WO2022014580A1 - Marqueur de la stéatose hépatique non alcoolique, méthode de détection de la stéatose hépatique non alcoolique, et réactif et trousse d'analyse à utiliser dans ladite méthode - Google Patents

Marqueur de la stéatose hépatique non alcoolique, méthode de détection de la stéatose hépatique non alcoolique, et réactif et trousse d'analyse à utiliser dans ladite méthode Download PDF

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WO2022014580A1
WO2022014580A1 PCT/JP2021/026266 JP2021026266W WO2022014580A1 WO 2022014580 A1 WO2022014580 A1 WO 2022014580A1 JP 2021026266 W JP2021026266 W JP 2021026266W WO 2022014580 A1 WO2022014580 A1 WO 2022014580A1
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fatty liver
liver disease
alcoholic fatty
marker
concentration
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PCT/JP2021/026266
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English (en)
Japanese (ja)
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直樹 田中
岳史 木村
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国立大学法人信州大学
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor

Definitions

  • the present invention relates to a non-alcoholic fatty liver disease marker for detecting a non-alcoholic fatty liver disease that causes various diseases of the liver, and a method using the same.
  • the present application claims priority based on Japanese Patent Application No. 2020-11806 filed on 13 July 2020, the contents of which are incorporated herein by reference.
  • Non-alcoholic fatty liver disease is mainly caused by obesity, glucose tolerance disorder, or dyslipidemia of non-drinkers, and is a chronic disease that is often seen in Japan with the increase of these metabolic diseases. It has become to. In Europe, the United States and Asia, about 30% of the population has non-alcoholic fatty liver disease, and in Japan, non-alcoholic fatty liver disease has more than tripled in 30 years, and the rate of increase exceeds diabetes, and the world It is a disease for which an increase has become a problem.
  • non-alcoholic steatohepatitis which is seen in advanced cases, is a neutral fatty degeneration of the liver with histologically inflammatory necrosis, balloon-like swelling of hepatocytes, and peri-sinus. / Characterized by perivenous fibrosis, presenting with fatty liver, accompanied by inflammation, hepatocellular injury or fibrosis. Fatty liver due to non-alcoholic fatty liver has a poorer prognosis than simple fatty liver, and may progress to cirrhosis, liver cancer, and liver failure, and the incidence of cardiovascular disease and death due to liver causes is high. Due to its high rate, it has been reported that the mortality rate is high even when compared with the average mortality rate due to simple fatty liver. Therefore, early detection and treatment of non-alcoholic fatty liver disease, which increases the mortality rate as it progresses, are strongly desired.
  • a subject who is not non-alcoholic steatohepatitis has a lower alanine aminotransferase (ALT) value or aspartate aminotransferase (AST) value obtained by a blood test.
  • ALT alanine aminotransferase
  • AST aspartate aminotransferase
  • Markers known as fibrosis markers of liver tissue such as hyaluronic acid, type 4 collagen, and M2BPGi are detected, and the overall score value of this combination is used to determine the severity of the disease. Neither specificity is sufficient.
  • imaging tests such as elastography are also performed, but the testing equipment is expensive and there is a problem that the accuracy is reduced in obese cases.
  • liver biopsy is highly invasive, and the physical burden on the subject and the burden of examination and hospitalization costs are large, and even with liver biopsy, the judgment results are biased depending on the subjectivity of the pathologist and the collection site. .. For these reasons, it is difficult to perform liver biopsy on all patients, including patients in the non-severe stage of non-alcoholic fatty liver disease, and we would like to regularly check the therapeutic effect and the course after treatment. In some cases, there are many challenges to judge by liver biopsy.
  • Patent Document 1 by the present inventors describes any of ferritin, thioredoxin, and free fatty acid derived from blood collected from a non-alcoholic steatohepatitis patient, or Cu, Zn-super derived from the liver collected from the patient.
  • a marker for determining the therapeutic effect of non-alcoholic steatohepatitis in blood or liver and a marker for determining the pathological condition or therapeutic effect of non-alcoholic steatohepatitis, which is a cytokeratin 18 fragment and is measured as a change in its content.
  • This document mainly aims to provide a marker for accurately determining the effect of treatment with a liver function improving drug in patients with non-alcoholic fatty liver disease (NAFLD).
