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Early Virological Response (early + virological_response)
Selected AbstractsVirological response to antiviral therapy at week 12 indicates a great reduction of intrahepatic hepatitis B virus DNA and cccDNA in HBeAg-positive chronic hepatitis B patientsJOURNAL OF VIRAL HEPATITIS, Issue 2010H. Y. Lu Summary., Early virological response is considered to be a predictor for the outcome of anti-hepatitis B virus (HBV) therapy. To analyze its correlation to intrahepatic HBV DNA and covalently closed circular DNA (ccc)DNA, 71 hepatitis B virus e antigen (HBeAg)-positive chronic hepatitis B patients were recruited: 34 patients were treated with lamivudine; 13 with interferon-,2b; and 24 with sequential therapy of lamivudine,interferon-,2b for 48 weeks. Intrahepatic HBV DNA and cccDNA load were measured at the baseline and at Week 48. Fifty-seven patients had virological response at Week 12. Median decreases of serum HBV DNA in patients with or without virological response at Week 12 were 4.0 log10 (max. 6.2, min. 2.2) and 1.1 log10 (max. 2.1, min. 0) (Z = ,5.766, P = 0.0000), respectively. At Week 48 they were 4.1 log10 (max. 7.4, min. 1.0) and 2.3 log10 (max. 7.5, min. 0.3) (Z = ,2.760, P = 0.006), respectively. For intrahepatic HBV DNA load they were 1.3 log10 (max. 4.3, min. ,1.2) and 0.6 log10 (max. 3.5, min. ,0.8), respectively, and for HBV cccDNA load they were 1.1 log10 (max. 4.8, min. ,0.5) and 0.5 log10 (max. 3.0, min. ,0.8) (Z = ,2.097, P = 0.036), respectively at Week 48. Step-wise logistic regression analysis indicated that the baseline intrahepatic HBV DNA load effected virological response at Week 12 [odds ratio (OR) 0.405; 95% confidence interval (CI) 0.174,0.944; P = 0.036] and HBeAg seroconversion at Week 48 (OR 0.292; 95% CI 0.131,0.649; P = 0.003). In conclusion, virological response at Week 12 indicated a great reduction of intrahepatic DNA and cccDNA load in HBeAg-positive CHB patients. The baseline intrahepatic HBV DNA load affected virological response at Week 12 and HBeAg seroconversion at Week 48. [source] Treatment with pegylated interferon and ribavarin in HCV infection with genotype 2 or 3 for 14 weeks: A pilot studyHEPATOLOGY, Issue 6 2004Olav Dalgard The aim of this study was to determine the efficacy of 14 weeks of treatment in patients infected with hepatitis C virus (HCV) genotype 2 or 3 who achieve early virological response (EVR). In a noncontrolled multicenter trial, 122 treatment-naive patients received 1.5 ,g/kg pegylated interferon alfa-2b subcutaneously once weekly and 800 to 1,400 mg/d ribavirin based on body weight. Treatment was stopped at week 14 in patients with EVR, defined as undetectable HCV RNA at weeks 4 and 8. Patients without EVR were assigned to 24 weeks of treatment. The primary end point was sustained virological response (SVR), defined as undetectable HCV RNA 24 weeks after end of treatment. Among the 122 patients, 95 (78%) had EVR and received 14 weeks of treatment. The remaining 27 (22%) were treated for 24 weeks. SVR was obtained in 85 (90%) of 95 patients in the 14-week treatment group and 15 of (56%) 27 in the 24-week treatment group. Altogether, SVR was obtained in 100 of 122 patients (82%; 95% CI, 75%-89%). SVR after 14 weeks of treatment was achieved more frequently among genotype 3a patients with low viral load compared with high viral load (98% vs. 79%; P = .019). Logistic regression analysis showed that absence of bridging fibrosis/cirrhosis was the only independent predictor of SVR. In conclusion, patients with genotype 2 or 3 and EVR obtained a high SVR after 14 weeks of treatment. The results need to be confirmed in a randomized, controlled study before this treatment approach can be recommended, particularly for patients with genotype 3 and high viral load or severe fibrosis. (HEPATOLOGY 2004;40: 1260,1265.) [source] Efficacy and tolerability of peginterferon alfa-2a or