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Current Drug Metabolism

Editor-in-Chief

ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

Review Article

Chinese Herbal Medicine Hepatotoxicity: The Evaluation and Recognization Based on Large-scale Evidence Database

Author(s): Zhi Liu, Xin He*, Lili Wang, Yunhua Zhang, Yue Hai and Rui Gao

Volume 20, Issue 2, 2019

Page: [138 - 146] Pages: 9

DOI: 10.2174/1389200219666180813144114

open access plus

Abstract

Background: Due to the special nature of Chinese Herbal medicine and the complexity of its clinical use, it is difficult to identify and evaluate its toxicity and resulting herb induced liver injury (HILI).

Methods: First, the database would provide full profile of HILI from the basic ingredients to clinical outcomes by the most advanced algorithms of artificial intelligence, and it is also possible that we can predict possibilities of HILI after patients taking Chinese herbs by individual patient evaluation and prediction. Second, the database would solve the chaos and lack of the relevant data faced by the current basic research and clinical practice of Chinese Herbal Medicine. Third, we can also screen the susceptible patients from the database and thus prevent the accidents of HILI from the very beginning.

Results: The Roussel Uclaf Causality Assessment Method (RUCAM) is the most accepted method to evaluate DILI, but at present before using the RUCAM evaluation method, data resource collection and analysis are yet to be perfected. Based on existing research on drug-metabolizing enzymes mediating reactive metabolites (RMs), the aim of this study is to explore the possibilities and methods of building multidimensional hierarchical database composing of RMs evidence library, Chinese herbal evidence library, and individualized reports evidence library of herb induced liver injury HILI.

Conclusion: The potential benefits lie in its ability to organize, use vast amounts of evidence and use big data mining techniques at the center for Chinese herbal medicine liver toxicity research, which is the most difficult key point of scientific research to be investigated in the next few years.

Keywords: Drug-induced Liver Injury (DILI), Herb-induced Liver Injury (HILI), Evidence-based Medicine, Reactive Metabolites (RMs), evidence library, hepatotoxicity individualized, clinical study, Chinese herbal recognition evidence library, RUCAM.