  • Patent Document 2 includes a step of measuring one or more factors selected from the group consisting of IL-1 receptor antagonist, sCD40, HMGB1, sPLA2groupIIA and PLA2 activity in a biological sample of a subject as a marker, and thrombospondin 1 Is further disclosed as a method for detecting or assessing the severity of nonalcoholic steatohepatitis, which comprises the step of measuring as a marker. Since this document provides useful indicators for detection / diagnosis of NASH (non-alcoholic steatohepatitis) and evaluation of severity / therapeutic effect, it is possible that NASH and NAFLD are easily affected. Subjects can be detected, and the severity of NASH and NAFLD and the therapeutic effect can be evaluated.
  • the therapeutic effect can be easily evaluated. It is possible to do so, and since it is not necessary to perform a biopsy, it is intended to provide a method that can reduce the burden on the patient and the burden on the medical staff.
  • the cytokeratin 18 fragment of Patent Document 1 shows a certain correlation with the state of non-alcoholic fatty liver disease. However, it may not correlate with liver fibrosis that can occur with the progression of non-alcoholic fatty liver disease. Therefore, more appropriate markers and methods are desired in order to comprehensively determine the degree of progression and therapeutic effect of non-alcoholic fatty liver disease.
  • Patent Documents 1 and 2 can also be used in place of the judgment by liver biopsy to determine the state of non-alcoholic fatty liver disease, morbidity risk, therapeutic effect, etc. Therefore, markers and methods with higher sensitivity and specificity are desired.
  • the present invention has been made based on the above background, and an object thereof has high sensitivity and specificity for non-alcoholic fatty liver disease, non-alcoholic fatty liver disease, and risk of morbidity. , Or a method used for testing a non-alcoholic fatty liver disease marker, a method used for testing a non-alcoholic fatty liver disease marker, a reagent used thereof, and an analysis kit capable of accurately determining a state such as a therapeutic effect. There is something in it.
  • a non-alcoholic fatty liver disease marker used for detecting a target non-alcoholic fatty liver disease A non-alcoholic fatty liver disease marker containing thrombospondin-2 contained in a blood sample collected from the subject.
  • the non-alcoholic fatty liver disease marker wherein the non-alcoholic fatty liver disease marker is thrombospondin-2 protein.
  • the non-alcoholic fatty liver disease marker wherein the blood sample is serum.
  • Non-alcoholic fat including a step of measuring the concentration of thrombospondin-2 using thrombospondin-2 contained in a blood sample collected from a subject as a marker for non-alcoholic fatty liver disease.
  • a method for detecting sexual liver disease A method for detecting sexual liver disease.
  • the step of measuring the concentration of thrombospondin-2 is a step of measuring the protein concentration of thrombospondin-2 in the blood sample in order to detect the non-alcoholic fatty liver disease. the method of.
  • the step of measuring the protein concentration of thrombospondin-2 is a method for detecting the non-alcoholic fatty liver disease using an immunological method.
  • a method for detecting the non-alcoholic fatty liver disease using the tronspondin-2 as a marker for the degree of progression of fibrosis of liver tissue [10] Assuming that the total value N of the NAS (NAFLD activity score) of the target and the numerical value F of the stage of fibrosis of the liver tissue is the total value S, the degree of progression S is assumed. A method for detecting non-alcoholic fatty liver disease, wherein the degree of progression S increases when the concentration of thrombospondin-2 in the blood sample increases. [11] The subject is a method for detecting the non-alcoholic fatty liver disease, which is a subject who has been treated for the non-alcoholic fatty liver disease in the past.
  • An analytical reagent for detecting non-alcoholic fatty liver disease which comprises a reagent for detecting the non-alcoholic fatty liver disease marker.
  • An analytical kit for detecting non-alcoholic fatty liver disease which comprises an analytical reagent for detecting the non-alcoholic fatty liver disease.
  • the present invention has high sensitivity and specificity for non-alcoholic fatty liver disease, activity of non-alcoholic fatty liver disease, progress of fibrosis (high fibrosis / cirrhosis), and morbidity.
  • a method used for testing a non-alcoholic fatty liver disease marker and a non-alcoholic fatty liver disease marker that can accurately determine a state such as a risk or a therapeutic effect can be obtained.
  • Non-alcoholic fatty liver disease marker is a marker used for detecting a target non-alcoholic fatty liver disease.
  • the subject is a person to be examined and detected for a condition related to the non-alcoholic fatty liver disease such as the possibility of the non-alcoholic fatty liver disease, the presence or absence and the situation of the disease, and the therapeutic effect.
  • Nonalcoholic Fatty Liver Disease is a general term for non-alcoholic fatty liver diseases caused by alcohol, and is a non-alcoholic fatty liver disease (NAFL).
