Improved Responses to Pegylated Interferon Alfa-2b and Ribavirin by Individualizing Treatment for 24–72 Weeks

Sarrazin, Christoph; Schwendy, Susanne; Möller, B.; Dikopoulos, Nektarios; Buggisch, Peter; Encke, Jens; Teuber, G.; Goeser, Tobias; Thimme, Robert; Klinker, Hartwig; Boecher, Wulf O.; Schulte‐Frohlinde, E.; Prinzing, R.; Herrmann, Eva; Zeuzem, Stefan; Berg, Thomas

doi:10.1053/j.gastro.2011.07.019

Cited by 36 publications

(38 citation statements)

References 34 publications

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“…A significant number of our patients (14/19) displayed RVR with non-detectable viral load at treatmentweeks 4, and all patients with SVR achieved RVR. RVR4 has been reported to be an important predictor of SVR [19] and response-guided therapy is well established in non-LT patients [20,21] . This is reflected in our cohort, as all patient achieving SVR24, had a HCV viral load below LLOQ (12 IU/mL) at TW 4.…”

Section: Discussionmentioning

confidence: 99%

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Management of telaprevir-based triple therapy for hepatitis C virus recurrence post liver transplant

Herzer¹

2015

WJH

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AIM: To characterize management of telaprevir (TVR)-based triple therapy of hepatitis C virus (HCV) reinfection after liver transplantation (LT). METHODS:We retrospectively analyzed safety and efficacy of telaprevir -based triple therapy in a single center cohort of 19 patients with HCV genotype (GT) 1 recurrence after LT, with respect to factors possibly predicting sustained viral response (SVR) or non-SVR. All patients were treated with TVR, pegylated (PEG) and ribavirine (RBV) for 12 wk followed by a dual phase with PEG/RBV for 12 wk in 7 patients and for 36 wk in 5 patients. RESULTS:In total 11/19 (58%) of patients achieved a sustained response. All (11/11) SVR patients showed a rapid viral response at treatment weeks 4 and 11/14 rapid virological response (RVR) patients achieved SVR. Notably, all (7/7) patients who completed 48 wk of therapy and 80% (4/5) patients who completed Management of telaprevir-based triple therapy for hepatitis C virus recurrence post liver transplant Retrospective Study ORIGINAL ARTICLE24 wk of therapy achieved SVR24. Treatment failure was significantly (P > 0.049) more frequent in GT1a infection (5/7) compared to GT1b (3/12) infection and was associated with emergence of resistance-associated mutations in the NS3 protease domain. Bilirubin level at baseline is also related to SVR (P > 0.030). None of the patients had to discontinue treatment due to side effects.CONCLUSION: RVR, GT and bilirubin are clearly related to achievement of SVR. Providing a thorough patient selection and monitoring, a full course of TVR-based triple therapy in LT patients is feasible and achieves high SVR rates.

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Section: Discussionmentioning

confidence: 99%

“…For the assessment of efficacy, viral load was monitored in plasma using the ABBOTT Real Time HCV assay (Abbott Molecular, United States; lower limit of detection 12 IU/mL) at baseline and then at week 1, 2, 3, 4,8,12,16,20,24, 36 and 48. Genotypes were determined using phylogenetic analyses of the core region.…”

Section: Antiviral Treatment Regimenmentioning

confidence: 99%

Management of telaprevir-based triple therapy for hepatitis C virus recurrence post liver transplant

Herzer¹

2015

WJH

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“…We examined slow responders who received 72 weeks of combination therapy with Peg-IFN and RBV. Slow responders are potential candidates for treatment intensification, and several previous trials have reported the virological benefits of prolonged 72-week combination therapy in such patients (9,11,(13)(14)(15)(16). In addition, a recent pooled analysis of slow responders found that 33% of the patients who received 72-week therapy achieved SVR, whereas only 27% of those who received 48 weeks of therapy did so (p=0.02), with relapse rates in the 72-and 48-week treatment groups of 32% and 51% (p=0.007), respectively (22).…”

Section: Discussionmentioning

confidence: 99%

“…Several clinical trials have investigated the efficacy of prolonged treatment with Peg-IFN and RBV in an attempt to improve the rate of SVR in patients with chronic HCV genotype 1 (9)(10)(11)(12)(13)(14)(15)(16). The findings of these studies indicate that extending the treatment time from 48 to 72 weeks significantly reduces the rate of viral relapse in patients with a slow on-treatment virological response, defined as a 2-log decrease in the viral load from baseline to week 12, followed by the subsequent loss of serum HCV RNA before week 24 (9,11,(13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