alfa-2b plus ribavirin in the daily routine treatment of patients with chronic hepatitis C in Germany: The PRACTICE StudyJOURNAL OF VIRAL HEPATITIS, Issue 7 2010T. Witthoeft Summary., In randomized clinical trials, treatment with peginterferon plus ribavirin (RBV) results in a sustained virological response (SVR) in around half of hepatitis C virus genotype 1-infected and 80% of genotype 2/3-infected individuals. This study aimed to evaluate efficacy and tolerability of peginterferon alfa-2a plus RBV compared with peginterferon alfa-2b plus RBV for the treatment of chronic hepatitis C in routine clinical practice. The intent-to-treat cohort consisted of 3414 patients treated with either peginterferon alfa-2a plus RBV (Group A) or peginterferon alfa-2b plus RBV (Group B) in 23 centres participating in the large, multicentre, observational PRACTICE study. Collected data included baseline characteristics, treatment regimen, RBV dose and outcome. Rates of early virological response, end of treatment response and SVR were 76.6%, 75.7% and 52.9% in Group A, and 70.2%, 65.6% and 50.5% in Group B, respectively. In patients matched by baseline parameters, 59.9% of patients in Group A and 55.9% in Group B achieved an SVR (P , 0.051). In genotype 1-infected patients matched by baseline parameters and cumulative RBV dose, SVR rates were 49.6% and 43.7% for Group A and Group B, respectively (P , 0.047); when matched by baseline parameters and RBV starting dose, SVR rates were 49.9% and 44.6%, respectively (P = 0.068). Overall, 21.8% of group A and 29.6% of group B patients discontinued treatment (P , 0.0001). The efficacy and tolerability of peginterferon plus RBV in this large cohort of patients treated in routine daily practice was similar to that in randomized clinical trials. In matched pairs analyses, more patients achieved an SVR with peginterferon alfa-2a compared with peginterferon alfa-2b. [source] Response to pegylated interferon plus ribavirin in HIV-infected patients with chronic hepatitis C due to genotype 4JOURNAL OF VIRAL HEPATITIS, Issue 10 2008L. Martín-Carbonero Summary., Hepatitis C virus (HCV) genotypes 1 and 4 respond less well to pegylated interferon (pegIFN) plus ribavirin (RBV) therapy. For this reason most studies merge these two genotypes when assessing virological response. However, in most trials the HCV genotype 4 population is rather small, and conclusions are mainly derived from what occurs in HCV-1 patients. All HCV-4 patients coinfected with HIV who received pegIFN plus RBV in two different multicentre studies, PRESCO and ROMANCE, conducted respectively in Spain and Italy, were retrospectively analyzed. Baseline plasma HCV-RNA, proportion of patients with HCV-RNA <10 IU,/,mL at week 4 (rapid virological response), and HCV-RNA declines >2 logs at week 12 (early virological response, EVR) were all assessed as predictors of sustained virological response (SVR). Overall, 75 patients (60 men) were evaluated. Median age was 40 years and median CD4 count 598 cells,/,mm3; 49% had plasma HIV-RNA <50 copies,,/,,mL; 71% had elevated liver enzymes and 31% had advanced liver fibrosis (Metavir F3,F4). Median serum HCV-RNA was 5.7 log IU,/,mL. Rapid virological response was attained by 10 (20%) patients and EVR by 26 (42%). Using intention-to-treat and on-treatment (OT) analyses, SVR was achieved by 21,/,75 (28%) and 21,/,62 (34%) of HCV-4 patients, respectively. In the multivariate analysis (OT), baseline HCV-RNA (OR 0.09 for every log increment; 95% CI: 0.01,0.7) and EVR (OR: 7.08; 95% CI: 1.8,27.2) were significantly and independently associated with SVR. This is the largest series of HIV-infected patients with chronic hepatitis C due to HCV-4 treated with pegIFN plus RBV examined so far and the results show that HCV-4 behaves similarly to HCV-1. Therefore, these patients should be considered as difficult to treat population. Baseline serum HCV-RNA and EVR are the best predictors of SVR in HCV-4,/,HIV-coinfected patients. [source] Role of rapid virological response in prediction of sustained virological response to Peg-IFN plus ribavirin in HCV,/,,HIV co-infected individualsJOURNAL OF VIRAL HEPATITIS, Issue 7 2008D. O. Shea Summary., The objective of the study was to evaluate the role of rapid virological response (RVR) in predicting sustained virological response (SVR) rates to hepatitis C virus (HCV) therapy. 