摘要
AIM: To study the amino acid substitutions in the carboxy (C)-terminal part of E2 protein and in the interferon (IFN) sensitivity determining region (ISDR) and their correlation with response to IFN and viral load in 85 hepatitis C virus (HCV)-lb-infected patients treated with IFN. METHODS: The C-terminal part of E2 (codons 617-711) including PKR/eIF2a phosphorylation homology domain (PePHD) and ISDR was sequenced in 85 HCV-1b-infected patients treated by IFN monotherapy. RESULTS: The amino acid substitutions in PePHD detected only in 4 of 85 patients were not correlated either with response to IFN or with viral load. The presence of substitutions in a N-terminal variable region (codons 617-641) in the C-terminal part of E2 was significantly correlated with both small viral load (33.9% vs 13.8%, P = 0.0394) and sustained response to IFN (25.0% vs 6.9 %, P = 0.0429). Four or more substitutions in ISDR were significantly correlated with both small viral load (78.6% vs 16.2%, P < 0.0001) and sustained response to IFN (85.7% vs 2.9%, P < 0.0001). In multivariate analysis, ISDR in nonstructural (NS) 5A (OR = 0.39, P < 0.0001) and N-terminal variable region (OR = 0.51, P = 0.039) was selected as the independent predictors for small viral load, and ISDR (OR = 39.0, P < 0.0001) was selected as the only independent predictor for sustained response. CONCLUSION: The N-terminal variable region in the C-terminal part of E2 correlates with both response to IFN monotherapy and viral load and is one of the factors independently associated with a small viral load.
AIM： To study the amino acid substitutions in the carboxy （C）-terminal part of E2 protein and in the interferon （IFN） sensitivity determining region （ISDR） and their correlation with response to IFN and viral load in 85 hepatitis C virus （HCV）-lb-infected patients treated with IFN.
METHODS： The C-terminal part of E2 （codons 617-711） including PKR/eIF2α phosphorylation homology domain （PePHD） and ISDR was sequenced in 85 HCV-1b-infected patients treated by IFN monotherapy. RESULTS： The amino acid substitutions in PePHD detected only in 4 of 85 patients were not correlated either with response to iFN or with viral load. The presence of substitutions in a N-terminal variable region （codons 617-641） in the C-terminal part of E2 was significantly correlated with both small viral load （33.9% vs 13.8%, P = 0.0394） and sustained response to iFN （25.0% vs 6.9 %, P = 0.0429）. Four or more substitutions in ISDR were significantly correlated with both small viral load （78.6% vs 16.2%, P 〈 0.0001） and sustained response to iFN （85.7% vs 2.9%, P 〈 0.0001）. In multivariate analysis, ISDR in nonstructural （NS） 5A （OR = 0.39, P 〈 0.0001） and N-terminal variable region （OR = 0.51, P = 0.039） was selected as the independentpredictors for small viral load, and ISDR （OR = 39.0, P 〈 0.0001） was selected as the only independent predictor for sustained response. CONCLUSION： The N-terminal variable region in the C-terminal part of E2 correlates with both response to IFN monotherapy and viral load and is one of the factors independently associated with a small viral load.
