Wng Xinxin(王欣欣),nd Zhu Weiping (朱維平)

a: Institute of Integrative Medicine, Medical College of Qingdao University, Qingdao 266021, China

b: Qingdao Haici hospital, Qingdao 266000, China

OBJECTIVE:To analyze the distribution and characteristics of TCM constitution in patients with primary biliary cholangitis(PBC).METHODS:138 PBC patients who met the inclusion criteria were divided into 3 groups according to the stage of disease development: group A (group of basic normal), group B (group of symptom stage) and group C (group of decompensation stage).Each group collected 46 cases, and every patient was reexamined,which included blood routine examination, liver function test,image ultrasound examination, autoantibody examination and immunoglobulin test. Then, the patients’ clinical symptoms were observed and recorded, and their constitution of traditional Chinese medicine were classi fi ed.RESULTS:(1) For 138 patients with PBC, their TCM constitution was characterized by biased constitution,among which constitution of Qi stagnation (19.57%) was the majority, which was followed by constitution of Qi asthenia (15.94%), constitution of Yin asthenia (15.94%) and constitution of damp-heat (14.49%). There was no signi fi cant correlation between the type of constitution and the age of onset (P＞0.05). (2) The constitution types of group A and B were mainly constitution of Qi stagnation, constitution of Qi asthenia and constitution of damp-heat, while group C was mainly composed of constitution of blood stasis, constitution of Yin asthenia and constitution of Yang asthenia. (3) The highest positive rate of autoantibodies in patients with PBC was constitution of Qi stagnation, which was followed by constitution of damp-heat, constitution of Yin asthenia and constitution of Qi asthenia. The most abnormal liver function and immunoglobulin were constitution of Qi stagnation, which was followed by constitution of Qi asthenia, constitution of Yin asthenia, constitution of damp-heat.CONCLUSION:Constitution of Qi stagnation, constitution of Qi asthenia, constitution of damp-heat and constitution of Yin asthenia were the susceptible constitutions of PBC patients.

Primary biliary cholangitis (PBC); Traditional Chinese medicine; Constitution type; Clinical stage

BACKGROUND

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease with specific intrahepatic bile ducts. Its pathological features are progressive and non-suppurative intrahepatic cholangitis, which can eventually develop into cirrhosis. Primary biliary cholangitis was renamed as primary biliary cholangitis in 2015, and still retained the acronym for PBC1. There is no record of the name, etiology and pathogenesis of PBC, of which the clinical symptoms are diversified in traditional Chinese medicine. Modern medicine believes that the factors of immune damage and genetic susceptibility are related to its pathogenesis, which has something to do with the constitution theory of TCM.The discussion of TCM constitution was first seen in Huangdi Neijing. After a long period of exploration and research, the Chinese Medical Association published the criteria for determining the constitution of Chinese medicine on April 9, 2009, which made the classi fi cation of TCM constitution more standardized and scienti fi c2.It is found that there is almost no investigation on the TCM constitution of PBC patients after searching the related literature. As PBC is an autoimmune disease,the study of constitution has certain guiding value for the clinical treatment of PBC. Therefore, the clinical investigation of physical fi tness of PBC patients is great signi fi cance.

METHODS

Inclusion and exclusion criteria

Inclusion criteria: patients who met the diagnostic criteria of PBC and were able to successfully cooperate with the clinical investigation. Exclusion criteria:pregnant or lactating women, those who do not cooperate with the survey, and those who suffered from AMA positive other diseases, such as acute functional failure (lead to AMA transient positive), chronic hepatitis C, idiopathic thrombocytopenic purpura,pulmonary tuberculosis, etc..

Diagnostic criteria

Referring to the consensus on the diagnosis and treatment of primary biliary cholangitis (also referred to as primary biliary cholangitis) published in 2015 by the Chinese Medical Association and Hepatology branch1. If it is in accordance with two of the following three standards, it can be diagnosed as PBC, which include: (1)biochemical indicators what reflect cholestasis such as elevated ALP; (2)serum AMA or AMA-M2 was positive; (3)the histopathology of liver was consistent with PBC. Grouping criteria is based on the development stage of PBC natural history3.Group A (group of basic normal) was consisted of preclinical stage and asymptomatic phase, and the former was positive for AMA, but there was no obvious abnormality in biochemical indexes, while the latter was mainly characterized by abnormal biochemical indexes, but there were no obvious clinical symptoms.Group B (group of symptom stage) showed fatigue,pruritus and other clinical symptoms. Group C (group of decompensations) showed gastrointestinal bleeding,ascites, hepatic encephalopathy and other clinical manifestations.

