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Natural prevalence of NS3 gene resistance-associated substitutions (RASs) in patients with chronic hepatitis C from the state of Pará/Brazil.
da Silva, DL, Nunes, HM, Freitas, PEB
Virus research. 2021;:198251
Abstract
The resistance of hepatitis C virus (HCV) to direct-acting antiviral agents, used in chronic hepatitis C treatment, consists of a natural process resulting from resistance-associated substitutions (RASs) at specific amino acid regions. To identify and establish the natural prevalence of RASs in the NS3 gene in patients with chronic hepatitis C in the state of Pará, northern Brazil. Molecular analysis was performed on a total of 35 patients infected with HCV genotype 1, who were treatment-naive to protease inhibitors. HCV RNA was extracted from plasma and the NS3 region was amplified and submitted to DNA sequencing (Sanger). The general natural prevalence of RASs in the NS3 gene was 37.5 % (Y56F and S122T). The substitutions Y56F (34.3 %), S122T (3.1 %), V132I (15.6 %) and V170I (9.3 %) were identified. Y56F and S122T provide resistance to the protease inhibitors grazoprevir and simeprevir, respectively. All amino acid substitutions in the NS3 gene, including RASs, identified in patients from the state of Pará were present in other Brazilian studies. The natural presence of RASs in this study reflects the elevated genetic variability of HCV.
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Real-world effectiveness and safety of sofosbuvir plus daclatasvir with or without ribavirin for genotype 2 chronic hepatitis C in Taiwan.
Cheng, PN, Chiu, YC, Chien, SC, Chiu, HC
Journal of the Formosan Medical Association = Taiwan yi zhi. 2019;(5):907-913
Abstract
BACKGROUND AND PURPOSE Sofosbuvir (SOF) and daclatasvir (DCV) treatment achieves excellent efficacy and safety in treating chronic hepatitis C (CHC) with various genotypes. Real world experience of SOF/DCV regimen to treat genotype 2 CHC was scanty in Asia. This study aimed to evaluate the effectiveness and safety of SOF/DCV with or without ribavirin to treat genotype 2 CHC patients in real world practice in Taiwan. METHODS Patients with genotype 2 CHC treated with 12-week of SOF/DCV or SOF/DCV/ribavirin were enrolled prospectively. Effectiveness was evaluated by sustained virological response (SVR) which was defined as undetectable hepatitis C virus (HCV) RNA at post-treatment week 12. Adverse events were recorded for safety analysis. RESULTS In total of 32 patients were enrolled from October 2016 to June 2017. All were infected with genotype 2 HCV. Sixteen patients (50%) exhibited cirrhosis including 6 patients with decompensation. Regimens of SOF/DCV and SOF/DCV/ribavirin were used to treat 14 and 18 patients, respectively. SVR was achieved in all 31 patients (100%) who completed follow-up. Significantly higher levels of cholesterol (p = 0.013) and higher low density lipoprotein-cholesterol (p = 0.015) were exhibited after successful viral clearance. SOF/DCV/ribavirin regimen resulted in more adverse events, significantly higher bilirubin levels, and decline of hemoglobin during treatment than SOF/DCV regimen. Four patients with chronic kidney disease maintained renal function during treatment. Overall, SOF/DCV or SOF/DCV/ribavirin treatment was well tolerated. CONCLUSION SOF/DCV with or without ribavirin is highly effective and safe for patients with genotype 2 HCV infection in real-world experience in Taiwan.
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3.
Anatomical and Functional Retinal Complications of Combined Sofosbuvir and Ribavirin Therapy in Patients With Chronic Hepatitis C Virus.
Elgouhary, SM, Said-Ahmed, KE, Mowafy, MA
Ophthalmic surgery, lasers & imaging retina. 2019;(1):39-41
Abstract
BACKGROUND AND OBJECTIVE To evaluate the anatomical and functional retinal complications of combined sofosbuvir and ribavirin therapy in patients with chronic hepatitis C virus (HCV). PATIENTS AND METHODS Three hundred patients with chronic HCV were recruited for this prospective, observational study from the National Liver Institute of Menoufia University from November 2015 to September 2017. Ophthalmic examination and follow-up were performed in the outpatient clinic of the Ophthalmology Department at Menoufia University. All patients received the same regimen (sofosbuvir and ribavirin) for 6 months. Patients were followed up during the period of treatment (6 months) and for 6 months after treatment completion. Complete ophthalmic examination, fundus fluorescein angiography (FFA) (to detect retinal ischemia), optical coherence tomography (OCT) (to detect retinal nerve fiber layer [RNFL] thickness and central macular thickening), and electroretinogram (ERG) (to detect rod and cone functions) tests were performed before and after treatment completion. RESULTS The mean age of the patients was 46.17 years ± 11.38 years (range: 20 years to 60 years). The study included 138 men (46%) and 162 women (54%). During follow-up, there were no signs of retinopathy or optic nerve affection. There were also no signs of retinal ischemia (by FFA), RNFL affection, macular edema (by OCT), or rod or cone affection (by ERG). CONCLUSION Combined treatment (sofosbuvir and ribavirin) may be safe without causing anatomical or functional retinal complications. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:39-42.].
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Disparate access to treatment regimens in chronic hepatitis C patients: data from the TRIO network.