Graphical Abstract
[1]
Zhang, S.T.; Wan, G.J.; Li, L. Research advances in the mechanism of drug-induced liver injury. Pharm. Care Res, 2017, 17, 39.
[2]
Qi, Y.B.; Qiu, L.; Jiang, H.L. Clinical characteristics of drug-induced liver injury: An analysis of 394 cases. Clin. Hepatol, 2014, 30, 438-441.
[3]
Bjornsson, E.S.; Bergmann, O.M.; Bjornsson, H.K.; Kvaran, R.B.; Olafsson, S. Incidence, presentation, and outcomes in patients with drug-induced liver injury in thegeneral population of ice land. Gastroenterology, 2013, 144, 1419-1425.
[4]
Fontana, R.J.; Watkins, P.B.; Bonkovsky, H.L.; Chalasani, N.; Davern, T.; Serrano, J.; Rochon, J. Drug-induced Liver Injury Network (DILIN) prospective study: Rationale, design and conduct. Drug Saf., 2009, 32, 55-68.
[5]
Devarbhavi, H. An update on drug-induced liver injury. J. Clin. Exp. Hepatol., 2012, 2, 247-259.
[6]
Dayakar, K.; Mahesh, G.; Priyanka, V.; Kishore, V. Metronidazole induced liver injury: A rare immune-mediated drug reaction. Case Rep. Gastrointest. Med., 2013, 20, 1-4.
[7]
Bjornsson, E.S.; Bergmann, O.M.; Bjornsson, H.K.; Kvaran, R.B.; Olafsson, S. Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of iceland. Gastroenterology, 2013, 144, 1419-1425.
[8]
Li, L.; Jiang, W.; Wang, J.Y. Clinical analysis of 275 cases of acute drug-induced liver disese. Front. Med. China, 2007, 1, 58-61.
[9]
Dağ, M.S.; Aydinli, M.; Oztürk, Z.A.; Türkbeyler, I.H.; Koruk, I.; Savaş, M.C.; Koruk, M.; Kadayifci, A. Drug and herb-induced liver injury: A case series from a single center. Turk. J. Gastroenterol., 2014, 25, 41-42.
[10]
Teschke, R.; Danan, G. Prospective indian study of dili with confirmed causality using the roussel uclaf causality assessment method (rucam): A report of excellence. Ann. Hepatol., 2017, 16, 324-325.
[11]
Dannan, G.; Benichou, C. Causality assessment of adverse reactions to drugs-I. A novel method based on the conclusions of international consensus meetings: application to drug-induced liver injuries. J. Clin. Epidemiol., 1993, 46, 1323-1330.
[12]
Teschke, R.; Schulze, J.; Schwarzenboeck, A.; Eickhoff, A.; Frenzel, C. Herbal hepatotoxicity: suspected cases assessed for alternative causes. Eur. J. Gastroenterol. Hepatol., 2013, 25, 1093-1098.
[13]
Chalasani, N.P.; Hayashi, P.H.; Bonkovsky, H.L.; Navarro, V.J.; Lee, W.M.; Fontana, R.J. ACG clinical guideline: The diagnosis and management of idiosyncratic drug-induced liver injury. Am. J. Gastroenterol., 2014, 109, 950-966.
[14]
Zhu, Y.; Niu, M.; Chen, J.; Zou, Z.S.; Ma, Z.J.; Liu, S.H.; Wang, R.L.; He, T.T.; Song, H.B.; Wang, Z.X. Comparison between Chinese herbal medicine and western medicine-induced liver injury of 1985 patients. J. Gastroenterol. Hepatol., 2016, 31, 1476-1482.
[15]
Tiwari, S.V.; Seijas, J.A.; Vazquez-Tato, M.P.; Sarkate, A.P.; Karnik, K.S.; Nikalje, A.P. Facile synthesis of novel coumarin derivatives, antimicrobial analysis, enzyme assay, docking study, ADMET prediction and toxicity study. Molecules, 2017, 22, 1-7.
[16]
Wang, X.; Lou, Y.J.; Wang, M.X.; Shi, Y.W.; Xu, H.X.; Kong, L.D. Furocoumarins affect hepatic cytochrome P450 and renal organic ion transporters in mice. Toxicol. Lett., 2012, 209, 67-77.
[17]
