IL28B polymorphism and cytomegalovirus predict response to treatment in Egyptian HCV type 4 patients.
OBJECTIVE
To test whether the status of positive cytomegalovirus (CMV) DNA detection adds to the predictive value of IL28B and to further categorize C/T allele carriers.


METHODS
This study included 166 chronic hepatitis C (CHC) patients who received combined interferon and ribavirin therapy for 48 wk, 84 spontaneous hepatitis C virus (HCV) resolvers who were positive for IgG anti-HCV antibody and negative for HCV RNA, and 100 healthy subjects who were negative for both HCV antibodies and RNA as controls. Genomic DNA from peripheral blood was used for IL28B rs.12979860 single nucleotide polymorphism (SNP) and CMV DNA detection. A 139 bp fragment containing IL28B SNP was amplified in all subjects by polymerase chain reaction using a specifically designed primer. Then the IL28B rs.12979860 SNP was detected by restriction fragment length polymorphism (RFLP) genotyping. The presence of CMV DNA was tested by amplification of the gB1 gene using nested polymerase chain reaction. The role of CMV and IL28B rs.12979860 SNP genotypes in determining the response rate to combined interferon therapy and clinical status of patients were statistically analyzed.


RESULTS
Current data showed that 67% of patients carrying the IL28B 12979860 C/C allele had a sustained viral response (SVR) while the genotypes C/T and TT were associated with lower SVR rates, 50% and 48%, respectively. SVR rates for the C/C allele were lower than other HCV genotypes and/or other populations. Genotype CC was associated with the response to interferon (P = 0.025). Genotype C/C was reduced from 48% in controls to 14% in CHC patients suggesting its protective role against progression to chronicity. The majority of spontaneously cleared subjects (86%) were C/C, confirming its protective role. The C/T allele was present in 71% of CHC patients compared with 38% of controls, so the use of IL28B SNP genotyping only in these patients may be of little value as a predictor of response. CMV reactivation occurred in 40% of CHC patients. Co-infection with CMV seriously diminished the response to interferon (IFN) therapy, with SVR rates in C/C genotypes 87.5% in CMV-negative patients and 12.5% in CMV-positive patients (P < 0.0001). SVR rates among C/T carriers were reduced to < 50% in patients with positive CMV DNA while the non-response rate doubled. These data indicate that a supplemental assay for CMV viremia adds to the prognostic value of IL28B genotyping.


CONCLUSIONS
The results suggest that both genetic (i.e., spontaneous) and therapeutic (IFN-based therapy) arms are complementary in the battle against HCV. CMV DNA testing may be of value to better predict the response to IFN, particularly in IL28B C/T carriers.
Department of Microbial Biotechnology, National Research Center, Cairo, Giza 12622, Egypt. mkawady@yahoo.com
Mostafa K
MK
El Awady
Noha G
NG
Bader El Din
Ashraf
A
Tabll
Yaser
Y
El Hosary
Ashraf O
AO
Abdel Aziz
Hesham
H
El Khayat
Mohsen
M
Salama
Tawfeek H
TH
Abdelhafez
D000328:Adult; D000483:Alleles; D000998:Antiviral Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D003587:Cytomegalovirus / Q000235:genetics*; D003586:Cytomegalovirus Infections / Q000150:complications; D004279:DNA, Viral / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011237:Predictive Value of Tests; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D000095022:Interferon Lambda
D000998:Antiviral Agents; D004279:DNA, Viral; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
Genetic polymorphisms; Hepatitis C; Human cytomegalovirus; Interleukin 28B; Spontaneous clearance