Table 1.
Demographics and clinical characteristics of participants in discovery, confirmatory, and replication cohorts
| n | Age, mean ± SD | Male/female (%) | Most frequent causative agents/conditions | ALT, IU/L median (IQR) | ALP, IU/L median (IQR) | TBL, mg/dL median (IQR) | |
|---|---|---|---|---|---|---|---|
| Discovery cohort | |||||||
| HV | 10 | 57 ± 13 | 60/40 | <45 | <130 | <1.2 | |
| DO | 10 | 60 ± 17 | 60/40 | Flucloxacillin (4), amoxicillin-clavulanate (2), atorvastatin (2) | 166 (106–294) | 272 (221–364) | 2.4 (1–4.6) |
| DF | 10 | 60 ± 17 | 60/40 | 32 (19–67) | 130 (89–164) | 0.8 (0.6–1.6) | |
| Mean days between DO and DF: 87 | |||||||
| NDO | 5 | 61 ± 15 | 20/80 | Acute biliary obstruction (2), viral hepatitis, autoimmune hepatitis, other | 241 (125–758) | 324 (260–365) | 2.9 (1.1–3.0) |
| NDF | 5 | 61 ± 15 | 20/80 | 41 (35–51) | 146 (89–198) | 0.8 (0.5–1.0) | |
| Mean days between NDO and NDF: 51 | |||||||
| NAFLD | 10 | 58 ± 15 | 60/40 | 51 (42–61) | 126 (84–163) | 0.8 (0.5–1.0) | |
| Confirmatory cohort | |||||||
| HV | 60 | 51 ± 13 | 32/68 | <45 | <130 | <1.2 | |
| DO | 82 | 54 ± 18 | 54/46 | Amoxicillin-clavulanate (14), atorvastatin (7), ipilimumab/nivolumab (6), flucloxacillin (5), infliximab (4), nitrofurantoin (4), ibuprofen (4), metamizole (3) | 339 (184–832) | 229 (136–344) | 3.6 (0.9–11) |
| DF | 77 | 54 ± 17 | 53/47 | 46 (28–90) | 96 (73–149) | 0.9 (0.6–1.2) | |
| Mean days between DO and DF: 71 | |||||||
| NDO | 34 | 51 ± 20 | 38/62 | Viral hepatitis (16), autoimmune hepatitis (10), other (8) | 686 (282–1251) | 237 (167–319) | 10 (3.8–19) |
| NDF | 22 | 56 ± 20 | 36/64 | 56 (29–214) | 124 (92–183) | 2.0 (0.6–10) | |
| Mean days between NDO and NDF: 47 | |||||||
| Replication cohort | |||||||
| HV | 34 | 41 ± 17 | 35/65 | <45 | <130 | <1.2 | |
| DO | 41 | 56 ± 17 | 27/73 | Flucloxacillin (8), atorvastatin (7), ipilimumab/nivolumab (3), herbal/dietary supplements (3), amoxicillin-clavulanate (2) | 371 (146–781) | 297 (141–410) | 4.8 (1.2–14) |
| DF | 33 | 57 ± 17 | 27/73 | 59 (30–141) | 124 (105–168) | 0.8 (0.6–2.4) | |
| Mean days between DO and DF: 63 | |||||||
| NDO | 24 | 53 ± 17 | 42/58 | autoimmune hepatitis (12), viral hepatitis (8), other (4) | 530 (245–998) | 210 (172–316) | 5.6 (2.1–21) |
| NDF | 15 | 54 ± 16 | 40/60 | 128 (78–514) | 202 (120–313) | 2.3 (1.1–11) | |
| Mean days between NDO and NDF: 57 | |||||||
ALP alkaline phosphatase, ALT alanine aminotransferase, DO DILI onset, DF DILI follow-up, HV healthy volunteers, IQR interquartile range, NAFLD nonalcoholic fatty liver disease, NDO non-DILI onset, NDF non-DILI follow-up, SD standard deviation, TBL total bilirubin.