Koenigs, L.L.; Trager, W.F. Mechanism-based inactivation of cytochrome P450 2A6 by furanocoumarins. Biochemistry, 1998, 37, 13184-13193.
[18]
Ji, L.; Lu, D.; Cao, J.; Zheng, L.; Peng, Y.; Zheng, J. Psoralen, a mechanism-based inactivator of CYP2B6. Chem. Biol. Interact., 2015, 240, 346-352.
[19]
Lu, D.; Ji, L.; Zheng, L.; Cao, J.; Peng, Y.; Zheng, J. Mechanismbased inactivation of cytochrome P450 2B6 by isopsoralen. Chem. Biol. Interact., 2015, 226, 1-7.
[20]
Cao, J.; Zheng, L.; Ji, L.; Lu, D.; Peng, Y.; Zheng, J. Mechanismbased inactivation of cytochrome P450 2B6 by isoimperatorin. Chem. Biol. Interact., 2015, 226, 23-29.
[21]
Zheng, L.; Cao, J.; Lu, D.; Ji, L.; Peng, Y.; Zheng, J. Imperatorin is a mechanism-based inactivator of CYP2B6. Drug Metab. Dispos., 2015, 43, 82-88.
[22]
Dai, J.; Zhang, F.; Zheng, J. Retrorsine, but not monocrotaline, is a mechanism-based inactivator of P450 3A4. Chem. Biol. Interact., 2010, 183, 49-56.
[23]
Tu, M.; Li, L.; Lei, H.; Ma, Z.; Chen, Z.; Sun, S.; Xu, S.; Zhou, H.; Zeng, S.; Jiang, H. Involvement of organic cation transporter 1 and CYP3A4 in retrorsine-induced toxicity. Toxicology, 2014, 322, 34-42.
[24]
Fashe, M.M.; Juvonen, R.O.; Petsalo, A.; Rahnastorilla, M.; Auriola, S.; Soininen, P.; Vepsäläinen, J.; Pasanen, M. Recognization of a new reactive metabolite of pyrrolizidine alkaloid retrorsine: (3H-pyrrolizin-7-yl) methanol. Chem. Res. Toxicol., 2014, 27, 1950-1957.
[25]
Tang, W.; Lu, A.Y. Metabolic bioactivation and drug-related adverse effects: current status and future directions from a pharmaceutical research perspective. Drug Metab. Rev., 2010, 42, 225-249.
[26]
Amacher, D.E. The primary role of hepatic metabolism in idiosyncratic drug-induced liver injury. Expert Opin. Drug Metab. Toxicol., 2012, 8, 335-347.
[27]
Xu, J.J.; Henstock, P.V.; Dunn, M.C. Cellular imaging predictions of clinical drug-induced liver injury. Toxicol. Sci., 2008, 105, 97-105.
[28]
Fontana, E.; Dansette, P.M.; Poli, S.M. Cytochrome P450 enzymes mechanism based inhibitors: Common sub-structures and reactivity. Curr. Drug Metab., 2005, 6, 413-454.
[29]
Feng, S.; He, X. Mechanism-based inhibition of CYP450: An indicator of drug-induced hepatotoxicity. Curr. Drug Metab., 2013, 14, 1-25.
[30]
He, L.N.; Yang, A.H.; Cui, T.Y.; Zhai, Y.R.; Zhang, F.L.; Chen, J.X.; Jin, C.H.; Fan, Y.W.; Wu, Z.J.; Wang, L.L.; He, X. Reactive metabolite activation by CYP2C19-mediated rhein hepatotoxicity. Xenobiotica, 2015, 45, 361-372.
[31]
Zhang, F.L.; He, X.; Zhai, Y.R.; He, L.N.; Zhang, S.C.; Wang, L.L.; Yang, A.H.; An, L.J. Mechanism-based inhibition of CYPs and RMs induced hepatoxicity by rutaecarpine. Xenobiotica, 2015, 45, 978-989.
[32]
Wang, L.L.; He, X.; Jin, C.H.; Ondieki, G. Mechanism-based inhibitors from phytomedicine: risks of hepatotoxicity and their potential hepatotoxic substructures. Curr. Drug Metab., 2016, 17, 971-991.
[33]
Wang, J.B.; Ma, Z.J.; Niu, M.; Zhu, Y.; Liang, Q.S.; Zhao, Y.L.; Song, J.Y.; Bai, Z.F.; Zhang, Y.M.; Zhang, P.; Li, N.; Meng, Y.K.; Li, Q.; Qin, L.S.; Teng, G.J.; Cao, J.L.; Li, B.S.; Chen, S.L.; Li, Y.G.; Zou, Z.S.; Zhou, H.H.; Xiao, X.H. Evidence chain-based causality recognization in herb-induced liver injury: exemplification of a well-known liver-restorative herb polygonum multiflorum. Front. Med., 2015, 9, 457-467.