  • NASH non-alcoholic steatohepatitis
  • Fatty liver disease may also be referred to as fatty liver disease.
  • a marker is an index for detecting information on a specific disease state of a target, and as described later, a protein, a nucleic acid encoding the marker, or other in vivo molecules (peptides, lipids, etc.).
  • the increase or decrease in its concentration in the living body is reflected in the information regarding the state of the specific disease.
  • the state of non-alcoholic fatty liver disease is non-alcoholic fat such as the presence, possibility, degree of progression, therapeutic effect, and other diseases or symptoms due to the influence of non-alcoholic fatty liver disease in the subject. Broadly refers to conditions related to sexual liver disease.
  • Used to detect non-alcoholic fatty liver disease broadly refers to obtaining information for investigating the state of the non-alcoholic fatty liver disease.
  • Detecting non-alcoholic fatty liver disease refers to, for example, acquiring and providing data related to non-alcoholic fatty liver disease. Specifically, for example, it refers to examining NAS (NAFLD activity score) indicating the state of non-alcoholic fatty liver disease.
  • NAFLD activity score indicating the state of non-alcoholic fatty liver disease.
  • it includes investigating various phenomena due to the influence of non-alcoholic fatty liver disease. More specifically, it includes degeneration, swelling or fibrosis of liver tissue. More specifically, there are hepatic triglyceride degeneration with inflammatory necrosis, balloon-like swelling (swelling) of hepatocytes, and peri-sinusoide / perivenous fibrosis.
  • the present embodiment it is preferable to use it for detecting non-alcoholic fatty liver disease, for example, to obtain information for continuously investigating the state of non-alcoholic fatty liver disease. In addition, it is more preferable to use it for examining the progress (presence or absence of improvement) after the treatment. That is, since the non-alcoholic fatty liver disease marker of the present embodiment has a correlation with the target NAS and fibrosis of liver tissue, the marker of the present embodiment alone has a correlation with the non-alcoholic fatty liver. Information on the state of the disease and the presence or absence of its effects can be obtained. In addition, since it can be detected relatively easily with a blood sample, it is also suitable for multiple detections such as continuous detection.
  • the sample collected from the subject broadly refers to a sample containing a component extracted from an organism, but in this embodiment, a blood sample using blood collected from a human as a sample is used.
  • a blood sample using blood collected from a human as a sample is used.
  • collected blood, serum, plasma, or the like can be used.
  • serum is easier to obtain and store than other body fluid samples such as blood and plasma.
  • body fluid samples such as blood and plasma.
  • a sample that is cryopreserved in the form of serum is generally common internationally, so it is a useful technique.
  • the non-alcoholic fatty liver disease marker of the present embodiment contains thrombospondin-2 contained in the blood sample.
  • Thrombospondin-2 (TSP2) is a protein belonging to the TSP family.
  • the TSP family plays a dynamic role in the extracellular matrix, which is associated with aggregates of extracellular molecules secreted by cells that structurally / biochemically support surrounding cells, such as fibrin, collagen, and hyaluronic acid. It is a substance that has and is known as a protein family that regulates cell migration, adhesion, proliferation, and the like.
  • the TSP family is thought to be involved in platelet aggregation, development, cell adhesion, angiogenesis, thrombus formation, cancer metastasis and wound healing.
  • Thrombospondin-2 is found in tissues such as fibroblasts and smooth muscle, and among the above-mentioned functions, it is known that it may be particularly involved in angiogenesis, cancer metastasis, wound healing and the like.
  • the present inventors have been diligently researching non-alcoholic fatty liver disease in order to find a highly sensitive marker that can be widely used for observing the susceptibility, risk, and course after treatment.
  • patients with non-alcoholic fatty liver disease it is known that there is a difference in expression in 64 genes between patients with mild fibrosis and patients with severe fibrosis (Moyan et al. Hepatology 2014, etc.). ..
  • the present inventors focused on the possibility that four of these genes, which may be secreted from the liver into blood, could be used as markers in blood samples, and used serum at the time of liver biopsy. It was measured by ELISA. As a result, it was found that the protein concentration of thrombospondin-2 was correlated with both NAS and the fibrosis stage in the blood sample. That is, it was found that it was significantly increased in severe fibrosis and cirrhosis.
  • the expression level can be used as a marker (index).
  • the protein concentration of thrombospondin-2 or the mRNA concentration of the thrombospondin-2 gene may be used as a marker.
