[Association between ribavirin plasma concentration and sustained virologic response in treatment of patients with genotype 1b chronic hepatitis C with pegylated interferon-α-2b and ribavirin].

OBJECTIVE: To investigate the association between the dose and plasma concentration of ribavirin (RBV) and sustained virologic response (SVR) during the anti-hepatitis C virus (HCV) treatment with pegylated interferon-α-2b (PEG-IFN-α-2b) and RBV. METHODS: A total of 40 patients with chronic hepatitis C (CHC) who were treated with PEG-IFN-α-2b and RBV as the antiviral treatment were enrolled, and according to the therapeutic effect (SVR was defined as HCV RNA maintained below the lower limit of detection at 24 weeks after drug discontinuation in patients who achieved virologic response at the end of treatment, and recurrence was defined as HCV RNA turning positive), these patients were divided into SVR group (20 patients aged 19-55 years, including 10 male patients) and recurrence group (20 patients aged 21-76 years, including 12 male patients). The HPLC-MS/MS was used to measure the RBV plasma concentration at weeks 4, 12, 24, and 48 of treatment. The t-test and receiver operating characteristic (ROC) curve were used for statistical analysis. RESULTS: During the antiviral treatment, the dose of RBV showed a significant difference between the two groups (15.01 ± 1.21 mg/kg vs 10.28 ± 2.81 mg/kg,t= 6.908,P= 0.000). The area under the ROC curve reached 0.96 (95%CI0.00-1.00,P= 0.000), suggesting that the dose of RBV had a high value in predicting SVR. When the dose of RBV was higher than 13.05 mg/kg (sensitivity 100%; specificity 85%), the possibility of achieving SVR was also increased. The RBV plasma concentrations in the SVR group at weeks 4,12, 24, and 48 of treatment were 1 894.8 ± 740.7 ng/ml, 2 029.9 ± 547.7 ng/ml, 2 011.8 ± 354.2 ng/ml, and2 093.5 ± 540.3 ng/ml, respectively, and those in the recurrence group were 1 223.1 ± 722.7 ng/ml, 1 286.9±685.4 ng/ml, 1304.7 ± 692.0 ng/ml, and 1 221.3 ± 655.3 ng/ml, respectively. The RBV plasma concentration at each time point showed significant differences between the two groups (t= 2.903,P= 0.006;t= 3.787,P= 0.001;t= 4.068,P= 0.000;t= 4.593,P= 0.000). The results of ROC analysis showed that the areas under the ROC curve at weeks 4, 12, 24, and 48 of treatment were 0.76 (95%CI0.61-0.92,P= 0.005), 0.83 (95%CI0.68-0.97,P= 0.000), 0.83 (95%CI0.69-0.98,P= 0.000), and 0.86 (95%CI0.72-1.00,P= 0.000), respectively, suggesting that the RBV plasma concentration had a high value in predicting SVR. When the cut-off values of RBV plasma concentration at weeks 4, 12, 24, and 48 of treatment were higher than 1262.5 ng/ml (sensitivity 90%; specificity 60%), 1432 ng/ml (sensitivity 100%; specificity 65%), 1427 ng/ml (sensitivity 100%; specificity 65%), and 1610 ng/ml (sensitivity 95%; specificity 80%), respectively, there was a greater possibility of achieving SVR. CONCLUSION: During the antiviral treatment with PEG-IFN-α-2b and RBV, the dose and plasma concentration of RBV have a high value in predicting the recurrence of CHC and the possibility of SVR.

Experimental analyses of the major parameters affecting the intensity of outbursts of coal and gas.

With an increase in mining depth and production, the intensity and frequency of outburst of coal and gas have a tendency to increase. Estimating the intensity of outbursts of coal and gas plays an important role because of its relation with the risk value. In this paper, we described the semiquantitative relations between major parameters and intensity of outburst based on physical experiments. The results showed increment of geostress simulated by horizontal load (from 1.4, 2.4, 3.2, to 3.4 MPa) or vertical load (from 2, 3, 3.6, to 4 MPa) improved the relative intensity rate (3.763-7.403% and 1.273-7.99%); the increment of porosity (from 1.57, 2.51, 3, to 3.6%) improved the relative intensity rate from 3.8 to 13.8%; the increment of gas pressure (from 0, 0.5, 0.65, 0.72, 1, to 1.5 Mpa) induced the relative intensity rate to decrease from 38.22 to 0%; the increment of water content (from 0, 2, 4, to 8%) caused the relative intensity rate to drop from 5.425 to 0.5%. Furthermore, sensitivity and range analysis evaluates coupled factors affecting the relative intensity. In addition, the distinction with initiation of outburst of coal and gas affected by these parameters is discussed by the relative threshold of gas content rate.