“…The findings of these studies indicate that extending the treatment time from 48 to 72 weeks significantly reduces the rate of viral relapse in patients with a slow on-treatment virological response, defined as a 2-log decrease in the viral load from baseline to week 12, followed by the subsequent loss of serum HCV RNA before week 24 (9,11,(13)(14)(15)(16). However, optimal methods for delivering Peg-IFN and RBV therapy in HCV genotype 1 slow responders have not yet been established.…”

Section: Introductionmentioning

confidence: 99%

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Long-term Pegylated Interferon Monotherapy Following 72 Weeks of Pegylated Interferon and Ribavirin in Hepatitis C Virus Genotype-1-infected Slow Responders

et al. 2015

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Objective Slow responders to pegylated interferon (Peg-IFN) and ribavirin (RBV) among patients infected with hepatitis C virus (HCV) genotype 1 may benefit from an extended treatment course. The aim of this study was to determine the efficacy of persistent negative serum HCV RNA over 96 weeks during long-term Peg-IFN monotherapy following 72 weeks of combination therapy. Methods A total of 46 HCV genotype 1-infected slow responders were treated for 72 weeks with Peg-IFN and RBV combination therapy alone (n=25) or additional long-term biweekly treatment with 90 μg of Peg-IFN-α2a (n=21). The criterion for the completion of long-term Peg-IFN monotherapy was defined as the attainment of constantly negative HCV RNA in the serum over 96 weeks during IFN treatment. Results The patients with sustained negative serum HCV RNA during 96 weeks of IFN treatment had a higher rate of sustained virological response (SVR) than those without (81 vs. 40%, p=0.012). A multivariate analysis identified sustained negativity of serum HCV RNA over 96 weeks of IFN treatment to be a predictive factor for SVR. Conclusion In the present study, sustained negative serum HCV RNA over 96 weeks during long-term Peg-IFN monotherapy following 72 weeks of combination therapy of Peg-IFN and RBV resulted in beneficial virological outcomes among HCV genotype 1-infected slow responders.

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Combined effects of different interleukin-28B gene variants on the outcome of dual combination therapy in chronic hepatitis C virus type 1 infection

Fischer¹,

Böhm²,

Scholz³

et al. 2012

Hepatology

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In patients with chronic hepatitis C virus (HCV) infection, several variants of the interleukin-28B (IL28B) gene have been shown to correlate significantly with a sustained virologic response (SVR). Recent evidence shows that determination of one single IL28B polymorphism, rs12979860, is sufficient for predicting treatment outcome. We examined whether the combined determination of the IL28B single-nucleotide polymorphisms (SNPs), rs12979860, rs8099917, rs12980275, and rs8103142, might improve the prediction of SVR in patients with HCV. In the study cohort, 54% of 942 patients with chronic HCV type 1 infection had SVR. The IL28B SNPs, rs12979860CC and rs8099917TT, correlated significantly with SVR (68% and 62%). The SNPs, rs12980275 and rs8103142, were in strong linkage disequilibrium with rs12979860 and were not included in further analysis. In homozygous carriers of the rs12979860 responder allele C, additional genotyping of the rs8099917 SNP had no effect on response prediction, whereas in carriers of the rs12979860 nonresponder allele, the rs8099917 SNP improved the response prediction. In heterozygous carriers of the rs12979860 nonresponder T allele, SVR rates were 55% in the presence of the rs8099917TT genotype and 40% in patients carrying the rs8099917 TG or GG genotype. Analysis of an independent confirmation cohort of 377 HCV type 1-infected patients verified the significant difference in SVR rates between the combined genotypes, rs12979860CT/rs8099917TT and rs12979860CT/rs8099917TG (38% versus 21%; P 5 0.018). Conclusion: Treatment outcome prediction could not be improved in homozygous carriers of the IL28B rs12979860 C responder allele by the additional determination of the rs8099917 SNP. There is evidence that a significant proportion of heterozygous carriers of the rs12979860 T nonresponder allele can profit with respect to SVR prediction by further determination of the rs8099917 SNP.

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Improved Responses to Pegylated Interferon Alfa-2b and Ribavirin by Individualizing Treatment for 24–72 Weeks

Cited by 36 publications

References 34 publications

Management of telaprevir-based triple therapy for hepatitis C virus recurrence post liver transplant

Management of telaprevir-based triple therapy for hepatitis C virus recurrence post liver transplant

Long-term Pegylated Interferon Monotherapy Following 72 Weeks of Pegylated Interferon and Ribavirin in Hepatitis C Virus Genotype-1-infected Slow Responders

Combined effects of different interleukin-28B gene variants on the outcome of dual combination therapy in chronic hepatitis C virus type 1 infection

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