CN106153923A - Prediction glutamate pyruvate transaminase is less than the system of the Patients with Chronic Hepatitis B inflammation degree of two times of upper limits of normal - Google Patents

Prediction glutamate pyruvate transaminase is less than the system of the Patients with Chronic Hepatitis B inflammation degree of two times of upper limits of normal Download PDF

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CN106153923A
CN106153923A CN201610452882.4A CN201610452882A CN106153923A CN 106153923 A CN106153923 A CN 106153923A CN 201610452882 A CN201610452882 A CN 201610452882A CN 106153923 A CN106153923 A CN 106153923A
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hepatitis
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CN106153923B (en
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王贵强
周继远
赵鸿
王艳
李俊
洪源
邓永琼
闫琳琳
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Peking University First Hospital
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Abstract

The present invention is directed to the prior art problem almost without the non-invasive diagnosis method its hepatic pathology state of crowd to confirm ALT < 2 times, a kind of system predicting that glutamate pyruvate transaminase is less than the Patients with Chronic Hepatitis B inflammation degree of two times of upper limits of normal is provided, including: detection module, for detecting hepatitis B core antibody content, glutamic oxaloacetic transaminase, GOT content and albumin content in the glutamate pyruvate transaminase Patients with Chronic Hepatitis B serum less than two times of upper limits of normal；Inf index1 computing module, for according to described hepatitis B core antibody content, glutamic oxaloacetic transaminase, GOT content and albumin content, calculates Inf index1；And inflammation degree prediction module, for being less than the inflammation degree of the Patients with Chronic Hepatitis B of two times of upper limits of normal according to described Inf index1 prediction glutamate pyruvate transaminase.According to clinical verification, present system is high less than the predictablity rate of the Patients with Chronic Hepatitis B inflammation degree of two times of upper limits of normal to glutamate pyruvate transaminase, provides new method for clinical diagnosis.

Description

Prediction glutamate pyruvate transaminase is suffered from less than the chronic viral hepatitis B of two times of upper limits of normal The system of person's inflammation degree
Technical field
The present invention relates to the Patients with Chronic Hepatitis B liver predicting glutamate pyruvate transaminase less than two times of upper limits of normal The system of degree of inflammation, belongs to biomedical sector.
Background technology
In China, it is the public health problem that serious threat our people is healthy that Chronic Hepatitis B Virus infects；According to Within 2006, national serum of hepatitis B Epidemiological study result shows, China 1～59 years old population HBsAg (hepatitis B surface Antigen: infected the mark of hepatitis B virus) carrying rate is 7.18%.Calculate accordingly, China's existing chronic HBV sense Dye person about 93,000,000 people, wherein chronic hepatitis B patient about 20,000,000 example.If chronic hepatitis B patient is without effectively treatment How can progress to hepatic fibrosis, liver cirrhosis, multiple life-threatening complication occurs.
(HBe resists by glutamate pyruvate transaminase (ALT), hepatitis B virus gene (HBVDNA), hepatitis B antigen for international and domestic guide Former) state is as the clinical indices weighing hepatitis B whether antiviral therapy；Wherein ALT is the most commonly used in being current clinic judges liver Dirty impaired, the serological index (goldstandard is liver puncture) of inflammation degree；When the glutamate pyruvate transaminase of hepatitis B patient is more than Or equal to two times of upper limits of normal (ALT >=2 times), be the standard of hepatitis activity, antiviral therapy must be carried out clinically；And for Glutamate pyruvate transaminase has less than the hepatitis B patient of two times of upper limits of normal (ALT < 2 times), document report about 30% such patient's liver Significantly fibrosis or middle hyperphlogosis, if treating not in time, may cause the delay of the state of an illness.
For the hepatitis B patient of ALT < 2 times, current methods is to judge that the pathological state of liver is entered by liver puncture Row clinical antiviral therapy decision-making；But transcutaneous aspiration biopsy of liver lesions is aggressive inspection, there is interpretation and error of sampling, and have Blood, gallbladder leak equivalent risk, and expense is not costly suitable for all patients.But at present in addition to invasive liver puncture, there is no Preferably judge the index of hepatic pathology state.Especially for the crowd of ALT < 2 times, international and domestic for this district patient group Research few, to the non-invasive diagnosis method of its hepatic pathology inflammatory conditions almost without.
Correlational study all shows, hepatitis B core antibody (Anti-HBc) level and the gpt level of chb patient (ALT) there is good dependency；The present invention is directed to this problem, enter group 590 example Chronic Hepatitis Bs and done liver puncture respectively Pathological analysis and serum Anti-HBc detection, obtain the phase of degree of inflammation in Anti-HBc level liver actual with chb patient Close sexual relationship.
