The Study Of Etiology Of Budd-Chiari Syndrome

Budd-Chiari Syndrome (BCS) is defined as hepatic venous outflow obstruction at any level from the small hepatic veins to the junction of the inferior vena cava and the right atrium, regardless of the cause of obstruction but the embolus that right atrial appendage extends to the inferior vena cava. Westerners' BCS refers mainly to obstruction of hepatic vein stem, especially prevalent thrombosis whereas Orient BCS that membranes of the inferior vena cava obstruction accounts for a considerable part.Since the first BCS reported, the incidence rate has increased, with the improvement of clinical medicine and the development of technology of diagnosis and treatment, and it has been realized that BCS is not uncommon disease. Because of complex etiology, clinical and pathological changes of many types, BCS becomes a severe disease of vascular surgery and abdominal surgery, and is always an emphasis, focus and difficult, that medicine, surgery, imaging, interventional radiology, and so on, carry on science research. Despite the long term efforts of scholars from different countries to explore and research BCS, with the development of interventional radiology, especially professor Han Xin-wei's breakthrough in the technology of big balloon dilation, blunt rupture of membrane, stirring thrombolysis, and track technology, the diagnosis and treatment of BCS is made significant progress, which is still unsatisfactory. BCS positioning diagnosis is a high degree of difficulty, with a high rate of early misdiagnosis and high recurrence rate of conservative treatment or symptom improvement after autologous compensatory high recur- rence rate. All of those are closely related with the unclear causes and mechanism so that BCS couldn't be removed the causes. Therefore, it is necessary to carry out the overall painstaking research of BCS etiology.The causes of BCS are numerous, which are different with the geographic, ethnic, gender, age and pathological types. BCS is traditionally regarded as a blood disease resulting from accentuation in the blood coagulation system or defects in the blood anticoagulation system with hypercoagulable state characterized, this view was widely accepted by scholars at home and abroad. In most Western countries BCS is due to blood abnormal coagulation with high rate of thrombosis, however, in recent years the membrane obstruction of inferior vena cava gradually increases. In the East nation (especially in China and Japan), membrane obstruction of inferior vena cava account for a great part,resulting mainly from inflammation, and in South Africa 47.5% BCS results from liver cancer. According to the previous reports, abnormal coagulation, infection, oral contraceptives, trauma or tumor can lead to BCS, However, about the etiology and pathogenesis of BCS, there are many problems that need urgent solution. Therefore, it is necessary to go on comprehensive and systematic exposition of China BCS etiology, which are of great significance at the clinical diagnosis and treatment and prevention of BCS in our country.In order to find the main cause of our BCS and its primary mechanism, the study uses three epidemiological study methods. First, the genetic ingredients and acquired causes leading to blood clotting abnormality are analyzed by the case-control study. Then, the distribution of BCS is carried on the descriptive epidemiological study. Finally, the ecological epidemiological study explores the main ingredients in our country.Methods1 .Sources of Specimens and Information Collection the patient group hospitalized in the department of interventional radiology, the First Affiliated Hospital of Zhengzhou University. Questionnaires were investigated and peripheral blood samples were collected before the treatment operation. The whole blood anticoagulated by EDTA were placed directly in -80℃refrigerator. The blood plasma separated from the whole blood anticoagulated by citrate were deposited in-80℃refrigerator. The control group one from the healthy family members of non-BCS patients hospitalized in the department of interventional radiology are investigated and collected blood samples, the blood plasmas separated from the blood samples were deposited in-80℃refrigerator. The control group two who are healthy outpatient carrying on physical examination at the First Affiliated Hospital, accepted the collection of peripheral vein blood, and the blood samples anticoagulated by EDTA were placed in-80℃refrigerator. Collected the demographic data of BCS patients followed by the department of interventional radiology for analysis.2. Genomic DNA Extraction using phenol and chloroform extraction genome DNA from 200μl whole blood cells.3. Polymorphism Analysis of the Gene Mutation PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) method