Grading method for evaluating severity of clinical symptoms of hypersplenism

Abstract

Provided in the present invention is a grading method for evaluating the severity of the clinical symptoms of hypersplenism. In the present invention, a model for evaluating the severity of the clinical symptoms of hypersplenism is constructed by means of performing logistic regression analysis on PLT, WBC and RBC to establish a nomogram, converting regression coefficients into a visual scoring system, separately performing score assignment on the basis of primary and secondary factors, and finally constructing a total-score-based hypersplenism grading prediction model. The model in the present invention is used to evaluate the severity of the clinical symptoms of hypersplenism in patients. By means of correlation analysis of peripheral blood cell testing results of patients with hypersplenism, hypersplenism grades of the patients are evaluated, such that personalized treatment plans can be provided to the patients in a timely manner, thereby avoiding delays in treatment.

Description

A grading method for evaluating the severity of clinical symptoms of hypersplenism Technical Field

[0001] This invention relates to the field of medical biotechnology, and in particular to a grading method for evaluating the severity of clinical symptoms of hypersplenism. Background Technology

[0002] Portal hypertension due to cirrhosis is a clinical syndrome caused by cirrhosis, primarily characterized by elevated pressure in the portal venous system. Symptoms of portal hypertension in cirrhosis include splenomegaly and hypersplenism (abbreviated as hypersplenism), which are very common clinically. Hypersplenism can manifest as decreased white blood cell, red blood cell, and platelet counts, leading to corresponding clinical symptoms such as infection, tissue hypoxia, anemia, and bleeding (e.g., spontaneous gingival bleeding, epistaxis), resulting in a poor prognosis. Due to the varying types and intensities of peripheral blood cell reduction, hypersplenism has long lacked effective classification, thus affecting the assessment of its severity and treatment. Therefore, finding an effective classification method suitable for the severity of hypersplenism and accurately guiding treatment is of great significance. Summary of the Invention

[0003] Therefore, the purpose of this 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 this invention is implemented 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, which are divided into training samples and test samples;

[0007] S2: Collect peripheral blood cell test results from the samples, including platelet, white blood cell, and red blood cell counts; using the training samples as a database, employ logistic multivariate regression analysis to determine primary and secondary factors, and assign scores based on these factors. The scoring is primarily based on the number of thrombocytopenic purpura cells, supplemented by the number of white blood cells and red blood cells. A grading prediction model for hypersplenism is established by calculating the total score, determining the scoring method for the severity of clinical symptoms of hypersplenism and the grading criteria for hypersplenism. Patients are classified into mild (Grade I), moderate (Grade II), and severe (Grade III) based on the severity of their clinical symptoms.

[0008] S3: Test the predictive performance of the hypersplenism grading prediction model using test samples;

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

[0010] A further approach is to randomly divide the cirrhotic splenomegaly samples into training samples and test samples according to a ratio of 7-8:2-3 between training samples and test samples.

[0011] A further approach is to assign a score including: platelet count 100-50×10⁻⁶. 9 / L, assigned 1 point, platelet count 50-30×10 9 / L, assigned 2 points, platelet count <30×10 9 / L, awarded 3 points;

[0012] The red blood cell count was 3.5-2.5 × 10⁻⁶. 12 / L, assigned 0 points, red blood cell count 2.5-1.5×10 12 / L, assigned 1 point, red blood cell count <1.5×10 12 / L, awarded 2 points;

[0013] The white blood cell count was 4-2 × 10⁻⁶. 9 / L, assigned 0 points, white blood cell count <2×10 9 / L, award 1 point.

[0014] A further proposed solution is to classify hypersplenism according to the assigned scores as follows: a total score of less than 2 points indicates mild hypersplenism, i.e., Grade I.

[0015] A total score of 2-3 points indicates moderate hypersplenism, i.e., grade II;

[0016] A total score of >3 for hypersplenism indicates severe hypersplenism, or grade III.

[0017] A further approach is to, based on the aforementioned hypersplenism grading criteria, if the hypersplenism is grade I, it indicates that the clinical symptoms of hypersplenism are mild, and the treatment plan adopts non-surgical treatment;

[0018] If the grade of hypersplenism is II, it means that the clinical symptoms of hypersplenism are moderate. The treatment plan is non-surgical treatment, and surgical treatment is used when the condition worsens.