[34]
Danan, G.; Teschke, R. RUCAM in drug and herb induced liver injury: The update. Int. J. Mol. Sci., 2016, 17, 14.
[35]
Gaby, D.; Rolf, T. Drug-induced liver injury: Why is the Roussel Uclaf Causality Assessment Method (RUCAM) still used 25 years after its launch. Drug Saf., 2018, 10, 1-7.
[36]
Rockey, D.C.; Seeff, L.B.; Rochon, J.; Freston, J.; Chalasani, N.; Bonacini, M.; Fontana, R.J.; Hayashi, P.H. Causality assessment in drug-induced liver injury using a structured expert opinion process: comparison to the roussel-uclaf causality assessment method. Hepatology, 2010, 51, 2117-2126.
[37]
Fontana, R.J.; Seeff, L.B.; Andrade, R.J.; Björnsson, E.; Day, C.P.; Serrano, J.; Jay, H.H. Standardization of nomenclature and causality assessment in drug-induced liver injury: Summary of a clinical research workshop. Hepatology, 2010, 52, 730-742.
[38]
Liss, G.; Rattan, S.; Lewis, J.H. Predicting and preventing acute drug-induced liver injury: What’s new in 2010? Expert Opin. Drug Metab. Toxicol., 2010, 6, 1047-1061.
[39]
Biour, M.; Ben, S.C.; Chazouillères, O.; Grangé, J.D.; Serfaty, L.; Poupon, R. Drug-induced liver injury; fourteenth updated edition of the bibliographic database of liver injuries and related drugs. Gastroenterol. Clin. Biol., 2004, 28, 720.
[40]
Biour, M.; Poupon, R.; Grangé, J.D.; Chazouillères, O. Drug-induced hepatotoxicity; thirteenth updated edition of the bibliographic database of drug-related liver injuries and responsible drugs. Gastroenterol. Clin. Biol., 2000, 24, 1052.
[41]
Biour, M.; Poupon, R.; Grangé, J.D.; Chazouillères, O.; Jaillon, P. Drug-induced liver injury; twelfth updated edition of the bibliographic database of liver injuries and related drugs. Gastroenterol. Clin. Biol., 1999, 23, 1310-1311.
[42]
Biour, M.; Poupon, R.; Grangé, J.D.; Chazouillères, O.; Jaillon, P. Drug-induced hepatotoxicity; eleventh update of the bibliographic database on liver injuries and responsible drugs. Gastroenterol. Clin. Biol., 1998, 22, 1004.
[43]
Biour, M.; Poupon, R.; Grange, J.D.; Chazouillères, O.; Lévy, V.G.; Jaillon, P. Hepatotoxicity of drugs; tenth update of the bibliographic database of hepatic involvements and responsible drugs. Gastroenterol. Clin. Biol., 1997, 21, 660.
[44]
Biour, M.; Poupon, R.; Grange, J.D.; Chazouillères, O.; Lévy, V.G.; Bodin, F.; Cheymol, G. Hepatotoxicity of drugs; ninth update of the bibliographic database of hepatic involvements and related drugs. Gastroenterol. Clin. Biol., 1996, 20, 744.
[45]
Biour, M.; Poupon, R.; Grangé, J.D.; Chazouillères, O.; Lévy, V.G.; Bodin, F.; Cheymol, G. Hepatotoxicity of drugs; eighth updated bibliographic database of hepatic lesions and responsible drugs. Gastroenterol. Clin. Biol., 1995, 19, 756.
[46]
Biour, M.; Poupon, R.; Grangé, J.D.; Chazouillères, O.; Levy, V.G.; Bodin, F.; Cheymol, G. Hepatotoxicity of drugs; seventh update of the bibliographic database of liver lesions and related drugs. Gastroenterol. Clin. Biol., 1994, 18, 574.
[47]
