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 ...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.展开更多
Backgrounds: Cardioversion for atrial fibrillation(AF) is the most effective treatment for the restoration of sinus rhythm(SR). Recently, an elevated level of hs-CRP has been shown to be associated with AF burden, sug...Backgrounds: Cardioversion for atrial fibrillation(AF) is the most effective treatment for the restoration of sinus rhythm(SR). Recently, an elevated level of hs-CRP has been shown to be associated with AF burden, suggesting that inflammation increases the propensity for persistence of AF. We examined whether the level of high-sensitivity C-reactive protein(hs-CRP) was predictive of the outcome of cardioversion for AF. Methods and results: One hundred and six patients with a history of symptomatic AF lasting ≥ 1 day(age 63± 14 years, mean± S.D.) underwent cardioversion. Echocardiography and hs-CRP assay were performed immediately prior to cardioversion. SR was restored in 84 patients(79% ). By using selected cutoff values,multiple discriminant analysis revealed significant associations between successful cardioversion and a shorter duration of AF(AF duration≤ 36 days, odds ratio(OR), 0.98; 95% confidence interval(CI), 0.97-0.99), smaller left atrial diameter(left atrial diameter ≤ 40 mm, OR 0.82, 95% CI 0.71-0.94), better-preserved left ventricular ejection fraction(left ventricular ejection fraction ≥ 60% , OR 0.92, 95% CI 0.86-0.99), and lower hs-CRP level(hs-CRP ≤ 0.12 mg/dL, OR 0.33, 95% CI 0.21-0.51). During a follow-up period of 140± 144 days, AF recurred in 64 patients(76% ). By using a cutoff value of hs-CRP ≥ 0.06 mg/dL, Cox proportional-hazards regression model found that only hs-CRP level was an independent predictor of AF recurrence(OR 5.30, 95% CI 2.46-11.5) after adjustment for coexisting cardiovascular risks. When patients were divided by the hs-CRP level of 0.06 mg/dL, percentage of maintenance of SR below and above the cutoff was 53% and 4% , respectively(log-rank test, p< 0.0001). Conclusions: hs-CRP level determined prior to cardioversion represents an independent predictor of both successful cardioversion for AF and the maintenance of SR after conversion.展开更多
文摘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.
基金Supported by the Research Committee of Intractable Diseases of the Pancreas (Chairman M. Otsuki) provided by the Ministry of Health, Labour, and Welfare, Japan
文摘Backgrounds: Cardioversion for atrial fibrillation(AF) is the most effective treatment for the restoration of sinus rhythm(SR). Recently, an elevated level of hs-CRP has been shown to be associated with AF burden, suggesting that inflammation increases the propensity for persistence of AF. We examined whether the level of high-sensitivity C-reactive protein(hs-CRP) was predictive of the outcome of cardioversion for AF. Methods and results: One hundred and six patients with a history of symptomatic AF lasting ≥ 1 day(age 63± 14 years, mean± S.D.) underwent cardioversion. Echocardiography and hs-CRP assay were performed immediately prior to cardioversion. SR was restored in 84 patients(79% ). By using selected cutoff values,multiple discriminant analysis revealed significant associations between successful cardioversion and a shorter duration of AF(AF duration≤ 36 days, odds ratio(OR), 0.98; 95% confidence interval(CI), 0.97-0.99), smaller left atrial diameter(left atrial diameter ≤ 40 mm, OR 0.82, 95% CI 0.71-0.94), better-preserved left ventricular ejection fraction(left ventricular ejection fraction ≥ 60% , OR 0.92, 95% CI 0.86-0.99), and lower hs-CRP level(hs-CRP ≤ 0.12 mg/dL, OR 0.33, 95% CI 0.21-0.51). During a follow-up period of 140± 144 days, AF recurred in 64 patients(76% ). By using a cutoff value of hs-CRP ≥ 0.06 mg/dL, Cox proportional-hazards regression model found that only hs-CRP level was an independent predictor of AF recurrence(OR 5.30, 95% CI 2.46-11.5) after adjustment for coexisting cardiovascular risks. When patients were divided by the hs-CRP level of 0.06 mg/dL, percentage of maintenance of SR below and above the cutoff was 53% and 4% , respectively(log-rank test, p< 0.0001). Conclusions: hs-CRP level determined prior to cardioversion represents an independent predictor of both successful cardioversion for AF and the maintenance of SR after conversion.
