Clinical value of on-treatment HCV RNA levels during different sofosbuvir-based antiviral regimens

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• 作者：Benjamin Maasoumy¹ ; ^&dagger ; ; Johannes Vermehren² ; ^&dagger ; ; Martin-Walter Welker² ; Birgit Bremer¹ ; Dany Perner² ; Christoph Hö ; ner zu Siederdissen¹ ; Katja Deterding¹ ; Patrick Lehmann¹ ; Gavin Cloherty³ ; Birgit Reinhardt⁴ ; Jean-Michel Pawlotsky⁵ ; Michael P. Manns¹ ; Stefan Zeuzem² ; Markus Cornberg¹ ; Heiner Wedemeyer¹ ; ^&Dagger ; ; Christoph Sarrazin² ; ^&Dagger ; ; ^{sarrazin@em.uni-frankfurt.de" class="auth_mail" title="E-mail the corresponding author}
• 关键词：SOF ; sofosbuvir ; CAP/CTM ; COBAS AmpliPrep/COBAS TaqMan v2.0 ; ART ; Abbott RealTime HCV test ; GT ; genotype ; RBV ; ribavirin ; PegIFN ; pegylated-interferon alfa ; SMV ; simeprevir ; HCV ; hepatitis C virus ; SVR ; sustained virological response ; DAA ; direct-acting antivirals ; PI ; protease inhibitor ; w ; weeks ; LOQ ; lower limit of quantification ; LOD ; lower limit of detection ; LDV ; ledipasvir ; TND ; target not detected ; DCV ; daclatasvir
• 刊名：Journal of Hepatology
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：65
• 期：3
• 页码：473-482
• 全文大小：1088 K

文摘

The European Association for the Study of the Liver (EASL) guidelines recommend HCV RNA measurements at specific time points during sofosbuvir(SOF)-therapy. However, it remains unclear, how these results should be interpreted. We aimed to analyze whether on-treatment HCV RNA levels predict relapse comparing the CobasAmpliPrep/CobasTaqMan v2.0 (CAP/CTM) and Abbott RealTime HCV (ART) assays.

Methods

Samples were collected from 298 patients (HCV genotypes; GT1-5) at weeks (w) 0, 1, 2, 4, 8, 12, 16, 20 and 24 during SOF-based therapy at two university clinics and tested for HCV RNA level by CAP/CTM and ART. Patients were treated with SOF/ribavirin (RBV) 12/24 w (n = 99), pegylated-interferon-alfa (PegIFN)/SOF/RBV 12 w (n = 51), SOF/simeprevir (SMV) ± RBV 12 w (n = 69) or SOF/daclatasvir ± RBV 12/24 w (n = 79).

Results

HCV RNA levels during the first 4 weeks of SOF/RBV therapy were significantly lower in GT3 patients who achieved SVR compared with those who relapsed. All GT3 patients with a week 2 result <45 IU/ml by CAP/CTM achieved SVR but only 33% of those with ⩾45 IU/ml (p = 0.0003). Similar results were documented with ART and 60 IU/ml as cut-off (SVR: 100% vs. 29%; p = 0.0002). In contrast, HCV RNA levels during early treatment phases were not significantly related to relapse in patients treated with other SOF-based regimens.

Residual HCV RNA was frequently detected by ART at later stages of therapy. However, SVR rates remained high in these patients. At the end of SOF/SMV ± RBV therapy HCV RNA was detectable with ART in 20% of patients, of whom 92% achieved SVR.

Conclusions

HCV RNA levels assessed at week 2 of SOF/RBV therapy can predict relapse in GT3-patients. Detectable HCV RNA results at later stages during SOF-based therapy may occur frequently with the more sensitive ART. However, this should not lead to treatment extension.

Lay summary

We analyzed the predictive value of hepatitis C virus (HCV) RNA levels measured at different time points for treatment efficacy. We found that the level of HCV RNA measured at week 2 of antiviral therapy can be used to predict treatment success in patients with HCV genotype 3 infection treated with sofosbuvir and ribavirin but not in patients treated with other sofosbuvir-based regimens. Low level HCV RNA is frequently detected by the RealTime HCV assay during later stages of antiviral therapy. However, this is not associated with reoccurrence of HCV RNA after the end of treatment.