Grading method for evaluating clinical symptoms of hypersplenic function

Abstract

The invention provides a grading method for evaluating the clinical symptoms of hypersplenism, and the method comprises the steps: constructing a model for evaluating the clinical symptoms of hypersplenism, carrying out the Logistic regression analysis of the model through PLT, WBC and RBC, building a column diagram, converting a regression coefficient into a visual grading system, carrying out the score assignment according to primary and secondary factors, and carrying out the evaluation of the clinical symptoms of hypersplenism. And finally, constructing a splenohyperactivity grading prediction model according to the total score. The severity of the clinical symptom of the hypersplenidism of a patient is evaluated by adopting the model, the splenidism grading of the patient is evaluated by utilizing the correlation analysis of the peripheral blood cell detection result of the hypersplenidism patient, a personalized treatment scheme can be given to the patient in time, and the illness state is prevented from being delayed.

Description

Technical Field

[0001] The present invention relates to the field of medical biotechnology, and particularly relates to a grading method for evaluating the severity of clinical symptoms of hypersplenism. Background Art

[0002] Cirrhotic portal hypertension is a clinical syndrome caused by cirrhosis, mainly manifested by elevated pressure in the portal vein system. The symptoms of cirrhotic portal hypertension include splenomegaly, hypersplenism (abbreviated as hypersplenism), etc., which are very common clinically and can be manifested as problems such as decreased white blood cells, red blood cells, and platelets, resulting in corresponding clinical symptoms such as infection, tissue hypoxia, anemia, bleeding (such as spontaneous gingival bleeding, epistaxis), etc., leading to poor prognosis. Due to the different types and intensities of peripheral blood cell reduction, hypersplenism has not been well graded for a long time, thus affecting the assessment and treatment of the severity of this disease to a certain extent. Therefore, finding an effective grading method applicable to the severity of hypersplenism, grading hypersplenism, and accurately guiding treatment is of great significance. Summary of the Invention

[0003] In view of this, the purpose of the present invention is to propose a grading method for evaluating the severity of clinical symptoms of hypersplenism. The established hypersplenism grading prediction model and new treatment plan are scientific and practical, and are of great significance for accurately guiding the treatment of hypersplenism.

[0004] The technical solution of the present invention is realized as follows:

[0005] A grading method for evaluating the severity of clinical symptoms of hypersplenism includes the following steps:

[0006] S1: Obtain samples of cirrhotic splenomegaly and divide them into training samples and test samples;

[0007] S2: Collect the examination results of peripheral blood cells of the samples, including the examinations of platelets, white blood cells, and red blood cells; using the training samples as a database, adopt logistic multiple regression analysis to determine the main factors and secondary factors, and assign scores according to the main factors and secondary factors. The score is mainly based on the reduction quantity of platelets, and supplemented by the reduction quantities of white blood cells and red blood cells. Establish a hypersplenism grading prediction model by calculating the total score, determine the scoring calculation method for the severity of the clinical symptoms of hypersplenism in patients and the grading criteria for hypersplenism in patients, and divide the patients into mild (Grade I), moderate (Grade II), and severe (Grade III) according to the severity of the clinical symptoms of hypersplenism;

[0008] S3: Use the test samples to detect the prediction performance of the hypersplenism grading prediction model;

[0009] S4: Before treating a new patient, calculate the hypersplenism score of the new patient and the corresponding hypersplenism grading standard according to the hypersplenism grading prediction model, and adopt different treatment plans based on the hypersplenism grading standard.

[0010] A further plan is to randomly divide the liver cirrhosis and splenomegaly samples into training samples and test samples according to the ratio of the number of training samples to the number of test samples being 7 - 8:2 - 3.