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

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

[0021] This invention employs an effective method to screen major factors affecting the prognosis of hypersplenism from a large number of cases and construct a hypersplenism grading prediction model using a scoring system. Based on the grading of hypersplenism, it can provide a reference for the treatment plan of patients with different clinical symptoms of hypersplenism.

[0022] This invention constructs a model for evaluating the severity of clinical symptoms of hypersplenism. The model uses logistic regression analysis of PLT, WBC, and RBC to create a nomogram, converting the regression coefficients into a visual scoring system. Scores are assigned based on primary and secondary factors, and finally, a hypersplenism grading prediction model is constructed based on the total score. Using this predictive model, the severity of clinical symptoms of hypersplenism in patients can be assessed. Correlation analysis of peripheral blood cell test results in hypersplenism patients can evaluate the grade of hypersplenism, allowing for timely and personalized treatment plans and preventing delays in diagnosis and treatment.

[0023] The hypersplenism grading prediction model constructed in this invention effectively avoids the impact of different types and intensities of peripheral blood cell reduction on the accurate judgment of the severity of hypersplenism, and has important significance and application prospects for precise guidance of hypersplenism treatment. Detailed Implementation

[0024] To better understand the technical content of this invention, specific embodiments are provided below to further illustrate the invention.

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

[0026] Unless otherwise specified, all materials and reagents used in the embodiments of this invention are commercially available.

[0027] Example 1

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

[0029] S1: The sample consisted of 2,542 patients with cirrhosis and splenomegaly from a multicenter cohort study between June 1999 and December 2016. Among them, there were 1,660 males (65.3%) and 882 females (34.7%), with a male-to-female ratio of approximately 1.88:1. The patients ranged in age from 16 to 84 years, with a mean age of 49.5 years.

[0030] The diagnostic criteria for splenomegaly in liver cirrhosis are: 1. CT or MRI scan showing a spleen extending more than 5 rib units or with a spleen length ≥ 15 cm; 2. Physical examination: the upper border of the spleen is located above the 9th intercostal space along the midaxillary line, and the lower border extends beyond the costal arch. Both criteria must be met for splenomegaly to be considered as such.

[0031] Diagnostic criteria for hypersplenism: First, through medical history and relevant examinations, exclude non-hypersplenism factors such as medications (especially chemotherapy drugs and antibiotics), damage to liver function and bone marrow caused by large-area radiotherapy or burns, severe infection, and blood loss leading to peripheral blood cell reduction; Second, splenomegaly, with enhanced splenic blood storage and blood cell destruction functions; Third, the presence of one or more types of peripheral blood cell reduction (based on the first peripheral venous blood test after admission, with a white blood cell (WBC) count <4×10⁻⁶). 9 / L, red blood cell (RBC) count <3.5×10 12 / L, platelet (PLT) count <100×10 9 / L is referred to as peripheral blood cell reduction; 4. After splenectomy or shunt surgery, the reduced blood cell count returns to normal or above normal levels. Condition 1 is mandatory, and if two of the following three conditions are also met, a diagnosis of hypersplenism can be made. This allows some patients who have not undergone surgery or who need surgery to be diagnosed with hypersplenism preoperatively.

[0032] Of the 2059 cases of cirrhosis caused by hepatitis B (81.0%), 280 cases by hepatitis C (11.0%), 63 cases by alcoholic cirrhosis (2.5%), 56 cases by biliary cirrhosis (2.2%), 51 cases by immune-mediated hepatitis (2.0%), and 33 cases by other types of cirrhosis (1.3%). All cases showed nodular cirrhosis and atrophy of the liver, and generalized splenomegaly, upon examination by ultrasound, CT, or MRI.

