Factors predictive of sustained virological response following 72 weeks of combination therapy for genotype 1b hepatitis C.
ABSTRACT Treatment of genotype 1b chronic hepatitis C virus (HCV) infection has been improved by extending peg-interferon plus ribavirin combination therapy to 72 weeks, but predictive factors are needed to identify those patients who are likely to respond to long-term therapy.
We analyzed amino acid (aa) substitutions in the core protein and the interferon sensitivity determining region (ISDR) of nonstructural protein (NS) 5A in 840 genotype 1b chronic hepatitis C patients with high viral load. We used logistic regression and classification and regression tree (CART) analysis to identify predictive factors for sustained virological response (SVR) for patients undergoing 72 weeks of treatment.
When patients were separately analyzed by treatment duration using multivariate logistic regression, several factors, including sex, age, viral load, and core aa70 and ISDR substitutions (P = 0.0003, P = 0.02, P = 0.01, P = 0.0001, and P = 0.0004, respectively) were significant predictive factors for SVR with 48 weeks of treatment, whereas age, previous interferon treatment history, and ISDR substitutions (P = 0.03, P = 0.01, and P = 0.02, respectively) were the only significant predictive factors with 72 weeks of treatment. Using CART analysis, a decision tree was generated that identified age, cholesterol, sex, treatment length, and aa70 and ISDR substitutions as the most important predictive factors. The CART model had a sensitivity of 69.2% and specificity of 60%, with a positive predictive value of 68.4%.
Complementary statistical and data mining approaches were used to identify a subgroup of patients likely to benefit from 72 weeks of therapy.
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ABSTRACT: In Hepatitis C virus (HCV)-related mixed cryoglobulinemia (MCG), the non-enveloped HCV core protein (HCV-Cp) is a constituent of the characteristic cold-precipitating immune complexes (ICs). A possible correlation between HCV-Cp, virological, laboratory and clinical parameters in both untreated MCG patients and those undergoing specific treatment was explored. HCV-Cp was quantified by a fully automated immune assay. Correlations between HCV-Cp and HCV RNA, cryocrit, and virus genotype (gt) were investigated in 102 chronically HCV-infected MCG patients. HCV-Cp concentrations strongly correlated with HCV RNA levels in baseline samples. An average ratio of 1,425 IU and 12,850 IU HCV RNA per pg HCV-Cp was estimated in HCV gt-1 and gt-2 patients, respectively. This equation allowed to estimate that, on average, HCV-Cp was associated with viral genome in only 3.4% of the former and in 35% of the latter group of patients. The direct relationship between HCV-Cp and the cryocrit level suggests that the protein directly influences the amount of cryoprecipitate. Although the therapy with rituximab (RTX) as a single agent resulted in the enhancement of HCV-Cp levels, in patients treated with RTX in combination with a specific antiviral therapy (pegylated interferon-alpha plus ribavirin) the prompt and effective clearance of HCV-Cp was documented. Our data provide evidence that HCV-Cp has a direct effect on cold-precipitation process in a virus genotype-dependence in HCV-related MCG patients.Arthritis research & therapy 03/2014; 16(2):R73. DOI:10.1186/ar4513 · 4.12 Impact Factor
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ABSTRACT: Aim: Dietary habits are involved in the development of chronic inflammation; however, the impact of dietary profiles of hepatitis C virus carriers with persistently normal alanine transaminase levels (HCV-PNALT) remains unclear. The decision-tree algorithm is a data-mining statistical technique, which uncovers meaningful profiles of factors from a data collection. We aimed to investigate dietary profiles associated with HCV-PNALT using a decision-tree algorithm. Methods: Twenty-seven HCV-PNALT and 41 patients with chronic hepatitis C were enrolled in this study. Dietary habit was assessed using a validated semiquantitative food frequency questionnaire. A decision-tree algorithm was created by dietary variables, and was evaluated by area under the receiver operating characteristic curve analysis (AUROC). Results: In multivariate analysis, fish to meat ratio, dairy product and cooking oils were identified as independent variables associated with HCV-PNALT. The decision-tree algorithm was created with two variables: a fish to meat ratio and cooking oils/ideal bodyweight. When subjects showed a fish to meat ratio of 1.24 or more, 68.8% of the subjects were HCV-PNALT. On the other hand, 11.5% of the subjects were HCV-PNALT when subjects showed a fish to meat ratio of less than 1.24 and cooking oil/ideal bodyweight of less than 0.23 g/kg. The difference in the proportion of HCV-PNALT between these groups are significant (odds ratio 16.87, 95% CI 3.40-83.67, P = 0.0005). Fivefold cross-validation of the decision-tree algorithm showed an AUROC of 0.6947 (95% CI 0.5656-0.8238, P = 0.0067). Conclusion: The decision-tree algorithm disclosed that fish to meat ratio and cooking oil/ideal bodyweight were associated with HCV-PNALT.Hepatology Research 03/2012; 42(10):982-9. DOI:10.1111/j.1872-034X.2012.01014.x · 2.22 Impact Factor
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ABSTRACT: Aim: We evaluated the efficacy of response-guided therapy in patients with hepatitis C virus (HCV) genotype 2. Methods: We studied 105 patients with an HCV genotype 2 load of higher than 5.0 Log IU/mL who received more than 75% of the target dose of pegylated interferon plus ribavirin. Among patients with rapid viral response (RVR; no HCV RNA detected at week 4), 14 selected 16 weeks of therapy (group A), and 28 selected 24 weeks of therapy (group B). Among non-RVR patients, 40 selected 24 weeks of therapy (group C), and 19 selected 48 weeks of therapy (group D). Results: All patients in group A and B achieved a sustained viral response (SVR). Clinical characteristics did not differ significantly between groups C and D. However, the proportion of patients in whom HCV RNA disappeared at a later week after starting treatment was higher in group D (P = 0.0578). SVR rate was 73% in C, and 79% in D. Among patients in whom HCV RNA disappeared between weeks 5 and 8, SVR was achieved in 28 (82%) of 34 patients in C and 10 (91%) of 11 patients in D. Among patients whose HCV RNA disappeared between weeks 9 and 12, SVR was achieved in one (20%) of five patients in C and five (63%) of eight patients in D (not statistically significant). Conclusions: 16 weeks of combination therapy could achieve an adequate antiviral effect for RVR patients. Extending therapy could not significantly improve SVR rate in non-RVR patients.Hepatology Research 02/2012; 42(6):549-57. DOI:10.1111/j.1872-034X.2011.00956.x · 2.22 Impact Factor