Molecular markers, diagnostic kits and their applications for evaluating the progression degree and prognosis of liver diseases

Abstract

The present invention provides a molecular marker for evaluating the prognosis and progression of liver diseases, and the molecular marker includes the platelet ADP inhibition rate. Research shows that in patients with chronic liver diseases and their progression stages, the ADP inhibition rate is positively correlated with the occurrence of systemic / organ failure, positively correlated with the severity of systemic / organ failure, and also positively correlated with the 28-day mortality rate. It can be seen that the magnitude of the platelet ADP inhibition rate is correlated with the degree of liver disease progression and the prognosis of liver diseases. The greater the platelet ADP inhibition rate, the more severe the degree of liver disease progression and the higher the degree of poor prognosis of liver diseases. Especially when the platelet ADP inhibition rate is greater than 30%, the prognosis of liver disease patients is significantly worse than that of liver disease patients with a platelet ADP inhibition rate less than 30%. Therefore, the platelet ADP inhibition rate can be used as a molecular marker for evaluating the degree of liver disease progression and the prognosis of liver diseases, and is used to accurately evaluate the degree of progression and prognosis of liver diseases, especially chronic liver diseases.

Description

[0001] This case claims the priority of the invention patent with an application date of December 28, 2023, an application number of 2023118407011, and an invention title of "Molecular Markers for Evaluating the Prognosis of Liver Diseases and Diagnostic Kits", and incorporates the full text thereof herein by reference. Technical Field

[0002] The present invention relates to molecular markers for evaluating the prognosis of liver diseases and diagnostic kits, belonging to the technical field of molecular biology. Background Art

[0003] Chronic liver disease refers to liver diseases with a course of more than 6 months, manifested as persistent or intermittent repeated abnormal liver function. Common chronic liver diseases mainly include hepatitis B virus, alcoholic hepatitis, hepatitis C virus, and autoimmune liver diseases, etc. Chronic liver disease is prone to progress to end-stage liver diseases such as compensated cirrhosis, decompensated cirrhosis, acute liver failure, acute-on-chronic liver failure, and chronic liver failure in the long term. Therefore, it is very important for patients with chronic liver disease to treat chronic liver disease in a timely manner to control its disease progression and reduce the incidence of system / organ failure in end-stage liver diseases. However, currently, due to unclear mechanisms, except for liver transplantation, there are no other clear treatment options for patients with chronic liver disease. The prognosis of liver disease mainly refers to the disease progression and survival status of liver disease patients after treatment. Evaluating the prognosis of liver disease can provide doctors and patients with information about the development trend of liver disease, and then guide the treatment decision of liver disease. Therefore, accurately evaluating the prognosis of liver disease is the key to effectively treating chronic liver disease and controlling its development.

[0004] At present, clinically, the prognosis of chronic liver disease is mainly evaluated by detecting the levels of molecular markers such as total bilirubin (TBil), international normalized ratio (INR), and serum creatinine (Cr) in the bodies of patients with chronic liver disease. However, these molecular markers still have defects. For example, an increase in total bilirubin can be a manifestation of multiple diseases, not limited to chronic liver disease. Therefore, its increase cannot determine a specific liver disease type or cause; an increase in total bilirubin is usually a late manifestation of impaired liver function, which means that it may not provide sufficient early risk warnings in the early stage of liver disease; the total bilirubin level is interfered by multiple factors, including hemolysis, biliary obstruction, and the influence of drugs, which may cause fluctuations in the total bilirubin level and make it unstable; at the same time, an increase in total bilirubin has little clinical guiding effect on treatment. The clinical treatment guiding significance of international normalized ratio (INR) and serum creatinine (Cr) in patients with chronic liver disease is even unclear, and it is impossible to directly correlate the two with the prognosis of chronic liver disease. A single indicator can only predict a single system / organ failure, such as bilirubin predicting liver failure and creatinine predicting renal failure. Whether a single indicator can be used to predict different system / organ failures is also unknown.

[0005] Studies have also found that patients with advanced chronic liver disease or cirrhosis often have mild to severe thrombocytopenia. In addition, studies have shown that in patients with chronic acute liver failure associated with hepatitis B virus infection, there is a rapid decline in platelet count. This rapid decrease in platelet count is not caused by platelet destruction or increased apoptosis, and has little to do with the state of platelet production (reticulated platelets, thrombopoietin). It is speculated that it is caused by platelet activation caused by acute liver injury, liver sinusoidal endothelial damage, etc., which causes a large amount of platelet aggregation and platelet consumption in the liver. In addition, studies have found that in patients with acute and chronic liver failure, platelet counts also decline further. However, platelet count alone is not an independent risk factor for short-term prognosis of liver disease. It can be seen that platelet count cannot be used as a molecular marker for accurately assessing the prognosis of liver disease. Therefore, it is urgent to find molecular markers that are more strongly associated with the risk of progression and prognosis of chronic liver disease to assess the risk of progression and prognosis of chronic liver disease and overcome the defects of the existing technology.