[0033] Peripheral venous blood tests showed that 92% of patients (2339 / 2542) had one or more types of peripheral blood cell reduction. Gastroscopy and CT scans revealed moderate to severe varices in the lower esophagus and gastric fundus. Except for 203 patients with normal blood cell counts, all patients underwent surgical treatment. This included 887 patients (37.9%-67%) who underwent esophageal and gastric fundus vein transection and splenectomy due to poor response to endoscopic banding or TIPS (transjugular intrahepatic portosystemic shunt) for massive gastrointestinal bleeding (≥1000mL), with 92 patients also undergoing splenorenal shunt. 397 patients (17.0%) underwent splenectomy due to enlarged spleen (below the level of the abdominal midline or bilateral anterior superior iliac spines) affecting their quality of life, with 26 patients also undergoing splenorenal shunt. 770 patients (32.9%) underwent splenectomy and portacaval vein transection due to moderate to severe hypersplenism. 262 patients (11.2%) underwent splenectomy alone. 18 patients (0.8%) underwent portosystemic shunt alone. 5 patients (0.2%) underwent liver transplantation alone. Liver tissue was routinely harvested during the operation and sent for pathological examination, which revealed cirrhosis.

[0034] S2: From the large number of cases in the above multicenter study, cases were randomly divided into a training set and a test set at a ratio of 8:2. The training set used logistic regression to create a nomogram, and the regression coefficients were converted into a visual scoring system. Scores were assigned according to the primary and secondary factors, and finally, a grading prediction model for hypersplenism was constructed based on the total score. The test set was used to evaluate the performance of the grading prediction model for hypersplenism.

[0035] The training set consisted of 2034 cases (80%), and the test set consisted of 508 cases (20%). In the training set, 1871 cases (92.0%) had one or more peripheral blood cell reductions, while 163 cases (8.0%) had normal blood cell counts. Logistic multivariate regression analysis showed that thrombocytopenia (PLT) was the main prognostic factor, with PLT reduction as the primary scoring criterion, supplemented by leukocyte (WBC) and red blood cell (RBC) reductions. Specific scoring and hypersplenism grading methods were as follows: The reduced blood cell counts were first scored (Table 1). PLT 100-50×10⁻⁶ 9 / L rating 1 point, 50-30×10 9 / L rating: 2 points, <30×10 9 / L rating 3 points; RBC 3.5-2.5×10 12 / L rating 0 points, 2.5-1.5×10 12 / L rating: 1 point, <1.5×10 12 2 points; WBC 4-2×10 9 / L rating 0, <2×10 9 / L score 1. Then, the scores were calculated and the hypersplenism was divided into 3 grades (degrees): total score <2 points was grade I (mild) 907 cases (44.6%), total score 2-3 points was grade II (moderate) 993 cases (48.8%), and total score >3 points was grade III (severe) 134 cases (6.6%); the treatment results of the three grades of hypersplenism were significantly different (H=12.958, P=0.002).

[0036] Table 1. Hypersplenism scoring and grading model

[0037] S3: Test Set results show that the splenomegaly grading prediction model performs well, with an AUC of 0.92, demonstrating strong predictive performance.

[0038] A new treatment plan was established based on the classification of hypersplenism:

[0039] For grade I hypersplenism with mild clinical symptoms, non-surgical treatment is recommended.

[0040] For grade II hypersplenism with moderate clinical symptoms, non-surgical treatment is generally recommended. Surgical treatment may be performed if the condition worsens.

[0041] For grade III hypersplenism with severe clinical symptoms, surgical treatment is required, including total splenectomy, shunt surgery, and liver transplantation.

[0042] Comparing the surgical and non-surgical treatment groups of 400 patients, there was no significant difference in efficacy between the two groups for grade I hypersplenism (p>0.05); the surgical group for grade II hypersplenism had significantly better efficacy than the non-surgical group (p<0.05); and the surgical group for grade III hypersplenism had significantly better efficacy than the non-surgical group (p<0.01), indicating that surgical treatment for grade III hypersplenism can improve efficacy.

[0043] The treatment outcomes of hypersplenism in the surgical and non-surgical groups were compared.

[0044] Criteria for evaluating therapeutic efficacy:

[0045] Cure: Clinical symptoms disappear, and routine examinations show that the reduced number of blood cells has returned to normal.

[0046] Improvement: Clinical symptoms have lessened, and routine tests show improvement in the number of blood cells that were reduced, but they have not returned to normal levels.

[0047] As before: there were no changes in clinical symptoms or routine examinations.

[0048] Worsening: Clinical symptoms worsen, leading to death.

[0049] Effective includes cure and improvement, ineffective includes unchanged condition and worsening / death.

