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The association between race/ethnicity and the effectiveness of direct antiviral agents for hepatitis C virus infection.

https://arctichealth.org/en/permalink/ahliterature284948
Source
Hepatology. 2017 Feb;65(2):426-438
Publication Type
Article
Date
Feb-2017
Author
Feng Su
Pamela K Green
Kristin Berry
George N Ioannou
Source
Hepatology. 2017 Feb;65(2):426-438
Date
Feb-2017
Language
English
Publication Type
Article
Keywords
Adult
African Continental Ancestry Group - statistics & numerical data
Aged
Antiviral agents - therapeutic use
Asian Americans - statistics & numerical data
Cohort Studies
Continental Population Groups - statistics & numerical data
Databases, Factual
Drug Therapy, Combination
Ethnic Groups - statistics & numerical data
European Continental Ancestry Group - statistics & numerical data
Female
Hepacivirus - drug effects - genetics
Hepatitis C - diagnosis - drug therapy - ethnology - mortality
Hepatitis C, Chronic - diagnosis - drug therapy - ethnology
Hispanic Americans - statistics & numerical data
Humans
Interferon-alpha - therapeutic use
Logistic Models
Male
Middle Aged
Multivariate Analysis
Prognosis
Ribavirin - therapeutic use
Risk assessment
Simeprevir - therapeutic use
Sofosbuvir - therapeutic use
Survival Rate
Treatment Outcome
United States
Abstract
Black race and Hispanic ethnicity were associated with lower rates of sustained virologic response (SVR) to interferon-based treatments for chronic hepatitis C virus infection, whereas Asian race was associated with higher SVR rates compared to white patients. We aimed to describe the association between race/ethnicity and effectiveness of new direct-acting antiviral regimens in the Veterans Affairs health care system nationally. We identified 21,095 hepatitis C virus-infected patients (11,029 [52%] white, 6,171 [29%] black, 1,187 [6%] Hispanic, 348 [2%] Asian/Pacific Islander/American Indian/Alaska Native, and 2,360 [11%] declined/missing race or ethnicity) who initiated antiviral treatment with regimens containing sofosbuvir, simeprevir + sofosbuvir, ledipasvir/sofosbuvir, or paritaprevir/ombitasvir/ritonavir/dasabuvir during the 18-month period from January 1, 2014, to June 30, 2015. Overall SVR rates were 89.8% (95% confidence interval [CI] 89.2-90.4) in white, 89.8% (95% CI 89.0-90.6) in black, 86.0% (95% CI 83.7-88.0) in Hispanic, and 90.7% (95% CI 87.0-93.5) in Asian/Pacific Islander/American Indian/Alaska Native patients. However, after adjustment for baseline characteristics, black (adjusted odds ratio = 0.77, P
PubMed ID
27775854 View in PubMed
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Factors that predict response of patients with hepatitis C virus infection to boceprevir.

https://arctichealth.org/en/permalink/ahliterature124081
Source
Gastroenterology. 2012 Sep;143(3):608-18.e1-5
Publication Type
Article
Interactive/Multimedia
Date
Sep-2012
Author
Fred Poordad
Jean-Pierre Bronowicki
Stuart C Gordon
Stefan Zeuzem
Ira M Jacobson
Mark S Sulkowski
Thierry Poynard
Timothy R Morgan
Cliona Molony
Lisa D Pedicone
Heather L Sings
Margaret H Burroughs
Vilma Sniukiene
Navdeep Boparai
Venkata S Goteti
Clifford A Brass
Janice K Albrecht
Bruce R Bacon
Author Affiliation
Cedars-Sinai Medical Center, Los Angeles, California, USA. poordad@txliver.com
Source
Gastroenterology. 2012 Sep;143(3):608-18.e1-5
Date
Sep-2012
Language
English
Publication Type
Article
Interactive/Multimedia
Keywords
Adult
Antiviral agents - therapeutic use
Biological Markers - blood
Canada
Drug Therapy, Combination
Europe
Female
Genotype
Hepacivirus - drug effects - genetics - growth & development
Hepatitis C - diagnosis - drug therapy - genetics
Humans
Interferon-alpha - therapeutic use
Interleukins - genetics
Logistic Models
Male
Multivariate Analysis
Odds Ratio
Phenotype
Polyethylene Glycols - therapeutic use
Polymorphism, Single Nucleotide
Proline - analogs & derivatives - therapeutic use
Prospective Studies
RNA, Viral - blood
Recombinant Proteins - therapeutic use
Ribavirin - therapeutic use
Risk assessment
Risk factors
Time Factors
Treatment Outcome
United States
Viral Load
Abstract
Little is known about factors associated with a sustained virologic response (SVR) among patients with hepatitis C virus (HCV) infection to treatment with protease inhibitors.
Previously untreated patients (from the Serine Protease Inhibitor Therapy 2 [SPRINT-2] trial) and those who did not respond to prior therapy (from the Retreatment with HCV Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol 2 [RESPOND-2] trial) received either a combination of peginterferon and ribavirin for 48 weeks or boceprevir, peginterferon, and ribavirin (triple therapy) after 4 weeks of peginterferon and ribavirin (total treatment duration, 28-48 wk). A good response to interferon was defined as a = 1 log(10) decrease in HCV RNA at week 4; a poor response was defined as a
PubMed ID
22626609 View in PubMed
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Outcomes of chronic hepatitis C therapy in patients treated in community versus academic centres in Canada: final results of APPROACH (a prospective study of peginterferon alfa-2a and ribavirin at academic and community centres in Canada).