[0006] Thromboelastography (TEG) is a test method used to evaluate the overall picture of coagulation function and platelet function. TEG and thromboelastography-platelet mapping (TEG-PM) not only reflect the cumulative effect of interactions between different levels of coagulation, including plasma components (coagulation proteins) and cellular components (platelets, erythrocytes and microparticles), but also measure platelet activity as a response to adenosine diphosphate (ADP) or arachidonic acid (AA). In TEG and TEG-PM, firstly, ADP inhibition rate and AA inhibition rate are two intuitive and easy-to-measure indicators that can be easily obtained in clinical practice; secondly, compared with traditional platelet function test methods (such as photoaggregometry), TEG and TEG-PM can provide more comprehensive and dynamic information such as ADP inhibition rate and AA inhibition rate, so as to provide doctors with timely and real-time information on patients' platelet function, which helps to more accurately assess patients' bleeding and thrombosis risks, and helps doctors adjust antiplatelet therapy according to the actual situation of patients. At present, there are no relevant research reports on whether platelet function in patients with chronic liver disease can be used as a molecular marker for evaluating the risk of progression and prognosis of chronic liver disease, and there are no relevant research reports on whether platelet function in patients with chronic liver disease measured by TEG or TEG-PM can be used as a molecular marker for evaluating the risk of progression and prognosis of chronic liver disease. Summary of the invention

[0007] To solve the above problems, the present invention first provides a molecular marker for evaluating the progression and prognosis of chronic liver disease, wherein the molecular marker includes platelet ADP inhibition rate.

[0008] In one embodiment of the present invention, the molecular marker is the platelet ADP inhibition rate measured by thromboelastogram (TEG) and / or thromboelastogram - platelet map (TEG - PM).

[0009] In one embodiment of the present invention, the chronic liver disease is a liver disease characterized by persistent abnormal liver function or intermittent and recurrent abnormal liver function.

[0010] In one embodiment of the present invention, the degree of progression of the chronic liver disease is the occurrence of single - system / organ failure or multiple - system / organ failure.

[0011] In one embodiment of the present invention, the degree of progression of the chronic liver disease is the occurrence of one or more of liver failure, coagulation failure, renal failure, and central nervous system failure.

[0012] In one embodiment of the present invention, the prognosis of the liver disease is the short - term mortality rate.

[0013] In one embodiment of the present invention, the short - term mortality rate refers to the mortality rate within 28 / 90 days after the patient is admitted to the hospital.

[0014] In one embodiment of the present invention, taking the ADP inhibition rate ≤ 30% as low risk, 30% - 70% as medium risk, and ≥ 70% as high risk as the risk criteria for the occurrence of each system / organ failure.

[0015] In one embodiment of the present invention, when the platelet ADP inhibition rate is less than 30%, the end - stage liver disease system / organ failure score (Chronic Liver Failure - sequential Organ Failure Assessment Score, CLIF - OF) of liver disease patients is 7 points (interquartile range is 6 - 8 points) (low risk); when the platelet ADP inhibition rate is 30% - 70%, the end - stage liver disease system / organ failure score of liver disease patients is 8 points (interquartile range is 6 - 10 points) (medium risk); when the platelet ADP inhibition rate is greater than 70%, the end - stage liver disease system / organ failure score of liver disease patients is 10 points (interquartile range is 9 - 12 points) (high risk).

[0016] In one embodiment of the present invention, when the platelet ADP inhibition rate is less than 30%, the short-term survival rate of liver disease patients is 98.3% (95% confidence interval is 96.3 - 100%) (low risk). When the platelet ADP inhibition rate is 30 - 70%, the short-term survival rate of liver disease patients is 87.5% (95% confidence interval is 79.3 - 96.6%) (medium risk). When the platelet ADP inhibition rate is greater than 70%, the short-term survival rate of liver disease patients is 14.8% (95% confidence interval is 6.0 - 36.6%) (high risk).

[0017] On the other hand, the present invention provides the use of the platelet ADP inhibition rate as a molecular marker for evaluating the degree of progression and / or prognosis of chronic liver disease.