Biour, M.; Poupon, R.; Grangé, J.D.; Chazouillères, O.; Levy, V.G.; Bodin, F.; Cheymol, G. Hepatotoxicity of drugs; an updated bibliographic database of liver disorders and responsible drugs. Gastroenterol. Clin. Biol., 1993, 17, 86-115.
[48]
Bourgeois, A.L.; Auriche, P.; Palmaro, A.; Montastruc, J.L.; Bagheri, H. Risk of hormonotherapy in transgender people: Literature review and data from the french database of pharmacovigilance. Ann. Endocrinol., 2016, 77, 14-21.
[49]
Fontana, E.; Dansette, P.M.; Poli, S.M. Cytochrome P450 enzymes mechanism based inhibitors: Common sub-structure and reactivity. Curr. Drug Metab., 2005, 6, 413-454.
[50]
Feng, S.; He, X. Mechanism-based inhibition of CYP450: an indicator of drug-induced hepatotoxicity. Curr. Drug Metab., 2013, 14, 921-945.
[51]
Silverman, R.B. Methods in enzymology Biol. Mass. Spectrum., 1995, 249, 240-283.
[52]
Guhlin, J.; Silverstein, K.; Zhou, P.; Tiffin, P.; Young, N.D. ODG: Omics database generator-a tool for generating, querying, and analyzing multi-omics comparative databases to facilitate biological understanding. BMC Bioinformatics, 2017, 18, 367.
[53]
Vinel, J.P.; Pascal, J.P. Database on hepatotoxic drugs available through minitel. Gastroenterol. Clin. Biol., 1993, 17, 121-122.
[54]
Ruedazárate, H.A.; Imazrosshandler, I.; Cárdenasovando, R.A.; Castillofernández, J.E.; Noguezmonroy, J.; Rangelescareño, C. A computational toxicogenomics approach identifies a list of highly hepatotoxic compounds from a large microarray database. PLoS One, 2017, 12, 1-11.
[55]
Shantakumar, S.; Nordstrom, B.L.; Djousse, L.; Hall, S.A.; Gagnon, D.R.; Fraeman, K.H.; Herk-Sukel, M.; Chagin, K.; Nelson, J. Occurrence of hepatotoxicity with pazopanib and other anti-VEGF treatments for renal cell carcinoma: An observational study utilizing a distributed database network. Cancer Chemother. Pharmacol., 2016, 78, 559-566.
[56]
Hebels, D.G.; Jetten, M.J.; Aerts, H.J.; Herwig, R.; Theunissen, D.H.; Gaj, S.; Delft, J.H.; Kleinjans, J.C. Evaluation of database-derived pathway development for enabling biomarker discovery for hepatotoxicity. Biomarkers Med., 2014, 8, 185-200.
[57]
Watkins, P.B. How to diagnose and exclude drug-induced liver injury. Dig. Dis., 2015, 33, 472-474.
[58]
Jin, R.; Gu, H.Y.; Li, L.L.; Sun, L.L. Current status of Chinese herbal preparations included in Livertox database. China. J. Hepatol., 2016, 24, 817-823.
[59]
Ming, Y.N.; Liu, X.L.; Mao, Y.M. A brief introuduction of ACG clinical guideline: The diagnosis and management of idiosyncratic drug-induced liver injury. Chin. Hepatol., 2014, 19, 564-569.
[60]
Hu, B. The diagnosis and management guideline of herb-induced liver injury released. China News T. C.M., 2016, 3, 18.
[61]
Martin, B.K.; Rada, R. Building a relational database for a physician document index. Med. Inform., 1987, 12, 187-201.
[62]
Gupta, P.; Koushal, V.; Narayan, C.; Anand, A. Building genetic database at medical institutes: Implement patient cost audit and improve biomedical research. Ann. Neurosci., 2017, 24, 3-4.
[63]
Imatoh, T.; Sai, K.; Fukazawa, C.; Hinomura, Y.; Nakamura, R.; Okamoto-Uchida, Y.; Segawa, K.; Saito, Y. Association between infection and severe drug adverse reactions: An analysis using data from the Japanese adverse drug event report database. Eur. J. Clin. Pharmacol., 2017, 73, 1643-1653.
