Concordance in a World without a Gold Standard: A New Non-Invasive Methodology for Improving Accuracy of Fibrosis Markers

Abstract

BackgroundAssessing liver fibrosis is traditionally performed by biopsy, an imperfect gold standard. Non-invasive techniques, liver stiffness measurements (LSM) and biomarkers [FibroTest® (FT)], are widely used in countries where they are available. The aim was to identify factors associated with LSM accuracy using FT as a non-invasive endpoint and vice versa.MethodsThe proof of concept was taken using the manufacturers recommendations for excluding patients at high risk of false negative/positive. The hypothesis was that the concordance between LSM and FT, would be improved by excluding high-risk patients. Thereafter, the impact of potential variability factors was assessed by the same methods. Liver biopsy and independent endpoints were used to validate the results.ResultsApplying manufacturers' recommendations in 2,004 patients increased the strength of concordance between LSM and FT (P<0.00001). Among the 1,338 patients satisfying recommendations, the methodology identified a significant LSM operator effect (P = 0.001) and the following variability factors (all P<0.01), related to LSM: male gender, older age, and NAFLD as a cause of liver disease. Biopsy confirmed in 391 patients these results.ConclusionThis study has validated the concept of using the strength of concordance between non-invasive estimates of liver fibrosis for the identification of factors associated with variability and precautions of use.

Non-invasive assessment of liver fibrosis in chronic hepatitis C

“…TE is thus ''the test to be beaten'' for those developing alternative methods [106]. In order to increase diagnostic accuracy, new approaches using a combination of TE and serum markers [69,107,108] have been proposed. For instance, using an algorithm to evaluate the agreement between TE and FibroTest Ò , liver biopsy can be avoided for the diagnosis of significant fibrosis in around 75% of patients with chronic hepatitis C [69].…”

“…A combination of two unrelated methods, such as TE and Fibrotest Ò , may have certain advantages over the combination of two biomarkers, in that TE provides more direct measurement of the liver structure than serum markers and that there is no relationship between the applicability of TE (success rate and interquartile range) and Fibrotest Ò (Gilbert's syndrome, hemolysis, and sepsis) [107].…”

Applicability and variability of liver stiffness measurements according to probe position

“…We demonstrated previously that the strength of concordance between LSM and FT could be used to identify LSM www.wjgnet.com Ingiliz P et al . Liver stiffness measurements according to probe position variability factors [27] . The results strongly sug gest that the reference position for LSM has two weaknesses in comparison with a more anterior position: a significantly lower applicability and a possible higher variability for the diagnosis of advanced fibrosis using the 7.1 kPa cutoff.…”

Karaciğer Fibrozisinin İnvazif Olmayan Dolaylı Biyokimyasal Belirteçleri

“…Klinik pratikte, hastalardaki belirgin fibrozisin (≥ F2) ve/veya sirozun (F4) tanısı ve dışlanmasında 0.85'den büyük AUC değerine sahip dolaylı biyokimyasal belirteçlerin kullanımı uygun denilebilir. Son yaklaşımlarda birden fazla biyokimyasal belirtecin kombine edilmesinin [36][37][38][39][40] bu hastalardaki tanısal doğruluğu arttıracağı ileri sürülmüştür. Ayrıca, yapılan çalışmalar incelendiğinde siroz hastalarında dolaylı biyokimyasal belirteçlerin daha iyi bir performansa sahip olduğu dikkatimizi çekmiştir 20,25,37,[40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59] .…”