ABSTRACT
BACKGROUND: Chronic HCV represents one of the common causes of chronic liver disease worldwide with Egypt having the highest prevalence, namely genotype 4. Interleukin IL-28B gene polymorphism has been shown to relate to HCV treatment response, mainly in genotype1. OBJECTIVES: We aim to evaluate the predictive power of the rs12979860 IL28B SNP and its protein for treatment response in genotype 4 Egyptian patients by regression analysis and decision tree analysis. PATIENTS AND METHODS: The study included 263 chronic HCV Egyptian patients receiving peg-interferon and ribavirin therapy. Patients were classified into 3 groups; non responders (83patients), relapsers (76patients) and sustained virological responders (104 patients). Serum IL 28 B was performed, DNA was extracted and analyzed by direct sequencing of the SNP rs 12979860 of IL28B gene. RESULTS: CT, CC and TT represented 56 %, 25 % and 19% of the patients, respectively. Absence of C allele (TT genotype) was significantly correlated with the early failure of response while CC was associated with sustained virological response. The decision tree showed that baseline alpha fetoprotein (AFP ≤ 2.68 ng/ml) was the variable of initial split (the strongest predictor of response) confirmed by regression analysis. Patients with TT genotype had the highest probability of failure of response. CONCLUSIONS: Absence of the C allele was significantly associated with failure of response. The presence of C allele was associated with a favorable outcome. AFP is a strong baseline predictor of HCV treatment response. A decision tree model is useful for predicting the probability of response to therapy.
ABSTRACT
INTRODUCTION: Decision-tree analysis; a core component of data mining analysis can build predictive models for the therapeutic outcome to antiviral therapy in chronic hepatitis C virus (HCV) patients. AIM: To develop a prediction model for the end virological response (ETR) to pegylated interferon PEG-IFN plus ribavirin (RBV) therapy in chronic HCV patients using routine clinical, laboratory, and histopathological data. PATIENTS AND METHODS: Retrospective initial data (19 attributes) from 3719 Egyptian patients with chronic HCV presumably genotype-4 was assigned to model building using the J48 decision tree-inducing algorithm (Weka implementation of C4.5). All patients received PEG-IFN plus RBV at Cairo-Fatemia Hospital, Cairo, Egypt in the context of the national treatment program. Factors predictive of ETR were explored and patients were classified into seven subgroups according to the different rates of ETR. The universality of the decision-tree model was subjected to a 10-fold cross-internal validation in addition to external validation using an independent dataset collected of 200 chronic HCV patients. RESULTS: At week 48, overall ETR was 54% according to intention to treat protocol. The decision-tree model included AFP level (<8.08 ng/ml) which was associated with high probability of ETR (73%) followed by stages of fibrosis and Hb levels according to the patients' gender followed by the age of patients. CONCLUSION: In a decision-tree model for the prediction for antiviral therapy in chronic HCV patients, AFP level was the initial split variable at a cutoff of 8.08 ng/ml. This model could represent a potential tool to identify patients' likelihood of response among difficult-to-treat presumably genotype-4 chronic HCV patients and could support clinical decisions regarding the proper selection of patients for therapy without imposing any additional costs.
