Fold change (compared to healthy subjects) in physiological parameters as a function of liver impairment

ParametersMildModerateSevere
GFR [4]0.700.580.55
Renal blood flow [5]0.880.650.48
Portal blood flow [18]0.720.600.13
Albumin [18]0.840.690.53
Bilirubin [19]1.102.503.50
Sum4.245.025.19
Functional liver size [18]0.910.810.64

The numbers in parenthesis are reference numbers. The values are ratios, therefore, without any unit. Bilirubin values widely vary across subjects with mild, moderate, and severe liver impairment. Bilirubin values in Table 1 are based on FDA guidance (< 2, 2–3, and > 3 mg/dL for mild, moderate, and severe liver impairment, respectively) [1] and severity grading in drug induced liver injury [19]. Any value of bilirubin > 1 or < 2 is considered mild liver impairment therefore, a value slightly > 1 (1.1) was chosen for subjects with mild liver impairment. According to severity grading, this value will be > 1–1.5. A mid-point of 2.5 was chosen for subjects with moderate liver impairment (2–3) [1]. According to severity grading, this value will be > 1.5–2.5. Any value can be > 3 for subjects with severe liver impairment therefore, a value slightly > 3 (3.5) was chosen for subjects with severe liver impairment [1]. According to severity grading, this value will be > 2.5–5. FDA: Food and Drug Administration; GFR: glomerular filtration rate