Summary of the invention
It is an object of the invention to for above-mentioned prior art problem, it is provided that a kind of prediction glutamate pyruvate transaminase is normal less than two times The system of the Patients with Chronic Hepatitis B inflammation degree of the upper limit (ALT < 2 times), present system is according to Gu Bingzhuan Ammonia enzyme turns less than hepatitis B core antibody content and millet straw in the serum of the Patients with Chronic Hepatitis B of two times of upper limits of normal Ammonia enzyme content, it was predicted that the degree of inflammation of its liver, thus judge whether that needs are treated；According to clinical verification, present system Glutamate pyruvate transaminase is less than the predictablity rate of the Patients with Chronic Hepatitis B inflammation degree of two times of upper limits of normal High.
One aspect of the present invention provides a kind of chronic virus b liver predicting that glutamate pyruvate transaminase is less than two times of upper limits of normal The system of scorching patient's inflammation degree, it is characterised in that described system includes:
Detection module, for detecting the glutamate pyruvate transaminase Patients with Chronic Hepatitis B blood less than two times of upper limits of normal Hepatitis B core antibody content, glutamic oxaloacetic transaminase, GOT content and albumin content in clear；
Inf-index1 computing module, for according to described hepatitis B core antibody content, glutamic oxaloacetic transaminase, GOT content and white egg Bai Hanliang, calculates Inf-index1；And,
Inflammation degree prediction module, for normal less than two times according to described Inf-index1 prediction glutamate pyruvate transaminase The inflammation degree of the Patients with Chronic Hepatitis B of the upper limit；
Wherein, described Inf-index1 is inflammation index.
Wherein, described detection module includes detecting the reagent needed for described hepatitis B core antibody content.
Particularly, described detection module includes detecting the reagent needed for described glutamic oxaloacetic transaminase, GOT content.
Especially, described detection module includes detecting the reagent needed for described albumin content.
Particularly, described detection module includes detecting the test kit needed for described hepatitis B core antibody content.
Especially, described detection module includes detecting the test kit needed for described glutamic oxaloacetic transaminase, GOT content.
Particularly, described detection module includes detecting the test kit needed for described albumin content.
Especially, described detection module includes detecting the instrument needed for described hepatitis B core antibody content.
Particularly, described detection module includes detecting the instrument needed for described glutamic oxaloacetic transaminase, GOT content.
Especially, described detection module includes detecting the instrument needed for described albumin content.
Particularly, to glutamate pyruvate transaminase less than two times just present invention preferably employs dual-antigen sandwich method enzyme linked immunosorbent assay Often the hepatitis B core antibody content in the Patients with Chronic Hepatitis B serum of the upper limit detects.
Especially, other existing detection glutamate pyruvate transaminase are suffered from less than the chronic viral hepatitis B of two times of upper limits of normal The method of hepatitis B core antibody content, reagent and/or test kit and/or instrument in person's serum are all applicable to the present invention.
Particularly, present invention preferably employs enzyme performance rate method sick less than the chronic type b of two times of upper limits of normal to glutamate pyruvate transaminase Glutamic oxaloacetic transaminase, GOT content in virus hepatitis patients serum detects.
Especially, other existing detection glutamate pyruvate transaminase are suffered from less than the chronic viral hepatitis B of two times of upper limits of normal The method of glutamic oxaloacetic transaminase, GOT content, reagent and/or test kit and/or instrument in person's serum are all applicable to the present invention.
Particularly, present invention preferably employs Bromocresol green and glutamate pyruvate transaminase is less than the chronic type b of two times of upper limits of normal Albumin content in Patients with Viral Hepatitis serum detects.
Especially, other existing detection glutamate pyruvate transaminase are suffered from less than the chronic viral hepatitis B of two times of upper limits of normal The method of the albumin content in person's serum, reagent and/or test kit and/or instrument are all applicable to the present invention.
Wherein, described Inf-index1 is calculated via below equation:
Inf-index1=A1 × log10Anti-HBc+A2×AST-A3×Albumin-A4；
Wherein, described Anti-HBc is the Patients with Chronic Hepatitis B that glutamate pyruvate transaminase is less than two times of upper limits of normal Hepatitis B core antibody content in serum, unit is log10IU/mL。
Particularly, described AST is the Patients with Chronic Hepatitis B blood that glutamate pyruvate transaminase is less than two times of upper limits of normal Glutamic oxaloacetic transaminase, GOT content in clear, unit is IU/L.
Especially, described Albumin is the chronic viral hepatitis B trouble that glutamate pyruvate transaminase is less than two times of upper limits of normal Person's Human Serum Albumin content, unit is g/L.
Wherein, described A1, A2, A3, A4 are coefficient；A1=1.251 (± 10%)；A2=0.03 (± 10%)；A3= 0.061 (± 10%)；A4=3.845 (± 10%).