65 HIV,/,HCV co-infected patients commenced HCV treatment per protocol. HIV,/,HCV patients with a mean CD4 count of 502 were treated for 24,48 weeks depending on genotype. Virological response was assessed at weeks 4 (RVR), 12 [early virological response (EVR)], 24, at end of treatment (EOTR) and 24 weeks post-completion of treatment (SVR). Primary end-point was defined as undetectable HCV RNA at 24 weeks post-treatment completion. Fifty-five per cent of co-infected patients were on highly active anti-retroviral therapy. A majority of patient group were male. 60% of HIV,/,HCV patients achieved SVR (35% genotype 1,/,4; 77% genotype 2,/,3). 24 HIV,/,HCV patients achieved undetectable HCV levels compared with baseline by week 4. The positive predictive value (PPV) of RVR at week 4 for subsequent SVR in HIV,HCV co-infected patients was 100%; the negative predictive value (NPV) was 57%. Significant variables associated with SVR were: (i) lower median pre-treatment HCV viral load, (ii) genotype 2,/,3 disease and (iii) achievement of RVR. Independent variables associated with RVR were low pre-treatment HCV viral load and genotype 2,/,3 disease. Achievement of RVR, a negative HCV-PCR, at week 4 of treatment is predictive of SVR in this cohort of patients. This may be used to guide optimal treatment duration in patient groups. More significantly, the data serve to highlight the subgroup of patients who, on achieving RVR, should be actively supported to complete HCV treatment with full dose therapy, especially patients co-infected with G2,/,3 disease for whom 6 months' full dose therapy may be sufficient to obtain a SVR. [source] Assessment of hepatitis C virus-RNA clearance under combination therapy for hepatitis C virus genotype 1: performance of the transcription-mediated amplification assayJOURNAL OF VIRAL HEPATITIS, Issue 1 2008D. Ferraro Summary., Monitoring of HCV-RNA in blood during antiviral therapy is performed mostly by commercially available reverse transcription polymerase chain reaction-based (RT-PCR) assays, with a lower detection limit of 30,50 IU/mL of HCV-RNA. Use of different tests in the pivotal trials of combination therapy has generated some discordance, in terms of predictive value of the early virological response (EVR). To evaluate whether the use of a more sensitive test, as a qualitative assay based on transcription mediated amplification (TMA) with a lower detection limit of 5,10 IU/mL of HCV-RNA, may obtain a better prediction of EVR and of the ultimate virological outcome, we retrospectively evaluated serial samples from 108 naïve patients with HCV genotype 1 chronic hepatitis, treated with pegylated ,2b interferon plus ribavirin for 48 weeks and with a 24 weeks stopping rule. Serum samples of patients, obtained during treatment at weeks 4, 12, 24 and 48 and after treatment at week 24, were evaluated by TMA. Comparison of the RT-PCR and TMA assays for the qualitative detection of HCV-RNA showed no significant differences in performance when these tests were used at the end of the treatment period for assessing patients without an on-treatment virological response and those who eventually obtain a sustained virological response. Our results show instead that the use of TMA assay to detect HCV-RNA at 12 and 24 weeks of the combination therapy is more effective than RT-PCR in identifying patients with the highest probability of sustained HCV-RNA clearance. [source] Critical role of ribavirin for the achievement of early virological