13 Predicting the Risks of Drug-Induced Liver Injury …
273
8. Lewis W et al (1996) Fialuridine and its metabolites inhibit DNA polymerase gamma at sites of
multiple adjacent analog incorporation, decrease mtDNA abundance, and cause mitochondrial
structural defects in cultured hepatoblasts. Proc Natl Acad Sci 93(8):3592–3597
9. Chen M et al (2013) Liver Toxicity Knowledge Base (LTKB)—a systems approach to a complex
end point. Clin Pharmacol Ther 95(5):409–412
10. Chen M et al (2014) Toward predictive models for drug-induced liver injury in humans: are we
there yet? Biomark Med 8(2):201–213
11. Chen M, Borlak J, Tong W (2013) High lipophilicity and high daily dose of oral medications
are associated with significant risk for drug-induced liver injury. Hepatology 58(1):388–396
12. Chen M, Borlak J, Tong W (2016) A model to predict severity of drug-induced liver injury in
humans. Hepatology 64(3):931–940
13. Chen M et al (2013) Quantitative structure-activity relationship models for predicting druginduced liver injury based on FDA-approved drug labeling annotation and using a large collection of drugs. Toxicol Sci 136(1):242–249
14. Chen M et al (2015) Drug-induced liver injury: interactions between drug properties and host
factors. J Hepatol 63(2):503–514
15. Chen M et al (2016) DILIrank—the largest reference drug list ranked by the risk for developing
drug-induced liver injury in humans. Drug Discov Today 21(4):648–653
16. Chen M et al (2014) An improved testing strategy to predict risk for drug-induced liver injury
in humans using high-content screening assays and the ‘Rule-of-two’ model. Arch Toxicol
88(7):1439–1449
17. Liu Z et al (2011) Translating clinical findings into knowledge in drug safety evaluation–drug
induced liver injury prediction system (DILIps). PLoS Comput Biol 7(12):e1002310
18. Mishra P, Chen M (2017) Application of “Rule-of-two” model to direct-acting antivirals for
treatment of chronic hepatitis C: can it predict potential for hepatotoxicity? Gastroenterology
152(6):1270–1274
19. Wang Y et al (2013) A unifying ontology to integrate histological and clinical observations for
drug-induced liver injury. Am J Pathol 182(4):1180–1187
20. Yu K et al (2014) High daily dose and being a substrate of cytochrome P450 enzymes are two
important predictors of drug-induced liver injury. Drug Metab Dispos 42(4):744–750
21. Yu K et al (2014) Mining hidden knowledge for drug safety assessment: topic modeling of
LiverTox as a case study. BMC Bioinform 15(Suppl 17):S6
22. Przybylak KR, Cronin MT (2012) In silico models for drug-induced liver injury—current
status. Expert Opin Drug Metab Toxicol 8(2):201–217
23. Abboud G, Kaplowitz N (2007) Drug-induced liver injury. Drug Saf 30(4):277–294
24. Greene N et al (2010) Developing structure-activity relationships for the prediction of hepatotoxicity. Chem Res Toxicol 23(7):1215–1222
25. Gustafsson F et al (2013) A correlation between the in vitro drug toxicity of drugs to cell lines
which express human P450s and their propensity to cause liver injury in humans. Toxicol Sci
137(1):189–211
26. Suzuki A et al (2010) Drugs associated with hepatotoxicity and their reporting frequency of
liver adverse events in VigiBase: unified list based on international collaborative work. Drug
Saf 33(6):503–522
27. Ursem CJ et al (2009) Identification of structure-activity relationships for adverse effects of
pharmaceuticals in humans. Part A: use of FDA post-market reports to create a database of
hepatobiliary and urinary tract toxicities. Regul Toxicol Pharmacol 54(1):1–22
28. Rodgers AD et al (2010) Modeling liver-related adverse effects of drugs using k nearest neighbor quantitative structure-activity relationship method. Chem Res Toxicol 23(4):724–732
29. Zhu X, Kruhlak NL (2014) Construction and analysis of a human hepatotoxicity database
suitable for QSAR modeling using post-market safety data. Toxicology 321:62–72
30. Sakatis MZ et al (2012) Preclinical strategy to reduce clinical hepatotoxicity using in vitro
bioactivation data for >200 compounds. Chem Res Toxicol 25(10):2067–2082
31. Lammert C et al (2008) Relationship between daily dose of oral medications and idiosyncratic
drug-induced liver injury: search for signals. Hepatology 47(6):2003–2009