Wherein, according to the normal or slight chronic HBV raised of described Inf-index1 prediction glutamate pyruvate transaminase The inflammation degree of the infected includes:
Inflammation degree according to the normal or slight chronic HBV infection crowd raised of glutamate pyruvate transaminase Statistical data, determines the marginal value needing to carry out treating hepatitis B；
Described Inf-index1 is compared process with described marginal value；
When comparative result be Inf-index1 be more than described marginal value time, it was predicted that described glutamate pyruvate transaminase normally or slightly rises The inflammation degree of high chronic hepatitis B virus infecton has reached the degree needing to carry out treating.
Particularly, described marginal value is 0.21, if during Inf-index1 dividing value >=0.21 of described detection object, it was predicted that This detection object is obvious inflammation patient, and its inflammation degree has reached the degree needing to carry out treating；If it is described When detecting the Inf-index1 dividing value ＜ 0.21 of object, it was predicted that this detection object is without obvious inflammation patient.
Wherein, the input of described computing module connects the output of described prediction module.
Particularly, the input of described prediction module connects the output of described computing module.
Another aspect of the present invention provides a kind of and obtains the normal or slight chronic HBV raised of glutamate pyruvate transaminase The method of the infected's inflammation index, it is characterised in that including:
In the normal or slight chronic hepatitis B virus infecton serum raised of detection glutamate pyruvate transaminase, hepatitis B core resists Body burden, glutamic oxaloacetic transaminase, GOT content and albumin content；
According to described hepatitis B core antibody content, glutamic oxaloacetic transaminase, GOT content and albumin content, calculate Inf-index1；
Wherein, described Inf-index1 is inflammation index.
Particularly, to glutamate pyruvate transaminase less than two times just present invention preferably employs dual-antigen sandwich method enzyme linked immunosorbent assay Often the hepatitis B core antibody content in the Patients with Chronic Hepatitis B serum of the upper limit detects.
Especially, other existing detection glutamate pyruvate transaminase are suffered from less than the chronic viral hepatitis B of two times of upper limits of normal The method of hepatitis B core antibody content, reagent and/or test kit and/or instrument in person's serum are all applicable to the present invention.
Particularly, present invention preferably employs enzyme performance rate method sick less than the chronic type b of two times of upper limits of normal to glutamate pyruvate transaminase Glutamic oxaloacetic transaminase, GOT content in virus hepatitis patients serum detects.
Especially, other existing detection glutamate pyruvate transaminase are suffered from less than the chronic viral hepatitis B of two times of upper limits of normal The method of glutamic oxaloacetic transaminase, GOT content, reagent and/or test kit and/or instrument in person's serum are all applicable to the present invention.
Particularly, present invention preferably employs Bromocresol green and glutamate pyruvate transaminase is less than the chronic type b of two times of upper limits of normal Albumin content in Patients with Viral Hepatitis serum detects.
Especially, other existing detection glutamate pyruvate transaminase are suffered from less than the chronic viral hepatitis B of two times of upper limits of normal The method of the albumin content in person's serum, reagent and/or test kit and/or instrument are all applicable to the present invention.
Wherein, described Inf-index1 is calculated via below equation:
Inf-index1=A1 × log10Anti-HBc+A2×AST-A3×Albumin-A4；
Wherein, described Anti-HBc is the Patients with Chronic Hepatitis B that glutamate pyruvate transaminase is less than two times of upper limits of normal Hepatitis B core antibody content in serum, unit is log10IU/mL。
Particularly, described AST is the Patients with Chronic Hepatitis B blood that glutamate pyruvate transaminase is less than two times of upper limits of normal Glutamic oxaloacetic transaminase, GOT content in clear, unit is IU/L.
Especially, described Albumin is the chronic viral hepatitis B trouble that glutamate pyruvate transaminase is less than two times of upper limits of normal Person's Human Serum Albumin content, unit is g/L.
Wherein, described A1, A2, A3, A4 are coefficient；A1=1.251 (± 10%)；A2=0.03 (± 10%)；A3= 0.061 (± 10%)；A4=3.845 (± 10%).
Further aspect of the present invention provides a kind of chronic hepatitis b disease predicting that glutamate pyruvate transaminase is less than two times of upper limits of normal The method of poison the infected's inflammation degree, it is characterised in that including:
In the normal or slight chronic hepatitis B virus infecton serum raised of detection glutamate pyruvate transaminase, hepatitis B core resists Body burden, glutamic oxaloacetic transaminase, GOT content and albumin content；
According to described hepatitis B core antibody content, glutamic oxaloacetic transaminase, GOT content and albumin content, calculate Inf-index1；
Wherein, described Inf-index1 is inflammation index.
Particularly, to glutamate pyruvate transaminase less than two times just present invention preferably employs dual-antigen sandwich method enzyme linked immunosorbent assay Often the hepatitis B core antibody content in the Patients with Chronic Hepatitis B serum of the upper limit detects.
