Validation of liver fibrosis biomarker (FibroTest) for assessing liver fibrosis

StephenW

http://www.sciencedirect.com/science/article/pii/S0168827812003479
Research Article
Validation of liver fibrosis biomarker (FibroTest) for assessing liver fibrosis progression: Proof of concept and first application in a large population

    Thierry Poynard1, Corresponding author contact information, E-mail the corresponding author,
    Mona Munteanu2,
    Olivier Deckmyn2,
    Yen Ngo2,
    Fabienne Drane2,
    Jean Marie Castille2,
    Chantal Housset1, 3,
    Vlad Ratziu1,
    Françoise Imbert-Bismut1

    1 APHP UPMC Paris Liver Center, Paris, France
    2 Biopredictive, Paris, France
    3 INSERM UMR S680, France

    Received 6 February 2012. Revised 5 April 2012. Accepted 14 April 2012. Available online 18 May 2012.

    http://dx.doi.org/10.1016/j.jhep.2012.04.025, How to Cite or Link Using DOI
    Cited by in Scopus (2)

Background & Aims

Time-dependent statistics have been used to assess liver fibrosis progression (LFP) in liver diseases from birth to first biopsy, in a limited number of patients. Non-invasive biomarkers such as FibroTest (FT) should allow the estimation of LFP on larger populations. We aimed at validating this concept by comparing LFP using FT vs. biopsy (P1) and then at applying the non-invasive method to a large population (P2).
Methods

In P1, LFP was assessed using biopsy and FT in 2472 untreated patients: 770 with chronic hepatitis C, 723 with hepatitis B, 761 with non-alcoholic fatty liver disease (NAFLD), and 218 with alcoholic fatty liver disease (ALD). In P2, 342,346 interpretable FT prospectively measured were used. LFP was estimated using transition rates (cumulative hazard rate) to cirrhosis (F4) or to minimal fibrosis (>F0).
Results

In P1, there was a significant concordance between FT and biopsy estimates of hazards with intraclass correlation (ICC) = 0.961 (95% CI 0.948–0.970) and 0.899 (95% CI 0.135–0.969) for F4 and >F0, respectively. This concordance persisted according to the disease and the gender. The more rapid LFP to F4 (biopsy/FT) was observed for men with ALD (1.44/1.62), and the slower for women with NAFLD (0.09/0.02).

In P2, the LFP started to increase for men at the age of 30 years. The cumulative fibrosis progression rate to minimal fibrosis in women crossed the “man curve” around the age of 80 years. The following factors were associated with LFP to F4 (all p <0.0001): male gender (Relative Risk = 3.29), HIV co-infection (2.33), and residency in Middle East (2.67) or Eastern Europe (2.15).
Conclusions

Validated biomarkers such as FibroTest should allow powerful analysis of fibrosis progression in chronic liver diseases and better identification of risk factors.
Keywords

StephenW

研究文章
肝纤维化的生物标志物评估肝纤维化的进展（FibroTest）验证：在一个人口众多的概念和首次申请证明

    蒂埃里Poynard1，通讯作者的联系信息，电子邮件的通讯作者，
    蒙娜丽莎Munteanu2
    奥利维尔Deckmyn2
    日元Ngo2
    fabienne Drane2
    吉恩Marie Castille2，
    尚塔尔Housset1，3，
    弗拉德Ratziu1
    弗朗索瓦·英伯特，Bismut1

    UPMC的巴黎1 APHP肝脏中心，法国巴黎
    2 Biopredictive，法国巴黎
    法国INSERM的UMR S680，3

    2012年2月6日。 2012年4月5日。 2012年4月14日。网上提供2012年5月18日。

    http://dx.doi.org/10.1016/j.jhep.2012.04.025，如何来引用或链接使用分类号
    引用文献（2）

   

背景与目的

时间依赖的统计数据已被用来评估从出生第一次活检在肝脏疾病的肝纤维化的进展（LFP），在数量有限的患者。 FibroTest（FT），如非侵入性标志物，应允许在人口较多的LFP的估计。我们的目的是在验证这个概念比较LFP的使用在金融时报活检（P1），然后申请一个人口众多（P2）的非侵入性的方法。
方法

在P1，LFP的使用活检和FT 2472未经治疗的患者：慢性丙型肝炎，乙型肝炎723，761与非酒精性脂肪肝病（NAFLD）的，218 770酒精性脂肪性肝病（ALD）的评估。在P2，342346可解释金融时报“前瞻性测量。 LFP的估计过渡率（累积危险率），肝硬化（F4）或最小的纤维化（F0）的使用。
结果

P1中，有一个FT和活检组内相关（ICC）= 0.961（95％CI 0.948-0.970）和0.899（95％CI 0.135-0.969），F4和> F0的危害估计之间的显着的一致性。坚持这种一致性根据疾病和性别。更快速的LFP的F4（活检/ FT）与醛固酮（1.44/1.62）的男子，妇女与非酒精性脂肪肝（0.09/0.02）慢。

在P2，LFP的开始，到30岁的男性增加。累计纤维化进展率最小纤维化妇女越过男子的80岁左右的“曲线”。与LFP F4（P <0.0001）：男性（相对风险= 3.29），艾滋病毒感染（2.33）和居住在中东（2.67），东欧（2.15）下列因素有关。
结论

验证生物标志物，如FibroTest应该允许强大的分析纤维化慢性肝病的进展和更好地识别风险因素。

StephenW

http://en.wikipedia.org/wiki/FibroTest
FibroTest, known as FibroSure in the US, is a patented biomarker test that uses the results of six blood serum tests to generate a score that is correlated with the degree of liver damage in people with a variety of liver diseases. FibroTest has the same prognostic value as a liver biopsy.