273
8. Lewis W et al (1996) Fialuridine and its metabolites inhibit DNA polymerase gamma at sites of
multiple adjacent analog incorporation, decrease mtDNA abundance, and cause mitochondrial
structural defects in cultured hepatoblasts. Proc Natl Acad Sci 93(8):3592–3597
9. Chen M et al (2013) Liver Toxicity Knowledge Base (LTKB)—a systems approach to a complex
end point. Clin Pharmacol Ther 95(5):409–412
10. Chen M et al (2014) Toward predictive models for drug-induced liver injury in humans: are we
there yet? Biomark Med 8(2):201–213
11. Chen M, Borlak J, Tong W (2013) High lipophilicity and high daily dose of oral medications
are associated with significant risk for drug-induced liver injury. Hepatology 58(1):388–396
12. Chen M, Borlak J, Tong W (2016) A model to predict severity of drug-induced liver injury in
humans. Hepatology 64(3):931–940
13. Chen M et al (2013) Quantitative structure-activity relationship models for predicting druginduced liver injury based on FDA-approved drug labeling annotation and using a large collection of drugs. Toxicol Sci 136(1):242–249
14. Chen M et al (2015) Drug-induced liver injury: interactions between drug properties and host
factors. J Hepatol 63(2):503–514
15. Chen M et al (2016) DILIrank—the largest reference drug list ranked by the risk for developing
drug-induced liver injury in humans. Drug Discov Today 21(4):648–653
16. Chen M et al (2014) An improved testing strategy to predict risk for drug-induced liver injury
in humans using high-content screening assays and the ‘Rule-of-two’ model. Arch Toxicol
88(7):1439–1449
17. Liu Z et al (2011) Translating clinical findings into knowledge in drug safety evaluation–drug
induced liver injury prediction system (DILIps). PLoS Comput Biol 7(12):e1002310
18. Mishra P, Chen M (2017) Application of “Rule-of-two” model to direct-acting antivirals for
treatment of chronic hepatitis C: can it predict potential for hepatotoxicity? Gastroenterology
152(6):1270–1274
19. Wang Y et al (2013) A unifying ontology to integrate histological and clinical observations for
drug-induced liver injury. Am J Pathol 182(4):1180–1187
20. Yu K et al (2014) High daily dose and being a substrate of cytochrome P450 enzymes are two
important predictors of drug-induced liver injury. Drug Metab Dispos 42(4):744–750
21. Yu K et al (2014) Mining hidden knowledge for drug safety assessment: topic modeling of
LiverTox as a case study. BMC Bioinform 15(Suppl 17):S6
22. Przybylak KR, Cronin MT (2012) In silico models for drug-induced liver injury—current
status. Expert Opin Drug Metab Toxicol 8(2):201–217
23. Abboud G, Kaplowitz N (2007) Drug-induced liver injury. Drug Saf 30(4):277–294
24. Greene N et al (2010) Developing structure-activity relationships for the prediction of hepatotoxicity. Chem Res Toxicol 23(7):1215–1222
25. Gustafsson F et al (2013) A correlation between the in vitro drug toxicity of drugs to cell lines
which express human P450s and their propensity to cause liver injury in humans. Toxicol Sci
137(1):189–211
26. Suzuki A et al (2010) Drugs associated with hepatotoxicity and their reporting frequency of
liver adverse events in VigiBase: unified list based on international collaborative work. Drug
Saf 33(6):503–522
27. Ursem CJ et al (2009) Identification of structure-activity relationships for adverse effects of
pharmaceuticals in humans. Part A: use of FDA post-market reports to create a database of
hepatobiliary and urinary tract toxicities. Regul Toxicol Pharmacol 54(1):1–22
28. Rodgers AD et al (2010) Modeling liver-related adverse effects of drugs using k nearest neighbor quantitative structure-activity relationship method. Chem Res Toxicol 23(4):724–732
29. Zhu X, Kruhlak NL (2014) Construction and analysis of a human hepatotoxicity database
suitable for QSAR modeling using post-market safety data. Toxicology 321:62–72
30. Sakatis MZ et al (2012) Preclinical strategy to reduce clinical hepatotoxicity using in vitro
bioactivation data for >200 compounds. Chem Res Toxicol 25(10):2067–2082
31. Lammert C et al (2008) Relationship between daily dose of oral medications and idiosyncratic
drug-induced liver injury: search for signals. Hepatology 47(6):2003–2009