Differential inhibition features of direct-acting anti-hepatitis C virus agents against human organic anion transporting polypeptide 2B1
Direct-acting antiviral (DAA) agents are orally administered drugs that strongly inhibit hepatitis C virus (HCV) protein functions. The introduction of the DAAs telaprevir (TLV) and boceprevir (BOC) has resulted in significant improvements in therapeutic success rates [1]. In addition, the more recently developed agents, including simeprevir (SMV), asunaprevir (ASV), daclatasvir (DCV) and sofosbuvir (SOF), are expected to further advance the success rates of sustained virological response to >80% owing to their higher efficacy and the lower risk of severe adverse effects [2]. (Source: International Journal of Antimicrobial Agents)
Source: International Journal of Antimicrobial Agents - June 24, 2015 Category: Drugs & Pharmacology Authors: Tomomi Furihata, Zhongguo Fu, Yuki Suzuki, Shogo Matsumoto, Hanae Morio, Akihito Tsubota, Sayaka Matsumoto, Kan Chiba Source Type: research
Betulinic acid exerts anti‐hepatitis C virus activity via the suppression of NF‐κB and MAPK‐ERK1/2‐mediated cyclooxygenase‐2 expression
Conclusions and implicationsBA inhibits HCV replication through the suppression of NF‐κB and the ERK1/2‐mediated COX‐2 pathway and may serve as a promising compound for drug development or as a potential supplement for use in the treatment of HCV‐infected patients. (Source: British Journal of Pharmacology)
Source: British Journal of Pharmacology - June 23, 2015 Category: Drugs & Pharmacology Authors: Chun‐Kuang Lin, Chin‐Kai Tseng, Kai‐Hsun Chen, Shih‐Hsiung Wu, Chih‐Chuang Liaw, Jin‐Ching Lee Tags: Research Paper Source Type: research
Protease inhibitors‐based therapy induces acquired spherocytic‐like anemia and ineffective erythropoiesis in chronic HCV patients
ConclusionsThe bimodal pattern of anemia in chronic HCV patients on triple therapy might be due to acquired spherocytic‐like anemia in the early phase, followed by hyporegenerative anemia, most likely related to the combined effects of PR and TRV or BOC on erythropoiesis.This article is protected by copyright. All rights reserved. (Source: Liver International)
Source: Liver International - June 22, 2015 Category: Gastroenterology Authors: Francesca Lupo, Roberta Russo, Achille Iolascon, Donatella Ieluzzi, Angela Siciliano, Pierluigi Toniutto, Alessandro Matte’, Sara Piovesan, Elena Raffetti, Francesco Turrini, Denis Dissegna, Francesco Donato, Alfredo Alberti, Valeria Zuliani, Giovanna F Tags: Original Article Source Type: research
Costs and Resource Utilization Associated With Anemia and Rash in Chronic Hepatitis C Patients Treated With Direct-Acting Antiviral Agents in the United States.
Abstract
PURPOSE: The addition of 2 direct-acting antiviral (DAA) agents, telaprevir and boceprevir, to peginterferon and ribavirin therapy significantly improves sustained virologic response rates in patients treated for chronic hepatitis C virus (CHC) but is associated with a higher risk of adverse events (AEs), including anemia and rash. Using a large administrative claims database, this study compared the health care resource utilization and costs among CHC patients who developed anemia and/or rash while receiving DAA-based therapies (telaprevir and boceprevir) versus those who did not develop anemia o...