[0018] In one embodiment of the present invention, the molecular marker is the platelet ADP inhibition rate measured by thromboelastogram (TEG) and / or thromboelastogram - platelet map (TEG-PM).

[0019] In one embodiment of the present invention, the chronic liver disease is a liver disease characterized by persistent abnormal liver function or intermittent and repeated abnormal liver function.

[0020] In one embodiment of the present invention, the degree of progression of the chronic liver disease is the occurrence of single-system / organ failure or multi-system / organ failure.

[0021] In one embodiment of the present invention, the degree of progression of the chronic liver disease is the occurrence of one or more of liver failure, coagulation failure, renal failure, and central nervous system failure.

[0022] In one embodiment of the present invention, the prognosis of the liver disease is short-term mortality.

[0023] In one embodiment of the present invention, the short-term mortality refers to the mortality within 28 days or 90 days after the patient is admitted to the hospital.

[0024] In one embodiment of the present invention, taking ADP inhibition rate ≤ 30% as low risk, between 30% - 70% as medium risk, and ≥ 70% as high risk as the standard for the risk of each system / organ failure.

[0025] In one embodiment of the present invention, when the platelet ADP inhibition rate is less than 30%, the Chronic Liver Failure-sequential Organ Failure Assessment Score (CLIF-OF) of liver disease patients is 7 points (the interquartile range is 6 - 8 points) (low risk); when the platelet ADP inhibition rate is 30 - 70%, the CLIF-OF score of liver disease patients is 8 points (the interquartile range is 6 - 10 points) (medium risk); when the platelet ADP inhibition rate is greater than 70%, the CLIF-OF score of liver disease patients is 10 points (the interquartile range is 9 - 12 points) (high risk).

[0026] In one embodiment of the present invention, when the platelet ADP inhibition rate is less than 30%, the short-term survival rate of liver disease patients is 98.3% (the 95% confidence interval is 96.3 - 100%) (low risk); when the platelet ADP inhibition rate is 30 - 70%, the short-term survival rate of liver disease patients is 87.5% (the 95% confidence interval is 79.3 - 96.6%) (medium risk); when the platelet ADP inhibition rate is greater than 70%, the short-term survival rate of liver disease patients is 14.8% (the 95% confidence interval is 6.0 - 36.6%) (high risk).

[0027] The present invention also provides the use of a reagent for detecting the above-mentioned molecular marker in a sample to be tested in the preparation of a product for evaluating the risk of progression and prognosis of chronic liver disease.

[0028] In one embodiment of the present invention, the molecular marker is the platelet ADP inhibition rate measured by thromboelastogram (TEG) and / or thromboelastogram - platelet map (TEG-PM).

[0029] In one embodiment of the present invention, the chronic liver disease is a liver disease characterized by persistent abnormal liver function or intermittent and repeated abnormal liver function.

[0030] In one embodiment of the present invention, the degree of progression of the chronic liver disease is the occurrence of single system / organ failure or multiple system / organ failure.

[0031] In one embodiment of the present invention, the degree of progression of the chronic liver disease is the occurrence of one or more of liver failure, coagulation failure, renal failure, and central nervous system failure.

[0032] In one embodiment of the present invention, the prognosis of the chronic liver disease is short-term mortality.

[0033] In one embodiment of the present invention, the short-term mortality refers to the mortality rate within 28 days or 90 days after the patient is admitted to the hospital.

[0034] In one embodiment of the present invention, an ADP inhibition rate ≤ 30% is defined as low risk, 30% - 70% as medium risk, and ≥ 70% as high risk, serving as the criteria for the risk of each system / organ failure.

[0035] In one embodiment of the present invention, when the platelet ADP inhibition rate is less than 30%, the Chronic Liver Failure - sequential Organ Failure Assessment Score (CLIF - OF) of patients with liver disease is 7 points (interquartile range: 6 - 8 points) (low risk); when the platelet ADP inhibition rate is 30 - 70%, the CLIF - OF score of patients with liver disease is 8 points (interquartile range: 6 - 10 points) (medium risk); when the platelet ADP inhibition rate is greater than 70%, the CLIF - OF score of patients with liver disease is 10 points (interquartile range: 9 - 12 points) (high risk).

