Key result
A low viral load and a high number of amino acid mutations within the ISDR, but not the PePHD region, were significantly associated with long-term response to interferon in HCV-1b infected patients.
Why the study?
Does the genetic heterogeneity of the ISDR and PePHD regions of hepatitis C virus influence the long-term response to interferon therapy in patients with chronic hepatitis C?
Observational (n=86)
Does the genetic heterogeneity of the ISDR and PePHD regions of hepatitis C virus influence the long-term response to interferon therapy in patients with chronic hepatitis C?
Mutations in the ISDR region of HCV-1b, along with low baseline viral load, are predictive of long-term response to interferon therapy.
May inform interferon response prediction in HCV-1b; hypothesis-generating, requires prospective validation before guiding practice.
Two genomic regions of hepatitis C virus (HCV), the interferon sensitivity-determining region (ISDR) of the non-structural 5A gene (NS5A) and the protein kinase-RNA activated (PKR)-eukariotic transcription factor (eIF2-alpha) phosphorylation homology domain (PePHD) of the structural E2 gene, interact in vitro with the interferon-inducible cellular PKR protein kinase. Mutations within these regions might, therefore, influence the response to interferon therapy. Viral load at baseline and sequence heterogeneity of HCV in NS5A and E2 regions was studied in 74 HCV-1b and in 12 HCV-3a infected patients with chronic hepatitis C who were treated with interferon. As previously reported by us, in a smaller series of patients in which the ISDR region was analyzed [Saiz et al. (1998) Journal Infectious Diseases 177:839-847], in the present study a low viral load and a high number of amino acid mutations within the ISDR, but not within the PePHD region, were significantly associated with long-term response to interferon among HCV-1b infected patients. No relationship between these viral features and response to therapy was disclosed in patients infected with HCV-3a.
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Puig‐Basagoiti et al. (2001) conducted an observational in chronic hepatitis C (n=86). Viral load and sequence heterogeneity in ISDR and PePHD regions was evaluated on long-term response to interferon. A low viral load and a high number of amino acid mutations within the ISDR, but not the PePHD region, were significantly associated with long-term response to interferon in HCV-1b infected patients.
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