Journal of Medicine</title><idno type="eISSN">2384-0293</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Drug-induced liver injury (DILI), including herbal and dietary supplement hepatotoxicity, is often passed lightly; however, it can lead to the requirement of a liver transplant or may even cause death because of liver failure. Recently, the American College of Gastroenterology, Chinese Society of Hepatology and European Association for the Study of the Liver guidelines for the diagnosis and treatment of DILI have been established, and they will be helpful for guiding clinical treatment decisions. Roussel Uclaf Causality Assessment Method scoring is the most commonly used method to diagnose DILI; however, it has some limitations, such as poor validity and reproducibility. Recently, studies on new biomarkers have been actively carried out, which will help diagnose DILI and predict the prognosis of DILI. It is expected that the development of new therapies such as autophagy inducers and various other technologies of the fourth industrial revolution will be applicable to DILI research.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Chalasani, N" uniqKey="Chalasani N">N Chalasani</name></author><author><name sortKey="Fontana, Rj" uniqKey="Fontana R">RJ Fontana</name></author><author><name sortKey="Bonkovsky, Hl" uniqKey="Bonkovsky H">HL Bonkovsky</name></author><author><name sortKey="Watkins, Pb" uniqKey="Watkins P">PB Watkins</name></author><author><name sortKey="Davern, T" uniqKey="Davern T">T Davern</name></author><author><name sortKey="Serrano, J" uniqKey="Serrano J">J Serrano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hayashi, Ph" uniqKey="Hayashi P">PH Hayashi</name></author><author><name sortKey="Bjornsson, Es" uniqKey="Bjornsson E">ES 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Yeungnam Univ J Med</journal-id><journal-id journal-id-type="iso-abbrev">Yeungnam Univ J Med</journal-id><journal-id journal-id-type="publisher-id">YUJM</journal-id><journal-title-group><journal-title>Yeungnam University Journal of Medicine</journal-title></journal-title-group><issn pub-type="epub">2384-0293</issn><publisher><publisher-name>Yeungnam University College of Medicine</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31661757</article-id><article-id pub-id-type="pmc">6986960</article-id><article-id pub-id-type="doi">10.12701/yujm.2019.00297</article-id><article-id pub-id-type="publisher-id">yujm-2019-00297</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review Article</subject></subj-group></article-categories><title-group><article-title>Drug-induced liver injury</article-title><alt-title alt-title-type="right-running-head">Drug-induced liver injury</alt-title></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="false">http://orcid.org/0000-0002-3040-8766</contrib-id><name><surname>Suh</surname><given-names>Jeong Ill</given-names></name><xref ref-type="corresp" rid="c1-yujm-2019-00297"></xref></contrib><aff id="af1-yujm-2019-00297"> Department of Internal Medicine, College of Medicine, Dongguk Unversity, Gyeongju,<country>Korea</country></aff></contrib-group><author-notes><corresp id="c1-yujm-2019-00297">Corresponding author: Jeong Ill Suh, Department of Internal Medicine, College of Medicine, Dongguk University, 87 Dongdae-ro, Gyeongju 38067, Korea Tel: +82-54-770-8207, Fax: +82-54-770-8378, E-mail: <email>sujungil@dongguk.ac.kr</email></corresp></author-notes><pub-date pub-type="collection"><month>1</month><year>2020</year></pub-date><pub-date pub-type="epub"><day>27</day><month>8</month><year>2019</year></pub-date><volume>37</volume><issue>1</issue><fpage>2</fpage><lpage>12</lpage><history><date date-type="received"><day>30</day><month>7</month><year>2019</year></date><date date-type="rev-recd"><day>10</day><month>8</month><year>2019</year></date><date date-type="accepted"><day>22</day><month>8</month><year>2019</year></date></history><permissions><copyright-statement>Copyright © 2020 Yeungnam University College of Medicine</copyright-statement><copyright-year>2020</copyright-year><license><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/">http://creativecommons.org/licenses/by-nc/4.0/</ext-link>) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><abstract><p>Drug-induced liver injury (DILI), including herbal and dietary supplement hepatotoxicity, is often passed lightly; however, it can lead to the requirement of a liver transplant or may even cause death because of