Observational Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Nov 18, 2016; 8(32): 1392-1401
Published online Nov 18, 2016. doi: 10.4254/wjh.v8.i32.1392
Novel non-invasive biological predictive index for liver fibrosis in hepatitis C virus genotype 4 patients
Mahmoud Khattab, Mohamed Amin Sakr, Mohamed Abdel Fattah, Youssef Mousa, Elwy Soliman, Ashraf Breedy, Mona Fathi, Salwa Gaber, Ahmed Altaweil, Ashraf Osman, Ahmed Hassouna, Ibrahim Motawea
Mahmoud Khattab, Mohamed Abdel Fattah, Youssef Mousa, Elwy Soliman, Ibrahim Motawea, Department of Internal Medicine, Minia University, Minia 61111, Egypt
Mohamed Amin Sakr, Ashraf Breedy, Department of Tropical Medicine, Ain Shams University, Cairo 11566, Egypt
Mona Fathi, Department of Clinical Pathology, Ain Shams University, Cairo 11566, Egypt
Salwa Gaber, Department of Pathology, Minia University, Minia 61111, Egypt
Ahmed Altaweil, Department of Pathology, Ain Shams University, Cairo 11566, Egypt
Ashraf Osman, Department of Clinical Pathology, Minia University, Minia 61111, Egypt
Ahmed Hassouna, Department of Cardiothoracic Surgery, Ain Shams University, Cairo 11566, Egypt
Author contributions: Khattab M proposed study design and supervised all stages of the research; Saker MA, Fattah MA, Mousa Y, Soliman E, Breedy A and Motawea I shared patient recruitment, physical assessments and data interpretation; Fathi M and Osman A performed the laboratory investigations; Gaber S and Altaweil A assessed histopathological specimens of liver biopsies; Hassouna A processed the statistical analysis of our data.
Supported by The Governmental Foundation Scientific and Technology Development Foundation (STDF), Egypt, Project ID: 1538.
Institutional review board statement: The study protocol was approved by the Institutional ethics committee of Minia School of medicine in Egypt. The study was conducted in accordance with the ethical guidelines of the 1975 Helsinki declaration.
Informed consent statement: All patients signed informed consent to participate in the study.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: Participants gave informed consent to share in the study anonymously and risk of identification is low.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Mahmoud Khattab, MD, PhD, Professor of Medicine, Head of Liver Unit, Department of Internal Medicine, Minia University, Cornish Al Nile Road, Minia 61111, Egypt. mkhattabmed@hotmail.com
Telephone: +20-25-197818 Fax: +20-86-2156056
Received: June 26, 2016
Peer-review started: June 26, 2016
First decision: September 2, 2016
Revised: September 9, 2016
Accepted: October 5, 2016
Article in press: October 9, 2016
Published online: November 18, 2016

To investigate the diagnostic ability of a non-invasive biological marker to predict liver fibrosis in hepatitis C genotype 4 patients with high accuracy.


A cohort of 332 patients infected with hepatitis C genotype 4 was included in this cross-sectional study. Fasting plasma glucose, insulin, C-peptide, and angiotensin-converting enzyme serum levels were measured. Insulin resistance was mathematically calculated using the homeostasis model of insulin resistance (HOMA-IR).


Fibrosis stages were distributed based on Metavir score as follows: F0 = 43, F1 = 136, F2 = 64, F3 = 45 and F4 = 44. Statistical analysis relied upon reclassification of fibrosis stages into mild fibrosis (F0-F) = 179, moderate fibrosis (F2) = 64, and advanced fibrosis (F3-F4) = 89. Univariate analysis indicated that age, log aspartate amino transaminase, log HOMA-IR and log platelet count were independent predictors of liver fibrosis stage (P < 0.0001). A stepwise multivariate discriminant functional analysis was used to drive a discriminative model for liver fibrosis. Our index used cut-off values of ≥ 0.86 and ≤ -0.31 to diagnose advanced and mild fibrosis, respectively, with receiving operating characteristics of 0.91 and 0.88, respectively. The sensitivity, specificity, positive predictive value, negative predictive value and positive likelihood ratio were: 73%, 91%, 75%, 90% and 8.0 respectively for advanced fibrosis, and 67%, 88%, 84%, 70% and 4.9, respectively, for mild fibrosis.


Our predictive model is easily available and reproducible, and predicted liver fibrosis with acceptable accuracy.

Keywords: Liver fibrosis, Insulin resistance, Aspartate amino transaminase, Platelets, Age

Core tip: This observational study included a cohort of 332 recruited patients with hepatitis C virus (HCV) genotype 4 infections. The study assessed the status of demographic and biological variables at different stages of liver fibrosis. Liver biopsy with Metavir scoring was the reference standard used to classify patients into five stages of liver fibrosis (F0-F4). Patient regrouping to include three levels of fibrosis, mild (F0-F1), moderate (F2), and advanced (F3-F4), was performed to conform with practical guidelines for the management and follow-up of HCV patients. Age, aspartate transaminase enzyme (AST), insulin resistance (HOMA-IR), and platelet count were significant predictors of liver fibrosis as shown on univariate analysis. Log AST, log HOMA-IR, log platelet count and age were introduced into stepwise multivariate discriminative analysis, and a model for the prediction of liver fibrosis level was derived. Our predictive index exhibited an area under the curve (AUC) of 0.91 for the diagnosis of advanced stages of fibrosis and an AUC of 0.88 for the diagnosis of mild stages of fibrosis. The index exhibited a lower AUC of 0.64 in the diagnosis of moderate stages of fibrosis.