Table 3.
Associations between serum liver function biomarkers in quintiles and risk of IBD
| Quintile 1 | Quintile 2 | Quintile 3 | Quintile 4 | Quintile 5 | Per 1-SD increment | P-nonlinearity | |
|---|---|---|---|---|---|---|---|
| Albumin | 0.002 | ||||||
| Median (IQR) | 42.0 (41.0, 42.6) | 43.9 (43.5, 44.2) | 45.2 (44.9, 45.5) | 46.5 (46.2, 46.9) | 48.5 (47.9, 49.5) | ||
| Cases/person-years | 598/977,731 | 492/981,054 | 400/988,196 | 384/986,437 | 354/982,820 | ||
| HR (95% CI)a | Ref | 0.81 (0.72, 0.92) | 0.66 (0.58, 0.75) | 0.63 (0.55, 0.72) | 0.59 (0.51, 0.67) | 0.83 (0.79, 0.86) | |
| HR (95% CI)b | Ref | 0.87 (0.77, 0.98) | 0.72 (0.64, 0.82) | 0.71 (0.62, 0.81) | 0.67 (0.58, 0.77) | 0.86 (0.83, 0.90) | |
| HR (95% CI)c | Ref | 0.74 (0.57, 0.96) | 0.49 (0.38, 0.65) | 0.47 (0.35, 0.63) | 0.42 (0.31, 0.57) | 0.72 (0.67, 0.80) | |
| Alkaline phosphatase | 0.58 | ||||||
| Median (IQR) | 56.7 (51.1, 60.7) | 69.7 (67.0, 72.3) | 80.0 (77.4, 82.6) | 91.5 (88.3, 95.1) | 111.6 (104.5, 123.1) | ||
| Cases/person-years | 344/994,907 | 370/990,131 | 391/984,979 | 522/976,839 | 601/969,382 | ||
| HR (95% CI)a | Ref | 1.05 (0.91, 1.22) | 1.12 (0.96, 1.29) | 1.51 (1.32, 1.73) | 1.78 (1.56, 2.04) | 1.25 (1.20, 1.31) | |
| HR (95% CI)b | Ref | 1.02 (0.88, 1.18) | 1.05 (0.91, 1.21) | 1.37 (1.19, 1.57) | 1.49 (1.30, 1.71) | 1.18 (1.13, 1.24) | |
| HR (95% CI)c | Ref | 1.03 (0.85, 1.24) | 1.07 (0.88, 1.28) | 1.51 (1.25, 1.80) | 1.68 (1.41, 2.01) | 1.24 (1.17, 1.32) | |
| Alanine transaminase | 0.76 | ||||||
| Median (IQR) | 12.3 (10.7, 13.4) | 16.2 (15.3, 17.0) | 19.9 (18.9, 20.9) | 24.9 (23.4, 26.7) | 35.9 (31.7, 43.3) | ||
| Cases/person-years | 404/985,739 | 466/982,314 | 423/983,661 | 463/980,748 | 472/983,776 | ||
| HR (95% CI)a | Ref | 1.10 (0.96, 1.26) | 0.96 (0.84, 1.11) | 1.04 (0.90, 1.19) | 1.05 (0.91, 1.21) | 1.01 (0.96, 1.06) | |
| HR (95% CI)b | Ref | 1.12 (0.98, 1.28) | 0.96 (0.84, 1.11) | 1.02 (0.88, 1.17) | 1.00 (0.86, 1.15) | 0.99 (0.94, 1.04) | |
| HR (95% CI)c | Ref | 1.23 (0.96, 1.57) | 0.93 (0.73, 1.21) | 1.04 (0.79, 1.33) | 1.00 (0.76, 1.29) | 0.98 (0.89, 1.07) | |
| Aspartate transaminase | 0.29 | ||||||
| Median (IQR) | 18.3 (17.0, 19.3) | 21.6 (20.9, 22.2) | 24.2 (23.6, 24.9) | 27.4 (26.5, 28.5) | 33.7 (31.4, 37.8) | ||
| Cases/person-years | 464/991,971 | 444/1,002,541 | 457/961,705 | 447/996,168 | 416/963,853 | ||
| HR (95% CI)a | Ref | 0.90 (0.79, 1.02) | 0.93 (0.82, 1.06) | 0.86 (0.75, 0.98) | 0.81 (0.71, 0.93) | 0.94 (0.90, 0.98) | |
| HR (95% CI)b | Ref | 0.94 (0.82, 1.07) | 0.99 (0.87, 1.13) | 0.92 (0.80, 1.05) | 0.85 (0.74, 0.97) | 0.95 (0.91, 0.99) | |
