The changing landscape of hepatitis C virus therapy: focus on interferon-free treatment

Abstract

Chronic hepatitis C (CHC) affects over 185 million individuals worldwide, approximately 3% of the world's population. CHC can lead to quality of life impairment, cirrhosis, hepatocellular carcinoma (HCC), liver failure and liver-related death. While CHC has been associated with increases in HCC, liver-related mortality and all-cause mortality, being cured of CHC is associated with improvement in these outcomes. Older interferon-based regimens were complex and toxic and required 6-12 months of therapy, with cure rates averaging around 40-45% for HCV genotype 1. Newer interferon-free regimens are now available in the US, Europe, Japan and in other countries. These regimens have short durations, minimal side effects, low pill burden and efficacy approaching 90-100%. We may eventually see single-tablet regimens lasting no more than 4-6 weeks. This review will summarize the data regarding these interferon-free regimens, including Gilead's Harvoni (sofosbuvir/ledipasvir), AbbVie's Viekira Pak (paritaprevir/ritonavir/ombitasvir with dasabuvir), and Janssen's Olysio (simeprevir) with sofosbuvir. Some practical considerations as we move into an interferon-free era will also be discussed, such as patient adherence and drug-drug interactions.

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-2017 Update

“…Genel olarak etki ettikleri genom bölgesine göre [1] NS3/4 gen bölgesi proteinlerini etkileyen proteaz inhibitörleri, [2] NS5A gen bölgesi inhibitörleri ve [3] NS5B gen bölgesinde kodlanan RNA'ya bağımlı RNA polimeraz ("reverse" transkriptaz) enzim inhibitörleri olmak üzere üç grupta toplanırlar (64). KHC tedavisinde kullanılan Sofosbuvir SOF, HCV RNA'ya bağımlı RNA polimeraz enziminin pangenotipik inhibitörüdür.…”

Evaluation of 53 Cases With Chronic Hepatitis C Receiving Telaprevir-Based Triple Therapy

“…DEA ajanlar HCV'nin replikasyon siklusunu farklı basamaklarda inhibe ederler. Etki ettikleri ge- nom bölgesine göre NS3/4 gen bölgesi proteinlerini etkileyen proteaz inhibitörleri, NS5A gen bölgesi inhibitörleri ve NS5B gen bölgesinde kodlanan RNA'ya bağımlı RNA polimeraz ("reverse" transkriptaz) enzim inhibitörleri olmak üzere üçe ayrılırlar (14). 311'i naif, 148'i tedavi deneyimli 459 nonsirotik hastadan oluşan bir faz 3 çalışmada ombitasvir/paritaprevir/ ritonavir ve dasabuvir ± ribavirin (OBV/PTV/r + DSV±RBV) ile telaprevir + PegIFN/RBV kombinasyonları karşılaştırılmış olup KVY oranları sırasıyla %97 ve %82 olarak saptanmıştır.…”

Broadly neutralizing antibodies for therapy of viral infections

“…Both these therapies have disadvantages with regard to the many side effects associated with interferons, and with the PIs being limited to patients infected with genotype 1. 38,39 Small molecules including nucleoside and nucleotide NS5B polymerase inhibitors such as Sovaldi ® (Gilead, Foster City, CA, USA) have provided relief across all genotypes. Given the success of these small-molecules inhibitors, bNAbs that can target the HCV GP E2 would not be the first therapeutic option.…”