Non-steroidal anti-inflammatory drugs: What is the actual risk of liver damage?

Table 1 Results of population-based studies showing liver toxicity induced by non-steroidal anti-inflammatory drugs

Authors	Study design	Incidence rate of hepatotoxicity (ALT ≥ 3 ULN) per 100 000 patient-years (95% CI)
García Rodríguez et al[22], 1992	Retrospective cohort study, cross over design	9/100 000 (6-15)
Traversa et al[23], 2003	Retrospective cohort	1.4/100 000 (1.0-2.1)
de Abajo et al[24], 2004	Retrospective population-based case-control study	2.4/100 000 (2.0-2.8)
Rubenstein et al[26], 2004	Systematic review (hospitalization or death)	3.1 to 23.4/100 000
Rostom et al[21], 2005	Systematic review	0.29/100 000 (0.17-0.51)
Laine et al[25], 2009	Long-term prospective trial	2.1/100 000 (1.9-2.3)

ALT: Alanine transaminase; ULN: Upper limit of normal; CI: Confidence interval.

Table 2 Liver-related hepatotoxicity induced by non-steroidal anti-inflammatory drugs

Drug	Pattern of liver damage	Proposed mechanism	Incidence
Aspirin	Acute and chronic hepatitis	Dose dependent	Low
	Reye’s syndrome	> with high dose
Diclofenac	Acute and chronic hepatitis	Metabolic	Low
	Mixed damage and pure cholestasis	Immunologic
Sulindac	Acute hepatitis and mixed injury	Hypersensivity	Moderate
Ibuprofen	Acute hepatitis, ductopenia	Metabolic	Low
Naproxen	Cholestatic, mixed damage	Metabolic	Low
Coxibs	Acute hepatitis, mixed damage	Probably metabolic	Low
Oxicams	Acute hepatitis, massive and submassive necrosis, cholestasis and ductopenia	Metabolic	Low
Nimesulide	Acute hepatitis, pure cholestasis	Probably metabolic	Moderate