Significance of a reduction in HCV RNA levels at 4 and 12 weeks in patients infected with HCV genotype 1b for the prediction of the outcome of combination therapy with peginterferon and ribavirin (original) (raw)
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Intervirology, 2014
Some patients with chronic hepatitis C virus (HCV) infection fail to achieve complete early virologic response (EVR) despite a marked decrease in HCV RNA at 4 weeks. We investigated the characteristics and final treatment outcomes of this patient subpopulation. A total of 516 patients with HCV genotype 1 were enrolled. Background characteristics and final outcomes were compared between patients who achieved complete EVR and those who did not among patients whose HCV RNA levels decreased 3.0 log10 or more at 4 weeks. 78 of 334 patients (23.4%) with a ≥3.0 log10 reduction in HCV RNA levels at 4 weeks failed to achieve complete EVR. Female sex, higher pretreatment HCV RNA levels and lower baseline alanine aminotransferase (ALT) activity were independently associated with failure of complete EVR. The rate of sustained virologic response (SVR) in patients without complete EVR was 47.4%, significantly lower than that in patients with complete EVR (89.7%, p < 0.0001). Female patients, p...
American Journal of Therapeutics, 2016
This study was planned to investigate whether the decrease in the hepatitis C virus (HCV) RNA levels at the first week of combined pegylated interferon and ribavirin treatment of naive genotype 1 patients with HCV was predicting sustained virologic response (SVR). Fifty-two patients were enrolled into the study. HCV RNA levels were measured at the baseline, first, fourth, and 12th weeks of treatment. Thirty-four patients achieved SVR, which basal, first week, and fourth week HCV RNA levels were log 5.57, log 3.65, and log 1.92, respectively. Eighteen patients could not achieve SVR, which basal, first week, and fourth week HCV RNA levels were log 6.22, log 5.45, and log 3.84, respectively (P , 0.05). Patients were distributed in 2 groups according to the amount of decrease in HCV RNA levels at the first week as less or more than 1.5 log. There were 20 patients with 1.5logdecreaseintheHCVRNAlevelsatthefirstweek.Theywerenamedaspatientswithveryrapidvirologicresponse(VRVR).Allpatients(1001.5 log decrease in the HCV RNA levels at the first week. They were named as patients with very rapid virologic response (VRVR). All patients (100%) with VRVR were achieved SVR. In only 14 (44%) of the 32 patients without VRVR, SVR was achieved. In 16 (84%) of the 19 patients with rapid virologic response and 33 (79%) of the 42 patients with early virologic response, SVR was achieved. A 1.5logdecreaseintheHCVRNAlevelsatthefirstweek.Theywerenamedaspatientswithveryrapidvirologicresponse(VRVR).Allpatients(1001.5 log decrease (VRVR) in HCV RNA levels of patients with HCV at the first week of combined pegylated interferon and ribavirin treatment predicts SVR very strongly.
Iranian Red Crescent Medical Journal
Background: Sustained virologic response (SVR) to pegylated-interferon (PegIFN) and ribavirin (RBV) in hepatitis C virus (HCV)infected patients could be predicted by detection of serum HCV RNA whereas detection of HCV RNA in other reservoirs such as peripheral blood mononuclear cells (PBMCs) for prediction of treatment response is still a mystery. Objectives: This study aimed at assessing the prediction of SVR by detection of HCV RNA in PBMCs or serum in patients during treatment. Methods: In a cohort study (2011 to 2014), 100 chronic HCV patients at Tehran Hepatitis Center were treated with PegIFN and RBV. Serum HCV RNA level was measured at baseline, 4, 12, and 24 weeks during treatment and at 24 weeks after termination of treatment. Meanwhile, HCV RNA was evaluated in PBMCs at weeks 4, 12, and 24 during the treatment. Results: Out of 100 patients treated in this study, 91 completed the course of treatment. Most patients were young males infected with HCV genotype 1. Cirrhosis and previous history of treatment was found in 16.5% and 26.5% of patients. Sustained virologic response was achieved in 65 (71.4%) patients. Among baseline parameters, only female gender was significantly associated with SVR. Undetectable serum HCV RNA at week 4 (OR = 4.74) and week 12 (OR = 11.63) of treatment predicted SVR rate while the same was not true for detection of serum HCV RNA at week 24 of treatment. Moreover, detection of HCV RNA in PBMCs at weeks 4 and 12 of treatment was not associated with the rate of SVR, while absence of HCV RNA in PBMCs at week 24 of treatment was associated with SVR (OR = 4.55). Conclusions: Detection of HCV RNA in PBMCs, especially at week 24 of treatment with PegIFN and RBV, could be considered as an additional marker for prediction of treatment response. It is recommended to assess HCV on-treatment kinetic in PBMCs of patients treated with direct-acting antiviral agents for prediction of treatment response.
