274
M. Chen et al.
32. Weng Z et al (2015) A comprehensive study of the association between drug hepatotoxicity
and daily dose, liver metabolism, and lipophilicity using 975 oral medications. Oncotarget
6(19):17031–17038
33. Xu JJ et al (2008) Cellular imaging predictions of clinical drug-induced liver injury. Toxicol
Sci 105(1):97–105
34. Atienzar FA, Nicolas J-M (2018) Prediction of human liver toxicity using in vitro assays:
limitations and opportunities. In: Drug-induced liver toxicity. Springer, Berlin, pp 125–150
35. Thakkar S et al (2018) The Liver Toxicity Knowledge Base (LKTB) and drug-induced liver
injury (DILI) classification for assessment of human liver injury. Expert Rev Gastroenterol
Hepatol 12(1):31–38
36. 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
37. 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
38. Thakkar S et al (2018) Drug-induced liver injury (DILI) classification and its application on
human DILI risk prediction. In: Drug-induced liver toxicity. Springer, Berlin, pp 45–59
39. Regev A (2014) Drug-induced liver injury and drug development: industry perspective. Semin
Liver Dis 34(02):227–239
40. García-Cortés M et al (2011) Causality assessment methods in drug induced liver injury:
strengths and weaknesses. J Hepatol 55(3):683–691
41. Light DS, Aleo MD, Kenna JG (2018) Interpretation, integration, and implementation of in vitro
assay data: the predictive toxicity challenge. In: Drug-induced liver toxicity. Springer, Berlin,
pp 345–364
42. Ballet F (2010) Back to basics for idiosyncratic drug-induced liver injury: dose and metabolism
make the poison. Gastroenterol Clin Biol 34(6–7):348–350
43. Walgren JL, Mitchell MD, Thompson DC (2005) Role of metabolism in drug-induced idiosyncratic hepatotoxicity. Crit Rev Toxicol 35(4):325–361
44. Uetrecht JP (1999) New concepts in immunology relevant to idiosyncratic drug reactions: the
“danger hypothesis” and innate immune system. Chem Res Toxicol 12(5):387–395
45. Senior JR (2008) What is idiosyncratic hepatotoxicity? What is it not? Hepatology
47(6):1813–1815
46. Uetrecht J (2001) Prediction of a new drug’s potential to cause idiosyncratic reactions. Curr
Opin Drug Discov Dev 4(1):55–59
47. Lammert C et al (2010) Oral medications with significant hepatic metabolism at higher risk
for hepatic adverse events. Hepatology 51(2):615–620
48. Leeson PD, Springthorpe B (2007) The influence of drug-like concepts on decision-making in
medicinal chemistry. Nat Rev Drug Discov 6(11):881–890
49. Waring MJ (2010) Lipophilicity in drug discovery. Expert Opin Drug Discov 5(3):235–248
50. Leeson PD (2018) Impact of physicochemical properties on dose and hepatotoxicity of oral
drugs. Chem Res Toxicol 31(6):494–505
51. Shah F et al (2015) Setting clinical exposure levels of concern for drug-induced liver injury
(DILI) using mechanistic in vitro assays. Toxicol Sci 147(2):500–514
52. Mishra P, Chen M (2017) Direct-acting antivirals for chronic hepatitis C: can drug properties
signal potential for liver injury? Gastroenterology 152(6):1270–1274
53. Kaplowitz N (2013) Avoiding idiosyncratic DILI: two is better than one. Hepatology
58(1):15–17
54. Lewis JH (2014) Drug-induced liver injury, dosage, and drug disposition: is idiosyncrasy really
unpredictable? Clin Gastroenterol Hepatol 4(1):4–8
55. Aleo MD et al (2014) Human drug-induced liver injury severity is highly associated to dual inhibition of liver mitochondrial function and bile salt export pump. Hepatology 60(3):1015–1022