response to HCV therapy in HCV/HIV-coinfected patientsJOURNAL OF VIRAL HEPATITIS, Issue 6 2007B. Ramos Summary., The response to hepatitis C virus (HCV) therapy seems to be lower in HCV/HIV-coinfected patients than in HCV-monoinfected individuals. Given that most pivotal trials conducted in coinfected patients have used the combination of pegylated interferon (pegIFN) along with fixed low doses (800 mg/day) of ribavirin (RBV), it is unclear whether HIV itself and/or suboptimal RBV exposure could explain this poorer outcome. Two well-defined end points of early virological response were evaluated in Peginterferon Ribavirina España Coinfección (PRESCO), a multicentre trial in which the combination of pegIFN plus RBV (1000 mg if body weight <75 kg and 1200 mg if >75 kg) was prescribed to coinfected patients. For comparisons, we used unpublished data from early kinetics in two other large trials, one performed in HIV-negative patients [Pegasys International Study Group (PISG)] in which RBV 1000,1200 mg/day was used and another [AIDS Pegasys Ribavirin Coinfection Trial (APRICOT)] in which HIV-positive patients received fixed low RBV doses (800 mg/day). A total of 348 HCV/HIV-coinfected patients from the PRESCO trial were analysed as well as all patients treated with pegIFN plus RBV, who completed 12 weeks of therapy in the comparative studies (435 in PISG and 268 in APRICOT). Negative serum HCV-RNA at week 4 (which has the highest positive predictive value of sustained virological response, SVR) was attained in 33.3%, 31.2% and 13% of treated patients with HCV genotype 1, respectively, in PRESCO, PISG and APRICOT. For HCV genotypes 2/3, responses were 83.7%, 84.2% and 37%, respectively. A decline lower than 2 log10 at week 12 (which has the highest negative predictive value of SVR) was seen in 25.5%, 19.5% and 37% of HCV genotype-1-infected patients, and in 2.1%, 2.9% and 12% of genotypes-2/3-infected patients, respectively. Prescription of high RBV doses enhances the early virological response to HCV therapy in HCV/HIV-coinfected patients, with results approaching those seen in HCV-monoinfected patients. [source] Peginterferon alpha-2b plus ribavirin vs interferon alpha-2b plus ribavirin for chronic hepatitis C in HIV-coinfected patientsJOURNAL OF VIRAL HEPATITIS, Issue 4 2007M. Crespo Summary., Treatment of chronic hepatitis C in human immunodeficiency virus (HIV)-infected patients is associated with low response rates and high incidence of side effects. One hundred twenty-one hepatitis C virus (HCV),HIV-coinfected patients were randomized to receive interferon alpha-2b (3 MU thrice weekly; n = 61) or peginterferon alpha-2b (1.5 ,g/kg/week; n = 60), plus ribavirin (800 mg daily), for 24 (genotype 2 or 3) or 48 weeks (genotype 1 or 4). We assessed early virological response at 4, 8 and 12 weeks to predict sustained virological response (SVR). Safety assessment included frequent blood lactate measurement and relative quantitation of mitochondrial DNA (mtDNA) content in peripheral blood mononuclear cells. In intention-to-treat analysis, the SVR rate was higher in the peginterferon group (55%vs 26%; P = 0.002). The difference for HCV genotypes 1 and 4 was 45%vs 14% (P = 0.009) and 50%vs 27% (P = 0.387), respectively, and for genotype 2 or 3, 71%vs 43% (P = 0.12) Viral response at 4, 8 and 12 weeks of treatment was highly predictive of SVR. Among genotype 3 patients, 17 of 20 (85%) whose HCV RNA was already undetectable at 4 weeks had an SVR after 24 weeks of treatment. Hyperlactataemia occurred in 22 patients and was clinically significant in six, two of whom died. mtDNA decreased significantly 4,12 weeks after the start of treatment in patients developing clinically significant hyperlactataemia. Peginterferon alpha-2b plus ribavirin was more effective than interferon alpha-2b plus ribavirin in HIV-coinfected patients. Frequent monitoring of virological response may be very helpful to optimize