Source: Clinical Therapeutics - June 22, 2015 Category: Drugs & Pharmacology Authors: Le TK, Macaulay D, Kalsekar A, Yuan Y, Sorg RA, Wei J, Wu EQ Tags: Clin Ther Source Type: research
Telaprevir versus simeprevir for the treatment of recurrent hepatitis C after living donor liver transplantation
In conclusion, SMV‐based triple therapy was associated with fewer adverse events and drug interactions with cyclosporine, and possibly less antiviral properties to TVR. Interferon‐mediated graft dysfunction is a significant clinical problem that warrants particular caution following living donor liver transplantation. (Source: Hepatology Research)
Source: Hepatology Research - June 19, 2015 Category: Internal Medicine Authors: Toru Ikegami, Tomoharu Yoshizumi, Yoshihro Yoshida, Takeshi Kurihara, Norifumi Harimoto, Shinji Itoh, Masahiro Shimokawa, Takasuke Fukuhara, Ken Shirabe, Yoshihiko Maehara Tags: Original Article Source Type: research
Naturally Occurring Resistance-Associated Variants of Hepatitis C Virus Protease Inhibitors in Poor Responders to Pegylated Interferon-Ribavirin [Virology]
The pretherapeutic presence of protease inhibitor (PI) resistance-associated variants (RAVs) has not been shown to be predictive of triple-therapy outcomes in treatment-naive patients. However, they may influence the outcome in patients with less effective pegylated interferon (pegIFN)-ribavirin (RBV) backbones. Using hepatitis C virus (HCV) population sequence analysis, we retrospectively investigated the prevalence of baseline nonstructural 3 (NS3) RAVs in a multicenter cohort of poor IFN-RBV responders (i.e., prior null responders or patients with a viral load decrease of <1 log IU/ml during the pegIFN-RBV lead-in ph...
Source: Journal of Clinical Microbiology - June 18, 2015 Category: Microbiology Authors: Larrat, S., Vallet, S., David-Tchouda, S., Caporossi, A., Margier, J., Ramiere, C., Scholtes, C., Haim-Boukobza, S., Roque-Afonso, A.-M., Besse, B., Andre-Garnier, E., Mohamed, S., Halfon, P., Pivert, A., LeGuillou-Guillemette, H., Abravanel, F., Guivarch Tags: Virology Source Type: research
Formal Synthesis of Telaprevir
Synfacts 2015; 11: 0684-0684DOI: 10.1055/s-0034-1380904© Georg Thieme Verlag Stuttgart · New YorkArticle in Thieme eJournals:Table of contents | Full text (Source: Synfacts)
Source: Synfacts - June 17, 2015 Category: Chemistry Tags: Synthesis of Natural Products and Potential Drugs Source Type: research
Effectiveness of triple therapy with simeprevir for chronic hepatitis C genotype 1b patients with prior telaprevir failure
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 p...
Source: Journal of Viral Hepatitis - June 15, 2015 Category: Infectious Diseases Authors: E. Ogawa, N. Furusyo, K. Dohmen, E. Kajiwara, A. Kawano, H. Nomura, K. Takahashi, T. Satoh, K. Azuma, M. Nakamuta, T. Koyanagi, K. Kotoh, S. Shimoda, J. Hayashi, Tags: Original Article Source Type: research
High Frequency of Severe Telaprevir-associated Skin Eruptions in Clinical Practice.
Abstract
Since the introduction of telaprevir, administered in combination with pegylated interferon and ribavirin for the treatment of patients with chronic hepatitis C, the incidence and severity of skin eruptions have increased significantly. The aim of this prospective study is to assess the frequency of drug-induced skin eruptions and their clinical and histological characteristics in patients who received the above treatment in daily clinical practice at our hospital. A total of 60 patients was included. The frequency of telaprevir-associated skin eruptions was 48.3%, which is slightly below, but clo...
Source: Acta Dermato-Venereologica - June 15, 2015 Category: Dermatology Authors: Carrascosa R, Capusan TM, Llamas-Velasco M, García-Buey L, Gordillo C, Sánchez-Pérez J Tags: Acta Derm Venereol Source Type: research
Comparative effectiveness and safety study of triple therapy with simeprevir or telaprevir for non‐cirrhotic patients with chronic hepatitis C virus genotype 1b infection
ConclusionsConsidering the effectiveness and safety, simeprevir‐based triple therapy will continue to be a useful treatment option in Japan for treatment‐naïve or prior relapse patients with a favorable IL28B genotype. (Source: Journal of Gastroenterology and Hepatology)
Source: Journal of Gastroenterology and Hepatology - June 11, 2015 Category: Gastroenterology Authors: Eiichi Ogawa, Norihiro Furusyo, Eiji Kajiwara, Hideyuki Nomura, Akira Kawano, Kazuhiro Takahashi, Kazufumi Dohmen, Takeaki Satoh, Koichi Azuma, Makoto Nakamuta, Toshimasa Koyanagi, Kazuhiro Kotoh, Shinji Shimoda, Jun Hayashi, Tags: Original Article ‐ Hepatology (Clinical) Source Type: research
Hepatitis C virus: Virology, diagnosis and treatment.