liver failure. Recently, the American College of Gastroenterology, Chinese Society of Hepatology and European Association for the Study of the Liver guidelines for the diagnosis and treatment of DILI have been established, and they will be helpful for guiding clinical treatment decisions. Roussel Uclaf Causality Assessment Method scoring is the most commonly used method to diagnose DILI; however, it has some limitations, such as poor validity and reproducibility. Recently, studies on new biomarkers have been actively carried out, which will help diagnose DILI and predict the prognosis of DILI. It is expected that the development of new therapies such as autophagy inducers and various other technologies of the fourth industrial revolution will be applicable to DILI research.</p></abstract><kwd-group><kwd>Diagnosis</kwd><kwd>Drug-induced liver injury</kwd><kwd>Herb</kwd><kwd>Management</kwd></kwd-group></article-meta></front><floats-group><fig id="f1-yujm-2019-00297" orientation="portrait" position="float"><label>Fig. 1.</label><caption><p>Spectrum of drug-induced liver injury. The spectrum of drug-induced liver injury is variable and broad from asymptomatic to liver failure. Drugs can damage not only hepatocytes but also cholangiocytes, stellate cells, sinusoidal endothelial cells, and they can cause acute hepatitis, chronic hepatitis, granulomatous hepatitis, neoplasia, cholestasis, cholangitis, vascular disease, and fibrosis.</p></caption><graphic xlink:href="yujm-2019-00297f1"></graphic></fig><fig id="f2-yujm-2019-00297" orientation="portrait" position="float"><label>Fig. 2.</label><caption><p>Mechanism of drug-induced liver injury. The hepatocyte injury mechanism is divided into three stages: (1) first stage (initial hepatocellular injury); initial injury is exerted through direct cell stress, direct mitochondrial inhibition, and/or specific immune reactions; (2) second stage (mitochondrial permeability transition); initial injury can lead to MPT. Direct cell stress causes MPT via the intrinsic pathway, and (3) final stage (hepatocyte death); MPT leads to necrosis or apoptosis depending on the availability of ATP, which is not uniformly progressive from the initial hepatocyte injury to the third stage, and damaged hepatocytes can be recovered depending on their defense and regeneration ability. Various environmental factors and genetic factors are involved in each step, and the degree of individual liver injury is different. MTP, mitochondrial permeability transition; ATP, adenosine triphosphate; CYP, cytochrome P450; NAt2, N-acetyltransferase 2; GST, glutathione S-transferase; UGT2B7, glycosyltransferase 2B7; BSEP, bile salt export pump; MDR3, multidrug resistance protein 3; MRP2, multidrug resistance-associated protein 2; OATP, organic-anion-transporting polypeptide; PXR, pregnane X receptor; CAR, constitutive androstane receptor; HLA, human leukocyte antigen; IL, interleukin; TNF-α, tumor necrosis factor-alpha; SOD2, superoxide dismutase 2; Nrf2, nuclear factor erythroid 2-related factor 2; GSH, glutathione S-transferase; EtOH, ethanol.</p></caption><graphic xlink:href="yujm-2019-00297f2"></graphic></fig><fig id="f3-yujm-2019-00297" orientation="portrait" position="float"><label>Fig. 3.</label><caption><p>Different mechanism of drug-induced cholestasis. Drug-induced cholestasis is caused by the degradation of the expression and function of the transport protein due to the environmental factors that directly inhibit the function of the transport protein and the genetic variation of the transport protein. In addition, the drug metabolite that exits through the canalicular membrane damages cholangiocyte, causing cholestasis. A liver injury may be exacerbated by drug accumulation in the liver via drug reabsorption through enterohepatic or cholehepatic circulation. Directly inhibtion of BSEP function is cis-inhibtion, whereas indirectly inhibition of BSEP function from the canalicular lumen is trans-inhibtion. OATP, organic-anion-transporting polypeptide; MRP2, multidrug resistance-associated protein 2; BSEP, bile salt export pump; MDR3, multidrug resistance protein 3.</p></caption><graphic xlink:href="yujm-2019-00297f3"></graphic></fig><fig id="f4-yujm-2019-00297" orientation="portrait" position="float"><label>Fig. 4.