RDW-SD is Superior to RDW-CV in Reflecting Liver Fibrosis Stage in Patients with Chronic Hepatitis B

Figures & data

Table 1 The Demographic and Clinical Characteristics of CHB Patients and Healthy Controls

Variables	CHB Patients	Healthy Controls	p-value
	(n=720)	(n=578)
Age, years	36.71 ± 10.51	36.12 ± 12.25	0.348
Gender, Male/Female	424/296	361/217	0.209
TP, g/L	69.38 ± 6.18	74.18 ± 3.80	<0.001
Albumin, g/L	40.78 ± 4.36	46.34 ± 2.43	<0.001
Globulin, g/L	28.61 ± 4.41	27.85 ± 3.16	<0.001
ALT, U/L	44.00 (28.00–77.00)	16.00 (12.00–24.00)	<0.001
AST, U/L	31.00 (23.00–46.00)	19.00 (17.00–22.00)	<0.001
TBIL, μmol/L	15.53 ± 12.85	14.19 ± 4.59	0.017
ALP, U/L	85.29 ± 36.54	81.43 ± 19.42	0.022
γ-GGT, U/L	25.00 (16.00–42.00)	24.00 (16.00–36.00)	<0.001
BUN, mmol/L	4.76 ± 1.30	4.78 ± 1.06	0.718
Creatinine, μmol/L	72.38 ± 17.86	56.38 ± 12.95	<0.001
Uric acid (μmol/L)	305.62 ± 80.05	318.55 ± 53.15	0.001
WBC, ×10^9 /L	6.32 ± 1.76	6.13 ± 1.37	0.784
Neutrophils, ×10^9/L	3.30 ± 1.23	3.41 ± 1.00	0.973
Lymphocytes, ×10^9/L	2.25 ± 0.69	2.13 ± 0.57	0.795
Monocytes, ×10^9/L	0.59 ± 0.20	0.43 ± 0.13	0.145
RBC, ×10^12/L	4.67 ± 0.49	4.91 ± 0.44	<0.001
Hemoglobin, g/L	141.79 ± 16.42	143.47 ± 13.93	0.044
MCV, fL	90.62 ± 5.05	89.29 ± 3.75	<0.001
MCH, pg	30.31 ± 2.13	29.25 ± 1.57	<0.001
MCHC, g/L	335.24 ± 12.02	327.61 ± 10.75	<0.001
RDW-CV, %	13.13 ± 0.09	13.06 ± 0.72	0.137
RDW-SD, fL	43.36 ± 3.12	42.46 ± 2.53	<0.001
Platelet, ×10^9/L	169.23 ± 54.87	235.03 ± 52.47	<0.001
PDW, %	15.07 ± 2.68	13.76 ± 2.42	<0.001
MPV, fL	11.55 ± 1.46	11.23 ± 1.05	<0.001
HBsAg, Log10 IU/mL	3.59 ± 0.94	–	–
HBeAg status, -/+	342/378	–	–
HBV DNA, Log10 IU/mL	4.94 ± 2.59	–	–
Fibrosis stage, n (%)
F0	43 (6.0%)	–	–
F1	358 (49.7%)
F2	185 (25.7%)	–	–
F3	82 (11.4%)	–	–
F4	52 (7.2%)	–	–

Abbreviations: TP, total protein; ALT, alanine aminotransferase; AST, aspartate aminotransferase; TBIL, total bilirubin; ALP, alkaline phosphatase; γ-GGT, gamma-glutamyl transpeptidase; BUN, blood urea nitrogen; WBC, white blood count; RBC, red blood cell; MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin; MCHC, mean cell hemoglobin concentration; RDW-CV, red blood cell distribution width-coefficient of variation; RDW-SD, red blood cell distribution width- standard deviation; PDW, platelet distribution width; MPV, mean platelet volume; HBsAg, hepatitis B surface antigen; HBeAg, hepatitis B e antigen; HBV DNA, hepatitis B virus DNA.

Figure 1 Associations between RDW-CV, RDW-SD, and liver fibrosis stages. (A) Comparisons of RDW-CV across liver fibrosis stages. (B) Comparisons of RDW-SD across liver fibrosis stages. (C) Correlations between RDW-CV and liver fibrosis stages. (D) Correlations between RDW-SD and liver fibrosis stages. (E) Comparison of RDW-CV between patients with and without significant fibrosis. (F) Comparison of RDW-SD between patients with and without significant fibrosis.