Antiviral Therapy
Background Viral kinetics during therapy provides information on how to individualize treatment. To determine the benefit of assessing positive predictive values (PPVs) and negative predictive values (NPVs) of rapid virological responses (RVRs) and early virological responses (EVRs), on-treatment outcomes in chronic hepatitis C patients were examined. Methods A total of 408 patients (221 treatment-naive) treated with pegylated interferon-α2b and ribavirin were included. Hepatitis C virus (HCV) RNA was measured at baseline, 4 weeks and 12 weeks. RVR was defined as undetectable HCV RNA at 4 weeks and EVR as ≥2 log10 decrease in HCV RNA at 12 weeks. The additive value of RVR on predicting sustained virological response (SVR) was assessed with receiver operating characteristic (ROC) curves. Results SVR, RVR and EVR were observed in 46%, 23% and 78% of patients, respectively. PPVs of RVR were 96%, 100% and 100% in treatment-naive patients, relapsers and non-responders, respectively. NPVs...
Antiviral therapy, 2007
Current stopping rules during pegylated interferon (peg-IFN)/ribavirin (RBV) treatment rely on week 12 HCV RNA response, but earlier identification of non-responders offers clinical and economic advantages. To evaluate, among 129 HCV-genotype-1-infected, treatment-naive patients receiving peg-IFN/RBV, the feasibility of predicting treatment failure using receiver operating characteristics (ROC) curves after measuring week 4 HCV RNA decreases, and to assess baseline predictors of not achieving sustained virological response (SVR). Peg-IFN-alpha2b was used in 84.5% of patients. Fifty-three (41%) reached SVR. The best cutoff value of HCV RNA decrease at week 4 to predict non-SVR corresponded to 1 log10 IU/ml: sensitivity and negative predictive value: 100%; specificity: 64%; positive predictive value: 66%; ROC curve area: 0.91 (95% confidence interval [CI]: 0.86-0.96). By applying this threshold, treatment could have been discontinued at week 4 in 64% of virological non-responders (49/...
Journal of Viral Hepatitis, 2010
Rapid virologic response (RVR) and complete early virologic response (cEVR) are associated with sustained virologic response to hepatitis C virus (HCV) therapy. We retrospectively examined baseline and on-treatment factors associated with RVR (HCV RNA undetectable at week 4) and cEVR (HCV RNA undetectable at week 12, regardless of week 4 response). The analysis comprised 1550 HCV genotype-1 patients from five clinical trials, including three enriched with difficult-to-treat populations, randomized to peginterferon alfa-2a 180 lg/week plus ribavirin 1000-1200 mg/day. Overall, 15.6% achieved RVR and 54.0% achieved cEVR. Baseline factors predictive of RVR were serum HCV RNA £ 400 000 IU/mL (OR: 7.34; P < 0.0001), alanine aminotransferase >3 · ULN (OR: 2.01; P < 0.0001), non-cirrhotic status (OR: 1.92; P = 0.0087), age £ 40 years (OR: 1.56; P = 0.0085), white non-Latino ethnicity (OR: 1.41; P = 0.0666) and individual study (P < 0.0001). These factors plus body mass index £ 27 kg/ m 2 were predictive of cEVR. After adjusting for these factors, mean on-treatment ribavirin dose >13 mg/kg/day was predictive of RVR (OR: 1.69; P = 0.005) and cEVR (OR: 1.24; P = 0.09), whereas peginterferon alfa-2a dose reduction was not. Greater decreases in haematologic parameters were observed in patients who achieved cEVR compared with patients who did not. In conclusion, several baseline and on-treatment factors were associated with RVR and cEVR to peginterferon alfa-2a plus ribavirin in difficultto-treat HCV genotype-1 patients, providing important prognostic information on the antiviral response in a patient cohort that is reflective of the general chronic hepatitis C population.