https://arctichealth.org/en/permalink/ahliterature131364
Source
Can J Gastroenterol. 2011 Sep;25(9):503-10
Publication Type
Article
Date
Sep-2011
Author
Robert P Myers
Curtis Cooper
Morris Sherman
Richard Lalonde
Helga Witt-Sullivan
Magdy Elkashab
Paul Harris
Robert Balshaw
Chistopher Usaty
Paul J Marrotta
Author Affiliation
University of Calgary, alberta. rpmyers@ucalgary.ca
Source
Can J Gastroenterol. 2011 Sep;25(9):503-10
Date
Sep-2011
Language
English
Publication Type
Article
Keywords
Academic Medical Centers
Adult
Antiviral Agents - adverse effects - pharmacology - therapeutic use
Canada
Efficiency - drug effects
Female
Genotype
Hepacivirus - drug effects - genetics
Hepatitis C, Chronic - drug therapy
Hospitals, Community
Humans
Interferon-alpha - adverse effects - pharmacology - therapeutic use
Male
Middle Aged
Office Visits - utilization
Polyethylene Glycols - adverse effects - pharmacology - therapeutic use
Prospective Studies
Quality of Life
Recombinant Proteins - adverse effects - pharmacology - therapeutic use
Ribavirin - adverse effects - pharmacology - therapeutic use
Viral Load - drug effects
Work
Abstract
In patients chronically infected with the hepatitis C virus (HCV), it is not established whether viral outcomes or health-related quality of life (HRQoL) differ between individuals treated at academic or community centres.
In the present observational study, adults with chronic HCV were treated with peginterferon alfa-2a 180 ìg/week plus ribavirin at 45 Canadian centres (16 academic, 29 community). The primary efficacy end point was sustained virological response (SVR). Other outcome measures included HRQoL (assessed using the 36-item Short-Form Health Survey), heath resource use, and workplace productivity and absences within a 60-day interval.
In treatment-naive patients infected with HCV genotype 1, significantly higher SVR rates were achieved in those treated at academic (n=54) compared with community (n=125) centres (52% versus 32% [P=0.01]), although rates of dosage reduction and treatment discontinuation were similar across settings. SVR rates among patients infected with genotype 2/3 were similar between academic (n=59) and community (n=100) centres (64% versus 67% [P=0.73]). Following antiviral therapy, patients with genotype 1 who achieved an SVR (n=67) had significantly higher mean scores on the physical (P=0.005) and mental components of the 36-item Short-Form Health Survey (P=0.043) compared with those without an SVR (n=111). In contrast, HRQoL scores were similar in HCV genotype 2/3 patients with and without an SVR. There were no differences in workplace productivity or absences between patients with and without an SVR. The most frequently used health care resources by all patients were visits and phone calls to hepatitis nurses, and general practice or walk-in clinics.
Patients infected with HCV genotype 1 achieved higher SVR rates when treated at academic rather than community centres in Canada. The reasons for this difference require additional investigation.
Notes
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PubMed ID
21912762 View in PubMed
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Pretreatment resistance to hepatitis C virus protease inhibitors boceprevir/telaprevir in hepatitis C virus subgenotype 1a-infected patients from Manitoba.