Table 2 The Demographic and Clinical Characteristics of CHB Patients with and without Significant Fibrosis

Variables	No Significant Fibrosis	Significant Fibrosis	p-value
	(n=401)	(n=319)
Age, years	35.74 ± 1.04	37.95 ± 1.05	0.003
Gender, Male/Female	220/181	381/217	0.006
TP, g/L	69.34 ± 5.71	69.43 ± 6.72	0.993
Albumin, g/L	41.19 ± 4.03	40.26 ± 4.70	0.004
Globulin, g/L	28.11 ± 4.07	29.24 ± 4.75	0.004
ALT, U/L	40.00 (25.00–64.00)	50.00 (33.00–92.00)	<0.001
AST, U/L	27.00 (22.00–40.00)	37.00 (27.00–55.00)	<0.001
TBIL, μmol/L	13.85 ± 7.58	61.82 ± 96.46	<0.001
ALP, U/L	79.17 ± 30.99	92.98 ± 41.28	<0.001
γ-GGT, U/L	22.00 (15.00–35.00)	32.00 (20.00–58.00)	<0.001
BUN, mmol/L	4.71 ± 1.24	4.83 ± 1.38	0.369
Creatinine, μmol/L	71.29 ± 18.17	73.75 ± 17.38	0.076
Uric acid (μmol/L)	303.15 ± 79.38	308.71 ± 80.89	0.604
WBC, ×10^9 /L	6.52 ± 1.71	6.08 ± 1.79	0.001
Neutrophils, ×10^9/L	3.41 ± 1.16	3.17 ± 1.31	0.003
Lymphocytes, ×10^9/L	2.35 ± 0.68	2.14 ± 0.69	<0.001
Monocytes, ×10^9/L	0.55 ± 0.21	0.57 ± 0.20	0.440
RBC, ×10^12/L	4.70 ± 0.51	4.63 ± 0.46	0.033
Hemoglobin, g/L	142.23 ± 15.58	141.43 ± 17.07	0.753
MCV, fL	89.70 ± 4.98	91.76 ± 4.92	<0.001
MCH, pg	29.95 ± 2.20	30.75 ± 1.94	<0.001
MCHC, g/L	335.24 ± 12.02	335.24 ± 12.04	0.869
RDW-CV, %	13.03 ± 0.92	13.26 ± 0.95	<0.001
RDW-SD, fL	42.38 ± 2.75	44.58 ± 3.12	<0.001
Platelet, ×10^9/L	187.28 ± 51.91	146.53 ± 49.90	<0.001
PDW, %	14.74 ± 2.48	15.48 ± 2.86	<0.001
MPV, fL	11.42 ± 1.40	11.71 ± 1.50	0.003
HBsAg, Log10 IU/mL	3.71 ± 0.99	3.43 ± 0.86	<0.001
HBeAg status, -/+	184/217	158/161	0.367
HBV DNA, Log10 IU/mL	5.14 ± 2.58	4.68 ± 2.57	0.011

Table 3 Univariate and Multivariate Analysis of Clinical Parameters Associated with Significant Liver Fibrosis

