Correlation Between Total Bilirubin, Total Bilirubin/Albumin Ratio with Disease Activity in Patients with Rheumatoid Arthritis

Figures & data

Figure 1 Plasma total bilirubin and total bilirubin/albumin ratio levels in healthy controls (n=197) and patients with RA (n=197). (A) Plasma total bilirubin levels were significantly lower in the patients with RA than in the healthy controls. **p < 0.001. (B) Plasma total bilirubin/albumin ratio levels were significantly lower in the patients with RA than in the healthy controls. **p < 0.001.

Table 1 Patient Characteristics and Results of Univariate Analysis

Variables	DAS28-ESR<3.2	3.2≤DAS28-ESR≤5.1	DAS28-ESR>5.1	p value
	(n=73)	(n=54)	(n=70)
Demographic data
Female	64 (87.70)	43 (79.60)	55 (78.60)	0.306
Age (y)	46.53 ± 11.35	48.91 ± 11.63	55.70 ± 13.31	<0.001*
Disease duration (m)	48 (18–114)	60 (24–120)	12 (48–120)	0.486
BMI (kg/m^2)	22.88 ± 3.01	23.43 ± 3.22	22.75 (20.81–25.15)	0.736
Smoke	7 (9.60)	8 (14.80)	7 (10.00)	0.605
Drinking	2 (2.70)	11 (20.40)	5 (7.10)	0.002*
Hypertension	8 (11.00)	6 (11.30)	15 (21.40)	0.149
Diabetes	2 (2.70)	3 (5.60)	11 (15.70)	0.013*
Hyperlipidemia	20 (27.40)	16 (29.60)	22 (31.40)	0.869
Laboratory data
TBIL (μmol/L)	14.50 (11.05–15.90)	8.10 (9.50–11.70)	7.38 (9.50–11.13)	<0.001*
Uric acid (μmol/L)	259.51 ± 75.30	286.66 ± 69.04	274.98 ± 92.85	0.164
Albumin (g/L)	47.38 ± 2.62	44.79 ± 3.95	40.50 ± 4.84	<0.001*
AST (U/L)	21.66 ± 4.88	19.00 (16.00–22.25)	16.00 (13.00–19.25)	<0.001*
ALT (U/L)	14.00 (10.00–19.00)	12.00 (9.00–15.00)	11.50 (9.00–16.00)	0.036*
CRP (mg/L)	1.26 (0.37–3.11)	9.67 (2.97–24.38)	45.80 (25.70–68.70)	<0.001*
ESR (mm/h)	12.00 (6.00–17.50)	33.00 (24.25–42.50)	62.50 (43.75–77.00)	<0.001*
Neutrophils (10^9/L)	3.53 (2.75–5.02)	4.94 ± 1.62	5.11 (3.80–7.02)	<0.001*
Lymphocytes (10^9/L)	1.41 (1.12–1.75)	1.50 (1.24–1.77)	1.36 (1.01–1.77)	0.309
Platelets (10^12/L)	193.00 (162.00–230.50)	227.50 (202.75–257.25)	284.00 (223.50–320.50)	<0.001*
Interleukin-2	1.39 (0.82–2.04)	1.49 (0.42–2.44)	1.78 (0.96–3.44)	0.069
Interleukin-4	1.39 (0.67–2.38)	0.98 (0.39–2.23)	1.79 (0.26–3.51)	0.192
Interleukin-6	6.42 (3.8312.75)	11.68 (5.15–29.61)	36.80 (13.60–87.58)	<0.001*
Interleukin-10	3.11 (1.24–3.76)	2.46 (1.27–3.89)	3.39 (2.26–4.97)	0.026*
Interleukin-17A	5.07 (0.00–14.52)	0.01 (0.00–9.56)	3.38 (0.00–17.49)	0.057
TNF-α	2.53 (1.47–5.10)	1.78 (0.73–4.92)	3.45 (1.45–8.86)	0.063
Interferon-γ	1.14 (0.59–2.04)	0.63 (0.02–1.39)	1.54 (0.66–3.01)	0.001*
Positive of RF-IgM	31 (42.50)	33 (61.10)	62 (88.60)	<0.001*
Positive of ACPA	55 (75.30)	49 (90.70)	62 (88.60)	0.029*
DMARDs
Tofacitinib	20 (27.40)	10 (18.50)	4 (5.70)	0.003*
Biologic DMARDs	26 (35.60)	11 (20.40)	8 (11.40)	0.002*

