The Effect of IP-10 Level and HLA-DP/DQ Polymorphisms on Response to Nucleoside/ Nucleotide Analogues Treatment among Hepatitis B Egyptian Patients

Background: The efficacy of anti-viral drugs used in treatment of HBV is high but these drugs are expensive, associated with many side effects and drug resistance has evolved. Thus selection of patients with the highest probability of response is essential for clinical practice. Recent genome-wide association studies have revealed some polymorphisms in the HLA region to be associated with liver diseases, susceptibility for HBV infection, chronic HBV infection or even spontaneous HBV clearance. Additionally, IP-10 is one of the main chemokine in the recruitment of immune cells to the liver and induction of cellular immunity against viral infections, especially HBV.

Aims: This study aimed to investigate HLA-DQ.rs3920, HLA-DP.rs3077 SNP and IP-10 serum levels in relations to nucleoside/ nucleotide analogues (NAs) treatment among CHB infected Egyptian patients.

Subjects and Methods: The current study was conducted on 30 HBV infected patients (naïve, responder and non-responder) and 10 healthy volunteers, as control group. Measuring HBV DNA levels using real time PCR, IP-10 levels using ELISA and genotyping of HLA-DQ.rs3920, HLA-DP.rs3077 SNP using 5' nuclease assay were done.

Results: The expression of HLA-DP rs3077 allele A was higher among naïve and non-responder HBV patients while expression of rs3077 allele G was higher among responder HBV patients and healthy controls. While for HLA-DQ rs3920, the GG genotype was highly expressed in the different groups of HBV patients. Correlation analysis revealed association between HLA-DQ.rs3920 AA genotype and HBV-DNA in non-responder. IP-10 level was significantly increased in non-responder group compared with naïve, responder control groups, especially in patients carrying HLA-DP-rs3077 AG allele and those carrying HLA-DQ-rs3920 GG allele.

Conclusion: Genetic variations of HLA-DP.rs3077 and HLA-DQ.rs3920 could be associated with HBV risk and resistance to treatment with nucleoside/ nucleotide analogues. Moreover, IP-10 could be a promising predictor of response to treatment among HBV infected patients.