treatment compliance, to tailor treatment duration and to minimize side effects. [source] Partial splenic embolization and peg-IFN plus RBV in liver transplanted patients with hepatitis C recurrence: safety, efficacy and long-term outcomeCLINICAL TRANSPLANTATION, Issue 3 2010Rafael Bárcena Bárcena R, Moreno A, Foruny JR, Blázquez J, Graus J, Riesco JM, Blesa C, García-Hoz F, Sánchez J, Gil-Grande L, Nuño J, Fortún J, Rodriguez-Sagrado MA, Moreno A. Partial splenic embolization and peg-IFN plus RBV in liver transplanted patients with hepatitis C recurrence: safety, efficacy and long-term outcome. Clin Transplant 2010: 24: 366,374. © 2009 John Wiley & Sons A/S. Abstract:,Background:, There is limited information on the long-term outcome in liver transplant (LT) subjects undergoing partial splenic embolization (PSE) prior to full dose pegylated interferon/ribavirin (peg-IFN/RBV). Methods:, Retrospective review of eight LT subjects after PSE and antiviral therapy. Results:, Baseline platelets and neutrophils were <50 000 cells/mL and <1000 cells/mL in 75% and 50%. Mean splenic infarction volume was 85 ± 13%. PSE produced major complications in three (37.5%): recurrent sterile netrophilic ascites and renal insufficiency (n = 2), and splenic abscess (n = 1). Full-dose peg-IFN/RBV was started in seven (87.5%), with two early withdrawals (28.6%) despite early virological response (toxicity and infection); both subjects died. Anemia led to RBV dose-adjustment in six (86%), with human recombinant erythropoietin (EPO) use in four (57%). No peg-IFN adjustments or granulocyte-colonies stimulating factor were needed. Two patients reached sustained virological response (SVR) (28.6%). Two non-responders maintained prolonged therapy with biochemical/histological improvement. After a median follow-up of 151 wk, we observed significant improvements in hematological parameters, aspartate aminotransferase, alanine aminotransferase, international normalized ratio, and prothrombin activity. Conclusions:, Extensive PSE after LT produced significant morbidity (37.5%). Peg-IFN/RBV was completed in five out of seven (71%), with SVR in two (28.6%). RBV adjustement due to anemia was high despite EPO use. Only patients able to complete or maintain antiviral therapy survived, with long-term significant benefits in hematological parameters and liver function tests. [source] Sustained virological responses following standard anti-viral therapy in decompensated HCV-infected cirrhotic patientsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2009A. IACOBELLIS Summary Background, Little data is available about predictors of sustained virological response (SVR) during anti-viral therapy of patients with decompensated HCV cirrhosis. Aims, To determine whether rapid and early virological responses (RVR and EVR) could predict SVR and help optimize treatment in these patients. Methods, A total of 94 cirrhotics underwent treatment with peg-interferon alfa-2b (1.5 ,g/kg weekly) and ribavirin (800/1200 mg daily) for 48 or 24 weeks for genotypes 1/4 or genotypes 2/3, respectively. Results, Overall, SVR was achieved in 33 patients (35.1%), 16% with genotype 1/4 and 56.8% with genotype 2/3 (P < 0.01). At treatment week 4, 34 patients had undetectable HCV-RNA, 10 with genotype 1/4 and 24 with genotype 2/3. Of RVR patients, 24 achieved SVR (70.5%), 6 and 18 with genotypes 1 and non-1. At the multivariate analysis, only EVR, genotypes 2 and 3, and adherence to full course and dosage of therapy retained their independent predictive power, with corresponding ORs of 25.5 (95% CI 3.0,217.3), 4.2 (95% CI 1.2,15.3) and 9.1 (95% CI 2.2,38.0), respectively. Conclusion, In decompensated cirrhotic patients, anti-viral therapy with current regimens is feasible and associated with an overall SVR rate of 35.1%. Treatment ought to be pursued among patients who attain an EVR, and maintain a full course and dosage of therapy. [source] | ||||||||||