Especially, other existing detection glutamate pyruvate transaminase are suffered from less than the chronic viral hepatitis B of two times of upper limits of normal The method of hepatitis B core antibody content, reagent and/or test kit and/or instrument in person's serum are all applicable to the present invention.
Particularly, present invention preferably employs enzyme performance rate method sick less than the chronic type b of two times of upper limits of normal to glutamate pyruvate transaminase Glutamic oxaloacetic transaminase, GOT content in virus hepatitis patients serum detects.
Especially, other existing detection glutamate pyruvate transaminase are suffered from less than the chronic viral hepatitis B of two times of upper limits of normal The method of glutamic oxaloacetic transaminase, GOT content, reagent and/or test kit and/or instrument in person's serum are all applicable to the present invention.
Particularly, present invention preferably employs Bromocresol green and glutamate pyruvate transaminase is less than the chronic type b of two times of upper limits of normal Albumin content in Patients with Viral Hepatitis serum detects.
Especially, other existing detection glutamate pyruvate transaminase are suffered from less than the chronic viral hepatitis B of two times of upper limits of normal The method of the albumin content in person's serum, reagent and/or test kit and/or instrument are all applicable to the present invention.
Wherein, described Inf-index1 is calculated via below equation:
Inf-index1=A1 × log10Anti-HBc+A2×AST-A3×Albumin-A4；
Wherein, described Anti-HBc is the Patients with Chronic Hepatitis B that glutamate pyruvate transaminase is less than two times of upper limits of normal Hepatitis B core antibody content in serum, unit is log10IU/mL。
Particularly, described AST is the Patients with Chronic Hepatitis B blood that glutamate pyruvate transaminase is less than two times of upper limits of normal Glutamic oxaloacetic transaminase, GOT content in clear, unit is IU/L.
Especially, described Albumin is the chronic viral hepatitis B trouble that glutamate pyruvate transaminase is less than two times of upper limits of normal Person's Human Serum Albumin content, unit is g/L.
Wherein, described A1, A2, A3, A4 are coefficient；A1=1.251 (± 10%)；A2=0.03 (± 10%)；A3= 0.061 (± 10%)；A4=3.845 (± 10%).
Wherein, according to the normal or slight chronic HBV raised of described Inf-index1 prediction glutamate pyruvate transaminase The inflammation degree of the infected includes:
The inflammation journey of the chronic HBV infection crowd of two times of upper limits of normal it is less than according to glutamate pyruvate transaminase Degree statistical data, determines the marginal value needing to carry out treating hepatitis B；
Described Inf-index1 is compared process with described marginal value；
When comparative result be Inf-index1 be more than described marginal value time, it was predicted that described glutamate pyruvate transaminase is normal less than two times The inflammation degree of the Patients with Chronic Hepatitis B of the upper limit has reached the degree needing to carry out treating.
Particularly, described marginal value is 0.21, if during Inf-index1 dividing value >=0.21 of described detection object, it was predicted that This detection object is obvious inflammation patient, and its inflammation degree has reached the degree needing to carry out treating；If it is described When detecting the Inf-index1 dividing value ＜ 0.21 of object, it was predicted that this detection object is without obvious inflammation patient.
Advantages of the present invention and Advantageous Effects are as follows:
The present invention is using hepatitis B core antibody content, glutamic oxaloacetic transaminase, GOT content and albumin content as being used for that variable is set up Prediction glutamate pyruvate transaminase is less than the system of the inflammation degree of the chronic hepatitis B patient of two times of upper limits of normal to including ALT Less than the inflammation degree of the chronic hepatitis B patient of two times of upper limits of normal (≤2ULN), there is preferable diagnostic value.Right 222 example glutamate pyruvate transaminase show, at ALT less than the chronic hepatitis B patient area under curve analysis result of two times of upper limits of normal In≤2 times of upper limits of normal patients, Inf-index1 diagnoses the area under curve (area of obvious inflammation degree (HAI > 4) Under the curve, AUC) area is 0.779 (95%CI:0.717-0.841)；When Inf-index1 >=0.21 is dividing value When diagnosing more than obvious inflammation degree (HAI >=5), its sensitivity is 62.7%, and specificity is 82.0%, negative diagnostic rate 72.5%, positive diagnosing rate 74.4%, accuracy rate 73.2%；Cross validation shows: Inf-index1 can correctly be diagnosed to be The patient of 73.2%.Separately the analysis result of experimenter's area under curve (ROC) of 221 example HAI >=4 is shown, apply Inf- Index1 Evaluation of Inflammation model and the cutoff value determined, its sensitivity diagnosing more than obvious degree of inflammation (HAI >=5) is 49.5%, specificity is 86.6%, negative diagnostic rate 66.5%, positive diagnosing rate 76.1%, accuracy rate 70.1%；With checking team Row diagnostic evaluation index is suitable.