</label><caption><p>Risk factors contributing to hepatotoxicity of herbal remedies. There are many causative factors for herb-induced liver injury such as the misidentification of the plant, mislabeling of the final product, unstandardized dose, plant-specific toxic substances, various ingredients, denaturalization during inadequate storage, illegal drug incorporation, contamination of the plant by various chemicals, heavy metals, microorganisms, individual difference due to genetic or environmental factors, and herb-drug interactions.</p></caption><graphic xlink:href="yujm-2019-00297f4"></graphic></fig><table-wrap id="t1-yujm-2019-00297" orientation="portrait" position="float"><label>Table 1.</label><caption><p>Roussel Uclaf Causality Assessment Method scale</p></caption><table frame="hsides" rules="groups"><thead><tr><th valign="middle" align="left" rowspan="1" colspan="1">Category</th><th valign="middle" align="center" rowspan="1" colspan="1">Score</th><th valign="middle" align="center" rowspan="1" colspan="1">Likelihood (%)</th><th valign="middle" align="center" rowspan="1" colspan="1">Description</th></tr></thead><tbody><tr><td valign="top" align="left" rowspan="1" colspan="1">Highly probable</td><td valign="top" align="center" rowspan="1" colspan="1">>8</td><td valign="top" align="center" rowspan="1" colspan="1">>75</td><td valign="top" align="left" rowspan="1" colspan="1">Highly probable, including “highly likely” and “definite.” The evidence for the drug causing the injury is beyond a reasonable doubt, clear, and convincing</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Probable</td><td valign="top" align="center" rowspan="1" colspan="1">6–8</td><td valign="top" align="center" rowspan="1" colspan="1">50–74</td><td valign="top" align="left" rowspan="1" colspan="1">The preponderance of the evidence supports the link between the drug and the liver injury</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Possible</td><td valign="top" align="center" rowspan="1" colspan="1">3–5</td><td valign="top" align="center" rowspan="1" colspan="1">25–49</td><td valign="top" align="left" rowspan="1" colspan="1">The evidence for the drug causing the injury is equivocal but present</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Unlikely</td><td valign="top" align="center" rowspan="1" colspan="1">1–3</td><td valign="top" align="center" rowspan="1" colspan="1"><25</td><td valign="top" align="left" rowspan="1" colspan="1">There is evidence that an etiological factor other than a drug caused the injury</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Excluded</td><td valign="top" align="center" rowspan="1" colspan="1"><1</td><td valign="top" align="center" rowspan="1" colspan="1">0</td><td valign="top" align="left" rowspan="1" colspan="1">Causes could be excluded</td></tr></tbody></table></table-wrap><table-wrap id="t2-yujm-2019-00297" orientation="portrait" position="float"><label>Table 2.</label><caption><p>Drug-induced Liver Injury Network scale</p></caption><table frame="hsides" rules="groups"><thead><tr><th valign="middle" align="left" rowspan="1" colspan="1">Category </th><th valign="middle" align="center" rowspan="1" colspan="1">Score</th><th valign="middle" align="center" rowspan="1" colspan="1">Likelihood (%)</th><th valign="middle" align="center" rowspan="1" colspan="1">Description</th></tr></thead><tbody><tr><td valign="top" align="left" rowspan="1" colspan="1">Definite</td><td valign="top" align="center" rowspan="1" colspan="1">1</td><td valign="top" align="center" rowspan="1" colspan="1">>95</td><td valign="top" align="left" rowspan="1" colspan="1">The evidence for the drug causing the injury is beyond a reasonable doubt</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Highly likely</td><td valign="top" align="center" rowspan="1" colspan="1">2</td><td valign="top" align="center" rowspan="1" colspan="1">75–95</td><td valign="top" align="left" rowspan="1" colspan="1">The evidence for the drug causing the injury is clear and convincing but not definite</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Probable</td><td valign="top" align="center" rowspan="1" colspan="1">3</td><td valign="top" align="center" rowspan="1" colspan="1">50–74</td><td valign="top" align="left" rowspan="1" colspan="1">The preponderance of the evidence supports the link between the drug and the liver injury</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Possible</td><td valign="top" align="center" rowspan="1" colspan="1">4</td><td valign="top" align="center" rowspan="1" colspan="1">25–49</td><td valign="top" align="left" rowspan="1" colspan="1">The evidence for the drug causing the injury is equivocal