Younossi, ZM, Bacon, BR, Dieterich, DT, Flamm, SL, Kowdley, K, Milligan, S, Tsai, N, Nezam, A
Journal of viral hepatitis. 2016;(6):447-54
Abstract
Despite the clinical success in the real-world of all oral hepatitis C virus (HCV) therapy with response rates approaching that seen in the clinical trials, access has been limited by many payers with discussion of prioritization of treatment based upon AASLD guidelines. We evaluated patients in the TRIO network who were prescribed sofosbuvir (SOF)-based regimens to determine reasons for not starting treatment. Trio Health is a disease management company that works in partnership with academic medical centres, community physicians and specialty pharmacies in the United States to optimize care for HCV. Data for 3841 patients prescribed a sofosbuvir-containing regimen between December 2013 and September 2014 were obtained through this programme. Of the entire group, 315 (8%) patients did not start the prescribed sofosbuvir-containing therapy. A total of 141 (45%) of the nonstart patients had a commercial plan as their primary insurance, 137 (44%) were primarily covered by Medicaid, 17 (5%) were primarily covered by Medicare, and 20 (6%) were either without coverage or coverage was not specified. Reasons for nonstarts were varied and overlapping. Only 15 patients (5% of nonstarts) did not start because they were unreachable or failed to complete required testing. Another 39 patients who did not start (12%) were following their physicians' direction to either wait for new treatment options or to hold treatment for an unspecified reason. Insurance-related processes and financial reasons accounted for 254 (81%) of the 315 nonstarts. The remaining 7 (2%) patients did not have a specified reason for not starting treatment. Nonstart rates were highest in the Medicaid-covered population at 35%. Medicare and Commercial nonstart rates were 2% and 6%, respectively. In a matched comparison, patients with commercial coverage were 6.5 times as likely to start SOF-based therapy compared to patients with Medicaid. Despite high SVR rates of SOF-based regimens in clinical practice, there are still barriers to access to care. In fact, almost half of the nonstart patients had advanced fibrosis scores (F3 or F4) and should have been prioritized to start treatment. As better treatment for HCV with high efficacy and low side effect rates become available, the disparity in access to treatment, as evidenced by the high nonstart rate in the Medicaid-covered group, must be resolved.
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Effectiveness of triple therapy with simeprevir for chronic hepatitis C genotype 1b patients with prior telaprevir failure.
Ogawa, E, Furusyo, N, Dohmen, K, Kajiwara, E, Kawano, A, Nomura, H, Takahashi, K, Satoh, T, Azuma, K, Nakamuta, M, et al
Journal of viral hepatitis. 2015;(12):992-1001
Abstract
Favourable efficacy and safety profiles for simeprevir in combination with pegylated interferon alpha (PEG-IFNα) and ribavirin (triple therapy) have been shown in clinical trials. This study was carried out to evaluate the effectiveness of simeprevir-based triple therapy for patients with prior telaprevir treatment failure. This multicentre, observational cohort consisted of 345 consecutive Japanese patients infected with HCV genotype 1b, including 20 who had experienced telaprevir-based triple therapy. Amino acid substitutions in the NS3/4A region were identified by direct sequencing at the time of relapse or breakthrough in treatment with telaprevir and at the initiation of treatment with simeprevir. Patients were stratified according to prior response to PEG-IFNα and ribavirin. Of the 20 patients with telaprevir treatment failure, 10 (50.0%) achieved sustained virological response at week 12 after the end of treatment (SVR12). For patients treatment naïve [3/4 (75.0%)] or with prior relapse [1/1 (100%)] or partial response [5/6 (83.3%)] to PEG-IFNα and ribavirin, almost all achieved SVR12, mainly because of the improvement of treatment adherence, especially to direct-acting antiviral agent and ribavirin. However, of the nine patients with prior null response to PEG-IFNα and ribavirin, only one (11.1%) achieved SVR12, despite all having received an adequate treatment dosage, and five (55.6%) achieved rapid virological response. The treatment outcome of simeprevir-based triple therapy for HCV genotype 1b patients with prior telaprevir failure depended on the prior response to PEG-IFNα and ribavirin. For patients with prior null response to PEG-IFNα and ribavirin, retreatment with simeprevir-based triple therapy is not a useful option.
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Renal dysfunction associated with telaprevir-containing triple therapy for chronic hepatitis C: is early prediction possible?
Rémy, AJ, Lesgourgues, B, Nalet, B, Causse, X, Henrion, J, Denis, J, Arotçarena, R, Hagège, H, Pariente, A, ,
European journal of gastroenterology & hepatology. 2014;(9):996-1002
Abstract
INTRODUCTION Renal dysfunction has recently been described as a potential complication of tritherapy with telaprevir (TVR) in patients with chronic hepatitis C. This study aimed to identify predictive factors for and consequences of TVR-associated renal dysfunction. PATIENTS AND METHODS A retrospective-prospective study was carried out in 96 patients with chronic hepatitis C, genotype 1, treated with TVR-based tritherapy in 2012-2013, in whom regular serum creatinine measurements were performed during the first 12 weeks of treatment. The patients received standard doses of peginterferon, ribavirin and TVR (2250 mg/day). The estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease formula. RESULTS eGFR decreased significantly from baseline at weeks 4, 8 and 12, the mean maximum decrease being 22.0±23.6 ml/min, with a significant correlation between baseline and minimum eGFR (r=0.58, P<10), stronger between week 2 and minimum eGFR in the subgroup of 62 patients in whom creatinine measurement was performed at week 2. Thirteen patients had an eGFR below 60 ml/min during treatment. Age and baseline eGFR were independent predictors of eGFR below 60 ml/min in the entire population, and only week 2 eGFR when available. The decrease in haemoglobin was significantly correlated with the decrease in eGFR. Age, baseline haemoglobin and the maximum variation in eGFR were independent predictors for minimum haemoglobin. The patients with decreased eGFR had more severe anaemia, and received more blood transfusions and erythropoietin. Renal dysfunction regressed in all patients after stopping TVR. CONCLUSION The reversible decrease in eGFR in patients receiving TVR-containing tritherapy can be predicted early, possibly allowing measures aimed at preventing anaemia.