Variables	Univariate Regression		Multivariate Regression^a		Multivariate Regression^b
	OR (95% CI)	p-value	OR (95% CI)	p-value	OR (95% CI)	p-value
Age, years	1.020 (1.006–1.035)	0.005	0.990 (0.972–1.009)	0.310	0.989 (0.970–1.008)	0.259
Gender, Male/Female	1.459 (1.080–1.973)	0.014	1.692 (1.174–2.438)	0.005	1.649 (1.140–2.385)	0.008
TP, g/L	1.002 (0.979–1.026)	0.849
Albumin, g/L	0.951 (0.919–0.985)	0.004	0.953 (0.910–0.997)	0.037	0.957 (0.914–1.002)	0.058
Globulin, g/L	1.061 (1.025–1.097)	0.001	1.089 (1.042–1.138)	<0.001	1.085 (1.038–1.135)	<0.001
ALT, U/L	1.003 (1.001–1.005)	0.001	1.000 (0.996–1.004)	0.987	1.000 (0.996–1.004)	0.973
AST, U/L	1.007 (1.003–1.011)	<0.001	1.001 (0.995–1.008)	0.683	1.002 (0.995–1.008)	0.653
TBIL, μmol/L	1.034 (1.016–1.052)	<0.001	1.016 (0.994–1.039)	0.154	1.014 (0.992–1.037)	0.200
ALP, U/L	1.013 (1.008–1.018)	<0.001	1.008 (1.002–1.015)	0.007	1.008 (1.002–1.015)	0.008
GGT, U/L	1.009 (1.005–1.014)	<0.001	1.001 (0.996–1.007)	0.626	1.001 (0.996–1.007)	0.659
BUN, mmol/L	1.073 (0.958–1.201)	0.223
Creatinine, μmol/L	1.008 (0.999–1.016)	0.068
Uric acid (μmol/L)	1.001 (0.999–1.003)	0.355
WBC, ×10^9 /L	0.865 (0.793–0.943)	0.001	1.433 (0.755–2.719)	0.272	1.364 (0.713–2.611)	0.349
Neutrophils, ×10^9/L	0.853 (0.755–0.964)	0.011	0.703 (0.341–1.451)	0.341	0.744 (0.357–1.549)	0.429
Lymphocytes, ×10^9/L	0.637 (0.510–0.796)	<0.001	0.565 (0.260–1.228)	0.149	0.611 (0.278–1.344)	0.221
Monocytes, ×10^9/L	1.384 (0.674–2.843)	0.376
RBC, ×10^12/L	0.728 (0.537–0.987)	0.041	1.535 (0.959–2.456)	0.074	1.572 (0.983–2.513)	0.059
Hemoglobin, g/L	1.003 (0.994–1.012)	0.517
MCV, fL	1.098 (1.060–1.137)	<0.001	1.106 (1.035–1.182)	0.003	0.990 (0.919–1.068)	0.802
MCH, pg	1.235 (1.133–1.347)	<0.001	1.183 (0.998–1.403)	0.053	1.201 (1.015–1.422)	0.033
MCHC, g/L	1.000 (0.988–1.012)	0.994
RDW-CV, %	1.308 (1.109–1.543)	0.001	1.921 (1.452–2.543)	<0.001
RDW-SD, fL	1.292 (1.221–1.368)	<0.001			1.272 (1.171–1.383)	<0.001
Platelet, ×10^9/L	0.984 (0.981–0.987)	<0.001	0.982 (0.977–0.987)	<0.001	0.982 (0.978–0.987)	<0.001
PDW, %	1.111 (1.050–1.175)	<0.001	0.958 (0.872–1.052)	0.371	0.974 (0.885–1.072)	0.593
MPV, fL	1.149 (1.036–1.274)	0.008	1.017 (0.860–1.202)	0.848	0.977 (0.820–1.163)	0.791
HBsAg, lg IU/mL	0.717 (0.610–0.843)	<0.001	0.731 (0.572–0.935)	0.013	0.738 (0.576–0.946)	0.017
HBeAg status, -/+	1.157 (0.862–1.554)	0.331
HBV DNA, lg IU/mL	0.933 (0.881–0.988)	0.018	1.068 (0.975–1.170)	0.154	1.071 (0.977–1.175)	0.144

Notes: Multivariate regression ^a and Multivariate regression ^b are two independent multivariate logistic regression analyses. The former includes RDW-CV along with other parameters, while the latter incorporates RDW-SD along with other parameters.

Figure 2 ROC curves of RDW-CV and RDW-SD. (A) ROC curves for diagnosing significant fibrosis using RDW-CV and RDW-SD in CHB patients. (B) ROC curves for diagnosing significant fibrosis using RPR and RsdPR in CHB patients. (C) ROC curves for diagnosing significant fibrosis using RDW-CV and RDW-SD in CHB patients younger than 30. (D) ROC curves for diagnosing significant fibrosis using RDW-CV and RDW-SD in CHB patients aged 30 or older. (E) ROC curves for diagnosing significant fibrosis using RDW-CV and RDW-SD in female CHB patients. (F) ROC curves for diagnosing significant fibrosis using RDW-CV and RDW-SD in male CHB patients. (G) ROC curves for diagnosing significant fibrosis using RDW-CV and RDW-SD in HBeAg-negative CHB patients. (H) ROC curves for diagnosing significant fibrosis using RDW-CV and RDW-SD in HBeAg-positive CHB patients.

Data Sharing Statement

The datasets generated and/or analyzed during the current study are not publicly available due to privacy restrictions but are available from the corresponding author on reasonable request.