[0011] A further plan is that the score assignment includes: for a platelet count of 100 - 50×10 9 / L, assign 1 point; for a platelet count of 50 - 30×10 9 / L, assign 2 points; for a platelet count < 30×10 9 / L, assign 3 points;

[0012] For a red blood cell count of 3.5 - 2.5×10 12 / L, assign 0 points; for a red blood cell count of 2.5 - 1.5×10 12 / L, assign 1 point; for a red blood cell count < 1.5×10 12 / L, assign 2 points;

[0013] For a white blood cell count of 4 - 2×10 9 / L, assign 0 points; for a white blood cell count < 2×10 9 / L, assign 1 point.

[0014] A further plan is that according to the assigned score, the hypersplenism grading standard is: the total hypersplenism score < 2 points is mild, that is, grade I;

[0015] The total hypersplenism score of 2 - 3 points is moderate, that is, grade II;

[0016] The total hypersplenism score > 3 points is severe, that is, grade III.

[0017] A further plan is that according to the hypersplenism grading standard, if the hypersplenism level is grade I, it indicates that the clinical symptoms of hypersplenism are mild, and non - surgical treatment is adopted in the treatment plan;

[0018] If the hypersplenism level is grade II, it indicates that the clinical symptoms of hypersplenism are moderate, non - surgical treatment is adopted in the treatment plan, and surgical treatment is adopted when the condition worsens;

[0019] If the hypersplenism level is grade III, it indicates that the clinical symptoms of hypersplenism are severe, and surgical treatment is adopted in the treatment plan; the surgical treatment includes at least one of total splenectomy, devascularization, shunt surgery, or liver transplantation.

[0020] Compared with the prior art, the beneficial effects of the present invention are:

[0021] The present invention screens the main factors affecting the prognosis of hypersplenism from a large number of cases, and adopts an effective method of assigning scores to construct a prediction model for hypersplenism grading. According to the hypersplenism grading, it can provide a reference for the treatment plans of patients with different clinical symptoms of hypersplenism.

[0022] The present invention constructs a model for evaluating the severity of clinical symptoms of hypersplenism. The model establishes a nomogram through logistic regression analysis of PLT, WBC, and RBC, converts the regression coefficients into a visual scoring system, assigns scores according to the primary and secondary factors respectively, and finally constructs a prediction model for hypersplenism grading according to the total score. Using the prediction model of the present invention, the severity of the clinical symptoms of hypersplenism in patients can be evaluated. By using the correlation analysis of the peripheral blood cell test results of hypersplenism patients, the hypersplenism grading of the patients can be evaluated, and a personalized treatment plan can be given to the patients in time to avoid delaying the condition.

[0023] The prediction model for hypersplenism grading constructed by the present invention effectively avoids the situation that the accurate judgment of the severity of hypersplenism is affected by different types and intensities of peripheral blood cell reduction, and has important significance and application prospects for accurately guiding the treatment of hypersplenism. Detailed implementation mode

[0024] In order to better understand the technical content of the present invention, specific examples are provided below to further illustrate the present invention.

[0025] Unless otherwise specified, the experimental methods used in the embodiments of the present invention are all conventional methods.

[0026] Unless otherwise specified, the materials, reagents, etc. used in the embodiments of the present invention can all be obtained from commercial channels.

[0027] Example 1

[0028] The grading method for evaluating the severity of clinical symptoms of hypersplenism is as follows:

[0029] S1: The samples were 2542 patients with liver cirrhosis and splenomegaly in a multi-center cohort study from June 1999 to December 2016, including 1660 males (65.3%) and 882 females (34.7%). The male-female ratio was about 1.88:1, the age was 16 to 84 years old, and the average age was 49.5 years old.

[0030] The judgment criteria for liver cirrhosis and splenomegaly are as follows: 1. In CT or MRI scans, the spleen exceeds 5 rib units; 2. Physical examination: The upper border of the spleen is above the 9th intercostal space in the midaxillary line, and the lower border of the spleen exceeds the costal arch. If both criteria are met, it is called splenomegaly.

