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Diagnostic potential of serum direct markers and non-invasive fibrosis models in patients with chronic hepatitis B


  • Author contribution:Özge Gümüşay was responsible for collecting blood samples, informing volunteers and data collection; Seren Özenirler organized research; Ayşegül Atak and Cemile Sönmez performed immunological analysis of the samples; Seçil Özkan performed statistical analysis of data; Ayşe Fıtnat Tuncel performed analysis of liver function tests; and Güldal Yılmaz and Gülen Akyol evaluated liver tissue samples and determined fibrosis stage.

Dr Özge Gümüşay, Departments of Internal Medicine, Gazi University Faculty of Medicine, 06510 Beşevler, Ankara, Turkey. Email:


Aim:  Liver biopsy is recommended in the majority of patients with chronic viral hepatitis for fibrosis evaluation. Because of the disadvantages of liver biopsy, many studies related to non-invasive biomarkers and scores have been performed. In this study, we aimed to assess the diagnostic value of serum direct markers and non-invasive fibrosis models to predict liver fibrosis in the treatment-naive chronic hepatitis B (CHB) patients and to compare their diagnostic performance.

Methods:  This study included 58 patients with a diagnosis of CHB virus infection and 30 healthy controls. Hyaluronic acid, tissue inhibitor of matrix metalloproteinase 1 and amino-terminal propeptide of type III procollagen were measured by enzyme-linked immunosorbent assay; and the Original European Liver Fibrosis panel, the Enhanced Liver Fibrosis (ELF) panel, PP score, aspartate aminotransferase to platelet ratio index (APRI) and FIB-4 indexes were calculated using the formulas taken from previous publications. Fibrosis stage was determined using Ishak's scoring system.

Results:  The fibrosis stages identified upon liver biopsy was F0 in 12 patients (20.7%), F1–2 in 36 (62.1%) and F3–5 in 10 (17.2%). The diagnostic value of all the non-invasive indices was low to detect mild fibrosis. We demonstrated that the diagnostic accuracy of HA is the best for predicting fibrosis of F3 or more (area under the receiver–operator curve, 0.902). In our study, the results from a combination of tests showed that ELF and APRI had the highest diagnostic value sensitivity of 90%, specificity of 100%, positive predictive value of 100% and negative predictive value of 96.4% for detection of fibrosis of F3 or more.

Conclusion:  In CHB patients, combination of ELF and APRI has a better diagnostic value in predicting fibrosis of F3 or more.

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