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Acta Pharmaceutica Sinica. B Jan 2016Unlike human immunodeficiency virus (HIV) and hepatitis B virus (HBV), hepatitis C virus (HCV) infection is a curable disease. Current direct antiviral agent (DAA)... (Review)
Review
Unlike human immunodeficiency virus (HIV) and hepatitis B virus (HBV), hepatitis C virus (HCV) infection is a curable disease. Current direct antiviral agent (DAA) targets are focused on HCV NS3/4A protein (protease), NS5B protein (polymerase) and NS5A protein. The first generation of DAAs includes boceprevir and telaprevir, which are protease inhibitors and were approved for clinical use in 2011. The cure rate for genotype 1 patients increased from 45% to 70% when boceprevir or telaprevir was added to standard PEG-IFN/ribavirin. More effective and less toxic second generation DAAs supplanted these drugs by 2013. The second generation of DAAs includes sofosbuvir (Sovaldi), simeprevir (Olysio), and fixed combination medicines Harvoni and Viekira Pak. These drugs increase cure rates to over 90% without the need for interferon and effectively treat all HCV genotypes. With these drugs the "cure HCV" goal has become a reality. Concerns remain about drug resistance mutations and the high cost of these drugs. The investigation of new HCV drugs is progressing rapidly; fixed dose combination medicines in phase III clinical trials include Viekirax, asunaprevir+daclatasvir+beclabuvir, grazoprevir+elbasvir and others.
PubMed: 26904396
DOI: 10.1016/j.apsb.2015.09.008 -
Hospital Pharmacy Sep 2013Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The...
Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. A drug class review is now published monthly with The Formulary Monograph Service. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, call The Formulary at 800-322-4349. The September 2013 monograph topics are trametinib, simeprevir, paroxetine mesylate, and empagliflozin. The DUE/MUE is on aripiprazole.
PubMed: 24421538
DOI: 10.1310/hpj4808-668 -
BMJ Clinical Evidence Jun 2015About 60% to 85% of people infected with hepatitis C virus will go on to develop chronic hepatitis C, which is now believed to affect 3% of the world's population. (Review)
Review
INTRODUCTION
About 60% to 85% of people infected with hepatitis C virus will go on to develop chronic hepatitis C, which is now believed to affect 3% of the world's population.
METHODS AND OUTCOMES
We conducted a systematic overview and aimed to answer the following clinical questions: What are the effects of interferon-free treatments in treatment-naïve people with chronic hepatitis C infection without cirrhosis? What are the effects of interferon-free treatments in treatment-naïve people with chronic hepatitis C infection with cirrhosis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this review).
RESULTS
After deduplication and removal of conference abstracts, 30 records were screened for inclusion in the review. Appraisal of titles and abstracts led to the exclusion of 11 studies and the further review of 19 full publications. Of the 19 full articles evaluated, two systematic reviews and one RCT were added. We performed a GRADE evaluation for two PICO combinations.
CONCLUSIONS
In this systematic overview, we categorised the efficacy for 12 different intervention/comparison combinations, based on information relating to the effectiveness and safety of sofosbuvir (with or without ribavirin), sofosbuvir (with or without ribavirin) plus ledipasvir, and sofosbuvir (with or without ribavirin) plus simeprevir, all in people with and without cirrhosis.
Topics: Antiviral Agents; Hepatitis C, Chronic; Humans; Treatment Outcome
PubMed: 26107930
DOI: No ID Found -
International Journal of Molecular... Mar 2015The current treatments for chronic hepatitis C virus (HCV) genotype 1 infection are combinations of direct-acting antivirals, and faldaprevir is one of the new... (Review)
Review
The current treatments for chronic hepatitis C virus (HCV) genotype 1 infection are combinations of direct-acting antivirals, and faldaprevir is one of the new generation of HCV NS3/4A protease inhibitors. At the end of 2013, the US Food and Drug Administration (FDA) approved the HCV NS3/4A protease inhibitor simeprevir and the HCV NS5B polymerase inhibitor sofosbuvir. Simeprevir or sofosbuvir in combination with pegylated interferon and ribavirin are available for clinical use. Faldaprevir, another HCV NS3/4A protease inhibitor that also has fewer adverse events than telaprevir or boceprevir, is under development. Of interest, faldaprevir in combination with pegylated interferon and ribavirin, and interferon-free treatment with faldaprevir in combination with deleobuvir plus ribavirin provides high sustained virological response rates for HCV genotype 1 infection. The aim of this article is to review these data concerning faldaprevir. Faldaprevir in combination with pegylated interferon and ribavirin treatment appears to be associated with fewer adverse events than telaprevir or boceprevir in combination with pegylated interferon and ribavirin, and may be one of the therapeutic options for treatment-naive patients with HCV genotype 1. The interferon-free combination of faldaprevir and deleobuvir with ribavirin was effective for HCV genotype 1 infection and may hold promise for interferon-ineligible and interferon-intolerant patients.
Topics: Aminoisobutyric Acids; Antiviral Agents; Drug Therapy, Combination; Hepacivirus; Hepatitis C; Humans; Interferon-alpha; Leucine; Oligopeptides; Polyethylene Glycols; Proline; Quinolines; Thiazoles; Viral Nonstructural Proteins
PubMed: 25749475
DOI: 10.3390/ijms16034985 -
Visceral Medicine Apr 2016Treatment of chronic hepatitis C infection is most urgent in patients with severe liver fibrosis and cirrhosis because of the high risk of decompensation, hepatocellular... (Review)
Review
BACKGROUND
Treatment of chronic hepatitis C infection is most urgent in patients with severe liver fibrosis and cirrhosis because of the high risk of decompensation, hepatocellular carcinoma, and consecutively death. The development and approval of several direct-acting antiviral drugs (DAA) in the past years has revolutionized antiviral therapy especially for patients with liver cirrhosis.
METHODS
This review will focus on recent data from clinical trials and recommendations for the therapy of hepatitis C-infected patients with compensated cirrhosis.
RESULTS
Clinical data for cirrhotic patients mainly exist for a combination of the nucleotide analog sofosbuvir with either a protease inhibitor (simeprevir) or an NS5A inhibitor (daclatasvir, ledipasvir) or a three-DAA combination consisting of an NS3 protease inhibitor, an NS5A inhibitor, and a non-nucleoside NS5B inhibitor (paritaprevir/ritonavir, ombitasvir, and dasabuvir). Rates of sustained virologic response in patients with compensated cirrhosis are comparable to patients without cirrhosis; however, the addition of ribavirin and/or longer treatment durations are especially recommended when other negative predictors are present, such as prior treatment failure, features of advanced cirrhosis, or the presence of baseline resistance.
CONCLUSION
Nowadays, a highly active, short, and safe interferon-free treatment regimen is available for almost all patients.
PubMed: 27413726
DOI: 10.1159/000445330