9 A Pair Ranking (PRank) Method for Assessing Assay …
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Table 9.2 Assay transferability for different hepatotoxic endpoints
Categories
Number of
compounds
InVitro_RatInVivo
InVitro_HumanInVivo
InVitro_RatInVitro_Human
All the compounds 120
0.71
0.58
0.77
Drug-induced liver injury (DILI)
Most-DILI
concern
46
0.76
0.62
0.74
Xu’s label
47
0.82
0.53
0.73
Sakatis’s label
51
0.77
0.63
0.73
Hepatic failure
24
0.77
0.72
0.82
Other hepatotoxic endpoints
Biochemical parameters
AST increased
13
0.69
0.62
0.78
ALT increased
9
0.81
0.52
0.88
Hepatic enzyme
increased
8
0.71
0.68
0.80
Blood bilirubin
increased
6
0.81
–
–
Liver injury patterns
Cholestasis
7
0.95
0.71
0.70
Hepatocellular
injury
16
0.75
0.57
0.89
Hepatobiliary abnormality
Cholelithiasis
6
0.86
–
–
Foetor hepaticus
7
0.81
0.62
0.96
Hepatomegaly
5
0.89
0.59
0.50
Jaundice
49
0.69
0.63
0.76
Jaundice
cholestatic
21
0.40
0.61
0.74
Histologic findings
Hyperbilirubinaemia 7
0.84
0.68
0.78
Hepatitis
43
0.70
0.61
0.73
Hepatic cirrhosis
7
0.80
0.44
0.89
Liver disorder
8
0.82
0.68
0.96
Hepatic function
abnormal
33
0.77
0.62
0.71
Steatosis
13
0.67
0.70
0.85
Hepatic necrosis
13
0.64
0.63
0.68
Cytolytic hepatitis 10
–
0.61
0.87
Total (%) of
IVIVE score
increased
78.3
73.9
43.5