Notes: Data are presented as mean ± standard deviation, n (%) or median (range); *p < 0.05. The levels of lipid profile that satisfied one of following four conditions were defined as dyslipidemia: total cholesterol (TC) ≥ 5.72 mmol/L, triglyceride (TG) ≥ 1.80 mmol/L, low-density lipoprotein cholesterol (LDL-C) ≥ 3.40 mmol/L or high-density lipoprotein cholesterol (HDL-C) < 1.60 mmol/L. Biological DMARDs, including tumor necrosis factor-inhibitors and interleukin-6-inhibitors.

Abbreviations: BMI, body mass Index; TBIL, total bilirubin; AST, aspartate transaminase; ALT, alanine transaminase; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; TNF-α, Tumor necrosis factor alpha; RF, rheumatoid factor; ACPA, anti–cyclic citrullinated peptide antibodies; DMARDs, disease-modifying antirheumatic drugs.

Table 2 Results of Multivariate Ordered Logistic Regression Analysis for Variables Affecting Disease Activity

Variables	p value	OR (95% CI)
Total bilirubin	<0.001*	0.77 (0.67, 0.89)
Albumin	0.001*	0.80 (0.70, 0.91)
Tofacitinib	<0.001*	0.04(0.01, 0.17)
Biological DMARDs	0.005*	0.21(0.07, 0.63)
ESR	<0.001*	1.07(1.04, 1.11)
CRP	0.001*	1.05(1.02, 1.09)
Interleukin-6	0.027*	1.01(1.00, 1.02)
RF-IgM	0.022*	3.14(1.18, 8.33)

Notes: Ordered logistic regression is used to assess the association between independent factors and increasing disease activity. Protection and risk factors were assessed independently in the univariable analysis. Univariable factors with p<0.05 were included in the multivariable ordered logistic regression analysis. * p<0.05.

Table 3 Correlations of Bilirubin and Total Bilirubin/Albumin Ratio with Inflammatory and Immunological Indexes

	Total Bilirubin		Direct Bilirubin		Indirect Bilirubin		TBIL/Albumin
	rs	P	rs	P	rs	P	rs	P
DAS28-ESR	−0.487	<0.001*	−0.404	<0.001*	−0.492	<0.001*	−0.323	<0.001*
Leukocytes (10^9/L)	−0.219	0.002*	−0.202	0.004*	−0.214	0.003*	−0.233	0.001*
Neutrophils (10^9/L)	−0.206	0.004*	−0.181	0.011*	−0.208	0.003*	−0.208	0.003*
ESR (mm/h)	−0.449	<0.001*	−0.389	<0.001*	−0.446	<0.001*	−0.305	<0.001*
CRP (mg/L)	−0.353	<0.001*	−0.300	<0.001*	−0.358	<0.001*	−0.198	0.005*
PLT (10^12/L)	−0.419	<0.001*	−0.391	<0.001*	−0.393	<0.001*	−0.354	<0.001*
IL-6 (pg/mL)	−0.181	0.011*	−0.197	0.006*	−0.173	0.015*	−0.089	0.214
IL-10 (pg/mL)	−0.114	0.111	−0.147	0.039*	−0.103	0.150	−0.083	0.246
RF-IgM (IU/mL)	−0.131	0.067	−0.084	0.240	−0.143	0.045*	−0.018	0.804

Note: *p<0.05.

Figure 2 Accuracy of total bilirubin and total bilirubin/albumin ratio to predict disease activity in rheumatoid arthritis (DAS28-ESR<3.2 vs DAS28-ESR≥3.2).