Hepatic Fibrosis Assessed Using Fibrosis-4 Index Is Predictive of All-Cause Mortality in Patients with Chronic Obstructive Pulmonary Disease

Figures & data

Figure 1 Flow chart for the selection of the study population. A total of 1282 patients with suspected COPD were considered eligible. Of these, 453 patients without PFT results, history of asthma, and not COPD were excluded. Then, 73 patients with known chronic liver diseases were further excluded. Finally, 756 patients with COPD were selected for the statistical analysis.

Abbreviations: COPD, chronic obstructive pulmonary disease; PFT, pulmonary function test.

Table 1 Baseline Characteristics at the Time of COPD Diagnosis (n=756)

Variables	Values
Demographic Variables
Age, years	67.9 ± 8.9
Sex, male	643 (85.1)
Body mass index, kg/m^2	22.5 ± 3.2
Comorbidities
Malignancy	152 (20.1)
Cerebral vascular disease	67 (8.9)
Coronary artery occlusive disease	113 (14.9)
Congestive heart failure	93 (12.3)
Chronic kidney disease	54 (7.1)
Diabetes mellitus	131 (17.3)
Hypertension	254 (33.6)
Bronchiectasis	69 (9.1)
Destroyed lung	47 (6.2)
Smoking (n=731)
Ever smoker	603 (82.5)
Never smoker	128 (17.5)
Pulmonary Function Test Variables
FEV1, L	1.39 ± 0.52
FEV1, % predicted	57.0 ± 18.9
FVC, L	2.48 ± 0.79
FVC, % predicted	69.9 ± 18.6
FEV1/FVC, %	56.1 ± 10.1
Laboratory Variables
Hemoglobin, g/dL	13.7 ± 1.7
Platelet count, ×1000/μL	270.2 ± 93.8
Erythrocyte sedimentation, mm/hr	41.0 ± 36.1
C-reactive protein, mg/L	23.8 ± 48.5
Serum albumin, g/dL	4.2 ± 0.5
Blood urea nitrogen, mg/dL	16.5 ± 7.9
Serum creatinine, mg/dL	1.05 ± 0.33
Aspartate aminotransferase, IU/L	24.9 ± 23.3
Alanine aminotransferase, IU/L	23.2 ± 21.5
Total bilirubin, mg/dL	0.7 ± 1.1
FIB-4	1.53 ± 1.20

Note: Values are expressed as mean ± standard deviation or number (%).

Abbreviations: COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in 1 s; FVC, forced vital capacity; FIB-4, fibrosis-4 index.