Authors: Li HC, Lo SY
Abstract
More than twenty years of study has provided a better understanding of hepatitis C virus (HCV) life cycle, including the general properties of viral RNA and proteins. This effort facilitates the development of sensitive diagnostic tools and effective antiviral treatments. At present, serologic screening test is recommended to perform on individuals in the high risk groups and nucleic acid tests are recommended to confirm the active HCV infections. Quantization and genotyping of HCV RNAs are important to determine the optimal duration of anti-viral therapy and predict the like...
Source: World Journal of Hepatology - June 10, 2015 Category: Gastroenterology Tags: World J Hepatol Source Type: research
Antiviral therapies for chronic hepatitis C virus infection with cirrhosis.
Authors: Nakamoto S, Kanda T, Shirasawa H, Yokosuka O
Abstract
Patients who are infected with hepatitis C virus (HCV) and also have advanced fibrosis or cirrhosis have been recognized as "difficult-to-treat" patients during an era when peginterferon and ribavirin combination therapy is the standard of care. Recent guidelines have clearly stated that treatment should be prioritized in this population to prevent complications such as decompensation and hepatocellular carcinoma. Recent advances in the treatment of chronic hepatitis C have been achieved through the development of direct-acting antiviral agents...
Source: World Journal of Hepatology - June 10, 2015 Category: Gastroenterology Tags: World J Hepatol Source Type: research
Dermatologic adverse events of protease inhibitor-based combination therapy in patients with chronic hepatitis C.
CONCLUSIONS: In patients with chronic hepatitis C who received the triple therapy, the anorectal paresthesias were observed only in patients treated with telaprevir. The predisposing factors for this adverse event were: female gender and advanced liver fibrosis. The risk factors for other dermatological adverse were: 1) being a male over 45 years, for skin rashes and pruritus (for telaprevir), 2) coexistence of autoimmune thyroiditis for skin rashes (for boceprevir), 3) being a female, for pruritus (for boceprevir).
PMID: 25621089 [PubMed] (Source: Journal of Dermatological Case Reports)
Source: Journal of Dermatological Case Reports - June 4, 2015 Category: Dermatology Tags: J Dermatol Case Rep Source Type: research
The clinical significance of HCV core antigen detection during Telaprevir/Peg-Interferon/Ribavirin therapy in patients with HCV 1 genotype infection
Hepatitis C virus (HCV) is a worldwide public health problem and the main cause of chronic liver disease with an estimated 170 million people infected worldwide [1]. Chronic HCV patients are at high risk for progressive hepatic fibrosis and cirrhosis, with consequent indication for liver transplantation [2]. In 2011, the first HCV protease inhibitors, telaprevir (TPV) and boceprevir (BOC), were approved for use in combination with Peg-IFN and RBV for genotype 1HCV infection. This new therapeutic regimen improved the SVR rate among patients with genotype 1, both naïve (65-75%) and non-responder (30%) to standard of care (S...
Source: Journal of Clinical Virology - June 4, 2015 Category: Virology Authors: Anna Rosa Garbuglia, Raffaella Lionetti, Daniele Lapa, Chiara Taibi, Ubaldo Visco-Comandini, Marzia Montalbano, Gianpiero D'Offizi, Filippo Castiglione, Maria Rosaria Capobianchi, Paola Paci Source Type: research
Management of telaprevir-based triple therapy for hepatitis C virus recurrence post liver transplant.
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.
PMID: 26019745 [PubMed] (Source: World Journal of Hepatology)
Source: World Journal of Hepatology - May 30, 2015 Category: Gastroenterology Tags: World J Hepatol Source Type: research
