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Journal of Chinese Integrative Medicine ›› 2012, Vol. 10 ›› Issue (12): 1382-1387.doi: 10.3736/jcim20121208

• Original Clinical Research • Previous Articles     Next Articles

Diagnostic value of clinical indices in syndrome differentiation of chronic hepatitis B: an exploration based on receiver operating characteristic curves and stepwise discriminant analysis

 Yu Zhao1, Jing-hua Peng1, Xue-mei Li1,2, Qi-lin Fu1, Tuan Cui1, Qi Li1, Ya-jun Tang1,3, Qin Feng1, Hua Zhang1, Hua Zhou1, Yi-yang Hu1()   

  1. 1. Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
    2. Department of Hepatology, First Affiliated Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin 300192, China
    3. Department of Traditional Chinese Medicine, Ningbo Jiangdong District Hospital of Chinese Medicine, Ningbo 315040, Zhejiang Province, China
  • Received:2012-05-22 Accepted:2012-07-10 Online:2012-12-20 Published:2018-12-15

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Objective: To explore the diagnostic value of 75 commonly used clinical laboratory markers for differentiation of traditional Chinese medicine syndromes such as liver and gallbladder damp-heat and liver depression and spleen deficiency in patients with chronic hepatitis B.
Methods: A total of 422 patients with chronic hepatitis B (CHB) were enrolled, including 300 patients with damp-heat in liver and gallbladder syndrome, and 122 patients with liver depression and spleen deficiency syndrome. Seventy-five commonly used clinical markers were selected, including liver and kidney function, clotting function, the quantitative detection of hepatic B virus (HBV) markers, HBV-DNA, blood count, hormones levels, cellular immunity indicators, humoral immunity indicators, lipid panel, protein electrophoresis, alpha-fetoprotein and liver fibrosis indicators. Receiver operating characteristic (ROC) curve was used to detect the diagnostic efficiency of single differential indicators, and stepwise discriminant analysis model was used to explore the discrimination efficiency of differential indices between two TCM syndromes in CHB.
Results: The differential indices between two CHB Chinese syndromes were albumin, prothrombin time, immunoglobulin A, immunoglobulin M, blood urea nitrogen, blood uric acid, basophils, basophil percentage and mean platelet volume. The area under ROC curve (AUC) of these indices was between 0.42 and 0.62, and the total false positive rate of own validation of stepwise discriminant analysis model, which was established by differential indices combination, was 35.3%, and the jackknife total error rate was 35.3%.
Conclusion: Neither single differential index nor multiple differential indices determinant models provided appropriate determination of the TCM syndromes of patients with chronic hepatitis B, suggesting that clinical indicators have limited value in determining traditional Chinese medicine syndromes.

Key words: symptom complex, discriminant analysis, ROC curve, hepatitis B,chronic, clinical trial

Table 1

Basic information of cases (Median, range)"

Syndrome n Gender (n, %) Age (Median
(range), years)		 BMI (Median
(range), kg/m2)		 Disease duration (Median
(range), years)
Male Female
Damp-heat in liver and gallbladder 300 242/80.67 58/19.33 36 (17, 69) 22 (16, 32) 9 (2, 41)
Liver depression and spleen deficiency 122 98/80.33 24/19.67 36 (17, 66) 22 (15, 31) 10 (3, 29)
Z/χ2 空 0.01 -0.60 -0.02 -0.87 空
P value 空 0.94 0.55 0.98 0.38 空

Table 2

Clinical variants with different distribution between two syndromes of chronic hepatitis B"

Indicator (Median (P25,P75)) Damp-heat in liver and gallbladder
(n=300)		 Liver depression and spleen
deficiency (n=122)		 Zvalue Pvalue
Albumin (g/L) 30.71 (28.63, 42.19) 29.28 (27.62, 31.72) -3.79 0.00
Prothrombin time (s) 13.00 (11.80, 14.27) 13.40 (12.40, 15.00) -2.21 0.03
IgA (g/L) 3.24 (2.46, 4.38) 3.08 (2.13, 3.89) -2.13 0.03
IgM (g/L) 1.56 (1.10, 2.23) 1.84 (1.29, 2.53) -2.47 >0.01
Blood urea nitrogen (mmol/L) 4.14 (3.58, 4.91) 3.91 (3.52, 4.61) -2.07 0.04
Blood uric acid (μmol/L) 279.47 (245.61, 310.24) 263.94 (222.33, 298.75) -2.67 <0.01
Basophil count (109/L) 0.01 (0.01, 0.03) 0.01 (0.01, 0.02) -4.06 0.00
Percent of basophils (%) 0.30 (0.20, 0.50) 0.20 (0.20, 0.39) -3.96 0.00
Mean platelet volume (fL) 10.30 (9.4, 11.2) 10.65 (9.8, 11.73) -2.57 >0.01

Table 3

Diagnostic efficiency of single variant of chronic hepatitis B syndromes analyzed by ROC"

Indicator Group AUC 95% CI P value
Albumin (g/L) Damp-heat in liver and gallbladder 0.62 (0.56-0.68) 0.00
Liver depression and spleen deficiency 0.38 (0.32-0.44)
Prothrombin time (s) Damp-heat in liver and gallbladder 0.43 (0.37-0.49) 0.02
Liver depression and spleen deficiency 0.57 (0.51-0.63)
IgA (g/L) Damp-heat in liver and gallbladder 0.57 (0.51-0.63) 0.03
Liver depression and spleen deficiency 0.43 (0.37-0.49)
IgM (g/L) Damp-heat in liver and gallbladder 0.42 (0.36-0.48) >0.01
Liver depression and spleen deficiency 0.58 (0.52-0.64)
Blood urea nitrogen (mmol/L) Damp-heat in liver and gallbladder 0.57 (0.51-0.63) 0.03
Liver depression and spleen deficiency 0.43 (0.37-0.49)
Blood uric acid (μmol/L) Damp-heat in liver and gallbladder 0.59 (0.52-0.65) <0.01
Liver depression and spleen deficiency 0.41 (0.35-0.48)
Basophil count (109/L) Damp-heat in liver and gallbladder 0.61 (0.56-0.67) 0.00
Liver depression and spleen deficiency 0.39 (0.33-0.44)
Percent of basophils (%) Damp-heat in liver and gallbladder 0.62 (0.56-0.68) 0.00
Liver depression and spleen deficiency 0.38 (0.32-0.44)
Mean platelet volume (fL) Damp-heat in liver and gallbladder 0.42 (0.36-0.48) >0.01
Liver depression and spleen deficiency 0.58 (0.52-0.64)

Table 4

Stepwise discriminant function of two syndromes"

Indicator Damp-heat in liver and gallbladder Liver depression and spleen deficiency
Constant -30.56 -30.82
PT 2.61 2.77
BUA 0.09 0.09
BC -0.49 -25.25

Table 5

Stepwise discriminant function false positive rate (%)"

False positive rate Damp-heat in liver and gallbladder Liver depression and spleen deficiency Total error rate
One by one return
on behalf		 34.4 35.7 35.3
Jackknife 34.4 35.7 35.3
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