56. Stephens C, Andrade RJ, Lucena MI (2014) Mechanisms of drug-induced liver injury. Curr
Opin Allergy Clin Immunol 14(4):286–292
57. Park BK et al (2011) Managing the challenge of chemically reactive metabolites in drug
development. Nat Rev Drug Discov 10(4):292–306
M. Chen et al.
32. Weng Z et al (2015) A comprehensive study of the association between drug hepatotoxicity
and daily dose, liver metabolism, and lipophilicity using 975 oral medications. Oncotarget
6(19):17031–17038
33. Xu JJ et al (2008) Cellular imaging predictions of clinical drug-induced liver injury. Toxicol
Sci 105(1):97–105
34. Atienzar FA, Nicolas J-M (2018) Prediction of human liver toxicity using in vitro assays:
limitations and opportunities. In: Drug-induced liver toxicity. Springer, Berlin, pp 125–150
35. Thakkar S et al (2018) The Liver Toxicity Knowledge Base (LKTB) and drug-induced liver
injury (DILI) classification for assessment of human liver injury. Expert Rev Gastroenterol
Hepatol 12(1):31–38
36. 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
37. 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
38. Thakkar S et al (2018) Drug-induced liver injury (DILI) classification and its application on
human DILI risk prediction. In: Drug-induced liver toxicity. Springer, Berlin, pp 45–59
39. Regev A (2014) Drug-induced liver injury and drug development: industry perspective. Semin
Liver Dis 34(02):227–239
40. García-Cortés M et al (2011) Causality assessment methods in drug induced liver injury:
strengths and weaknesses. J Hepatol 55(3):683–691
41. Light DS, Aleo MD, Kenna JG (2018) Interpretation, integration, and implementation of in vitro
assay data: the predictive toxicity challenge. In: Drug-induced liver toxicity. Springer, Berlin,
pp 345–364
42. Ballet F (2010) Back to basics for idiosyncratic drug-induced liver injury: dose and metabolism
make the poison. Gastroenterol Clin Biol 34(6–7):348–350
43. Walgren JL, Mitchell MD, Thompson DC (2005) Role of metabolism in drug-induced idiosyncratic hepatotoxicity. Crit Rev Toxicol 35(4):325–361
44. Uetrecht JP (1999) New concepts in immunology relevant to idiosyncratic drug reactions: the
“danger hypothesis” and innate immune system. Chem Res Toxicol 12(5):387–395
45. Senior JR (2008) What is idiosyncratic hepatotoxicity? What is it not? Hepatology
47(6):1813–1815
46. Uetrecht J (2001) Prediction of a new drug’s potential to cause idiosyncratic reactions. Curr
Opin Drug Discov Dev 4(1):55–59
47. Lammert C et al (2010) Oral medications with significant hepatic metabolism at higher risk
for hepatic adverse events. Hepatology 51(2):615–620
48. Leeson PD, Springthorpe B (2007) The influence of drug-like concepts on decision-making in
medicinal chemistry. Nat Rev Drug Discov 6(11):881–890
49. Waring MJ (2010) Lipophilicity in drug discovery. Expert Opin Drug Discov 5(3):235–248
50. Leeson PD (2018) Impact of physicochemical properties on dose and hepatotoxicity of oral
drugs. Chem Res Toxicol 31(6):494–505
51. Shah F et al (2015) Setting clinical exposure levels of concern for drug-induced liver injury
(DILI) using mechanistic in vitro assays. Toxicol Sci 147(2):500–514
52. Mishra P, Chen M (2017) Direct-acting antivirals for chronic hepatitis C: can drug properties
signal potential for liver injury? Gastroenterology 152(6):1270–1274
53. Kaplowitz N (2013) Avoiding idiosyncratic DILI: two is better than one. Hepatology
58(1):15–17
54. Lewis JH (2014) Drug-induced liver injury, dosage, and drug disposition: is idiosyncrasy really
unpredictable? Clin Gastroenterol Hepatol 4(1):4–8
55. Aleo MD et al (2014) Human drug-induced liver injury severity is highly associated to dual inhibition of liver mitochondrial function and bile salt export pump. Hepatology 60(3):1015–1022
56. Stephens C, Andrade RJ, Lucena MI (2014) Mechanisms of drug-induced liver injury. Curr
Opin Allergy Clin Immunol 14(4):286–292
57. Park BK et al (2011) Managing the challenge of chemically reactive metabolites in drug
development. Nat Rev Drug Discov 10(4):292–306