[0036] In one embodiment of the present invention, when the platelet ADP inhibition rate is less than 30%, the short - term survival rate of patients with liver disease is 98.3% (95% confidence interval: 96.3 - 100%) (low risk); when the platelet ADP inhibition rate is 30 - 70%, the short - term survival rate of patients with liver disease is 87.5% (95% confidence interval: 79.3 - 96.6%) (medium risk); when the platelet ADP inhibition rate is greater than 70%, the short - term survival rate of patients with liver disease is 14.8% (95% confidence interval: 6.0 - 36.6%) (high risk).

[0037] The present invention also provides a diagnostic kit for evaluating the prognosis of liver disease, and the diagnostic kit includes reagents for detecting the above - mentioned molecular markers in a test sample.

[0038] In one embodiment of the present invention, the aforementioned diagnostic reagent or kit is used for detecting whole peripheral blood.

[0039] The technical solution of the present invention has the following advantages:

[0040] 1. The present invention provides a marker for evaluating the risk of progression and prognosis of chronic liver disease, and the molecular marker includes the platelet ADP inhibition rate.

[0041] 2. The marker provided by the present invention is used for patients who have not yet developed system / organ failure, and has greater diagnostic significance compared to the prior art for patients with liver failure.

[0042] 3. The biomarker provided by the present invention is positively correlated with the occurrence of single or multiple system / organ failures. The ADP inhibition rate is positively correlated with the severity of system / organ failures, and the ADP inhibition rate is positively correlated with the 28 / 90-day mortality rate. Description of the Drawings

[0043] Figure 1 : To verify the predictive ability of the ADP inhibition rate for the 28 / 90-day case fatality rate in the validation cohort. A is the ROC curve for the 28-day case fatality rate, and B is the ROC curve for the 90-day case fatality rate.

[0044] Figure 2 : Heat map of the correlation between the ADP inhibition rate and the scores of each system / organ failure in the learning cohort (the numbers in the figure are the correlations)

[0045] Figure 3 : Heat map of the correlation between the ADP inhibition rate and the scores of each system / organ failure in the validation cohort (the numbers in the figure are the correlations).

[0046] Figure 4 : Predictive ability of the ADP inhibition rate for the occurrence of single system / organ failure in the learning cohort (ROC curve), A: Circulatory failure, B: Central nervous system failure, C: Liver failure, D: Renal failure, E: Coagulation failure, F: Respiratory failure.

[0047] Figure 5 : Predictive ability of the ADP inhibition rate for the occurrence of single system / organ failure in the validation cohort (ROC curve), A: Circulatory failure, B: Central nervous system failure, C: Liver failure, D: Renal failure, E: Coagulation failure, F: Respiratory failure.

[0048] Figure 6 : In the validation cohort, statistical differences in the scores of various systems / organs of failure after grouping with the ADP inhibition rate ≤ 30% as low risk, 30% - 70% as medium risk, and ≥ 70% as high risk, A: Circulatory failure, B: Central nervous system failure, C: Liver failure, D: Renal failure, E: Coagulation failure, F: Respiratory failure..

[0049] Figure 7 : Predictive value and trend changes of the ADP inhibition rate for high risk (disease progression) of system / organ failure in the learning cohort, A: ROC curve of the comprehensive system / organ failure score, B: Correlation curve between the comprehensive system / organ failure score and the ADP inhibition rate.

[0050] Figure 8 : Predictive value and trend changes of the ADP inhibition rate for high risk (disease progression) of system / organ failure in the validation cohort, A: ROC curve of the comprehensive system / organ failure score, B: Correlation curve between the comprehensive system / organ failure score and the ADP inhibition rate.

[0051] Figure 9 : Statistical analysis of the differences in the scores of overall system / organ failure after grouping according to the ADP inhibition rate in the validation cohort, with an ADP inhibition rate of ≤30% being low risk, 30% - 70% being medium risk, and ≥70% being high risk. Detailed implementation manner

[0052] The following embodiments are provided to better understand the present invention further, and are not limited to the best embodiment. They do not limit the content and protection scope of the present invention. Any product that is the same as or similar to the present invention obtained by anyone under the inspiration of the present invention or by combining the features of the present invention with other prior art features falls within the protection scope of the present invention.

[0053] For those in the following embodiments where specific experimental steps or conditions are not indicated, the operations or conditions of the conventional experimental steps described in the literature in this field can be followed. For reagents or instruments whose manufacturers are not indicated, they are all conventional reagent products that can be obtained through commercial purchase. The system / organ failure described in this application generally refers to the overall system / organ failure when no limiting terms are used, and only refers to the specific limited single system / organ failure when specifically limited. The degree of progression of the chronic liver disease described in this application is the occurrence of one or more of liver failure, coagulation failure, renal failure, and central nervous system failure, and can also be understood as the co-occurrence of one or more of liver failure, coagulation failure, renal failure, and central nervous system failure in chronic liver disease.