[0031] Diagnostic criteria for hypersplenism: First, through medical history inquiry and relevant examinations, exclude factors other than hypersplenism, such as drugs (especially chemotherapeutic drugs and antibiotics), damage to liver function and bone marrow caused by a large amount of viruses, extensive radiotherapy or burns, severe infections, and blood loss, etc., which cause peripheral cytopenia; The second item, splenomegaly, with enhanced blood storage function and blood cell destruction function of the spleen; The third item, there is one or more peripheral cytopenias in the blood (the patient is based on the first peripheral venous blood test after admission, the white blood cell (leukocyte, white blood cell, WBC) count < 4×10 9 / L, the red blood cell (RBC) count < 3.5×10 12 / L, the blood platelet (PLT) count < 100×10 9 / L is called peripheral cytopenia); The fourth item, the reduced blood cells return to normal or above normal levels after splenectomy or shunt surgery. The first item must be met, and if two of the latter three items are met, it can be diagnosed as hypersplenism. This can enable some patients who have not had surgery or need surgery to also obtain a diagnosis of hypersplenism before surgery.

[0032] There were 2059 cases (81.0%) of hepatitis B cirrhosis, 280 cases (11.0%) of hepatitis C cirrhosis, 63 cases (2.5%) of alcoholic cirrhosis, 56 cases (2.2%) of biliary cirrhosis, 51 cases (2.0%) of autoimmune hepatitis cirrhosis, and 33 cases (1.3%) of other types of cirrhosis. All cases were examined by B-ultrasound, CT or MRI, and the liver showed nodular sclerosis and atrophy, and the spleen was generally enlarged.

[0033] Peripheral venous blood tests showed that 92% of the patients (2339 / 2542) had one or more peripheral cytopenias. Gastroscopy and CT indicated moderate to severe varices in the lower esophagus and fundus of the stomach. Except for 203 cases with normal complete blood cells, all patients underwent surgical treatment, including 887 cases (37.9%67%) of esophagogastric devascularization + splenectomy due to ineffective endoscopic ligation treatment or Tips surgery (Transjugular intrahepatic portosystemic shunt, TIPS) for massive gastrointestinal bleeding (≥1000 mL), and 92 cases with additional splenorenal shunt; 397 cases (17.0%) of splenectomy due to a huge spleen (exceeding the midline of the abdomen or below the horizontal line of the anterior superior iliac spines on both sides), affecting the quality of life, and 26 cases with additional splenorenal shunt; 770 cases (32.9%) of splenectomy + portal-azygos disconnection due to moderate to severe hypersplenism; 262 cases (11.2%) of simple splenectomy; 18 cases (0.8%) of simple portacaval shunt; 5 cases (0.2%) of simple liver transplantation. During the operation, liver tissue was routinely taken for pathological examination, indicating cirrhosis.

[0034] S2: From the above-mentioned large-scale multi-center cases, the cases are randomly divided into a training set and a test set at a ratio of 8:2. The Logistic regression is used to establish a nomogram in the Training Set. The regression coefficients are converted into a visual scoring system, and scores are assigned according to the primary and secondary factors. Finally, a prediction model for hypersplenism grading is constructed based on the total score. The Test Set is used to evaluate the performance of the hypersplenism grading prediction model.

[0035] There are 2,034 cases (80%) in the training set (Training Set) and 508 cases (20%) in the test set (test set). Among the Training set, 1,871 cases (92.0%) have one or more peripheral blood cytopenias, and 163 cases (8.0%) have normal blood cells. Through logistic multiple regression analysis, the decrease in blood platelet (PLT) is the main factor affecting the prognosis. The score is mainly based on the decrease in PLT, and the scores for the decrease in leukocyte (white blood cell, WBC) and red blood cell (RBC) are supplementary. The specific scoring and hypersplenism grading methods are as follows: First, score the reduced blood cells (Table 1). PLT 100 - 50×10 9 / L is scored 1 point, 50 - 30×10 9 / L is scored 2 points, <30×10 9 / L is scored 3 points; RBC 3.5 - 2.5×10 12 / L is scored 0 point, 2.5 - 1.5×10 12 / L is scored 1 point, <1.5×10 12 is scored 2 points; WBC 4 - 2×10 9 / L is scored 0 point, <2×10 9 / L is scored 1 point. Then, comprehensively calculate the scoring results, and divide hypersplenism into 3 grades (degrees): The total score <2 points is grade I (mild), with 907 cases (44.6%); the total score of 2 - 3 points is grade II (moderate), with 993 cases (48.8%); the total score >3 points is grade III (severe), with 134 cases (6.6%). There are significant differences in the treatment results of the three grades of hypersplenism (H = 12.958, P = 0.002).

