Help
Subscribe


All of GastroHep is now free access! - Click here to register Read For FREE - Our full range of review articles
GastroHep.com - the global online resource for all aspects of gastroenterology, hepatology and endoscopy
GastroHep.com - the global online resource for all aspects of gastroenterology, hepatology and endoscopy Profile of Guido Tytgat Profile of Pete Peterson Profile of Peter Cotton Profile of Roy Pounder

Home

News  
Journals
Review Articles
Slide Atlas
Video Clips
Online Books
Advanced Digestive Endoscopy
Classical Cases
Conference Diary
PubMed
International GH Links
USA GH Links
National GH Links
National GI Societies
Other Useful Links




Emails on Gastroenterology and Hepatology
the National AIDS Treatment Advocacy Project
Visit the gastroenterology section of the EUMS

News

Emerging resistance using sequential direct-acting antiviral agents for Hepatitis C

A translational study published in the latest issue of the American Journal of Gastroenterology investigates resistance emergence using sequential direct-acting antiviral agents for Hepatitis C using ultra-deep sequencing.

News image

Direct-acting antiviral agents against hepatitis C virus (HCV) have recently been developed and are ultimately hoped to replace interferon-based therapy.

However, direct-acting antiviral agents monotherapy results in rapid emergence of resistant strains and direct-acting antiviral agents must be used in combinations that present a high genetic barrier to resistance, although viral kinetics of multidrug-resistant strains remain poorly characterized.

Dr Kazuaki Chayama and colleagues from Japan studied the emergence and fitness of resistance using combinations of telaprevir and NS5A or NS5B inhibitors with genotype 1b clones.

HCV-infected chimeric mice were treated with direct-acting antiviral agents, and resistance was monitored using direct and ultra-deep sequencing.

NS3-V36A telaprevir resistance mutation resulted in poor response to telaprevir monotherapy
American Journal of Gastroenterology

Combination therapy with telaprevir and BMS-788329 (NS5A inhibitor) reduced serum HCV RNA to undetectable levels.

The team noted that presence of an NS3-V36A telaprevir resistance mutation resulted in poor response to telaprevir monotherapy but showed significant HCV reduction when telaprevir was combined with BMS-788329.

However, a BMS-788329-resistant strain emerged at low frequency.

The team noted that infection with a BMS-788329-resistant NS5A-L31V mutation rapidly resulted in gain of an additional NS5A-Y93A mutation that conferred telaprevir resistance during combination therapy.

The research team found that infection with dual NS5AL31V/NS5AY93H mutations resulted in poor response to combination therapy and development of telaprevir resistance.

Although HCV RNA became undetectable soon after the beginning of combination therapy with BMS-788329 and BMS-821095 (NS5B inhibitor), rebound with emergence of resistance against all 3 drugs occurred.

Triple resistance also occurred following infection with the NS3V36A/NS5AL31V/NS5AY93H triple mutation.

Dr Chayama's team concludes, "Resistant strains easily develop from cloned virus strains."

"Sequential use of direct-acting antiviral agents should be avoided to prevent emergence of multidrug-resistant strains."

Am J Gastroenterol 2013; 108:1464–1472
03 October 2013

Go to top of page Email this page Email this page to a colleague

 05 March 2015

Advanced search
 05 March 2015 
EPHXI polymorphism and esophageal cancer risk
 05 March 2015 
Infliximab and immunosuppressant therapy in ulcerative colitis
 05 March 2015 
Neuroendocrine carcinoma of the colon and rectum
 04 March 2015 
Multidisciplinary management of rectal cancer
 04 March 2015 
Management of IBD
 04 March 2015 
Progression of Barrett's
 03 March 2015 
EPHX1 polymorphism and esophageal cancer risk
 03 March 2015 
Risk of anastomotic leak after colectomy
 03 March 2015 
GI bleeding in chronic kidney disease patients on aspirin
 02 March 2015 
Genes and early diagnosis of IBD
 02 March 2015 
Assessment of GERD
 02 March 2015 
Liver disease in patients awaiting liver transplant
 27 February 2015 
Obesity and weight-loss therapy
 27 February 2015 
MRE performance in staging liver fibrosis
 27 February 2015 
Bleeding in diverticulosis
 26 February 2015 
Familial colorectal cancer risk and primary cancer
 26 February 2015 
Herbal products and the liver
 26 February 2015 
Questionnaires for GERD
 25 February 2015 
Exercise and NAFLD
 25 February 2015 
IBD in Korea
 25 February 2015 
Immunosuppressive therapy and T. whipplei
 24 February 2015 
Clinical trials in pediatric IBD
 24 February 2015 
Reducing health care costs in IBD
 24 February 2015 
GI bleeding after anticoagulation interruption
 23 February 2015 
Visceral abdominal obesity and IBS
 23 February 2015 
Crohn's outcomes with infliximab
 23 February 2015 
Intestinal microbiota and celiac disease
 20 February 2015 
H. pylori eradication
 20 February 2015 
Antiviral treatment and Hep C outcomes
 20 February 2015 
C. diff testing in IBD
 19 February 2015 
Peptic ulcer bleeding mortality in liver disease
 19 February 2015 
Intestinal microbiota in IBS
 19 February 2015 
Fecal microbial transplant in active Crohn's disease
 18 February 2015 
Genetic testing and GI cancers
 18 February 2015 
Placebo analgesia in functional abdominal pain
 18 February 2015 
Successful Hep C virus therapy
 17 February 2015 
Quality measures and colonoscopist selection
 17 February 2015 
Global incidence of esophageal cancer
 17 February 2015 
Anti-viral treatment and survival in Hep C
 16 February 2015 
Saliva for the diagnosis of GERD
 16 February 2015 
H pylori eradication therapy
 16 February 2015 
Medical marijuana for digestive disorders
 13 February 2015 
Beta-blockers in cirrhosis
 13 February 2015 
Liver disease and peptic ulcer bleeding
 13 February 2015 
Prevalence of microscopic colitis
 12 February 2015 
Liver disease in chronic Hep C
 12 February 2015 
Patient-reported outcomes in Hep C
 12 February 2015 
Patients’ colonoscopist selection
 11 February 2015 
Hepatic decompensation in Hep C cirrhosis
 11 February 2015 
Guidelines for the diagnosis of hepatocellular carcinoma
 11 February 2015 
NAFLD and CVD
 10 February 2015 
Percutaneous endoscopic gastrostomy
 10 February 2015 
Factors that influence hepatic steatosis
 10 February 2015 
Gene variants and Crohn's susceptibility
 09 February 2015 
Factors that influence gallstone surgery
 09 February 2015 
Factors associated with increased mortality in cirrhosis
 09 February 2015 
Use of immunomodulators in IBD
 06 February 2015 
Colorectal cancer risk in IBD
 06 February 2015 
H. pylori and peptic ulcer bleeding
 06 February 2015 
IBS and somatization

Blackwell Publishing


GastroHep.com is a Blackwell Publishing registered trademark
© 2015 Wiley-Blackwell and GastroHep.com and contributors
Privacy Statement
Disclaimer
About Us