Table 5.
Studies addressing the long-term outcome of idiosyncratic drug-induced liver injury.
| Study (DILI criteria) | Chronicity criteria | Follow-up | Proportion chronicity |
Mean age, yr/female % |
Culprit drugs | Reference |
|---|---|---|---|---|---|---|
| Retrospective database/histology study (ALT>2 xULN, CB>2 xULN or combined elevations in AST, ALP and TB provided one of them is above 2 xULN) | Biochemical, radiological or histological evidence of liver injury >12 months | Median 5 years | 11/33* (33%) | 49/59% | Antibiotics NSAIDs Psycholeptics | Aithal et al., Gut 1999 [10] |
| Prospective registry study (ALT>2 xULN, CB>2 xULN or combined elevations in AST, ALP and TB provided one of them is above 2 xULN) | Persistent biochemical abnormality of HC>3 months after drug withdrawal or >6 months after chol/mix damage | Mean 20 months | 28/493 (5.7%) | 55/64% | Cardiovascular drugs (captopril, atorvastatin) and CNS drugs (bentazepam) | Andrade et al., Hepatology 2006 [13] |
| Retrospective database study (ALT>2 xULN, CB>2 xULN or combined elevations in AST, ALP and TB provided one of them is above 2 xULN, excluding ALF) | Persistent abnormality at follow-up at least 3 months after stopping drug treatment for HC and at least 6 months for chol/mix | Median 48 months | 3/50 (6%) | 49/67% | Antibiotics (nitrofurantoin, flucoxacillin, clindamycin) | Björnsson et al., AP&T 2007 [21] |
| Prospective registry study (ALT>5 xULN, ALP>2 xULN, INR>1.5 or TB>2.5 mg/dl with ALT, AST or ALP>1 xULN) | Persistent liver-related laboratory, radiologic, or histologic abnormalities at 6 months after DILI recognition | >6 months | 41/300 (13.6%) | n.a. | n.a. | Chalasani et al., Gastroenterology 2008 [7] |
| Retrospective database study (ALT>2 xULN, CB>2 xULN or combined elevations in AST, ALP and TB provided one of them is above 2 xULN) | Morbidity/mortality after DILI hospitalization | Mean 11 years | 23/685 (3.4%)** | n.a. | n.a. | Björnsson et al., J Hepatol 2009 [11] |
| Prospective registry study (AST or ALT>5 xULN, ALP>2 xULN, INR>1.5 or TB>2.5 mg/dl) | Persistently elevated AST, ALT, ALP or TB, histological evidence of ongoing liver injury, or radiological evidence of persistent liver injury ≥6 months after DILI onset | Mean 24 months | 113/598 (18.9%) | 49.7/ 67.3% | Antimicrobial, HDS, cardiovascular drugs, antineoplastic | Fontana et al., Gastroenterology 2014 [8] |
| Prospective registry study (AST or ALT>5, ALP>2 xULN, INR>1.5 or TB>2.5 mg/dl) | Persisters: ALP >ULN or AST, ALT>1.5 xULN at 12 months after DILI onset | Mean 24 months | 74/598 (12%) | 52.6/69% | Antimicrobial, antineoplastic, cardiovascular, HDS | Fontana et al., Am J Gastroenterol 2015 [16] |
*
7 patients failed to attend follow-up and 4 died.
**
5 patients had liver-related death.
n.a., not available; TB, total bilirubin; CB, conjugated bilirubin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; HDS, herbals and dietary supplements; Chol, cholestatic damage; HC, hepatocellular damage; Mix, mixed damage.