Hepatitis C therapy in non‐genotype 1 patients: the near future

Abstract

Worldwide, 50-70 million subjects are infected with an hepatitis C virus (HCV) genotype 2, 3, 4, 5 or 6. In these patients, the combination of PEG-INF-α and ribavirin remains the currently approved standard-of-care treatment. The identification of different potential therapeutic targets in the HCV life cycle has led to the development of both direct antiviral agents (DAAs) and reagents targeting host functions essential for viral replication. DAAs comprise so far first-generation, second-wave and second-generation NS3/4A protease inhibitors (PIs), nucleos(t)ide (NIs) and non-nucleoside inhibitors of the NS5B RNA polymerase and NS5A complex inhibitors. The main host-protein-directed antiviral agents are cyclophilin inhibitors and silibinin. Whereas the launch of first-generation PIs was a major landmark in the management of genotype 1 (GT-1)-infected patients, these drugs are inactive in most non-GT-1-infected patients. Several of these and other drugs have now reached phase II and even phase III clinical stage development. The purpose of this article is to provide an overview of the clinical results recently reported for the treatment for non-GT-1 HCV infection with a focus on the most promising new compounds and combinations.

Approaches to hepatitis C treatment and cure using NS5A inhibitors

“…According to the World Health Organization, six major HCV genotypes and several subtypes have been identified throughout the world. Subtypes 1a/b account for approximately 70% of all infections in the US, Europe, China and Japan,11 and the remainder are generally genotype 2, 3, and 4 12. The HCV genotype strongly predicts the response to the currently approved HCV treatments.…”

Saikosaponin b2 is a naturally occurring terpenoid that efficiently inhibits hepatitis C virus entry

“…Alternatively, liver transplantation is compounded by issues of donor shortage, graft rejection risk, recurrent infections, and absence of adequate therapy against reinfection [3]. While novel protease inhibitors such as Boceprevir and Telaprevir have been approved for treatment against hepatitis C, these drugs lack pan-genotype activity and are associated with drug toxicity and development of resistant mutants [4,5]. Furthermore, new improved second generation drugs, such as Simprevir, Sofosbuvir, and Daclatasvir, promise to be extremely expensive for managing chronic infections, making accessibility of therapy a potential difficulty.…”

Management of Chronic Hepatitis C Virus Infection: A Consensus Report of the Study Group for Viral Hepatitis of the Turkish Society of Clinical Microbiology and Infectious Diseases

“…SOF dozu tüm genotiplerde 400 mg/gün olarak önerilmektedir (98). Tedaviye yanıt olasılığını azaltan belirteçlerin (vücut kitle indeksi >25, insülin direnci, metabolik sendrom, ileri düzey fibroz, ileri yaş) bulunduğu olgularda kiloya ayarlı RBV tedavisinin KVY oranlarını artırdığı gösterilmiştir (120).…”