Human Leukocyte Antigen Class II Alleles (DQB1 and DRB1) as Predictors for Response to Interferon Therapy in HCV Genotype 4

Abstract

Human leukocyte antigens class II play an important role in immune response against HCV. We investigated whether HLA class II alleles influence susceptibility to HCV infection and response to interferon therapy. HLA-DRB1 and -DQB1 loci were genotyped using PCR-SSO Luminex technology. According to our regimen, 41 (66%) of patients achieved sustained virological response to combined treatment of IFN and ribavirin. Frequencies of DQB1∗0313 allele and DRB1∗04-DRB1∗11, DQB1∗0204-DQB1∗0313, DQB1∗0309-DQB1∗0313, and DQB1∗0313-DQB1∗0319 haplotypes were significantly more frequent in nonresponders than in responders. In contrast, DQB1∗02, DQB1∗06, DRB1∗13, and DRB1∗15 alleles were significantly more frequent in responders than in nonresponders. Similarly, DRB1∗1301, DRB1∗1361, and DRB1∗1369 alleles and DRB1∗1301-DRB1∗1328, DRB1∗1301-DRB1∗1361, DRB1∗1301-DRB1∗1369, DRB1∗1328-DRB1∗1361, and DRB1∗1328-DRB1∗1369 haplotypes were significantly found only in responders. Some alleles and linkages showed significantly different distributions between patient and healthy groups. These alleles may be used as predictors for response to treatment or to susceptibility to HCV infection in the Egyptian population.

The Association of HLA Class II Alleles with the Response to Alfa-Interferon/Ribavirin Therapy in Chronic Hepatitis C Patients

“…Our result concerning HLA DRB1*13 is in agreement with Shaker et al (2013) who reported that DRB1 * 1301, DRB1 * 1361, DRB1 * 1369, DRB1 * 13 alleles to be significantly more frequent in responders than in non responders. Concerning our results of HLA DRB1 *07, we agree with Zekri et al (2005) who showed that HLA class II allele DR* 07 was significantly encountered in HCV positive family members than negative members.…”

“…Before peg-IFN therapy, diagnosis of CHC was established on persistent (>6 months) elevation of Alanine aminotransferase (ALT) concentration 1.5 times above the upper limit of normal, positive results of antibody to HCV testing, positive HCV RNA testing in serum and histological evidence of chronic hepatitis and earlier fibrosis stages (Metavir stage ≤F2). The Metavir scoring system described as follows: For activity, A0 is no histological activity, A1 mild activity, A2 moderate activity and A3 severe activity; for fibrosis, F0 is no fibrosis, F1 portal tract expansion by fibrosis, F2 less than 50% bridging fibrosis, F3 more than 50% bridging fibrosis without cirrhosis and F4 established cirrhosis (Shaker et al, 2013). They were followed from March 2012 to March 2014 at outpatient clinics of hepatology unit, Al-Ahrar Hospital (Zagazig, Egypt) under the supervision of the National Committee for the Control of Viral Hepatitis (NCCVH).…”

“…Polymorphisms of the genes that regulate the immunity and the genes of Human Leukocyte Antigen (HLA) class I and II molecules are known to affect the clearance or persistence of viral antigens (Ocal et al, 2014). It was reported that HLA class II alleles, particularly DRB1 and DQB1 alleles, play a critical role in the outcome of HCV infection, influence susceptibility to or protection from HCV infection and also affect response to antiviral treatment (Shaker et al, 2013).…”

“…To our knowledge, HLA-associated alleles in Egyptian patients with hepatitis C have been studied using current methods include Sequence-Specific Oligonucleotide Probe Hybridization (SSOPH), Sequence-Specific Primers (SSP) and PCR-SSO luminex technology which are costly and require multiple steps (Shaker et al, 2013;Shaheen et al, 2013;Yosry et al, 2011).…”

Meta-analysis

“…Eighty-four studies were closely evaluated for eligibility[10–16, 18, 26–101]. Fourteen studies did not have extractable treatment outcomes data[26, 29, 36, 47, 50, 58, 61, 64, 74, 86, 87, 92, 100, 101]. Six were redundant[49, 51, 57, 68, 89, 99] and four were not relevant[30, 43, 60, 94].…”