Table 3: Outcome of studies indicating hepatotoxicity in this systematic review.

Number StudyIntervention (dose/day) Number of patients includedHepatotoxic outcome
Number of events (percentage of events)
AST > 3 ULNALT > 3 ULNALT, AST, or both > 3 ULNALP > 2 ULNHy’s casesLiver-related discontinuationLiver-related hospitalization

1Buxton et al. 1978 [16]Fenbufen 600 mg202 (10.0)3 (15.0)

5Kennedy et al. 1994 [20]Diclofenac 150 mg12114 (12.0) 
5 (4.1)

8McKenna et al. 2001 [23]Diclofenac 150 mg1992 (1.0)5 (2.5)

10Tugwell et al. 2004 [25] Diclofenac 150 mg3114 (1.4)13 (4.7)
Topical diclofenac 1.5% w/w 1.55 ml3111 (0.4)3 (1.1)

12Laine et al. 2009 [27] Diclofenac 150 mg17289246 (1.4) 
104 (0.6)
31 (0.2)
511 (3.0)
228 (1.3)
83 (0.5)
2 (0.012)461 (2.7)4 (0.023)
Etoricoxib 60 mg or 90 mg17412116 (0.7 ) 
38 (0.2)  
8 (0.05)
1 (0.006)57 (0.3)

13Dahlberg et al. 2009 [28] Diclofenac 100 mg4628 (1.7)
Celecoxib 200 mg4631 (0.2)

16Chopra et al. 2013 [31] Celecoxib 200 mg1102 (1.9)
SGCG & SCG22010 (4.5)7 (3.2)

17Altman et al. 2015 [32]Low dose SoluMatrix diclofenac 75–105 mg6018 (1.4)24 (4.1)16 (2.7)1 (0.2)23 (3.8)

Remark. Hy’s cases: ALT > 3 ULN, and bilirubin ≥ 2 ULN; more than 3–6 ULN; more than 5 ULN; more than 8 ULN; more than 10 ULN; more than 1.5 ULN.