Journal of Viral Hepatitis, 2005
To optimize treatment of chronic hepatitis C early identification of patients who will not achieve a sustained virological response (SVR) is desirable. We investigated hepatitis C virus (HCV) RNA kinetics at day 1 (in 15 patients; genotypes 1 and non-1, 9 and 6 respectively) at weeks 1, 4 and 12 (in 53 patients; genotypes 1 and non-1, 19 and 34, respectively) during treatment with pegylated interferon a-2a and ribavirin. Patients with SVR had a significantly more pronounced mean log 10 decline from baseline in HCV RNA levels at weeks 1 and 4 compared with patients who failed to achieve SVR (1.99 vs 0.85 at week 1, P ¼ 0.0003 and 2.89 vs 1.72 at week 4, P ¼ 0.0159), whereas no difference was noted after day 1. For patients with a 2-log 10 decrease in HCV RNA levels at day 7, the positive predictive value (PPV) for a SVR was 92%, whereas week 12 was the best time point for predicting a later nonresponse [negative predictive value (NPV) 92%] in patients failing to achieve a 2-log 10 drop. For patients with genotype non-1 and a 2-log 10 decrease in HCV RNA levels the PPV for a SVR was 89% week 1, and 79% weeks 4 and 12. The corresponding NPV for patients with genotype non-1 were 43, 40 and 100% respectively. During treatment with pegylated interferon a-2a plus ribavirin the HCV RNA decline at week 1 was an accurate predictor of SVR in patients who had achieved a 2-log 10 drop in HCV RNA levels, whereas the lack of such decline week 12 was an accurate marker of a nonresponse.
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2007
on Behalf of the Pegasys Ribavirina España Coinfección (PRESCO) Study Group Background: Relapse after achieving virologic response to antihepatitis C virus (HCV) treatment considerably reduces sustained virologic response rates. It is unclear what the main predictors of relapse in HCV/HIV-coinfected patients are. Patients and Methods: The Pegasys Ribavirina España Coinfección (PRESCO) study evaluated short and extended duration of treatment for chronic hepatitis C using pegylated interferon (peg-IFN)-a2a at a dose of 180 mg/wk plus weight-based ribavirin (RBV) at a dose of 1000 to 1200 mg/d in HIV-infected subjects. Patients with HCV-2/3 were treated for 6 or 12 months, and patients with HCV-1/4 were treated for 12 or 18 months. Results: Of 389 patients included in the trial, end-of-treatment response was achieved by 262 (67.3%): 106 with HCV-1 (55%), 137 with HCV-2/3 (90%), and 19 with HCV-4 (41%). Six patients were lost to follow-up after completing therapy. Of the remaining 256 patients, 62 (24%) relapsed: 33% of HCV-1 patients, 18% of HCV-2/3 patients, and 21% of HCV-4 patients. In multivariate logistic regression analysis, baseline serum HCV RNA level $500,000 IU/mL (relative risk [RR] = 4.81, 95% confidence interval [CI]: 1.52 to 15.22; P = 0.008) and lack of rapid virologic response, defined as undetectable HCV RNA level at week 4 (RR = 2.94, 95% CI: 1.22 to 7.09; P = 0.02) were the best independent predictors of HCV relapse. Use of concomitant antiretroviral therapy also predicted relapse (P = 0.04), and a trend toward a higher relapse rate was recognized for HCV genotypes 1 and 4 versus genotypes 2 and 3 (P = 0.08). Extended treatment did not result in a lower incidence of relapse, at least for HCV genotypes 2 and 3. Conclusion: High baseline serum HCV RNA level and lack of undetectable viremia at week 4 are the most significant predictors of relapse in HCV/HIV-coinfected patients treated with peg-IFN plus weight-based RBV.