Update on hepatitis C: Direct-acting antivirals

Seifert, Leon Louis; Perumpail, Ryan B.; Ahmed, Aijaz

doi:10.4254/wjh.v7.i28.2829

Cited by 34 publications

(26 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since the release of the first generation DAA's in 2011 there has been an explosion in the number and combination of DAA's available. Clinical trials have consistently reported SVR 12 rates >95% for most patient populations, including those patients co-infected with HIV, which have been supported by recent real world data (12)(13)(14). Treatment guidelines maintained as a living document online by the collaboration of American Association for the Study of Liver Disease (AASLD) and the Infectious Diseases Society of America (IDSA) are rapidly changing, however all oral DAA therapy is now the standard of care for all patient populations (15).…”

supporting

confidence: 54%

C-WORTHY: the beginning of the rise of elbasvir and grazoprevir for the treatment of hepatitis C genotype 1 mono and HIV co-infected patients

Sarpel

Dieterich

2016

Ann. Transl. Med.

View full text Add to dashboard Cite

supporting

confidence: 54%

C-WORTHY: the beginning of the rise of elbasvir and grazoprevir for the treatment of hepatitis C genotype 1 mono and HIV co-infected patients

Sarpel

Dieterich

2016

Ann. Transl. Med.

View full text Add to dashboard Cite

“…The standard-of-care therapy against HCV consists of pegylated alpha interferon (peg-IFN-␣) and ribavirin, which can cure approximately 50% of HCV-infected patients. Direct-acting antivirals (DAAs) have recently been used and have increased the cure rate to about 90% (3). Therefore, the development of an HCV vaccine and the identification of host factors for new anti-HCV targets remain significant challenges.…”

mentioning

confidence: 99%

Prolactin Regulatory Element Binding Protein Is Involved in Hepatitis C Virus Replication by Interaction with NS4B

Kong

Fujimoto

Nakamura

et al. 2016

J Virol

View full text Add to dashboard Cite

It has been proposed that the hepatitis C virus (HCV) NS4B protein triggers the membranous HCV replication compartment, but the underlying molecular mechanism is not fully understood. Here, we screened for NS4B-associated membrane proteins by tandem affinity purification and proteome analysis and identified 202 host proteins. Subsequent screening of replicon cells with small interfering RNA identified prolactin regulatory element binding (PREB) to be a novel HCV host cofactor. The interaction between PREB and NS4B was confirmed by immunoprecipitation, immunofluorescence, and proximity ligation assays. PREB colocalized with double-stranded RNA and the newly synthesized HCV RNA labeled with bromouridine triphosphate in HCV replicon cells. Furthermore, PREB shifted to detergent-resistant membranes (DRMs), where HCV replication complexes reside, in the presence of NS4B expression in Huh7 cells. However, a PREB mutant lacking the NS4B-binding region (PREBd3) could not colocalize with double-stranded RNA and did not shift to the DRM in the presence of NS4B. These results indicate that PREB locates at the HCV replication complex by interacting with NS4B. PREB silencing inhibited the formation of the membranous HCV replication compartment and increased the protease and nuclease sensitivity of HCV replicase proteins and RNA in DRMs, respectively. Collectively, these data indicate that PREB promotes HCV RNA replication by participating in the formation of the membranous replication compartment and by maintaining its proper structure by interacting with NS4B. Furthermore, PREB was induced by HCV infection in vitro and in vivo. Our findings provide new insights into HCV host cofactors. IMPORTANCEThe hepatitis C virus (HCV) protein NS4B can induce alteration of the endoplasmic reticulum and the formation of a membranous web structure, which provides a platform for the HCV replication complex. The molecular mechanism by which NS4B induces the membranous HCV replication compartment is not understood. We screened for NS4B-associated membrane proteins by tandem affinity purification and proteome analysis, followed by screening with small interfering RNA. We identified prolactin regulatory element binding (PREB) to be a novel HCV host cofactor. PREB is induced by HCV infection and recruited into the replication complex by interaction with NS4B. Recruited PREB promotes HCV RNA replication by participating in the formation of the membranous HCV replication compartment. To our knowledge, the effect of NS4B-binding protein on the formation of the membranous HCV replication compartment is newly described in this report. Our findings are expected to provide new insights into HCV host cofactors. H epatitis C virus (HCV) infects about 2% of the world's population and leads to several diseases, including chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). HCV is the most common reason for patients requiring a liver transplant in developed countries and is thus a significant health burden worldwide (1). To date,...

show abstract

“…Ombitasvir is approved for treatment of genotype 1 in combination with paritaprevir, ritonavir, and dasabuvir. Ledipasvir is approved for genotypes 1, 3, and 4 in combination with sofosbuvir +/− RBV [20]. Velpatasvir in combination with sofosbuvir was approved in June 2016 by the FDA and became the first regimen approved for genotypes 1-6 [21].…”

Section: Ns5a Inhibitorsmentioning

confidence: 99%

A Brief Update on the Treatment of Hepatitis C

Austria¹,

Ninčević²,

Wu³

2017

Update on Hepatitis C

View full text Add to dashboard Cite

Hepatitis C virus was discovered nearly 30 years ago, and for the first two decades, treatment was limited to agents with low response rates and substantial side effects. Since the introduction of direct-acting antivirals, there have been rapid advances made toward even higher sustained virologic responses (SVRs) and fewer side effects. This chapter provides a review of the newer agents for treatment of hepatitis C and highlights special populations, including those coinfected with HIV or hepatitis B, previously treated patients, and post-liver transplant patients.

show abstract

Update on hepatitis C: Direct-acting antivirals

Cited by 34 publications

References 39 publications

C-WORTHY: the beginning of the rise of elbasvir and grazoprevir for the treatment of hepatitis C genotype 1 mono and HIV co-infected patients

C-WORTHY: the beginning of the rise of elbasvir and grazoprevir for the treatment of hepatitis C genotype 1 mono and HIV co-infected patients

Prolactin Regulatory Element Binding Protein Is Involved in Hepatitis C Virus Replication by Interaction with NS4B

A Brief Update on the Treatment of Hepatitis C

Contact Info

Product

Resources

About