| HR (95% CI)c | Ref | 0.90 (0.70, 1.13) | 0.98 (0.78, 1.24) | 0.86 (0.67, 1.09) | 0.75 (0.58, 0.95) | 0.91 (0.85, 0.98) | |
| Gamma-glutamyl transferase | 0.56 | ||||||
| Median (IQR) | 14.5 (12.7, 15.8) | 19.8 (18.5, 21.2) | 26.0 (24.2, 27.9) | 35.7 (32.6, 39.5) | 61.1 (51.0, 80.3) | ||
| Cases/person-years | 393/997,279 | 383/995,403 | 449/971,545 | 473/982,310 | 530/969,701 | ||
| HR (95% CI)a | Ref | 0.92 (0.80, 1.06) | 1.08 (0.94, 1.24) | 1.10 (0.96, 1.27) | 1.25 (1.09, 1.43) | 1.10 (1.04, 1.15) | |
| HR (95% CI)b | Ref | 0.88 (0.76, 1.01) | 0.98 (0.85, 1.12) | 0.95 (0.83, 1.10) | 1.02 (0.88, 1.18) | 1.02 (0.97, 1.07) | |
| HR (95% CI)c | Ref | 0.84 (0.69, 1.01) | 0.97 (0.80, 1.17) | 0.93 (0.77, 1.14) | 1.03 (0.84, 1.25) | 1.03 (0.96, 1.10) | |
| Total bilirubin | < 0.001 | ||||||
| Median (IQR) | 5.3 (4.8, 5.7) | 6.7 (6.4, 7.0) | 8.0 (7.7, 8.4) | 9.7 (9.2, 10.3) | 13.6 (12.1, 16.7) | ||
| Cases/person-years | 548/984,901 | 442/980,557 | 419/985,883 | 431/984,052 | 388/980,845 | ||
| HR (95% CI)a | Ref | 0.77 (0.68, 0.88) | 0.70 (0.62, 0.80) | 0.70 (0.62, 0.80) | 0.62 (0.54, 0.71) | 0.87 (0.83, 0.91) | |
| HR (95% CI)b | Ref | 0.83 (0.73, 0.94) | 0.78 (0.69, 0.89) | 0.80 (0.70, 0.91) | 0.73 (0.63, 0.83) | 0.92 (0.87, 0.96) | |
| HR (95% CI)c | Ref | 0.77 (0.64, 0.92) | 0.70 (0.59, 0.85) | 0.73 (0.61, 0.88) | 0.64 (0.52, 0.77) | 0.89 (0.82, 0.94) | |
| Total protein | 0.011 | ||||||
| Median (IQR) | 67.5 (66.2, 68.4) | 70.3 (69.7, 70.8) | 72.3 (71.8, 72.8) | 74.4 (73.8, 75.0) | 77.7 (76.6, 79.4) | ||
| Cases/person-years | 478/987,545 | 421/990,675 | 475/984,922 | 401/980,838 | 453/972,258 | ||
| HR (95% CI)a | Ref | 0.88 (0.77, 1.00) | 1.00 (0.88, 1.14) | 0.85 (0.75, 0.97) | 0.97 (0.85, 1.10) | 0.97 (0.93, 1.02) | |
| HR (95% CI)b | Ref | 0.89 (0.78, 1.01) | 1.01 (0.89, 1.14) | 0.85 (0.75, 0.97) | 0.96 (0.84, 1.09) | 0.97 (0.93, 1.01) | |
| HR (95% CI)c | Ref | 0.78 (0.59, 1.02) | 1.02 (0.78, 1.32) | 0.71 (0.54, 0.94) | 0.92 (0.69, 1.20) | 0.94 (0.86, 1.02) | |
BMI body mass index, CI confidence interval, HR hazard ratio, IBD inflammatory bowel disease, IQR interquartile range, SD standard deviation
aModel 1 was adjusted for sex, age and ethnicity
bModel 2 was further adjusted for BMI, smoking status, physical activity level, alcohol consumption, Townsend deprivation index, C-reactive protein, healthy diet and Charlson Comorbidity Index based on Model 1
cRecalibrated multivariable estimates accounting for dilution bias using the intraclass correlation coefficients calculated in the subsample of participants with repeat measurements of circulating liver function markers