  • the method for detecting the non-alcoholic fatty liver disease of the present embodiment uses the non-alcoholic fatty liver disease marker, that is, a marker containing thrombospondin-2, and determines the concentration of the thrombospondin-2. Includes the step of measuring.
  • the step of measuring the concentration of thrombospondin-2 is preferably a step of measuring the protein concentration of thrombospondin-2 in the blood sample.
  • a known means for quantifying protein can be used.
  • examples of such means include mass spectrometry, chromatography, electrophoresis, microarray, immunoassay, and the like.
  • an immunological method can be used to measure the above-mentioned concentration.
  • an enzyme enzyme immunoassay, EIA, ELISA
  • a fluorescent substance fluorescent immunoassay, FIA
  • a radioactive substance radioactive substance
  • ELISA is preferable because it is relatively inexpensive, simple, and can analyze a large number of samples.
  • anti-thrombospondin-2 antibody used for ELISA in this embodiment either a monoclonal antibody or a polyclonal antibody can be used.
  • non-alcoholic fatty liver disease marker of the present embodiment a conventionally known substance that can be used for detecting non-alcoholic fatty liver disease may be used in combination with thrombospondin-2. ..
  • substances known to have a certain correlation with NAS include CK18 (cytokeratin 18 fragment), HA (hyaluronic acid), and 4C7S (type 4 collagen 7S).
  • CK18 correlates with balloon-like swelling (swelling) of hepatocytes in NAS.
  • Substances such as HA, 4C7S, M2BPGi, and ATX are known to have a certain correlation with fibrosis.
  • the method for detecting non-alcoholic fatty liver disease of the present embodiment may be used in combination with the value used for detection of other non-alcoholic fatty liver disease.
  • values used for detection APRI value, i.e. (AST / ULN) ⁇ 100 / number of platelets (10 9 / L) ratio (AST: aspartate transferase, ULN: AST upper normal limit), FIB-4
  • the method for detecting non-alcoholic fatty liver disease of the present embodiment is to detect non-alcoholic fatty liver disease multiple times in a patient with non-alcoholic fatty liver disease and compare the results. It is possible to judge the deterioration or improvement of the condition of the disease. In addition, detection is performed on healthy subjects who do not have the pathology of non-alcoholic fatty liver disease, and the result is used as a reference value to worsen or improve the condition of non-alcoholic fatty liver disease by comparison with the reference value. Can also be judged.
  • the status of non-alcoholic fatty liver disease is the morbidity of non-alcoholic fatty liver disease, the risk of morbidity, activity, the degree of progress of fibrosis (presence or absence of severe fibrosis / cirrhosis), and non-alcoholic fatty liver disease. These include the effects of liver disease. Effects resulting from non-alcoholic fatty liver disease include liver fibrosis and cirrhosis due to the progression of fibrosis.
  • the thoronspondin-2 can be used as a marker for the degree of progression of fibrosis of liver tissue. That is, since the concentration of tronspondin-2 has a correlation coefficient with the stage of fibrosis as described later, it can be used as a guide for measuring the progress of fibrosis. Therefore, it can also be used as a guide for directly detecting and determining the progress of fibrosis. The determination of the degree of fibrosis can also be used to detect and determine severe fibrosis or cirrhosis.
  • the concentration of the marker is increased. It can be determined that the above-mentioned state of alcoholic fatty liver disease is exacerbated. Further, if the concentration of the marker is decreased when the marker is detected later, it can be determined that the condition of the non-alcoholic fatty liver disease is improved.
  • the total value of all the target NAS values (0 to 4 points for each element, etc.) is set to N.
  • the degree of progression S can be said to be the overall degree of progression or deterioration of the symptoms caused by non-alcoholic fatty liver disease and the symptoms caused by the effects thereof.
  • the non-alcoholic fatty liver disease marker increases in correlation with both the NAS value and fibrosis, it can be determined that the degree of progression S has increased if the concentration of the marker is increased. .. That is, from the concentration of the non-alcoholic fatty liver disease marker of the present embodiment, it is possible to detect the overall degree of progression or deterioration of the symptoms caused by the non-alcoholic fatty liver disease and the symptoms caused by the effects thereof. .. This detection method can also be used to detect the degree of fibrosis (high fibrosis / cirrhosis).
  • the non-alcoholic fatty liver disease marker of the present embodiment can be applied to an analytical reagent for detecting non-alcoholic fatty liver disease or a kit containing the same.
  • the analytical reagent for detecting the non-alcoholic fatty liver disease of the present embodiment includes the reagent for detecting the above-mentioned non-alcoholic fatty liver disease marker.