Accompanying drawing explanation
Fig. 1 is hepatitis B core antibody content and chb patient's inflammation mobility correlation analysis figure；
Fig. 2 is used for for inflammation model Inf-index1 in modeling set of queues (Fig. 2 a.) and checking set of queues (Fig. 2 b.) The obvious inflammation of liver (HAI > 4) experimenter's area under curve analysis chart in the chb patient of diagnosis ALT≤2 times upper limits of normal.
Detailed description of the invention
Below in conjunction with detailed description of the invention, the present invention is further described in detail, it should be noted that the present invention Embodiment be only used to illustrate the present invention, and be not intended to limit the scope of the present invention.
For predicting that glutamate pyruvate transaminase is less than the Patients with Chronic Hepatitis B inflammation journey of two times of upper limits of normal The foundation of the system of degree and prediction effect thereof
1, object of study
(1) case source: in October, 2013 in December, 2015, from third turn of the 443 example paddy of 24 teaching hospitals in the whole nation Ammonia enzyme is less than the Patients with Chronic Hepatitis B of two times of upper limits of normal；
(2) group standard is entered: age 18-65 year；Anti-hepatitis A virus M immunoglobulin (anti-HAV-IgM), anti-third type Hepatitis virus (anti-HCV), anti-hepatitis E virus M/G immunoglobulin (anti-HEV-IgM/IgG), anti EB virus M globulin (anti-EBV-IgM), anti-cytomegalovirus M immunoglobulin (anti-CMV-IgM) are feminine gender；Ethanol except and, medicine, self Chronic hepatic injury caused by the other reasonses such as immunity；And:
A. Chronic HBV carriers's diagnostic criteria: HBsAg, HBeAg, HBV DNA quantifying positive, follows up a case by regular visits in 1 year 3 times continuously Below all show Serum ALT within the normal range of 10-40IU/L, AST is within the normal range of 10-40IU/L；
B. non-active hepatitis B s antigen carries diagnostic criteria: serum HBsAg is positive, HBeAg is negative, HBV DNA is quantitatively less than Monitoring lower-cut, follows up a case by regular visits in 1 year more than 3 times continuously, and ALT is all within the normal range of 10-40IU/L；
C. chronic hepatitis B diagnostic criteria: there is hepatitis B medical history or the HBsAg positive more than 6 months, existing HBsAg and (or) HBV DNA is still positive, ALT continues or repeatedly raises；
The most compensatory phase hbv-liver cirrhosis diagnostic criteria: there is hepatitis B medical history or the HBsAg positive more than 6 months, existing HBsAg and (or) HBV DNA is still positive；Iconography, biochemical, hematology or splanchnoscopy prompt door hypertension (such as hypersplenism and esophagus fundus ventricularis varication) evidence, but without treatment for esophageal varices bleeding, ascites or liver property The severe complications such as encephalopathy.
2, liver puncture histopathological examination
Enter to organize case and all under guidance of Doppler color, carry out transcutaneous aspiration biopsy of liver lesions according to the liver puncture of standard, use thick Pin punctures (16G), and taken liver organization checks that specimen length, at more than 2.0cm, comprises at least 11 complete portal areas.Liver Tissue penetration specimen through fixing, dehydration, transparent, waxdip, embed, cut into slices after, carry out routine and make HE dyeing, specific stain (includes Reticular fiber staining, Masson trichrome stain), immunohistochemical staining (HBsAg, HBAg and CK7).Then Pathologic specimen is via three The expert group of position Pathology Doctors ' composition uses Ishak standards of grading to carry out blind diagosis.
Inflammation and fiber interpretation are by stages with reference to Ishak standard, it may be assumed that do not have or mild inflammation (liver activity index (hepatic activity index, HAI) 0-4 divides), moderate inflammation (HAI5-6 divides), hyperphlogosis (HAI >=7 point)；No Or mild fibrosis (F=0-1), moderate fibrosis (F=2), hence it is evident that fibrosis (F=3), severe fibrosis (F >=7).
3, test in laboratory
(1) hematology and biochemical analysis are all as the criterion with constituent parts result in patient liver wears 4 weeks.
(2) content detection of serum hepatitis B surface antigen (HBSAg) uses Roche Holding Ag of U.S. test kit (RocheHBsAg II assay), hepatitis B virus DNA level uses Roche Holding Ag of U.S. COBAS AmpliPrep/ COBAS TaqMan is analyzed (detection range: 2.0 × 101 1.7 × 108IU/mL), and hepatitis B e antigen and e antibody are surveyed Surely U.S. Roche is usedAssays carries out qualitative analysis.
(3) Anti-HBc detection
Use Double antigen sandwich ELISA detection kit (ten thousand safe biological Pharmaceutical limited companies) detection Anti- HBc；Detecting instrument: enzyme connection detector (Bio-Rad Model 650Microplate Reader).