[0036] Table 1 Hypersplenism Scoring and Grading (Degree) Model

[0037]

[0038]

[0039] S3: The results of the Test Set show that the splenomegaly grading prediction model has good performance, with an AUC of 0.92, demonstrating strong predictive performance.

[0040] A new treatment plan was established based on the splenomegaly grading:

[0041] For grade I splenomegaly with mild clinical symptoms, non-surgical treatment is adopted;

[0042] For grade II splenomegaly with moderate clinical symptoms, non-surgical treatment is generally preferred. However, surgery may be considered if the condition worsens.

[0043] For grade III splenomegaly with severe clinical symptoms, surgical treatment is adopted, including total splenectomy, devascularization, shunt surgery, liver transplantation, etc.

[0044] When comparing the surgical treatment efficacy with that of the non-surgical treatment group (400 cases), there was no significant difference in the efficacy between the two groups for grade I splenomegaly (p > 0.05); for grade II splenomegaly, the efficacy of the surgical group was significantly better than that of the non-surgical group (p < 0.05); for grade III splenomegaly, the efficacy of the surgical group was significantly superior to that of the non-surgical group (p < 0.01), indicating that surgical treatment for grade III splenomegaly can improve the efficacy.

[0045] The treatment outcomes of the surgical group and the non-surgical group with stratified splenomegaly were compared.

[0046] Efficacy judgment criteria:

[0047] Cured: Clinical symptoms disappear, and the blood cells reduced by routine examinations return to normal.

[0048] Improved: Clinical symptoms are alleviated, and the blood cells reduced by routine examinations show improvement but do not return to the normal level.

[0049] Unchanged: There are no changes in clinical symptoms and routine examinations.

[0050] Deteriorated: Clinical symptoms worsen and lead to death.

[0051] Effective includes cured + improved, and ineffective includes unchanged + deteriorated / dead.

[0052] For the overall efficacy, there was no significant difference in the efficacy between the two groups for grade I splenomegaly (p > 0.05); for grade II splenomegaly, the efficacy of the surgical group was significantly better than that of the non-surgical group (p < 0.05); for grade III splenomegaly, the efficacy of the surgical group was significantly superior to that of the non-surgical group (p < 0.01). The comparison of the overall efficacy is shown in Table 2.

[0053] Table 2 Comparison of the overall efficacy of two different treatment methods for splenomegaly grading

[0054]

[0055] Application Example 1

[0056] Patient Wang Mozhong, male, 47 years old, was diagnosed with hepatitis B cirrhosis with portal hypertension due to massive hematemesis, hemorrhagic shock, and splenomegaly.

[0057] Table 3 Splenomegaly grading situation of Patient 1

[0058]

[0059] According to the detection of the peripheral blood cell count of the patient, the splenomegaly scoring and grading (degree) model of Example 1 was used, and the total score was 4 points. The splenomegaly was evaluated as grade III splenomegaly, and surgical treatment was adopted.

[0060] On November 22, 2000, a total splenectomy + pericardial devascularization with preservation of the main trunk of the vagus nerve was performed.

[0061] After the operation, the patient felt well, the peripheral blood cell count returned to normal, and the patient started to go to work normally 2 months after the operation. There has been no bleeding for 24 years so far, and the patient has now retired.