[0054] Experimental example 1: Screening of molecular markers

[0055] The full text of Experimental example 1 is incorporated by reference from Experimental example 1 of the patent application with the application number 2023118407011.

[0056] Experimental example 2: Verification of molecular markers

[0057] 1 Experimental method

[0058] 1.1 Cohort construction:

[0059] Based on the inclusion criteria of the original learning cohort (the cohort sample of Example 1 with the application number 2023118407011), the inclusion criterion of simply elevated liver enzymes was deleted in the validation cohort, aiming to observe more positive endpoints when constructing the validation cohort. A total of 133 patients with chronic liver disease were included in the validation cohort.

[0060] To increase the reliability of the data, when constructing the validation cohort, this study invited an independent third-party supervision agency that specializes in the supervision of medical research and data auditing. Its main responsibilities include: ensuring that the research design complies with ethical norms and scientific standards. Monitoring compliance and data integrity during the data collection process. Reviewing and validating the accuracy and authenticity of the data.

[0061] Table 2 Inclusion and exclusion criteria

[0062]

[0063]

[0064] 1.2 Sample collection and platelet function detection: Fasting blood was collected from each patient and placed in a test tube containing the corresponding anticoagulant. For the TEG common cup test (see the literature "Hartert.et al.Klinische Wochenschrift.1948" for details), a sodium citrate test tube containing sodium citrate anticoagulant was required to collect peripheral blood from patients. In addition, based on the TEG common cup, platelet function analysis was performed by thromboelastogram - platelet mapping (TEG - PM) (see the literature "Craft RM, Chavez JJ, Bresee SJ, Wortham DC, Cohen E, Carroll RC.A novel modification of the Thrombelastograph assay,isolating platelet function,correlates with optical platelet aggregation.J Lab Clin Med.2004;143(5):301 - 309." for details), and a lithium heparin test tube containing lithium heparin anticoagulant was required to collect peripheral blood from patients. The heparinized blood sample was used for TEG - PM detection, which included platelet response to ADP through the P2Y12 receptor pathway.

[0065] 1.3 Statistical analysis: The absolute frequencies and percentages of categorical variables were reported. Quantitative variables were reported as the median and interquartile range, or otherwise specified. The Fisher exact test was used for the comparison of categorical variables, and the Mann - Whitney test was used for the comparison of continuous variables. The Kaplan - Meier method was used to describe the survival function. Factors associated with 28 - day mortality were determined by bivariate analysis (Pearson correlation coefficient (R)). Factors showing statistically significant correlation in the bivariate analysis were selected as factors for the initial multivariate analysis. The Cox regression model was used to select the best predictive subset and evaluate the fitting characteristics. Binary classification (death / survival, presence / absence of system / organ failure) was used. On the coordinate plane, the curve was plotted with 1 - specificity on the x - axis and sensitivity on the y - axis. The area under the curve (AUC) was used to evaluate the performance of the model. The closer the AUC value is to 1, the stronger the predictive ability of the model. This process helps to visualize the performance of the model at different thresholds, thereby optimizing the predictive ability of the model.

[0066] Statistical analysis was performed using SPSS 22.0 (IBM Corp., Armonk, N.Y, USA), R software 3.6.0 (R Foundation for Statistical Computing, Vienna, Austria), and GraphPad Prism 9 software (CA, USA).

[0067] 2 Experimental implementation process

[0068] Patients meeting the inclusion and exclusion criteria were continuously enrolled (the inclusion and exclusion criteria are shown in Table 2, and the enrollment process is shown in Figure 1 ). On the first day of enrollment, patients were given free TEG-PM examinations, and relevant data on damage or failure of various systems / organs (liver, coagulation, kidney, central nervous system, respiration, and circulation) and biological samples (plasma, serum, urine, cell pellet, etc.) were completely collected and fully entered into the electronic medical record system; methods such as area under the curve and maximum selection test method were used to verify the ability of platelet ADP inhibition rate for system / organ failure and 4-week prognosis in patients with chronic liver disease.