The serum specimen of CHB patient is carried out according to the following step the detection by quantitative of anti-HBc.In view of CHB patients serum Anti-HBc level is generally the highest, generally by serum specimen with the PBS solution clear containing 20% N of fetal blood be diluted to 1:500,1: 2500,1:12500 and 1:62500 totally 4 dilution factors carry out quantitative ELISA detection.
Example reaction: take the most coated ELISA Plate, every hole adds 90 μ L sample diluents, every hole add 10 μ L specimen or Person's standard substance, after concussion mixing, are placed in 37 DEG C of incubators and react 30 minutes.
Enzyme marker is reacted: ELISA Plate PBST washing liquid (20mM PB7.4,150mM NaCl, 0.l%Tween20) washed Washing 5 times, every hole adds 100 μ L enzyme marker reactant liquors, is placed in 37 DEG C of incubators and reacts 30 minutes.
Chromogenic reaction: ELISA Plate PBST washing liquid (20mM PB7.4,150mM NaCl, 0.l%Tween20) is washed 5 Time, every hole adds TMB developer (being provided by Beijing Wantai Biological Pharmacy Enterprise Co., Ltd.) each 50 μ L, is placed in 37 DEG C of incubators anti- Answer 15 minutes.
Terminate reaction and readings detection: after question response is complete, hole every in ELISA Plate is added 50 μ L stop buffers (safe by Beijing ten thousand Biological Pharmaceutical limited company provides), and in microplate reader, detect the OD value in each hole.
Draw quantitation curves: measured value and corresponding concentration thereof to plasmid standards for quantitation carry out linear regression, draw out Quantitation curves.
Calculate the anti-HBc concentration of testing sample: the OD value that test serum specimen is measured is utilized standard curve and specimen Extension rate obtains the concrete concentration of anti-HBc.
(4) AST detection
Use AST detection kit (performance rate method) in automatic clinical chemistry analyzer (AU-400, Olympus, Japan) upper survey Determine AST.
(5) Albumin detection
Use albumin measuring reagent box (Bromocresol green) in automatic clinical chemistry analyzer (AU-400, Olympus, day Originally) Albumin is measured on.
4, statistical method
Statistical analysis is carried out with SPSS17.0 software；Measurement data mean ± standard deviation represents, uses Kruskal- Wallis and Mann-Whitney U-tests is analyzed；Group data uses Chi-squared test to be analyzed Binary logistic returns and is used for determining independent influencing factor.Variable diagnosis performance Fibrotic to inflammation ROC analyzes and carries out Evaluate, be expressed as area under curve (area under the curve, AUC), sensitivity, specificity, positive diagnosing rate, feminine gender Diagnosis and accuracy rate.
5, interpretation of result
(1) this enters group 655 example chronic type b patients altogether, and wherein the patient of transaminase level≤2 times upper limits of normal is 443 Example (67.63%)；443 example glutamate pyruvate transaminase are randomly divided into modeling set of queues less than the chb patient of two times of upper limits of normal (222 example) and checking set of queues (221 example)；Modeling queue in, inflammation mobility be the patient of >=5 be 102 examples (45.95%)；Checking queue in inflammation mobility be >=5 patient be 102 examples (46.15%)；Each group patient features retouches State and be shown in Table 1:
Patient context's data of table 1.ALT≤2 times upper limits of normal
(2) 443 example ALT≤2 times upper limits of normal chronic hepatitis B patient inflammation mobility scoring (HAI, Histological activity index) and the relation of hepatitis B core antibody content, result is as shown in Figure 1；Result shows Under different transaminase levels, inflammation mobility and Anti-HBc level have preferable dependency, i.e. substantially inflammation journey In degree (HAI > 4) patient, anti-HBc level is apparently higher than nothing or slight inflammation (HAI≤4) patient.
(3) Anti-HBc in the upper limits of normal patient of ALT≤2 times in single factor test and multiplicity modeling queue (222 example) Level and the correlation analysis of inflammation mobility (HAI0-4, HAI > 4) in various degree, be shown in Table 2.Single factor analysis shows Show, hence it is evident that constitutional index in inflammation (HAI > 4) degree, HBV DNA, anti-HBc, glutamic oxaloacetic transaminase, GOT, paddy acyl transpeptidase, Albumin, prothrombin time, Prothrombin activity, INR and platelet are apparently higher than nothing or mild inflammation Degree (HAI≤4) patient.
Table 2. single factor test and multiplicity
Patient normal or ALT≤2 times upper limits of normal to 222 examples ALT in modeling queue carries out binary further Logistic regression analysis, and result display Anti-HBc (OR=4.539, P < 0.001), glutamic oxaloacetic transaminase, GOT (OR=1.045, P= 0.024), albumin (OR=0.911, P=0.033) is the independent influencing factor of the obvious degree of inflammation of liver.