was used to detected Factor V Leiden mutation (FvL), prothrombin gene mutation (FII G21010A), methylenetetra-hydrofolate reductase gene mutation (MTHFRC677T),β-fibrinogen gene mutation (β-Fg-G455A).4. Analysis of Coagulation Factors and Anticoagulation Proteins The activity of factor II and V was determinated by endpoint method, antithrombin III (AT III) was determinated by the dynamic method, protein C and protein S were determined by clotting method.5. Determination of Anticardiolipin Antibodies Anticardiolipin IgG and IgM antibodies were detected by ELISA.6. Statistical Analysis Method The Questionnaire Data and the Follow-up Data were input Microsoft Office Excel2003, and tidied up for statistical analysis. T-test for continuous data statistical analysis,x~2 test for classification data, using bilateral test,α= 0.05. SAS9.13 was used for statistical analysis.Results1. The Mutation Gene Polymorphism Related with BCS FvL was found only at one case in the patient group, but did not be found in the control group. Case and control groups were not found at one case of FIIG20210A. The comparison of BCS patients and healthy control group genotype frequency of P-Fg-G455A:x~2= 0.545, P=0.761, not statistically significant; the comparison of BCS patients and healthy control group allele frequency ofβ-Fg-G455A: x~2= 0.155, P=0.694, not statistically significant. The comparison of BCS patients and healthy control group genotype frequency of MTHFRC677T: x~2= 0.052, P=0.974, not statistically significant; the comparison of BCS patients and healthy control group allele frequency of MTHFRC677T: x~2 = 0.143, P=0.705, not statistically signify- cant.2. Coagulation Factors and Anticoagulant Activity Related with BCS The comparison of BCS patients and healthy control group FⅡactivity: t = 1.479, P=0.068, not statistically significant; FV activity: t = -1.306, P=0.091, not statistically significant; ATⅢactivity : t = -1.235, P=0.109, not statistically significant; Protein C activity: t = -0.826. P=0.039, not statistically significant; Protein S activity t = 1.325, P = 0.085, not statistically significant.3. Anticardiolipin Antibody Related with BCS Positive Anticardiolipin IgM was not found in both the patient group and the control group; the comparison exact probability of BCS patients and the control group of anticardiolipin antibody IgG positive rate: P= 0.295, no statistical significance.4. The Circumstances of Illness of Patients with BCS The time span from the date of the onset to confirmed date can vary greatly in length, from 0.5 (diagnosed month) to 32 years, with an average 14.33 monthes. The frequency of the main symptoms and signs of BCS: weak 83.41%, abdominal distension 74.13%, abdominal pain13.01%, abdominal varices 82.36 %, liver big 90.65%, spleen big 89.58%, ascities 32.69%, lower extremity varicose veins 79.81%, lower extremity edema 70.49%, lower extremities pigmentation 73.16%, abnormal menstruation 23.87%, infertility 18.34%, gastrointestinal bleeding 9.68%, jaundice 6.45%; no final diagnosis in the town, the city-level final diagnosis accounted for 22.36%, the provincial hospital confirmed the diagnosis : accounting 77.64%; diagnosis evidence: relying solely on the color Doppler 28.34%, on the basis of CT or MRI assisted by color Doppler 66.57%, on the basis of angiographyles assisted by color Dopple5.09%.5. Living Habits Related with BCS The comparative analysis of BCS patients and healthy control group of living habits: smoking habits,x~2= 7.813, .P=0.005, having statistically significant; drinking,x~2 = 14.334, P = 0.000, having statistically significant; eating vegetables: x~2= 0.637, P = 0.425, statistically no significant.6. The Past History Related with BCS The comparison of BCS patients and the control group of the past history positive rate: x~2 = 3.342, P=0.068, no statistical significance.7. PV and ET Related with BCS No one case of patients with polycythemia vera, no one case of essential thrombocythemia patients.8. The distribution of BCS patients in Henan Province have the following characteristics : men and women's sex proportion , 59.05: 40.95; mean age, 42.04 years, 95% CI, [39.91, 44.16], patients occurring on every age segment, main young adult patients respect to man or woman; the occupation proportions of farmer, worker, student, teacher, and official take up 85%, 7%, 1%, 4%, and 3% respectively; no distinguished seasonality, hospitalizing through the whole year; the patients of Han people, 103, and the patients of Muslim population in china, 2; the features of the district distribution, patients of more eastern, less southern, and sporadic.Conclusions1. The main cause of BCS in our country aren't the blood hypercoagulable state.2. The main cause of BCS in our country may be environmental factors.