[0069] 3 Experimental results and analysis

[0070] 3.1 Results analysis of the application of platelet function ADP inhibition rate in thromboelastogram in predicting the prognosis of patients with chronic liver disease in the validation cohort samples is shown in Figure 1 , showing that the AUC values of the prediction ROC curve of ADP inhibition rate for 28 / 90-day mortality were 0.822 and 0.826 respectively, the sensitivities were 70.7% and 70.7 respectively, and the specificities were 82.1% and 82.9% respectively. It indicates that ADP inhibition rate has a high diagnostic value for the prognosis of patients with chronic liver disease.

[0071] 3.1 The results of ADP inhibition rate and scores of each system / organ failure are shown in Table 2, and the correlation heat map is shown in Figure 2 and Figure 3 .

[0072] As can be seen from the table and the heat map, whether in the samples of the learning cohort or the validation cohort, there is a highly significant positive correlation between ADP inhibition rate and scores of each system / organ failure.

[0073]

[0074] **. p value < 0.01

[0075] *. p value < 0.05

[0076] 3.2 The prediction ability of ADP inhibition rate for the occurrence of single system / organ failure is shown in Figure 4 ~Figure 6 . From Figures 4 to 5As can be seen, in both the learning cohort and the validation cohort, except for the less frequently occurring types of organ failure such as respiratory failure and circulatory failure (n = 2), the AUC in the ROC curve of the predictive ability of ADP inhibition rate for the occurrence of single-system / organ failure was between 0.71 and 98%, the p-value was less than 0.05, the sensitivity was between 71.2% and 100%, and the specificity was between 70.4% and 96.2%. This indicates that the ADP inhibition rate has a high diagnostic value for the progression of chronic liver disease (the risk of developing system / organ failure).

[0077] Figure 6 As shown, when grouped and compared with ADP inhibition rate ≤ 30% as low risk, 30% - 70% as medium risk, and ≥ 70% as high risk, there were significant differences between the groups of the remaining system / organ failures except for respiratory failure (n = 2). Therefore, ADP inhibition rate ≤ 30% can be used as low risk, 30% - 70% as medium risk, and ≥ 70% as high risk as the criteria for the risk of each system / organ failure.

[0078] 3.3 The predictive value and trend changes of ADP inhibition rate for the overall risk (disease progression) of system / organ failure are shown in Figures 7 to 9 . From Figures 7 to 8 As can be seen, in both the learning cohort and the validation cohort, after grouping patients according to whether the system / organ failure score is high risk, the ROC curve was used to show the prediction of ADP inhibition rate for medium and low risks. As can be seen from Figure A, the single indicator of ADP inhibition rate alone can effectively predict whether a patient is in the high-risk group of disease progression (AUROC = 0.73 - 0.77, p < 0.001). From the curve fitting diagram of CLIF-OF score and ADP inhibition rate, it can be seen that generally, the CLIF-OF score increases with the increase of ADP inhibition rate, showing a positive correlation; further observation shows that when the ADP inhibition rate is about greater than 30%, the CLIF-OF score and ADP inhibition rate are basically linearly correlated, verifying again the cutoff value of 30% of ADP inhibition rate mentioned above. According to Figure 9In the validation cohort, it was found that when the platelet ADP inhibition rate was less than 30%, the Chronic Liver Failure-sequential Organ Failure Assessment Score (CLIF-OF) of patients with liver disease was 7 points (interquartile range: 6 - 8 points) (low risk); when the platelet ADP inhibition rate was 30% - 70%, the CLIF-OF of patients with liver disease was 8 points (interquartile range: 6 - 10 points) (medium risk); when the platelet ADP inhibition rate was greater than 70%, the CLIF-OF of patients with liver disease was 10 points (interquartile range: 9 - 12 points) (high risk).

[0079] In summary, the ADP inhibition rate can be used as an effective marker for predicting the incidence of systemic / organ failure, the severity of systemic / organ failure, and short-term mortality in patients with chronic liver disease, which helps clinicians formulate more effective treatment plans and evaluate the prognosis.

[0080] Obviously, the above embodiments are only examples given for clear illustration and not limitations on the implementation manners. For those of ordinary skill in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all implementation manners here. And the obvious changes or modifications derived therefrom are still within the protection scope of the present invention.

Claims

1. Use of a reagent for detecting platelet ADP inhibition rate in the preparation of a product for assessing the risk of progression of chronic liver disease, characterized in that: The platelet ADP inhibition rate is the platelet ADP inhibition rate measured by thromboelastography. The chronic liver disease refers to a liver disease with a course of more than 6 months, which manifests as persistent liver function abnormalities or intermittent and recurrent liver function abnormalities. The risk of chronic liver disease progression is the risk of chronic liver disease developing liver failure, renal failure or central nervous system failure.

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