but present</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Unlikely</td><td valign="top" align="center" rowspan="1" colspan="1">5</td><td valign="top" align="center" rowspan="1" colspan="1"><25</td><td valign="top" align="left" rowspan="1" colspan="1">There is evidence that an etiological factor other than a drug caused the injury</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Not applicable</td><td valign="top" align="center" rowspan="1" colspan="1">0</td><td valign="top" align="center" rowspan="1" colspan="1">0</td><td valign="top" align="left" rowspan="1" colspan="1">Key elements of the drug exposure history, initial presentation, alternative diagnoses, and/or diagnostic evaluation prevent one from determining a causality score</td></tr></tbody></table></table-wrap><table-wrap id="t3-yujm-2019-00297" orientation="portrait" position="float"><label>Table 3.</label><caption><p>Risk factors of drug-induced liver injury</p></caption><table frame="hsides" rules="groups"><thead><tr><th valign="middle" align="center" rowspan="1" colspan="1">Genetic factor</th><th valign="middle" align="center" rowspan="1" colspan="1">Environmental factor</th></tr></thead><tbody><tr><td valign="top" align="left" rowspan="1" colspan="1">Phase 1 enzymes</td><td valign="top" align="left" rowspan="1" colspan="1">Age</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1</td><td valign="top" align="left" rowspan="1" colspan="1">Sex</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Phase 2 enzymes</td><td valign="top" align="left" rowspan="1" colspan="1">Race</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> NAT2, GSTM1, GSTT1, UGT2B7</td><td valign="top" align="left" rowspan="1" colspan="1">Drug interaction</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Phase 3 transporters</td><td valign="top" align="left" rowspan="1" colspan="1">Alcohol </td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> BSEP, MRP2, MDR3</td><td valign="top" align="left" rowspan="1" colspan="1">Inflammation </td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Phase 0 transporter</td><td valign="top" align="left" rowspan="1" colspan="1">Underlying disease</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> OATP</td><td valign="top" align="left" rowspan="1" colspan="1"></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Nuclear receptors </td><td valign="top" align="left" rowspan="1" colspan="1">Pre-existing liver disease</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> PXR, CAR</td><td valign="top" align="left" rowspan="1" colspan="1">HIV</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Immunologic</td><td valign="top" align="left" rowspan="1" colspan="1">Diabetes</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> HLA class antigen</td><td valign="top" align="left" rowspan="1" colspan="1"></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Cytokines</td><td valign="top" align="left" rowspan="1" colspan="1">Pregnancy</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> IL-4, IL-10, TNF-α</td><td valign="top" align="left" rowspan="1" colspan="1">Nutrition</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Mitochondrial mutation</td><td valign="top" align="left" rowspan="1" colspan="1">Previous history</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> DNA mutations (POLG), MnSOD</td><td valign="top" align="left" rowspan="1" colspan="1"></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Epigenetics</td><td valign="top" align="left" rowspan="1" colspan="1"></td></tr></tbody></table><table-wrap-foot><fn id="tfn1-yujm-2019-00297"><p>CYP, cytochrome P450; NAT2, N-acetyltransferase 2; GST, glutathione S-transferase; UGT2B7, glycosyltransferase 2B7; BSEP, bile salt export pump; MRP2, multidrug resistance-associated protein 2; MDR3, multidrug resistance protein 3; OATP, organic-anion-transporting polypeptide; PXR, pregnane X receptor; CAR, constitutive androstane receptor; HIV, human immunodeficiency virus; HLA, human leukocyte antigen; IL, interleukin; TNF-α, tumor necrosis factor-alpha; DNA, deoxyribonucleic acid; POLG, polymerase gamma; MnSOD, manganese-dependent superoxide dismutase.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc><affiliations><list></list><tree><noCountry><name sortKey="Suh, Jeong Ill" sort="Suh, Jeong Ill" uniqKey="Suh J" first="Jeong Ill" last="Suh">Jeong Ill Suh</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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