Genetic distance and heterogenecity between quasispecies is a critical predictor to IFN response in Egyptian patients with HCV genotype-4.
BACKGROUND
HCV is one of the major health problems in Egypt, where it is highly prevalent. Genotype 4 is the most common genotype of HCV and its response to treatment is still a controversy.


METHODS
HCV genotype 4 quasispecies diversity within the 5' untranslated region (5'UTR) was studied in a series of 22 native Egyptian patients with chronic hepatitis C virus with no previous treatment who satisfied all NIH criteria for combined treatment of pegylated IFN and ribavirine and was correlated with the outcome of treatment. The study also included 7 control patients with no antiviral treatment. HCV sequencing was done using the TRUGENE HCV 5-NC genotyping kit.


RESULTS
At the 48th week of treatment, 15 patients (68%) showed virological response. Whereas HCV-RNA was still detected in 7 patients (32%) in this period; of those, 6 experienced a partial virological response followed by viral breakthrough during treatment. Only one patient did not show any virological or chemical response. The four females included in this study were all responders. There was a significant correlation between the response rate and lower fibrosis (p = 0.026) as well as the total number of mutation spots (including all the insertions, deletions, transitions and transversions) (p = 0.007, p = 0.035).


CONCLUSIONS
Patients who responded to interferon treatment had statistically significant less number in both transitions (p = 0.007) and the genetic distances between the quasispecies (p = 0.035). So, viral genetic complexity and variability may play a role in the response to IFN treatment. The consensus alignment of all three groups revealed no characteristic pattern among the three groups. However, the G to A transitions at 160 was observed among non responders who need further study to confirm this observation.
Zekri
Abdel Rahman N
AR
Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt. ncizekri@yahoo.com
El-Din
Hanaa M Alam
HM
Bahnassy
Abeer A
AA
Khaled
Mohsen M
MM
Omar
Ashraf
A
Fouad
Inas
I
El-Hefnewi
Mahmoud
M
Thakeb
Fouad
F
El-Awady
Mostafa
M
D020121:5' Untranslated Regions / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004534:Egypt; D005260:Female; D018740:Genetic Heterogeneity; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010802:Phylogeny; D011092:Polyethylene Glycols; D011110:Polymorphism, Genetic; D012367:RNA, Viral / Q000235:genetics; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D017422:Sequence Analysis, DNA; D013223:Statistics as Topic; D016896:Treatment Outcome
D020121:5' Untranslated Regions; D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b