Table 2 Comparison Between Survivors and Non-Survivors

Variables	Survivors (n=582, 76.9%)	Non-Survivors (n=174, 23.1%)	P-value
Demographic Variables
Age, years	66.9 ± 9.1	71.3 ± 7.9	<0.001
Sex, male	484 (83.2)	159 (91.4)	0.007
Body mass index, kg/m^2	22.6 ± 3.2	22.4 ± 3.4	0.554
Comorbidities
Malignancy	84 (14.4)	68 (39.1)	<0.001
Cerebral vascular disease	42 (7.2)	25 (14.4)	0.006
Coronary artery occlusive disease	9 (11.9)	44 (25.3)	<0.001
Congestive heart failure	58 (10.0)	35 (20.1)	0.001
Previous tuberculosis	131 (22.5)	44 (25.3)	0.474
Chronic kidney disease	33 (57)	21 (12.1)	0.007
Diabetes mellitus	89 (15.3)	42 (24.1)	0.009
Hypertension	179 (30.8)	75 (43.1)	0.003
Bronchiectasis	58 (10.0)	11 (6.3)	0.177
Destroyed lung	35 (6.0)	12 (6.9)	0.720
Smoking (n=731)
Ever smoker	447/557 (80.3)	156/174 (89.7)	0.004
Never smoker	110/557 (19.7)	18/174 (10.3)
Pulmonary Function Test Variables
FEV1, L	1.41 ± 0.53	1.32 ± 0.46	0.044
FEV1, % predicted	57.4 ± 19.3	55.7 ± 17.8	0.281
FVC, L	2.52 ± 0.81	2.36 ± 0.73	0.013
FVC, % predicted	70.8 ± 18.9	67.1 ± 17.4	0.017
FEV1/FVC, %	56.2 ± 10.4	55.7 ± 9.4	0.526
Laboratory Variables
Hemoglobin, g/dL	13.8 ± 1.7	13.4 ± 1.8	0.066
Platelet count, ×1000/μL	268.8 ± 90.3	273.7 ± 106.1	0.558
Eosinophil,/μL	251 ± 267	225 ± 229	0.283
Eosinophil, %	3.2 ± 2.9	2.9 ± 2.8	0.329
Erythrocyte  sedimentation, mm/hr	37.2 ± 32.9	51.6 ± 42.5	0.057
C-reactive  protein, mg/L	21.0 ± 47.3	28.9 ± 50.4	0.124
Serum albumin, g/dL	4.3 ± 0.5	4.1 ± 0.6	0.006
Blood urea  nitrogen, mg/dL	15.9 ± 6.8	18.1 ± 10.3	0.054
Serum  creatinine, mg/dL	1.01 ± 0.29	1.14 ± 0.41	0.005
Aspartate  aminotransferase,  IU/L	24.2 ± 17.9	27.0 ± 35.8	0.321
Alanine  aminotransferase,  IU/L	22.8 ± 16.2	24.8 ± 33.5	0.452
Total bilirubin, mg/dL	0.6 ± 0.3	0.9 ± 2.1	0.219
FIB-4	1.4 ± 0.8	1.8 ± 2.0	<0.001

Note: Values are expressed as mean ± standard deviation or number (%).

Abbreviations: FEV₁, forced expiratory volume in 1 s; FVC, forced vital capacity; FIB-4, fibrosis-4 index.

Table 3 Multivariate Cox Hazard Model to Identify Independent Predictors of All-Cause Mortality

Variables	Hazard Ratio	95% CI	P-value
Demographic Variables
Age, years	1.05	1.03–1.07	<0.001
Sex, male	1.67	0.94–2.94	0.080
Body mass index, kg/m^2	0.95	0.89–0.99	0.031
Comorbidities
Malignancy	2.94	2.15–4.02	<0.001
Cerebral vascular disease	1.28	0.82–1.99	0.274
Coronary artery occlusive disease	1.58	1.10–2.26	0.013
Chronic kidney disease	1.38	0.84–2.25	0.205
Diabetes mellitus	1.29	0.88–1.88	0.187
Hypertension	1.10	0.78–1.56	0.570
Pulmonary Function Test Variables
GOLD stage, as one stage increases	1.26	1.02–1.56	0.036
FIB-4	1.15	1.03–1.27	0.010

Abbreviations: CI, confidence interval; FIB-4, fibrosis-4 index; GOLD, global initiative for chronic obstructive lung disease.

Figure 2 The cumulative survival rate according to FIB-4. When the study population was stratified into three risk groups (low [Q1], intermediate [Q2-3], and high [Q4] FIB-4 groups), the high FIB-4 (>1.57) group had a significantly lower cumulative survival rate than the low FIB-4 (≤1.05) group (P=0.031, Log-rank test).

Abbreviation: FIB-4, fibrosis-4 index.

Table 4 Multivariate Regression Analysis for the Relationship Between FIB-4 and Acute Exacerbation

Variables	Odds Ratio	95% CI	P-value
Age, years	0.99	0.98–1.01	0.277
Sex, male	1.21	0.93–1.59	0.155
Body mass index, kg/m^2	1.01	0.99–1.03	0.501
GOLD stage, as one stage increases	1.19	1.07–1.34	0.002
FIB-4	1.08	1.01–1.15	0.034

Abbreviations: CI, confidence interval; FIB-4, fibrosis-4 index; GOLD, global initiative for chronic obstructive lung disease.