[0062] Application Example 2

[0063] Patient Wang Molin, female, 35 years old, was diagnosed with hepatitis B cirrhosis with portal hypertension and splenomegaly due to hematemesis and fatigue every year, and the peripheral blood cell count was very low.

[0064] Table 4 Splenomegaly grading situation of Patient 2

[0065]

[0066] According to the detection of the peripheral blood cell count of the patient, the splenomegaly scoring and grading (degree) model of Example 1 was used, and the total score was 4 points. The splenomegaly was evaluated as grade III splenomegaly, and surgical treatment was adopted.

[0067] On November 5, 2001, a total splenectomy + pericardial devascularization with preservation of the main trunk of the vagus nerve was performed.

[0068] 23 years after the operation, the patient felt well, the peripheral blood cell count returned to the normal range, there was no ascites, and the patient is still working normally.

[0069] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A grading method for evaluating the severity of clinical symptoms of hypersplenism, characterized in that, It includes the following steps: S1: Obtain samples of liver cirrhosis with splenomegaly and divide them into training samples and test samples; S2: Collect the examination results of peripheral blood cells in the samples, including the examinations of white blood cells, red blood cells and platelets; Using the training samples as a database, adopt logistic multiple regression analysis to determine the main factors and secondary factors, and assign scores according to the main factors and secondary factors. The score is mainly based on the decreased platelet count, supplemented by the decreased white blood cell and red blood cell counts. Establish a prediction model for hypersplenism grading by calculating the total score, determine the scoring calculation method for the severity of the clinical symptoms of hypersplenism in patients and the grading criteria for hypersplenism in patients, and divide the patients into mild, moderate and severe according to the severity of the clinical symptoms of hypersplenism; S3: Use the test samples to detect the prediction performance of the hypersplenism grading prediction model; S4: Before treating new patients, calculate the score of hypersplenism in the new patients and the corresponding grading criteria for hypersplenism according to the hypersplenism grading prediction model, and adopt different treatment plans according to the grading criteria for hypersplenism.

2. The grading method according to claim 1, wherein Randomly divide the samples of liver cirrhosis with splenomegaly into training samples and test samples according to the quantity ratio of training samples to test samples of 7 - 8:2 - 3.

3. The grading method according to claim 1, characterized in that, The score assignment includes: for a platelet count of 100 - 50×10 9 / L, 1 point is assigned; for a platelet count of 50 - 30×10 9 / L, 2 points are assigned; for a platelet count < 30×10 9 / L, 3 points are assigned; The red blood cell count is 3.5 - 2.5×10 12 / L, and 0 points are assigned; the red blood cell count is 2.5 - 1.5×10 12 / L, and 1 point is assigned; the red blood cell count is < 1.5×10 12 / L, and 2 points are assigned; The white blood cell count is 4 - 2×10 9 / L, scoring 0 points. The white blood cell count < 2×10 9 / L, scoring 1 point.

4. The grading method according to claim 3, characterized in that, According to the assigned scores, the grading criteria for hypersplenism are: the total score of the hypersplenism score < 2 is mild, that is, grade I; the total score of the hypersplenism score of 2 - 3 is moderate, that is, grade II; the total score of the hypersplenism score > 3 is severe, that is, grade III.

5. The grading method according to claim 4, characterized in that According to the grading criteria for hypersplenism, if the level of hypersplenism is grade I, it indicates that the clinical symptoms of hypersplenism are mild, and non-surgical treatment is adopted in the treatment plan; if the level of hypersplenism is grade II, it indicates that the clinical symptoms of hypersplenism are moderate, and non-surgical treatment is adopted in the treatment plan, and surgical treatment is adopted when the condition worsens; if the level of hypersplenism is grade III, it indicates that the clinical symptoms of hypersplenism are severe, and surgical treatment is adopted in the treatment plan; The surgical treatment includes at least one of total splenectomy, devascularization, shunt operation or liver transplantation.

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