The advancement in hepatitis C virus (HCV) therapeutics has been profoundly enhanced by an improved understanding of viral life cycle in host cells, development of novel direct-acting antivirals (DAAs), and exploring other emerging treatment paradigms on the horizon. The approvals of first-, second-, and next-wave direct-acting antivirals highlight the swift pace of progress in the successful development of an expanding variety of therapeutic regimens for use in patients with chronic hepatitis C virus infection. Triple or quadruple therapies based on a combination of different direct-acting antivirals with or without pegylated interferon (IFN) and ribavirin (RBV) have raised the hopes to improve the current treatment strategies for other difficult-to-treat individuals. The development of more efficacious, well-tolerated, and cost-effective interferons with a low frequency of adverse events and short treatment durations is also in the pipeline. An experimental protective vaccine against hepatitis C virus demonstrated promise in preliminary human safety trials, and a larger phase II clinical trials are under consideration to further determine the efficacy of the vaccine. This pragmatic book chapter discusses the current state of knowledge in hepatitis C virus therapeutics and provides a conceptual framework of emerging and investigational treatment strategies directed against this silent epidemic.
Part of the book: Advances in Treatment of Hepatitis C and B
Angiogenesis, a natural phenomenon of developing new blood vessels, is an integral part of normal developmental processes as well as numerous pathological states in humans. The angiogenic assays are reliable predictors of certain pathologies in particular tumor growth, metastasis, inflammation, wound healing, tissue regeneration, ischemia, cardiovascular, and ocular diseases. The angiogenic inducer and inhibitor studies rely on both in vivo and in vitro angiogenesis methods, and various animal models are also standardized to assess qualitative and quantitative angiogenesis. Analogously, the discovery and development of anti-angiogenic agents are also based on the choice of suitable angiogenic assays and potential drug targeted sites within the angiogenic process. Similarly, the selection of cell types and compatible experimental conditions resembling the angiogenic disease being studied are also potential challenging tasks in recent angiogenesis studies. The imaging analysis systems for data acquisition from in vivo, in vitro, and in ova angiogenesis assay to preclinic, and clinical research also requires novel but easy-to-use tools and well-established protocols. The proposition of this pragmatic book chapter overviews the recent advances in angiogenesis assessment methods and discusses their applications in numerous disease pathogenesis.
Part of the book: Physiologic and Pathologic Angiogenesis
The expanded classification of hepatitis C virus (HCV) genome into various genotypes and numerous subtypes significantly correlates to therapeutic outcomes of interferon-free direct-acting antivirals (DAAs) in HCV treated patients. In particular, genotypes 3 and 4 are still harder to treat, and higher sustained virologic response (SVR) rates are not achieved in some difficult-to-treat specific populations (i.e., HCV subtype 1a patients, compensated and decompensated cirrhotic patients, HCV/HIV co-infection, and prior treatment failure with pegylated interferon plus ribavirin and first-generation protease inhibitor based therapeutic regimens). Furthermore, the pre-existing and treatment-emergent resistance associated substitutions (RAS) at specific amino acid positions within the viral quasispecies may increase the chances of viral breakthrough (HCV RNA remains lower limit of quantification, but increased to 100 IU/mL or 1.log10 during DAAs therapy), viral relapse (undetectable viral load at the end of treatment but positive within the follow-up of 6 months), and discontinuation of therapy in treated individuals. Although the clinical importance of RAS is not entirely elucidated, it is believed that such substitutions decrease the therapeutic efficacy of DAAs in treated individuals. Similarly, the emergence of multiclass hepatitis C virus resistance to interferon-free DAAs failure in real-world experiences demands eagerly tailored second-line anti-hepatitis C therapies. This book chapter comprehensively overviews the clinical correlation of HCV genotypes, viral quasispecies and harboring RAS to treatment outcomes of revolutionary interferon-free DAAs in hepatitis C-treated patients.
Part of the book: Genotyping