[64]
Sobhonslidsuk, A.; Poovorawan, K.; Soonthornworasiri, N.; Pan-Ngum, W.; Phaosawasdi, K. The incidence, presentation, outcomes, risk of mortality and economic data of drug-induced liver injury from a national database in Thailand: a population-base study. BMC Gastroenterol., 2016, 16, 135.
[65]
Udo, R. Maitland-van.; Zee, A.H.; Egberts, T.C.; Breeijen, J.H.; Leufkens, H.G.; Solinge, W.W.; Bruin, M.L. Validity of diagnostic codes and laboratory measurements to identify patients with idiopathic acute liver injury in a hospital database. Pharmacoepidemiol. Drug Saf., 2016, 25, 21-28.
[66]
Hunt, C.M.; Yuen, N.A.; Stirnadel-Farrant, H.A.; Suzuki, A. Age-related differences in reporting of drug-associated liver injury: data-mining of WHO safety report database. Regul. Toxicol. Pharmacol., 2014, 70, 519-526.
[67]
Brinker, A.D.; Lyndly, J.; Tonning, J.; Money, D.; Levine, J.G.; Avigan, M.I. Profiling cumulative proportional reporting ratios of drug-induced liver injury in the FDA adverse event reporting system (FAERS) database. Drug Saf., 2013, 36, 1169-1178.
[68]
Quinton, A.; Latry, P.; Biour, M. Hepatox: Database on hepatotoxic drugs. Gastroenterol. Clin. Biol., 1993, 17, 116-120.
[69]
Biour, M.; Poupon, R.; Calmus, Y.; Grange, J.D.; Levy, V.G.; Cheymol, G. Hepatox: A microcomputer database of drug-induced hepatic injury. Indian J. Gastroenterol., 1989, 8, 175-182.
[70]
Nippold, M.A.; Vigeland, L.M.; Frantz-Kaspar, M.W.; Ward-Lonergan, J.M. Language sampling with adolescents: Building a normative database with fables. Am. J. Speech Lang. Pathol., 2017, 26, 908-920.
[71]
Klungel, O.H.; Kurz, X.; Groot, M.C.; Schlienger, R.G.; Tcherny-Lessenot, S.; Grimaldi, L.; Groenwold, R.H.; Reynolds, R.F. Multi-centre, multi-database studies with common protocols: Lessons learnt from the imi protect project. Pharmacoepidemiol. Drug Saf., 2016, 25, 156-165.
[72]
Zhu, X.; Kruhlak, N.L. Construction and analysis of a human hepatotoxicity database suitable for qsar modeling using post-market safety data. Toxicology, 2014, 321, 62-72.
[73]
Yan, G.; Wang, X.; Chen, Z.; Wu, X.; Pan, J.; Huang, Y.; Wan, G.; Yang, Z. In silico ADME studies for new drug discovery: From chemical compounds to chinese herbal medicines. Curr. Drug Metab., 2017, 18, 535-539.
[74]
Li, H.; Wang, X.; Yu, H.; Zhu, J.; Jin, H.; Wang, A.; Yang, Z. Combining in vitro and in silico approaches to find new drugs targeting the pathological proteins related to the Alzheimer’s disease. Curr. Neuropharmacol., 2017, 10, 2174-1570.
[75]
Liao, W.; Zhang, T.T.; Gao, L.; Lee, S.S.; Xu, J.; Zhang, H.; Yang, Z.; Liu, Z.; Li, W. Integration of novel materials and advanced ‘omics’ technologies into new vaccine design. Curr. Top. Med. Chem., 2017, 17, 2286-2301.
[76]
Zheng, Y.; Qing, T.; Song, Y.; Zhu, J.; Yu, Y.; Shi, W.; Pusztai, L.; Shi, L. Standardization efforts enabling next-generation sequencing and microarray basedbiomarkers for precision medicine. Biomarkers Med., 2015, 9, 1265-1272.
[77]
Langreth, R.; Waldholz, M. New era of personalized medicine: Targeting drugs for each unique genetic profile. Oncologist, 1999, 4, 426-427.

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