Determination of constitution type of Chinese Medicine

According to the classification method of 9 kinds of constitutions by Professor Wang Qi of Beijing University of Chinese Medicine, the constitution is divided into constitution of Yang asthenia, constitution of Yin asthenia, constitution of Qi stagnation,constitution of phlegm-dampness, constitution of damp-heat, constitution of blood stasis, allergic constitution, constitution of Qi asthenia4.Then, the patients’ constitution type of TCM is determined and summarized according to the survey results. The type of constitution is investigated and determined by trained personnel.

Research method

Finally, the abnormal situation of ALT, AST, ALP,GGT, IgM, and the positive rates of autoantibodies ANA, AMA and AMA-M2 in PBC patients with different constitutional types were observed.

Statistical methods

SPSS 21.0 was used for statistical analysis.Measurement data were compared with analysis of variance, which was expressed in (); count data were compared with χ2analysis, and the available frequency or rate of description was used; descriptive statistical analysis was used for clinical feature and etiology characteristics of all cases. Rank sum test was used for the correlation anal

ysis of two categories;Fisher accurate test was applied for the association analysis of multi group and multi classification, and P＜0.05 indicated the inspection level.

RESULTS

Figure 1 showed that 138 patients with PBC were more likely to have biased constitution, including constitution of Qi stagnation (19.57%), which was followed by constitution of Qi asthenia (15.94%),constitution of Yin asthenia (15.94%), and constitution of damp-heat (14.49%).

Figure 1. Distribution of TCM Constitution Types in 138 patients with PBC One to Nine indicated constitution of Qi stagnation, constitution of Yang asthenia, constitution of Qi asthenia,constitution of blood stasis, constitution of Yin-Yang harmony, constitution of Yin asthenia, constitution of phlegm-dampness, constitution of damp-heat, allergic constitution.

Table 1 showed that there was no significant correlation between the type of constitution and the age of onset (P＞0.05), and the difference was not statistically signi fi cant.

Table 1. The relationship between constitutional types and age of onset

Excluding constitution of Yin-Yang harmony and allergic constitution of sample with less content, and sample size remained in 132 cases. Table 2 showed that the constitution types of group A and group B mainly were constitution of Qi stagnation, constitution of Qi asthenia and constitution of damp-heat, while C group was mainly composed of constitution of blood stasis, constitution of Yin asthenia and constitution of Yang asthenia. The Fisher test showed that there was a correlation between the type of constitution and clinical stage (P＜0.05). It was found that the distribution of body constitution was different in the course of disease progression. The changes were roughly as follows:there was a downward trend in the number of patients with constitution of Qi stagnation and constitution of damp-heat; the number of patients with constitution of Qi asthenia was unchanged at fi rst and then decreased;the number of patients with constitution of Yin asthenia,constitution of blood stasis and constitution of Yang asthenia showed an increasing trend, and reached the highest level in the decompensation period; while the number of patients with phlegm dampness was at a similar level. Because of the small sample size of PBC patients, the results were of certain clinical signi fi cance,the study needed to be explored further by increasing the clinical sample size.

Table 2. The relationship between constitutional types and clinical stages

Table 3 showed that ANA positive patients were found in 121 cases (87.68%), AMA positive patients were found in 115 cases (83.33%), and AMA-M2 positive patients were found in 81 cases (58.70%). The positive rate of autoantibodies was the highest. The type of constitution was constitution of Qi stagnation, which was followed by constitution of damp-heat, constitution of Yin asthenia and constitution of Qi asthenia.

Table 3. Autoantibodies in PBC patients with different constitutional types

Table 4 showed that 78 patients were with elevated AST, 84 patients were with elevated AST, 108 patients were with elevated ALP, 86 patients were with elevated GGT, and 81 patients were with elevated IgM. The most abnormal liver function and immunoglobulin in PBC patients were constitution of Qi stagnation, which was followed by constitution of Qi asthenia, constitution of Yin asthenia, and constitution of damp-heat. And the abnormal distribution of AST, ALT, ALP, GGT and IgM in different constitutions was different.

Table 4. Abnormal liver function and serum immunoglobulin in patients with different constitutional types of PBC

DISCUSSION

The clinical symptoms of PBC are complex and changeable. PBC in traditional Chinese medicine can be classified as “jaundice”, “hypochondriac pain”,“skin itching”, “asthenia labor” and other disease syndromes6. Modern medicine holds that physique can reflect the particularity of organism function, and the characteristics of the rise and fall of body Yin, Yang,Qi and blood. At the same time, it also determines the susceptibility to pathogenic factors, as well as the propensity to produce lesions type7.

