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; 108:14641472
03 October 2013

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

 28 August 2015

Advanced search
 28 August 2015 
Statin use and survival in pancreatic cancer
 28 August 2015 
Bacterial endotoxin and NAFLD
 28 August 2015 
Interferon-free regimens for Hep C
 27 August 2015 
HCV in Egypt
 27 August 2015 
Gene expression for hepatocellular carcinoma
 27 August 2015 
Liver abnormalities in celiac disease
 26 August 2015 
Medical management of diverticular disease
 26 August 2015 
Treatment of erosive esophagitis
 26 August 2015 
Dermatological complications of anti-TNF therapy in IBD
 25 August 2015 
Markers for colorectal cancer screening
 25 August 2015 
Long-term PPI use and serum gastrin levels
 25 August 2015 
Treatment for HCV and HIV-1 co-infection
 24 August 2015 
Treatment for HCV and HIV-1 co-infection
 24 August 2015 
Cirrhosis in Hepatitis C patients
 24 August 2015 
Aspirin use and colorectal cancer survival
 21 August 2015 
Activity indexes in ulcerative colitis
 21 August 2015 
Coffee and gallstone disease
 21 August 2015 
Alcoholic cirrhosis in relapse after liver transplant
 20 August 2015 
Cirrhosis in the USA
 20 August 2015 
Mortality causes in liver cirrhosis
 20 August 2015 
Risk of death in IBD
 19 August 2015 
Predicting intestinal surgery in Crohn's disease
 19 August 2015 
Improved screening colonoscopy quality
 19 August 2015 
Sleep positioning device reduces reflux
 18 August 2015 
Health insurance influences HCV screening outcomes
 18 August 2015 
Somatostatin analogues in polycystic liver disease
 18 August 2015 
Global consensus report on H. pylori gastritis
 17 August 2015 
Biomarker of fibrosis stage in NAFLD
 17 August 2015 
Prognostic score for primary biliary cirrhosis
 17 August 2015 
Measuring subjective health in patients with IBS
 14 August 2015 
Factors that influence ulcerative colitis procedure type
 14 August 2015 
H. pylori in African American and Hispanic veterans
 14 August 2015 
Hep E virus in decompensated chronic liver disease
 13 August 2015 
H. pylori in drinking water
 13 August 2015 
Sofosbuvir-regimens in HCV
 13 August 2015 
IBS among Japanese adolescents
 12 August 2015 
Infliximab in patients in IBD
 12 August 2015 
Peritoneal carcinomatosis in colorectal cancer
 12 August 2015 
Predictors of severity of IBD
 11 August 2015 
H. pylori and immune thrombocytopenic purpura
 11 August 2015 
Chemotherapy and intestinal microbiomes
 11 August 2015 
Sexual dysfunction after rectal cancer treatment
 10 August 2015 
Scoring systems to predict alcoholic hepatitis outcomes
 10 August 2015 
Sofosbuvir-based regimens in veterans with HCV
 10 August 2015 
Predicting lymph node metastasis in T1 colorectal cancer
 07 August 2015 
Factors associated with changes in ulcerative colitis
 07 August 2015 
Bariatric surgery and NASH in obese patients
 07 August 2015 
Caffeine and fibrosis in Hep C
 06 August 2015 
Disparities in colonoscopic examination
 06 August 2015 
Weight loss and NASH
 06 August 2015 
Diagnosis of IBS
 05 August 2015 
Gender differences in fecal immunochemical tests
 05 August 2015 
Adenoma detection rates with a screening colonoscopy program
 05 August 2015 
Extraintestinal manifestations in IBD diagnosis
 04 August 2015 
IBD environmental risk factors
 04 August 2015 
Measuring disease activity in Crohn's
 04 August 2015 
Gastric emptying and hyperglycemia in diabetes
 03 August 2015 
Vaccinations and IBD
 03 August 2015 
Lack of response to therapy in severe ulcerative colitis
 03 August 2015 
Nutritional vs biological therapy in Crohn's

Blackwell Publishing


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