According to the content of hepatitis B core antibody in chronic hepatitis B virus infecton serum, the content of glutamic oxaloacetic transaminase, GOT and Albuminous content is that index constructs inflammation model Inf-index1；Its formula is:
Inf-index1=1.251 × log10Anti-HBc+0.03×AST-0.061×Albumin-3.845
(3) hepatitis B core antibody (Anti-HBc) associating glutamic oxaloacetic transaminase, GOT (AST) and albumin in modeling queue (Albumin) it is used for distinguishing the analysis of experimenter's area under curve (ROC) of HAI<4, HAI>=4, sees Fig. 2.Under experimenter's curve Areal analysis result shows, in the upper limits of normal patient of ALT≤2 times Inf-index1 diagnose obvious inflammation degree (HAI > 4) area under curve (area under the curve, AUC) area is 0.779 (95%CI:0.717-0.841)；When When Inf-index1 >=0.21 diagnoses more than obvious inflammation degree for dividing value (HAI >=5), its sensitivity is 62.7%, special The opposite sex is 82.0%, negative diagnostic rate 72.5%, positive diagnosing rate 74.4%, accuracy rate 73.2% (Fig. 2 a)；Cross validation shows Show: Inf-index1 can correctly be diagnosed to be the patient of 73.2%, i.e. when being less than the chronic of two times of upper limits of normal with glutamate pyruvate transaminase When hepatitis B patient is for detection object, according to the above results, obtain testing result criterion as follows: if described detection is right During Inf-index1 dividing value >=0.21 of elephant, this detection object is obvious inflammation patient, if described detection object During Inf-index1 dividing value ＜ 0.21, this detection object is without obvious inflammation patient.
6, prediction effect
The system using above-mentioned steps to set up turns ammonia to hepatitis B core antibody (Anti-HBc) associating millet straw in checking queue Enzyme (AST) and albumin (Albumin) are used for distinguishing the analysis of experimenter's area under curve (ROC) of HAI<4, HAI>=4, see Fig. 2 b.Being analyzed from checking queue ROC, application models Inf-index1 Evaluation of Inflammation model in queue and the cutoff determined Value, its sensitivity diagnosing more than obvious degree of inflammation (HAI >=5) is 49.5%, and specificity is 86.6%, negative diagnostic rate 66.5%, positive diagnosing rate 76.1%, accuracy rate 70.1% (Fig. 2 b)；Suitable with checking queue diagnostic evaluation index.According to upper State result, obtain testing result criterion as follows: if during Inf-index1 dividing value >=0.21 of described detection object, this inspection Surveying object is obvious inflammation patient, if during the Inf-index1 dividing value ＜ 0.21 of described detection object, and this detection object For without obvious inflammation patient；The above results shows that noinvasive model Inf-index1 is to including that ALT is less than two times of upper limits of normal The inflammation degree of the chronic hepatitis B patient of (≤2ULN) has preferable diagnostic value.

Claims (10)

1. one kind is used for predicting that glutamate pyruvate transaminase is less than the Patients with Chronic Hepatitis B inflammation of two times of upper limits of normal The system of degree, it is characterised in that described system includes:
Detection module, for detecting in the glutamate pyruvate transaminase Patients with Chronic Hepatitis B serum less than two times of upper limits of normal Hepatitis B core antibody content, glutamic oxaloacetic transaminase, GOT content and albumin content；
Inf-index1 computing module, for containing according to described hepatitis B core antibody content, glutamic oxaloacetic transaminase, GOT content and albumin Amount, calculates Inf-index1；And,
Inflammation degree prediction module, for being less than two times of upper limits of normal according to described Inf-index1 prediction glutamate pyruvate transaminase The inflammation degree of Patients with Chronic Hepatitis B；
Wherein, described Inf-index1 is inflammation index.
System the most according to claim 1, it is characterised in that described Inf-index1 is calculated via below equation:
Inf-index1=A1 × log10Anti-HBc+A2×AST-A3×Albumin-A4；
Wherein, described Anti-HBc is the Patients with Chronic Hepatitis B serum that glutamate pyruvate transaminase is less than two times of upper limits of normal Middle hepatitis B core antibody content；
Described AST is that glutamate pyruvate transaminase is less than millet straw in the Patients with Chronic Hepatitis B serum of two times of upper limits of normal and turns ammonia Enzyme content；
Described Albumin is that glutamate pyruvate transaminase is less than in the Patients with Chronic Hepatitis B serum of two times of upper limits of normal white egg Bai Hanliang；
Wherein, described A1, A2, A3, A4 are coefficient；A1=1.251 (± 10%)；A2=0.03 (± 10%)；A3=0.061 (± 10%)；A4=3.845 (± 10%).