FibroTest has been evaluated in relation to liver biopsy (the current reference standard in liver disease assessment) in a large number of patients with hepatitis C,[1] hepatitis B,[2] alcoholic liver disease,[3] Non-alcoholic fatty liver disease[4] and in the general population. By 2008 it had been used in over 350,000 patients.[2] FibroTest has been validated for the initial diagnosis of fibrosis, but also for the monitoring of patients.[citation needed] In 2006, the French National Authority for Health recommended the use of FibroTest as a first-line assessment tool for fibrosis with untreated chronic hepatitis C.[5]
Validated biomarkers such as FibroTest should allow powerful analysis of fibrosis progression in chronic liver diseases and better identification of risk factors.
Procedure

The FibroTest score is calculated from the results of a six-parameter blood test, combining six serum markers with the age and gender of the patient: Alpha-2-macroglobulin, Haptoglobin, Apolipoprotein A1, Gamma-glutamyl transpeptidase (GGT), Total bilirubin, and Alanine transaminase (ALT). ALT is used in a second assessment called ActiTest that is part of FibroTest.

The equation for calculating the FibroTest score regression coefficient (logistic regression) is:[6]

z=4.467\times \log_{10} [\alpha2 macroglobulin (g/L)]-1.357\times\log_{10} [Haptoglobin (g/L)] + 1.017 \times \log_{10} [GGT (IU/L)] + 0.0281 \times [Age (years)]

    + 1.737 \times \log_{10} [Bilirubin (\mu mol/L)] - 1.184 \times [Apo A1 (g/L)] + 0.301 \times Sex (female=0, male=1)-5.54

Due to variability of components assays and analyzers, FibroTest assays can only be performed in validated laboratories.[7] FibroTest cannot be used without algorithms that detects false positives and false negatives; the equation alone is not a diagnosis tool.

The laboratory or physician connects to the BioPredictive website[8] for calculation of the test results and prints the results sheet, which is available immediately and is accompanied by an interpretation aid and precautions for use.

FibroTest，作为美国FibroSure，是一种获得专利的生物标志物的测试，使用6个血清测试的结果生成各种肝病的人肝脏损伤的程度密切相关的得分。 FibroTest作为肝活检有相同的预后价值。

，FibroTest已被评估关系在大量的患者，[1] B型肝炎，[2]酒精性肝病，[3]非酒精性脂肪肝肝炎（肝活检在肝脏疾病评估当前的参考标准）疾病[4]，在一般人群中。到2008年已超过35万患者使用。[2] FibroTest已验证初步诊断为肝纤维化，但也为患者的监测。[需要的引证] 2006年，法国国家卫生管理局建议使用FibroTest作为评估肝纤维化的第一线，与未经治疗的慢性丙型肝炎[5]工具
验证生物标志物，如FibroTest应该允许强大的分析纤维化慢性肝病的进展和更好地识别风险因素。
程序

FibroTest得分计算从六参数验血，结合病人的年​​龄和性别的6个血清标志物，结果：α-2-巨球蛋白，结合珠蛋白，载脂蛋白A1，γ-谷氨酰转移酶（GGT），总胆红素，丙氨酸转氨酶（ALT）。 ALT是在第二次评估称为ActiTest FibroTest的一部分。

的FibroTest得分的回归系数（logistic回归）的计算公式是：[6]

Z = 4.467 \times\ LOG_ {10} [\ alpha2巨球蛋白（g / L的）] -1.357 \times\ LOG_ {10} [结合珠蛋白（克/升）+ 1.017 \times\ LOG_ {10} [转肽酶（国际单位/ L），] + 0.0281 \ [年龄（岁）]

    + 1.737 \times\ LOG_ {10} [胆红素（\亩摩尔/升） -  1.184 \times[载脂蛋白A1（g / L的）] + 0.301 \times性别（女= 0，男= 1）-5.54

由于组件的检测和分析仪的可变性，FibroTest检测只能在实验室验证[7] FibroTest能不能用没有算法，可检测的误报和漏报;方程本身并不是一个诊断工具。

在实验室或医生的连接的BioPredictive网站，[8]计算的测试结果，并打印结果表，这是立即可用，并伴随着解释援助和使用时的注意事项。

MP4

哪位写EXCEL公式出来，通知我，我送分。

StephenW

回复 MP4 的帖子

MP4

http://www.biopredictive.com/intl/patient/home-patients/hbv

MP4

f=4.467×log[α2-macroglobulin (g/L)]−1.357×log[haptoglobin (g/L)]+1.017×log[γ-GGT (IU/L)]+0.0281×[age (in years)]+1.737×log[bilirubin (µmol/L)]−1.184×[apolipoprotein A1 (g/L)]+0.301×sex (female=0, male=1)−5.540

=

MP4

保加利亚论坛上的
http://translate.google.com.hk/translate?hl=zh-CN&sl=bg&tl=zh-CN&u=http%3A%2F%2Fhepatitis-bg.com%2Fforum%2FUpload%2Fdocs%2FNon-invasive.Tests.to.Examine.Fibrosis.and.Risk.for.HCC.xls

http://hepatitis-bg.com/forum/Upload/docs/Non-invasive.Tests.to.Examine.Fibrosis.and.Risk.for.HCC.xls