  • a reagent an antibody for detecting a protein of a non-alcoholic fatty liver disease marker can be used. This antibody can be used to detect a protein as a marker for non-alcoholic fatty liver disease by an ELISA method or the like.
  • the reagent for analysis of the present embodiment may contain other components contained in the reagent for immunoassay.
  • the analytical reagent of the present embodiment may be provided as an analytical kit for detecting a non-alcoholic fatty liver disease having a plurality of the above configurations.
  • a kit may include, for example, an antibody for detecting a protein of the above-mentioned non-alcoholic fatty liver disease marker.
  • the kit may also include a carrier, an ELISA plate, a color-developing substrate, an antibody, or the like for use in the above-mentioned quantification operation.
  • the non-alcoholic fatty liver disease marker of the present embodiment has a strong correlation with the NAS value and fibrosis. Specifically, the larger the value of NAS (fatty liver, lobular inflammation, hepatocellular balloon-like swelling, etc.) measured by histological examination of liver biopsy, the higher the concentration of the marker in serum. It gets higher. In addition, the concentration of the marker in serum also increases depending on the degree of fibrosis of liver tissue. With respect to these values, the marker of the present embodiment also has higher sensitivity than the conventionally known marker.
  • NAS fatty liver, lobular inflammation, hepatocellular balloon-like swelling, etc.
  • the marker of the present embodiment it is possible to determine with high sensitivity whether either or both of the NAS and the degree of fibrosis have increased, so that one type of marker can be used for non-alcoholic. It is possible to accurately determine whether or not the fatty liver disease and its effects have progressed comprehensively.
  • the non-alcoholic fatty liver disease marker of the present embodiment can obtain information on many factors related to non-alcoholic fatty liver disease by one kind of marker. Therefore, information on both NAS and fibrosis, which was conventionally performed by liver biopsy, can be obtained by examining the marker concentration in the blood sample. Blood samples are the most common clinical samples, are easily available, and blood collection is non-invasive compared to liver biopsy. Therefore, these detections can be performed with less time, physical strength, and cost burden on the patient as compared with liver biopsy. In addition, the time burden on the inspector, for example, the medical staff can be minimized.
  • the non-alcoholic fatty liver disease and the method of the present embodiment use a blood sample that can be easily collected, and use a small number of markers to obtain a comprehensive condition such as non-alcoholic fatty liver disease and fibrosis. Since information can be obtained, it is particularly effective because it is possible to reduce the time, physical strength, and cost burden when detecting the progress after treatment at regular intervals.
  • the non-alcoholic fatty liver disease marker and method of the present embodiment can be used for examination or diagnosis related to non-alcoholic fatty liver disease.
  • a diagnostic method by performing the above-mentioned detection, it is possible to diagnose the morbidity of non-alcoholic fatty liver disease, the risk of morbidity, and / or the degree of progression thereof.
  • a standard product of protein, a healthy blood sample, etc. are used as a standard product, a calibration curve, a comparison table, etc. are created, and the quantification results of the sample sample to be diagnosed are compared with the calibration curve, contrast table, etc.
  • the process used for diagnosis is also included. It should also be used to determine and diagnose liver cirrhosis that may be caused by non-alcoholic fatty liver disease, as well as morbidity, risk of morbidity, and / or the degree of its activity and progress of fibrosis. Can be done.
  • the pathological features of the 130 NAFLD patients referred to in this study are shown in Table 1.
  • the average age of the patients was 56 years, and 54 (42%) were male.
  • BMI values were in the wide range (21.4-36.8 kg / m 2 ).
  • the median TSP2 concentration in serum was 17.4 ng / mL (7.7-71.4).
  • the stages of liver fibrosis, which will be described later, were 27, 57, 15, 23, and 8 for F0, F1, F2, F3, and F4, respectively.
  • the state of fatty liver was set to the stage of S0 to S3 ( ⁇ 5%, 5-33%,> 33-66%, ⁇ 66%, respectively).
  • the state of lobular inflammation was the number of inflammatory lesions at the stage of L0 to L3 (no inflammation to ⁇ 2 inflammation / 200x range, 2-4 inflammation / 200x range,> 4 inflammation / 200x range, respectively).
  • the state of hepatocellular balloon-like swelling was set to the stage of B0 to B2 (none, several places, many).
  • the state of fibrosis is F0 to F4 (F0: none, F1: along the vas sinusoide or portal vein, F2: along the vasoide and along the portal vein, F3: with cross-linked fibrosis, F4: with cirrhosis) ..
