Table 4

Sensitivity analyses

Adjusted HR for composite liver outcomes with respect to anti-TNF-α agent* use
(95% CI)
OverallASIBDPsARA
Defining liver outcomes with only one encounter1.42 (1.30 to 1.55)1.33 (0.92 to 1.93)1.70 (1.48 to 1.96)1.17 (0.96 to 1.44)1.29 (1.12 to 1.48)
Adjustment for rates of clinical encounter1.35 (1.16 to 1.57)1.39 (0.74 to 2.60)≤4 years:†
1.53 (1.18 to 2.00)
>4 years:†
3.36 (1.65 to 6.87)		1.14 (0.79 to 1.66)1.14 (0.88 to 1.47)
Exclusion of other chronic liver diseases‡1.49 (1.29 to 1.72)1.92 (1.10 to 3.35)≤4 years:†
1.64 (1.26 to 2.13)
>4 years:†
3.46 (1.69 to 7.08)		1.27 (0.90,1.80)1.28 (1.01 to 1.63)
Stratification by age   
 18–341.69 (1.12 to 2.54)2.28 (0.56 to 9.27)1.48 (0.85 to 2.56)1.86 (0.48 to 7.25)2.16 (0.93 to 5.00)
 35–441.47 (1.08 to 2.00)2.06 (0.71 to 5.95)1.84 (1.15 to 2.94)0.94 (0.40 to 2.19)1.34 (0.77 to 2.32)
 45–541.47 (1.08 to 2.00)1.76 (0.66 to 4.67)1.74 (1.09 to 2.78)1.56 (0.92 to 2.65)1.23 (0.83 to 1.84)
 ≧551.37 (1.05 to 1.77)1.73 (0.52 to 5.79)1.86 (1.15 to 3.00)1.05 (0.57 to 1.95)1.27 (0.86 to 1.86)
Stratification by sex   
 Male1.28 (1.01 to 1.62)1.71 (0.82 to 3.55)≤2 years:†
1.24 (0.76 to 2.02)
>2 years:†
2.09 (1.26 to 3.47)		0.86 (0.50 to 1.48)≤1 year:†
2.21 (1.25 to 3.91)
>1 year:†
0.50 (0.21 to 1.14)
 Female1.60 (1.33 to 1.93)2.23 (0.95 to 5.24)1.84 (1.32 to 2.57)1.73 (1.09 to 2.72)1.37 (1.05 to 1.81)
Methotrexate users1.36 (0.97 to 1.90)N.E.N.E.1.20 (0.54 to 2.68)1.30 (0.88 to 1.90)
Methotrexate non-users1.42 (1.21 to 1.68)1.68 (0.92 to 3.06)≤4 years:†
1.58 (1.22 to 2.05)
>4 years:†
3.41 (1.67 to 6.96)		1.22 (0.83 to 1.80)1.21 (0.89 to 1.65)
Methotrexate or corticosteroids users1.24 (0.95 to 1.61)7.75 (0.70 to 85.68)1.41 (0.80 to 2.47)1.37 (0.69 to 2.70)1.10 (0.78 to 1.56)
Methotrexate and corticosteroids non-users1.49 (1.25 to 1.78)1.74 (0.96 to 3.18)1.75 (1.34 to 2.29)1.14 (0.76 to 1.72)1.37 (0.99 to 1.90)
Other hepatotoxic medications users§1.37 (0.63 to 2.97)N.E.1.37 (0.31 to 6.14)0.92 (0.10 to 8.30)1.77 (0.64 to 4.91)
Other hepatotoxic medications non-users§1.48 (1.27 to 1.71)1.90 (1.09 to 3.31)≤4 years:†
1.59 (1.22 to 2.06)
>4 years:†
3.48 (1.71 to 7.11)		1.27 (0.89 to 1.81)1.29 (1.01 to 1.65)

  • *Anti-TNF-α agent includes etanercept, adalimumab, certolizumab, golimumab and/or infliximab.

  • †Results of a piecewise Cox model due to a significant time interaction with anti-TNF-α agent use. After examination of the survival curve constructed in Simon and Makuch’s method, several cut-off time points were tested and the one with the lowest Akaike information criterion was selected.

  • ‡122 autoimmune hepatitis patients, 89 primary biliary cirrhosis patients, 318 primary sclerosing cholangitis patients, 29 Wilson's disease patients, 710 hemochromatosis patients, 41 alpha-1-antitrypsin deficiency patients, and 200 alcoholic liver disease patients were excluded.

  • §Other hepatotoxic medications include azathioprine, leflunomide and/or sulfasalazine.

  • AS, ankylosing spondylitis; IBD, inflammatory bowel disease;

  • N.E., not estimable; PsA, psoriatic arthritis; RA, rheumatoid arthritis; TNF, tumour necrosis factor.