The Impact of Interleukin 28b Gene Polymorphism on the Virological Response to Combined Pegylated Interferon and Ribavirin Therapy in Chronic HCV Genotype 4 Infected Egyptian Patients Using Data Mining Analysis

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.

Meta-analysis

“…The majority of studies (40/51, 78%) originated from the Middle East[10–13, 15, 16, 18, 27, 28, 34, 35, 37, 40–42, 45, 46, 53–56, 59, 62, 63, 66, 67, 69, 72, 75, 78, 80, 81, 83–85, 88, 91, 95] and Europe (9/51, 18%)[14, 38, 39, 65, 71, 76, 79, 93, 96]. One originated in Cameroon[77] and one multi-center study was conducted in 19 countries[73].…”

“…Eleven studies used the METAVIR scoring system[11, 62, 63, 66, 67, 69, 76, 77, 79, 80, 95], while three other studies used a different scoring system (Knodell, Ishak, or Scheuer) to classify patients as having either mild or severe fibrosis[42, 56, 78]. …”

“…In the eleven studies that evaluated levels of fibrosis with METAVIR scoring system[102], there were a total of 3,116 patients [1580 (51%) with mild fibrosis and 1536 (49%) with severe fibrosis] (Supplement Figure 4a)[17, 62, 63, 66, 67, 69, 76, 77, 79, 80, 95]. In this sub-group analysis, SVR in mild versus severe fibrosis was 65% (CI: 57–71%) and 38% (CI: 34–42%), respectively.…”

“…In a direct comparison, patients with mild fibrosis were more likely to achieve SVR, OR 3.00 (CI: 1.98–4.56) (Q-statistic = 27.96, p <0.05, I 2 = 64.23). In all but one study, mild fibrosis and severe fibrosis was defined as F0-F2 and F3-F4, respectively – the study by Khairy M et al defined mild fibrosis as F0-F1 and severe fibrosis as F2-F4[66]. On one study removed influence analysis, our pooled OR increased by 12%, from 3.003 to 3.374, showing a stronger association between mild fibrosis and SVR with omission of the study by Khairy M et al [66] (Supplement Figure 4b, Supplement Figure 4c).…”

“…In all but one study, mild fibrosis and severe fibrosis was defined as F0-F2 and F3-F4, respectively – the study by Khairy M et al defined mild fibrosis as F0-F1 and severe fibrosis as F2-F4[66]. On one study removed influence analysis, our pooled OR increased by 12%, from 3.003 to 3.374, showing a stronger association between mild fibrosis and SVR with omission of the study by Khairy M et al [66] (Supplement Figure 4b, Supplement Figure 4c). By including patients with METAVIR score of F2 into the severe fibrotic group, this study may have diminished the effect size between mild and severe fibrosis.…”