System the most according to claim 1, it is characterised in that be less than according to described Inf-index1 prediction glutamate pyruvate transaminase The inflammation degree of the Patients with Chronic Hepatitis B of two times of upper limits of normal includes:
Unite less than the inflammation degree of the chronic HBV infection crowd of two times of upper limits of normal according to glutamate pyruvate transaminase Data learned by meter, determine the marginal value needing to carry out treating hepatitis B；
Described Inf-index1 is compared process with described marginal value；
When comparative result be Inf-index1 be more than described marginal value time, it was predicted that described glutamate pyruvate transaminase be less than two times of upper limits of normal The inflammation degree of Patients with Chronic Hepatitis B reached the degree that needs to carry out treating.
System the most according to claim 1, it is characterised in that the input of described computing module connects described prediction module Output, the input of described prediction module connects the output of described computing module.
Application the most according to claim 1, it is characterised in that described detection module includes detecting described hepatitis B core antibody Reagent needed for content, glutamic oxaloacetic transaminase, GOT content and albumin content and/or test kit and/or instrument.
6. one kind obtains the glutamate pyruvate transaminase Patients with Chronic Hepatitis B inflammation index less than two times of upper limits of normal Method, it is characterised in that including:
Detection glutamate pyruvate transaminase is less than hepatitis B core antibody in the Patients with Chronic Hepatitis B serum of two times of upper limits of normal Content, glutamic oxaloacetic transaminase, GOT content and albumin content；
According to described hepatitis B core antibody content, glutamic oxaloacetic transaminase, GOT content and albumin content, calculate Inf-index1；
Wherein, described Inf-index1 is inflammation index.
Method the most according to claim 6, it is characterised in that described Inf-index1 is calculated via below equation:
Inf-index1=A1 × log10Anti-HBc+A2×AST-A3×Albumin-A4；
Wherein, described Anti-HBc is the Patients with Chronic Hepatitis B serum that glutamate pyruvate transaminase is less than two times of upper limits of normal Middle hepatitis B core antibody content；
Described AST is that glutamate pyruvate transaminase is less than millet straw in the Patients with Chronic Hepatitis B serum of two times of upper limits of normal and turns ammonia Enzyme content；
Described Albumin is that glutamate pyruvate transaminase is less than in the Patients with Chronic Hepatitis B serum of two times of upper limits of normal white egg Bai Hanliang；
Wherein, described A1, A2, A3, A4 are coefficient；A1=1.251 (± 10%)；A2=0.03 (± 10%)；A3=0.061 (± 10%)；A4=3.845 (± 10%).
8. the method predicting Patients with Chronic Hepatitis B inflammation degree, it is characterised in that including:
Detection glutamate pyruvate transaminase is less than hepatitis B core antibody in the Patients with Chronic Hepatitis B serum of two times of upper limits of normal Content, glutamic oxaloacetic transaminase, GOT content and albumin content；
According to described hepatitis B core antibody content, glutamic oxaloacetic transaminase, GOT content and albumin content, calculate Inf-index1；
The Patients with Chronic Hepatitis B of two times of upper limits of normal it is less than according to described Inf-index1 prediction glutamate pyruvate transaminase Inflammation degree；
Wherein, described Inf-index1 is inflammation index.
Method the most according to claim 8, it is characterised in that described Inf-index1 is calculated via below equation:
Inf-index1=A1 × log10Anti-HBc+A2×AST-A3×Albumin-A4；
Wherein, described Anti-HBc is the Patients with Chronic Hepatitis B serum that glutamate pyruvate transaminase is less than two times of upper limits of normal Middle hepatitis B core antibody content；Described AST is the chronic viral hepatitis B trouble that glutamate pyruvate transaminase is less than two times of upper limits of normal Glutamic oxaloacetic transaminase, GOT content in person's serum；Described Albumin is the chronic type b virus that glutamate pyruvate transaminase is less than two times of upper limits of normal Property hepatitis Human Serum Albumin content；
Wherein, described A1, A2, A3, A4 are coefficient；A1=1.251 (± 10%)；A2=0.03 (± 10%)；A3=0.061 (± 10%)；A4=3.845 (± 10%).
Method the most according to claim 8, it is characterised in that little according to described Inf-index1 prediction glutamate pyruvate transaminase Inflammation degree in the Patients with Chronic Hepatitis B of two times of upper limits of normal includes:
Unite less than the inflammation degree of the chronic HBV infection crowd of two times of upper limits of normal according to glutamate pyruvate transaminase Data learned by meter, determine the marginal value needing to carry out treating hepatitis B；
Described Inf-index1 is compared process with described marginal value；
When comparative result be Inf-index1 be more than described marginal value time, it was predicted that described glutamate pyruvate transaminase be less than two times of upper limits of normal The inflammation degree of Patients with Chronic Hepatitis B reached the degree that needs to carry out treating.
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