  • Serum was collected from each fasting patient the day before liver biopsy and stored at -80 ° C until measurement.
  • TSP2 and CK18 in serum are measured by the ELISA method (TSP2, R & D Systems, Minneapolis, MN; CK18, M30 Apoptosense ELISA PEVIVA, Bromma, Sweden), HA and 4C7S proteins are measured by the latex turbidimetric method and the RIA2 antibody method, respectively. SRL) was used.
  • APRI and FIB-4 were calculated from the formula.
  • FIGS. 1A to 1D show the correlation between the number of patients classified into each stage for each element of NAS and the TSP2 concentration (ng / ml) in serum for each patient.
  • 1A shows the S0 to S3 stage and TSP2 concentration of fatty liver
  • FIG. 1B shows the L0 to L3 stage and TSP2 concentration of lobular inflammation
  • FIG. 1C shows the B0 to B2 stage of hepatocellular balloon-like swelling.
  • FIG. 1D shows the correlation between the F1 to F4 stages of fibrosis and the TSP2 concentration, respectively.
  • n 130.
  • the P values were 0.005, 0.003, ⁇ 0.001, and ⁇ 0.001 for each, and the TSP2 concentration was significantly different from the NAS value and fibrosis, respectively. From this result, the TSP2 concentration in serum correlates with both the state of non-alcoholic fatty liver disease indicated by the NAS value and the fibrosis strongly associated with the effect, and TSP2 in serum. It was shown that it could be used as a marker.
  • TSP2 has a higher correlation coefficient r than other proteins having a correlation coefficient r of 0.214 to 0.484, and has a high correlation with the total score of NAS. That is, it was shown that it could be used as a marker with higher sensitivity than conventionally known proteins for the state of non-alcoholic fatty liver disease.
  • Typical fibrosis markers such as HA and 4C7S have correlation coefficients r of 0.51 and 0.58, respectively, and can be used as markers comparable to conventionally known proteins that reflect liver fibrosis. Sex was shown. Furthermore, when the ROC curve was created with and without fibrosis, the areas under the curve were the largest at TSP2 0.73, HA 0.72, 4C7S 0.71 and TSP2. From these results, it was shown that the marker may be an excellent marker for determining the presence or absence of fibrosis.
  • FIG. 3A shows the S0 to S3 stages of fatty liver and TSP1 concentration
  • FIG. 3B shows the L0 to L3 stages of lobular inflammation and TSP1 concentration
  • FIG. 3C shows the B0 to B2 stages of hepatocellular balloon-like swelling.
  • TSP1 concentration FIG. 3D shows the correlation between the F1 to F4 stages of fibrosis and the TSP1 concentration, respectively.
  • the present invention has high sensitivity and specificity for non-alcoholic fatty liver disease, and accurately determines the state of progression, morbidity risk, therapeutic effect, etc. of non-alcoholic fatty liver disease.
  • Possible non-alcoholic fatty liver disease markers, and methods used for testing non-alcoholic fatty liver disease markers are obtained.

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Abstract

L'invention concerne : un marqueur de la stéatose hépatique non alcoolique, qui présente une sensibilité et une spécificité élevées vis-à-vis de la stéatose hépatique non alcoolique et qui peut déterminer avec précision un état de la stéatose hépatique non alcoolique, par exemple, le degré de progression de la stéatose hépatique non alcoolique, le risque d'incidence de la stéatose hépatique non alcoolique ou l'effet thérapeutique sur la stéatose hépatique non alcoolique ; une méthode qui est utilisée pour détecter la stéatose hépatique non alcoolique ; et un réactif et une trousse d'analyse à utiliser dans la méthode. L'invention concerne : un marqueur de la stéatose hépatique non alcoolique, qui est utilisé pour la détection de la stéatose hépatique non alcoolique chez un sujet et qui comprend la thrombospondine-2 contenue dans un échantillon de sang collecté chez le sujet ; une méthode de détection de la stéatose hépatique non alcoolique ; et un réactif et une trousse d'analyse à utiliser dans la méthode.
PCT/JP2021/026266 2020-07-13 2021-07-13 Marqueur de la stéatose hépatique non alcoolique, méthode de détection de la stéatose hépatique non alcoolique, et réactif et trousse d'analyse à utiliser dans ladite méthode WO2022014580A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115869358A (zh) * 2022-12-13 2023-03-31 上海中医药大学附属曙光医院 一种治疗非酒精性脂肪性肝病的中药组合物及其应用

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