Primary biliary cholangitis (PBC) is a chronic progressive autoimmune disease, which is closely related to the constitution of Tradition Chinese Medicine(TCM). This study is carried out to investigate the type of constitution of 138 patients with PBC. It finds that the constitution type of TCM is mainly of constitution of Qi stagnation, which is followed by constitution of Qi asthenia, constitution of Yin asthenia, and constitution of damp-heat. It is speculated that these constitutions may be the susceptible constitution of PBC patients.Therefore, we should pay attention to the targeted methods to improve the constitution and combine the clinical treatment. Many studies have shown that PBC patients are mostly perimenopausal or amenorrhea elderly women,just as described in Su Wen the middleaged women are in Ren deficiency, liver and kidney function declining stage. The asthenia of Ren will block the virtual physiological function of spleen governing transportation and transformation, liver storing blood,Kidney dominating water and storing essence disorder,which could cause deficiency of Qi, blood and Yin essence. Li Hongyu and others think that liver plays the most important role in women’s physiological function, and the Yin essence and Yin blood of liver and kidney gradually wear away after their middle age, which can easily cause the de fi ciency of vital Qi8.At this time, if there is improper diet, overstrain, or feelings of evils, it can easily lead to positive imaginary evil. However, further research finds that there is no signi fi cant correlation between the physical type of PBC patients and their age. Therefore, this may be due to the inclusion of PBC patients more than 49 to 72 years old,their physical type has become mature and stable. In addition, statistics show that the constitution of type of patients with PBC who stay in the preclinical stage and asymptomatic phase are mainly of constitution of Qi stagnation, constitution of Qi asthenia, and constitution of damp-heat. However, the patients of decompensation stage are mainly constitution of blood stasis,constitution of Yin asthenia and constitution of Yang asthenia. The Fisher exact test suggests that there is a correlation between the constitution types and clinical staging (P＜0.05). With the progress of disease, the distribution of constitutional types of patients with PBC varies, which may be related to the clinical pathological changes of patients.

This study uses the academic thought of “preventive treatment of disease” in TCM, emphasizes the adjustability of constitution, and provides a theoretical basis and method for the prevention of PBC from the point of view of improving physique. Traditional Chinese medicine constitution can treat individual patient with different constitution from the diet, daily life, medicine and other aspects of the development of individualized treatment and PBC health nursing program. The clinical research of TCM constitution can better guide the clinical treatment and nursing of PBC patients. At present, western medicine treats PBC with drug ursodeoxycholic acid (UDCA) and Ocaliva(obeticholic acid), which is the second FDA approved drugs in the United States for the treatment of adult with PBC. More than 50% of the primary biliary cholangitis patients are treated effectively by UDCA, but nearly as many as 40% of the patients have inadequate response to UDCA, and 5% to 10% of patients have intolerance on UDCA.

On the one hand, ocaliva has side effects, such as a variety of skin itching, severe fatigue, joint pain,rash, and so on. The study fi nd that Chinese medicine has high safety and significant effects on PBC disease. Traditional Chinese medicine has obvious advantages in preventing and treating this disease.The physical research of PBC has some practical value. On the other hand, it can lay emphasis on the diet and daily life of the patients in the preclinical and asymptomatic periods, and make reasonable plans to prevent the disease from progressing to symptomatic period. Meanwhile, the symptoms of the period can be coped with the daily physical health care and clinical drug treatment to relieve the symptoms of patients with discomfort, slow down the development of disease. As for the decompensated patients, the treatment method of combining the clinical use of traditional Chinese medicine and western medicine based on physical type and TCM syndrome differentiation can improve the patient’s expectations of diet and sleep, improve their quality of life, increase the con fi dence to resist the disease.It is expected that individualized diagnosis and treatment program can be achieved based on the patient’s physical type and clinical symptoms, which can re fl ect the “people-oriented” thought.

In conclusion, the results of TCM constitution identi fi cation suggests that constitution of Qi stagnation,constitution of Qi asthenia, constitution of damp-heat and constitution of Yin asthenia are the susceptible constitutions of PBC patients. The Qi stagnation is caused by emotional discomfort, anxiety and rage.Emotional internal injury is the main cause of Qi depression, and it is easy to suffer from Qi stagnation,and if often has internal factors of Zangqi weakness.Qi deficiency is mostly due to the pressure of work,eating cold or greasy food, lack of exercise, and unhealthy lifestyle. And, Yin deficiency is because of acquired dystrophy formation, such as excessive sexual indulgence, consumption or work and life stress, living irregularly, exhaustion and so on. Damp heat is mainly because of smoking and drinking, staying up late,nourishing improper or the mood being not smooth.The specific etiology research needs to be combined with clinic. This study carries out physical survey only in Qingdao Haici medical group and the Sixth People’s Hospital of Qingdao city, which has certain limitations. It is expected to further expand the scope of investigation in the future research.

A larger research sample should be carried out with the use of modern diagnosis and treatment technology in order to further analyze the distribution characteristics and clinical practical value of TCM constitution in patients with PBC.

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