[0050] Overall, there was no significant difference in efficacy between the two groups for grade I hypersplenism (p>0.05); for grade II hypersplenism, the surgical group showed significantly better efficacy than the non-surgical group (p<0.05); and for grade III hypersplenism, the surgical group showed significantly better efficacy than the non-surgical group (p<0.01). The comparison of overall efficacy is shown in Table 2.

[0051] Table 2 Comparison of overall efficacy of two different treatment methods for hypersplenism grading

[0052] Application Example 1

[0053] Patient Wang Mouzhong, male, 47 years old, was diagnosed with portal hypertension due to hepatitis B cirrhosis after massive hematemesis, hemorrhagic shock, and splenomegaly.

[0054] Table 3: Grade of Hypersplenism in Patient 1

[0055] Based on the patient's peripheral blood cell count, the hypersplenism scoring and grading model of Example 1 was used to obtain a total score of 4 points, and the hypersplenism was assessed as grade III hypersplenism, which was then treated surgically.

[0056] On November 22, 2000, the patient underwent splenectomy with perigastric vessel transection while preserving the main trunk of the vagus nerve.

[0057] The patient felt well after the surgery, and his peripheral blood cell count returned to normal. He returned to work two months after the surgery and has not experienced any bleeding for 24 years. He is now retired.

[0058] Application Example 2

[0059] The patient, Ms. Wang, 35 years old, was diagnosed with portal hypertension due to hepatitis B cirrhosis and splenomegaly because she experienced hematemesis, fatigue, and very low peripheral blood cell count every year.

[0060] Table 4. Grade of Hypersplenism in Patient 2

[0061] Based on the patient's peripheral blood cell count, the hypersplenism scoring and grading model of Example 1 was used to obtain a total score of 4 points, and the hypersplenism was assessed as grade III hypersplenism, which was then treated surgically.

[0062] On November 5, 2001, the patient underwent splenectomy with preservation of the perigastric vessels connected to the main trunk of the vagus nerve.

[0063] Twenty-three years after the surgery, the patient is feeling well, his peripheral blood cell count has returned to the normal range, he has no ascites, and he is still working normally.

[0064] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should 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, Includes the following steps: S1: Obtain samples of cirrhotic splenomegaly, which are divided into training samples and test samples; S2: Collect peripheral blood cell test results from samples, including white blood cells, red blood cells, and platelets; using the training samples as a database, employ logistic multivariate regression analysis to determine primary and secondary factors, and assign scores based on these factors. The scoring is primarily based on the number of thrombocytopenic purpura cells, supplemented by the number of white blood cells and red blood cells. A grading prediction model for hypersplenism is established by calculating the total score, determining the scoring method for the severity of clinical symptoms of hypersplenism and the grading criteria for hypersplenism. Patients are classified into mild, moderate, and severe based on the severity of their clinical symptoms of hypersplenism. S3: Test the predictive performance of the hypersplenism grading prediction model using test samples; S4: Before treating a new patient, calculate the hypersplenism score and corresponding hypersplenism grading criteria of the new patient based on the hypersplenism grading prediction model, and adopt different treatment plans according to the hypersplenism grading criteria.

2. The grading method according to claim 1, characterized in that, The liver cirrhosis and splenomegaly samples were randomly divided into training samples and test samples according to a ratio of 7-8:2-3 between training samples and test samples.

3. The grading method according to claim 1, characterized in that, The assigned score includes: platelet count 100-50×10⁻⁶. 9 / L, assigned 1 point, platelet count 50-30×10 9 / L, assigned 2 points, platelet count <30×10 9 / L, awarded 3 points; The red blood cell count was 3.5-2.5 × 10⁻⁶. 12 / L, assigned 0 points, red blood cell count 2.5-1.5×10 12 / L, assigned 1 point, red blood cell count <1.5×10 12 / L, awarded 2 points; The white blood cell count was 4-2 × 10⁻⁶. 9 / L, assigned 0 points, white blood cell count <2×10 9 / L, award 1 point.

4. The grading method according to claim 3, characterized in that, Based on the assigned scores, the grading criteria for hypersplenism are as follows: a total score of <2 points indicates mild hypersplenism, i.e., Grade I. A total score of 2-3 for hypersplenism indicates moderate hypersplenism, i.e., grade II. A total score of >3 for hypersplenism indicates severe hypersplenism, or grade III.

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

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