Table 3.
Selected demographic, clinical, and laboratory features of subjects with drug-induced liver injury
| Characteristics | ‘Outpatient’ cases | Inpatient cases | P value |
|---|---|---|---|
| n = 122 (%) | n = 76 (%) | ||
| Gender, n (%) | |||
| - Male | 44 (36) | 40 (53) | |
| - Female | 78 (64) | 36 (47) | 0.03 |
| Age (years) mean ± standard deviation | 55.6 ± 17.2 | 55.0 ± 17.5 | NS |
| Grading, n (%) | |||
| - hepatocellular | 84 (68.9) | 35 (46.1) | <0.01 |
| - cholestatic | 11 (9) | 15 (19.7) | 0.0497 |
| - mixed | 24 (19.7) | 15 (19.7) | >0.05 |
| - unclassifiable | 3 (2.5) | 11 (14.5) | <0.01 |
| Signs of hypersensitivity†, n (%) | 27 (22.1) | 13 (17.1) | NS |
| ALT/ULN, mean ± standard deviation | 31.1 ± 28.2 | 15.8 ± 20.5 | <0.001 |
| AST/ULN, mean ± standard deviation | 24.7 ± 30.9 | 13.6 ± 29.4 | 0.01 |
| ALP/ULN, mean ± standard deviation | 1.9 ± 1.4 | 2.6 ± 3.8 | NS |
| Bilirubin total/ULN, mean ± standard deviation | 7.4 ± 8.6 | 3.3 ± 5.1 | <0.001 |
| Hyperbilirubinaemia‡, n (%) | 86 (70.5) | 30 (39.5) | <0.001 |
| Coagulopathy§, n (%) | 39 (32) | 9 (11.8) | <0.01 |
| Serology testing | |||
| - Hepatitis A virus | 104 (85.2) | 55 (72.4) | |
| - Hepatitis B virus | 116 (95.1) | 63 (82.9) | |
| - Hepatitis C virus | 113 (92.6) | 59 (77.6) | |
| - Cytomegalovirus | 40 (32.8) | 10 (13.2) | |
| - Epstein–Barr virus | 43 (35.2) | 14 (18.4) | |
| - Hepatitis E virus | 17 (13.9) | 1 (1.3) | |
| - Herpes simplex virus | 17 (13.9) | 3 (3.9) | |
| - Varicella zoster virus | 12 (9.8) | 3 (3.9) | |
| Autoimmune antibodies testing | 88 (72.1) | 27 (35.5) | |
| Abdominal sonography | 121 (99.2) | 70 (92.1) | |
| Histology | 62 (50.8) | 13 (17.1) | |
| Fatigue, n (%) | 81 (66.4) | 38 (50) | 0.03 |
| Jaundice, n (%) | 54 (44.3) | 19 (25) | <0.01 |
| Acholic faeces/dark urine, n (%) | 41 (33.6) | 12 (15.8) | <0.01 |
| Abdominal pain, n (%) | 44 (36.1) | 19 (25) | NS |
| ALF¶, n (%) | 6 (4.9) | 1 (1.3) | NS |
| - ALF requiring liver transplantation, n (%) | 1 (0.8) | 0 (0) | |
| Hepatic encephalopathy, n (%) | 6 (4.9) | 3 (3.9) | NS |
| Death, n (%) | 4 (3.3) | 4 (5.3) | NS |
| - liver injury as certain cause of death, n (%) | 1 (0.8) | 1 (1.3) | |
| Drug causality assessment | |||
| - ≥ 1 medication assessed as highly probable (CIOMS > 8) | 7 (5.7) | 4 (5.3) | |
| - ≥ 1 medication assessed as probable (CIOMS 6–8) | 55 (45.1) | 25 (32.9) | |
| - ≥ 1 medication assessed as possible (CIOMS 3–5 | 66 (54.1) | 54 (71.1) | |
| Challenge (time to onset) | |||
| - From the beginning of the drug: 5 days – 90 days | 46 (40.0)** | 52 (70.3)* | |
| - From the beginning of the drug: < 5 days – > 90 days | 69 (60.0)** | 27 (36.5)* | |
| - From drug cessation: < 15 days (<30 days in cholestatic / mixed cases) | 16 (13.9)** | 16 (21.6)* | |
| Dechallenge | |||
| - Strongly positive dechallenge*** | 49 (42.6)** | 36 (48.6)* | |
| - Slightly positive dechallenge**** | 38 (33.0)** | 27 (36.5)* | |
| - No information / negative dechallenge***** | 28 (24.3)** | 11 (14.9)* | |
| Comedication ascertainment | |||
| - No / no information | 5 (4.1) | 1 (1.3) | |
| - Concomitant / incompatible time course | 56 (45.9) | 22 (28.9) | |
| - Concomitant / compatible time course | 10 (8.2) | 7 (9.2) | |
| - Concomitant / compatible time course / hepatotoxic | 60 (49.2) | 50 (65.8) |
Based on n = 74 due to two cases without drug causality and thus without challenge or dechallenge.
Based on n = 115 due to seven cases without drug causality and thus without challenge or dechallenge.
ALT decrease ≥ 50% within 8 days (cases of hepatocellular DILI) or ALP decrease ≥ 50% within 180 days (cases of cholestatic/mixed DILI).
ALT decrease ≥ 50% within 9–30 days (cases of hepatocellular DILI) or ALP decrease ≤ 50% within 180 days (cases of cholestatic/mixed DILI).
All other items from the updated CIOMS scale regarding dechallenge.
Fever, rash, lymphadenopathy, arthralgia, myalgia and/or eosinophilia.
Bilirubin > 18.8 μmol l−1.
International normalized ratio > 1.2 or prothrombin time < 70%. ¶Severe coagulopathy (international normalized ratio > 1.5 or prothrombin time < 40%) and hepatic encephalopathy. ALF, acute liver failure; ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; NS, non-significant; ULN, upper limit of normal.