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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
[1] Chinese Society of Hepatology of Chinese Medical Association, Chinese Society of Infectious Diseases of Chinese Medical Association. The guideline of prevention and treatment for chronic hepatitis B. Zhonghua Gan Zang Bing Za Zhi. 2005; 13(12):881-891. Chinese.
doi: 10.3969/j.issn.1672-5069.2006.01.003
中华医学会肝病学分会,中华医学会感染病学分会. 慢性乙型肝炎防治指南.中华肝脏病杂志. 2005; 13(12):881-891
doi: 10.3969/j.issn.1672-5069.2006.01.003
[2] Ye YA, Jiang F, Zhao ZM, Li ZH, Zhang L, Liu HQ, Huang NY . Chinese medical pattern distribution of chronic type hepatitis B. Zhong Yi Za Zhi. 2007 ; 48(3) : 256-258. Chinese with abstract in English.
doi: 10.3321/j.issn:1001-1668.2007.03.034
叶永安, 江峰, 赵志敏, 李志红, 张良, 刘慧清, 黄宁宇 . 慢性乙型肝炎中医证型分布规律研究.中医杂志. 2007; 48(3) : 256-258.
doi: 10.3321/j.issn:1001-1668.2007.03.034
[3] Professional Committee of Liver Diseases of China Association of Chinese Medicine. Standards of traditional Chinese medicine syndrome differentiation for viral hepatitis (trial implementation) . Zhong Yi Za Zhi. 1992 ; ( 5):39-40. Chinese.
中国中医药学会内科肝病专业委员会. 病毒性肝炎中医辨证标准(试行).中医杂志. 1992; ( 5):39-40.
[4] Lii AP, Li S, Wang YY . Exploration of the scientific foundations of traditional Chinese medicine syndrome classification from the objective rules of subjective symptoms. Zhong Yi Za Zhi. 2005; 46(1):4-6. Chinese.
doi: 10.3321/j.issn:1001-1668.2005.01.002
吕爱平, 李梢, 王永炎 . 从主观症状的客观规律探索中医证候分类的科学基础.中医杂志. 2005; 46(1):4-6.
doi: 10.3321/j.issn:1001-1668.2005.01.002
[5] Lei Y, Wang ZH, Liu JG . Study on rules of TCM syndrome in patients with dyslipidemia and its objectification. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2007 ; 27(12):1074-1077. Chinese with abstract in English.
雷燕, 王振华, 刘剑刚 . 血脂异常中医证候规律及其客观化研究.中国中西医结合杂志. 2007; 27(12):1074-1077.
[6] Jiang J, Gao YQ, Wu X, Wang LT . Correlative study between Chinese medical syndrome and laboratory index in chronic hepatitis B. Shanghai Zhong Yi Za Zhi. 2002 ; ( 6):15-17. Chinese with abstract in English.
doi: 10.3969/j.issn.1007-1334.2002.06.010
蒋健, 高月求, 吴潇, 王灵台 . 慢性乙型肝炎中医证型与实验室指标相互关系的研究.上海中医药杂志. 2002; ( 6):15-17.
doi: 10.3969/j.issn.1007-1334.2002.06.010
[7] Yuan JL, Zhang H, Wang L, Lin Y, Hu XC, Zhang Q, Liu P . Biochemical characteristics of traditional Chinese medicine syndromes and their elements in patients with hepatitis B cirrhosis. J Chin Integr Med. 2011; 9(4):374-381. Chinese with abstract in English.
袁继丽, 张华, 王磊, 林彦, 胡鑫才, 张琴, 刘平 . 乙型肝炎后肝硬化患者中医证候要素的生物化学特征.中西医结合学报. 2011; 9(4):374-381.
[8] Swets JA . Measuring the accuracy of diagnostic systems. Science. 1988; 240(4857):1285-1293.
doi: 10.1126/science.3287615 pmid: 3287615
[9] Tian JZ, Wang YY, Shi J, Zhu AH, Zhang BL, Huang QF .Concept and attributes of syndrome manifestations .Beijing Zhong Yi Yao Da Xue Xue Bao. 2005; 28(5):6-8. Chinese with abstract in English.
田金洲, 王永炎, 时晶, 朱爱华, 张伯礼, 黄启福 . 证候的概念及其属性.北京中医药大学学报. 2005; 28(5):6-8.
[10] Hood L, Heath JR, Phelps ME, Lin B . Systems biology and new technologies enable predictive and preventative medicine. Science. 2004; 306(5696):640-643.
doi: 10.1126/science.1104635 pmid: 15499008
[11] Auffray C, Chen Z, Hood L . Systems medicine: the future of medical genomics and healthcare. Genome Med. 2009; 1(1) : 2.
doi: 10.1186/gm2 pmid: 19348689
[12] Li S, Wang YY . Relationship between systems theory and reductionism in medical research. Beijing Zhong Yi Yao Da Xue Xue Bao. 2005; 28(5):1-5. Chinese with abstract in English.
李梢, 王永炎 . 医学研究中系统论与还原论的关联关系.北京中医药大学学报. 2005; 28(5):1-5.
[13] Li S . Discussion on the characteristics of TCM syndromes from the concepts of dimensions and ranks: approaches to the standardization of TCM syndromes. Beijing Zhong Yi Yao Da Xue Xue Bao. 2003; 26(3):1-4. Chinese with abstract in English.
doi: 10.3321/j.issn:1006-2157.2003.03.001
李梢 . 从维度与阶度探讨中医证候的特征及标准化方法.北京中医药大学学报. 2003; 26(3):1-4.
doi: 10.3321/j.issn:1006-2157.2003.03.001
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