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RISS 인기검색어
- 검색키워드
- 저자 : ( Christoph Sarrazin ) (검색결과 3 건)
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( Christoph Sarrazin ),( Mark S. Sulkowski ),( Preethi Krishnan ),( Rakesh Tripathi ),( Gretja Schnell ),( Yan Xie ),( Daniel E. Cohen ),( Roger Trinh ),( Lino Rodrigues-jr. ),( Yan Luo3,Nancy S. Shul 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1
Aims: The 3 direct-acting antiviral (3-DAA) regimen of ombitasvir, ritonavir-boosted paritaprevir and dasabuvir ± RBV is approved in the US and EU for treatment of hepatitis C virus (HCV) genotype (GT) 1 infection. Baseline resistance associated variants (RAVs) in HCV NS3 or NS5A can impact response to other DAA regimens; we assessed the prevalence and impact of RAVs on response to the 3-DAA regimen. Methods: Next-generation sequencing (Illumina MiSeq) assessed baseline samples from treatment-naive (PEARL-IV), -experienced (SAPPHIRE- II), or cirrhotic (TURQUOISE-II) GT1a patients who received 3-DAA + RBV, and treatment-experienced (PEARL-II) or cirrhotic (TURQUOISE-III) GT1b patients who received 3-DAA alone. Thresholds of 1 and 15%, respectively, detected the prevalence and impact of baseline RAVs; impact of RAVs conferring ≥ 5-fold resistance to components of the 3-DAA regimen on response was determined by com- paring SVR rates in patients with or without RAVs. Results: SVR rates were 96% and 100% in patients with GT1a and GT1b, respectively. One or more NS5A RAVs were present in 11% of treatment-experienced or cirrhotic GT1a patients, whereas NS5A RAVs were found in 19% of GT1b patients (15% threshold). Similar SVR rates were seen in GT1a patients with or without NS5A RAVs. All GT1b patients with NS5A RAVs, including at position Y93, achieved SVR. NS3 RAVs were uncommon (≤2%). NS3 RAVs were not seen in any of the 14 virologic failures and an NS5B RAV was seen in 1 virologic failure. The presence of the GT1a NS3 Q80K polymorphism had no impact on SVR. Conclusions: Understanding impact of baseline NS5A RAVs on treatment outcomes is important for relevant HCV therapies. Patients with HCV GT1a-infection treated with the 3-DAA regimen + RBV achieved high SVR rates, regardless of the presence of baseline RAVs. All GT1b patients treated with the 3-DAA regimen alone achieved SVR.
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( Christoph Sarrazin ),( Curtis L. Cooper ),( Michael P. Manns ),( Rajender Reddy ),( Kris Kowdley ),( Sooji Lee ),( Hadas Dvory-Sobol ),( Evguenia Svarovskia ),( Ross Martin ),( Gregory Camus ),( Bri 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1
Aims: The pangenotypic combination of sofosbuvir (SOF) /velpatasvir (VEL)/voxilaprevir(VOX), inhibit distinct HCV targets, the NS5B polymerase, the NS5A protein, and NS3/4A protease, respectively. In Phase 3 studies, SOF/VEL/VOX administered for 12weeks demonstrated a 96% SVR12 rate in NS5A inhibitor-experienced patients in POLARIS-1, and a 97% SVR12 rate in DAA-experienced patient who had not previously received an NS5A inhibitor in POLARIS-4. Here, we evaluate the effect of baseline resistance associated substitutions (RASs) on treatment outcome and the emergence of RASs in patients who experienced virologic failure. Methods: NS3, NS5A, and NS5B deep sequencing was performed at baseline for all patients and at the time of virologic failure. NS3 and NS5A class RASs as well as VOX or VEL-specific RASs that confer >2.5-fold changes in EC50 were evaluated. Results: In POLARIS-1, 79% of NS5A inhibitor-experienced patients (205/260) had baseline NS3 and/or NS5A class RASs. Of these, 75% (196/260) had baseline NS5A RASs, the most common RASs. The SVR12 rates were similar in subjects with or without NS3 and/or NS5A class RASs, and with or without VOX or VEL-specific RASs(Table 1). RASs at NS5A position Y93 were present in 25% of patients, of whom 63(95%) achieved SVR12; all patients with ≥2 NS5A RASs achieved SVR12 (n=77). 95%(18/19) of patients with NS5B nucleoside inhibitor(NI) RASs achieved SVR12; 2 patients had S282T at baseline and achieved SVR12. In POLARIS-4, the overall prevalence of baseline NS3 and/or NS5A class RASs was 47%(83/178) and all achieved SVR12. All patients with. Conclusions: Baseline RASs had no impact on response in DAA-experienced patients following treatment with SOF/VEL/VOX for 12 weeks. Viral relapse was not associated with emergence of viral resistance.
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Christian Mölleken,Maike Ahrens,Anders Schlosser,Julia Dietz,Martin Eisenacher,Helmut E. Meyer,Wolff Schmiegel,Uffe Holmskov,Christoph Sarrazin,Grith Lykke Sorensen,Barbara Sitek,Thilo Bracht 대한간학회 2019 Clinical and Molecular Hepatology(대한간학회지) Vol.25 No.1
Background/Aims: An estimated 80 million people worldwide are infected with viremic hepatitis C virus (HCV). Even after eradication of HCV with direct acting antivirals (DAAs), hepatic fibrosis remains a risk factor for hepatocarcinogenesis. Recently, we confirmed the applicability of microfibrillar-associated protein 4 (MFAP4) as a serum biomarker for the assessment of hepatic fibrosis. The aim of the present study was to assess the usefulness of MFAP4 as a biomarker of liver fibrosis after HCV eliminating therapy with DAAs. Methods: MFAP4 was measured using an immunoassay in 50 hepatitis C patients at baseline (BL), the end-of-therapy (EoT), and the 12-week follow-up (FU) visit. Changes in MFAP4 from BL to FU and their association with laboratory parameters including alanine aminotransferase (ALT), aspartate aminotransferase (AST), platelets, the AST to platelet ratio index (APRI), fibrosis-4 score (FIB-4), and albumin were analyzed. Results: MFAP4 serum levels were representative of the severity of hepatic fibrosis at BL and correlated well with laboratory parameters, especially APRI (Spearman correlation, R²=0.80). Laboratory parameters decreased significantly from BL to EoT. MFAP4 serum levels were found to decrease from BL and EoT to FU with high statistical significance (Wilcoxon P<0.001 for both). Conclusions: Our findings indicate that viral eradication resulted in reduced MFAP4 serum levels, presumably representing a decrease in hepatic fibrogenesis or fibrosis. Hence, MFAP4 may be a useful tool for risk assessment in hepatitis C patients with advanced fibrosis after eradication of the virus.
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