Table 2.
Characteristics of Drug-Induced Livery Injury Patients Who Underwent Liver Transplantation or Died Within 6 Months of Drug-Induced Liver Injury Onset
| Characteristic | Liver transplant recipients (n = 30) | Liver-related death (n = 17) | Nonhepatic death (n = 15) | P valuea |
|---|---|---|---|---|
| Age, y, mean ± SD | 47.0 ± 13.5 | 57.9 ± 15.3 | 59.7 ± 15.9 | .02 |
| Female, % | 66.7 | 52.9 | 46.7 | .38 |
| Race, % | .97 | |||
| White | 62.1 | 76.5 | 66.7 | |
| Black | 17.2 | 11.8 | 20.0 | |
| Asian | 13.8 | 5.9 | 6.7 | |
| Others | 6.9 | 5.9 | 6.7 | |
| Body mass index, mean ± SD | 29.7 ± 7.5 | 30.6 ± 6.7 | 24.7 ± 4.8 | .04 |
| Medical history, % | ||||
| Diabetes mellitus | 33.3 | 52.9 | 53.3 | .27 |
| Heart disease | 20.0 | 23.5 | 53.3 | .08 |
| Kidney disease | 10.0 | 35.3 | 33.3 | .06 |
| Lung disease | 30.0 | 35.3 | 20.0 | .67 |
| Malignancy | 13.3 | 17.6 | 66.7 | <.01 |
| Active malignancy | 3.3 | 11.8 | 53.3 | <.01 |
| HIV+ | 3.3 | 0.0 | 0.0 | 1.00 |
| Self-reported drug allergies | 53.3 | 58.8 | 66.7 | .67 |
| Pre-existing liver disease | 30.0 | 23.5 | 13.3 | .51 |
| Prior alcohol use | 66.7 | 20.0 | 33.3 | <.01 |
| Implicated agents | ||||
| Duration of primary agent use, d, median (range) | 81 (2–2033) | 57 (5–1707) | 46 (3–3112) | .60 |
| Categories, % | .15 | |||
| Single drug | 46.7 | 70.6 | 60.0 | |
| Single HDS | 16.7 | 0.0 | 0.0 | |
| Multiple drug(s) and/or multiple HDS | 36.7 | 29.4 | 40.0 | |
| Primary implicated agent class, n (%) | .42 | |||
| Antimicrobial | 14 (46.7) | 9 (52.9) | 4 (26.7) | .29 |
| HDS | 8 (26.7) | 1 (5.9) | 1 (6.7) | .17 |
| Antineoplastic | 0 (0.0) | 2 (11.8) | 5 (33.3) | <.01 |
| Central nervous system | 3 (10.0) | 1 (5.9) | 2 (13.3) | .87 |
| Cardiovascular | 2 (6.7) | 2 (11.8) | 1 (6.7) | .84 |
| Rheumatologic | 1 (3.3) | 0 (0.0) | 1 (6.7) | .73 |
| Analgesic | 0 (0.0) | 0 (0.0) | 1 (6.7) | .24 |
| Endocrine | 1 (3.3) | 0 (0.0) | 0 (0.0) | 1.00 |
| Gastrointestinal | 1 (3.3) | 0 (0.0) | 0 (0.0) | 1.00 |
| Other | 0 (0.0) | 2 (11.8) | 0 (0.0) | .13 |
| Liver biochemistries at DILI onset | ||||
| Serum AST, U/L | 1478 (254–4925) | 556 (83–2644) | 276 (76–1972) | <.01 |
| Serum ALT, U/L | 1354 (205–4212) | 723 (23–2343) | 375 (123–1895) | <.01 |
| ALP, U/L | 180 (94–688) | 212 (108–942) | 220 (101–1004) | .51 |
| Total bilirubin, mg/dL | 11.7 (0.6–30.0) | 8.8 (0.4–27.5) | 3.7 (0.5–33.4) | .13 |
| INR | 2.1 (1.7–3.9) | 1.8 (1.0–6.2) | 1.2 (0.9–3.6) | .22 |
| Albumin, g/dL | 3.2 (2.0–4.2) | 2.9 (1.8–4.0) | 2.8 (1.1–4.0) | .27 |
| MELD score | 30.0 (7.0–40.0) | 22.0 (7.0–36.0) | 21.0 (6.0–32.0) | <.01 |
| Hy’s law, %b | 63.0 | 35.3 | 26.7 | .05 |
| R value | 17.7 (1.6–82.4) | 7.7 (0.2–27.6) | 3.4 (0.9–41.3) | <.01 |
| Pattern of injury, % | <.01 | |||
| Cholestatic | 3.3 | 29.4 | 20.0 | |
| Mixed | 0.0 | 5.9 | 53.3 | |
| Hepatocellular | 96.7 | 64.7 | 26.7 | |
| Peak liver biochemistriesc | ||||
| Peak serum AST, U/L | 1960 (655–6924) | 1475 (170–3668) | 377 (80–2500) | <.01 |
| Peak serum ALT, U/L | 1580 (551–5831) | 1378 (70–2583) | 504 (123–1895) | <.01 |
| Peak ALP, U/L | 296 (143–1051) | 302 (136–2414) | 672 (119–1484) | .20 |
| Peak total bilirubin, mg/dL | 26.3 (10.3–43.7) | 31.5 (12.0–59.0) | 17.1 (0.8–38.1) | .05 |
| Peak INR | 3.9 (2.0–12.9) | 5.1 (1.4–12.0) | 2.0 (1.1–4.7) | <.01 |
| Lowest albumin, g/dL | 2.1 (1.0–3.1) | 2.1 (1.2–2.8) | 2.0 (0.9–3.5) | .88 |
| Peak MELD score | 37.0 (15.0–40.0) | 36.0 (21.0–40.0) | 31.0 (11.0–34.0) | <.01 |
| Peak R value | 28.8 (8.1–210.4) | 15.9 (0.5–38.3) | 4.1 (1.0–41.5) | <.01 |
| Causality score, n (%)c | .79 | |||
| Definite | 8 (26.7) | 2 (11.8) | 3 (20.0) | |
| Very likely | 11 (36.7) | 8 (47.1) | 7 (46.7) | |
| Probable | 11 (36.7) | 7 (41.2) | 5 (33.3) | |
| Steroid use, %c | 90.0 | 76.5 | 71.4 | .23 |
| Ursodeoxycholic acid use, %c | 26.7 | 23.5 | 35.7 | .81 |
HIV, human immunodeficiency virus; SD, standard deviation.
a
Comparisons made across 3 patient groups.
b
Hy’s law criteria are subjects with ALT >3× ULN and total bilirubin >2.5 mg/dL at DILI onset with ALP <2× ULN.
c
Variables observed based on data from onset to the 6-month study visit. All other variables were either observed at DILI onset or at the baseline study visit where the values would be similar to DILI onset.