https://arctichealth.org/en/permalink/ahliterature108661
Source
Can J Gastroenterol. 2013 Jul;27(7):414-6
Publication Type
Article
Date
Jul-2013
Author
Anton Andonov
Kamran Kadkhoda
Carla Osiowy
Kelly Kaita
Author Affiliation
Public Health Agency of Canada, National Microbiology Laboratory, Winnipeg, Manitoba, Canada. anton.andonov@phac-aspc.gc.ca
Source
Can J Gastroenterol. 2013 Jul;27(7):414-6
Date
Jul-2013
Language
English
Publication Type
Article
Keywords
Adult
Aged
Antiviral Agents - administration & dosage - pharmacology
Drug Resistance, Viral
Female
Genotype
Hepacivirus - drug effects - genetics - isolation & purification
Hepatitis C - drug therapy - virology
Humans
Indians, North American
Male
Manitoba
Middle Aged
Mutation
Oligopeptides - administration & dosage - pharmacology
Proline - administration & dosage - analogs & derivatives - pharmacology
Protease Inhibitors - administration & dosage - pharmacology
Sequence Analysis, DNA
Viral Nonstructural Proteins - genetics
Young Adult
Abstract
Traditional therapy with pegylated interferon and ribavirin combined with the new protease inhibitors boceprevir or telaprevir has demonstrated improved outcomes in hepatitis C virus (HCV)-infected patients. Prevalence data regarding pre-existing drug-resistant variants to these two new virus inhibitors in the Canadian population are not available.
To detect pre-existing mutations conferring resistance to boceprevir and/or telaprevir in Canadian patients infected with HCV genotype 1a.
Resistance-associated mutations (RAMs) were evaluated in 85 patients infected with HCV genotype 1a who had not yet received antiviral therapy. The NS3 protease gene was sequenced and common RAMs were identified based on a recently published list.
The overall prevalence of pre-existing RAMs to boceprevir and telaprevir was higher compared with other similar studies. All of the observed RAMs were associated with a low level of resistance. A surprisingly high proportion of patients had the V55A RAM (10.6%). None of the mutations associated with a high level of resistance were observed. The simultaneous presence of two low-level resistance mutations (V36L and V55A) was observed in only one patient. Three other patients had both T54S RAM and V55I mutations, which may require a higher concentration of the protease drugs. The prevalence of various mutations in Aboriginal Canadian patients was higher (37.5%) compared with Caucasians (16.39%) (P=0.038).
The present study was the first to investigate pre-existing drug resistance to boceprevir/telaprevir in Canadian HCV-infected patients. A relatively high proportion of untreated HCV genotype 1a patients in Manitoba harbour low-level RAMs, especially patients of Aboriginal descent, which may contribute to an increased risk of treatment failure.
Notes
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PubMed ID
23862174 View in PubMed
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Prevalence of polymorphisms with significant resistance to NS5A inhibitors in treatment-naive patients with hepatitis C virus genotypes 1a and 3a in Sweden.

https://arctichealth.org/en/permalink/ahliterature272587
Source
Infect Dis (Lond). 2015 Aug;47(8):555-62
Publication Type
Article
Date
Aug-2015
Author
Ida Lindström
Midori Kjellin
Navaneethan Palanisamy
KÃ¥re Bondeson
Lars Wesslén
Anders Lannergard
Johan Lennerstrand
Source
Infect Dis (Lond). 2015 Aug;47(8):555-62
Date
Aug-2015
Language
English
Publication Type
Article
Keywords
Antiviral Agents - pharmacology - therapeutic use
Drug Resistance, Viral - genetics
Genotype
Hepacivirus - drug effects - genetics
Hepatitis C - virology
Hepatitis C, Chronic - virology
Imidazoles - therapeutic use
Mutation, Missense
Phylogeny
Polymerase Chain Reaction - methods
Polymorphism, Genetic
Prevalence
Protease Inhibitors - therapeutic use
Sequence Analysis
Sweden - epidemiology
Viral Nonstructural Proteins - antagonists & inhibitors - genetics
Abstract
The future treatment of hepatitis C virus (HCV) infection will be combinations of direct-acting antivirals (DAAs) that not only target multiple viral targets, but are also effective against different HCV genotypes. Of the many drug targets in HCV, one promising target is the non-structural 5A protein (NS5A), against which inhibitors, namely daclatasvir, ledipasvir and ombitasvir, have shown potent efficacy. However, since HCV is known to have very high sequence diversity, development of resistance is a problem against but not limited to NS5A inhibitors (i.e. resistance also found against NS3-protease and NS5B non-nucleoside inhibitors), when used in suboptimal combinations. Furthermore, it has been shown that natural resistance against DAAs is present in treatment-naïve patients and such baseline resistance will potentially complicate future treatment strategies.
A pan-genotypic population-sequencing method with degenerated primers targeting the NS5A region was developed. We have investigated the prevalence of baseline resistant variants in 127 treatment-naïve patients of HCV genotypes 1a, 1b, 2b and 3a.
The method could successfully sequence more than 95% of genotype 1a, 1b and 3a samples. Interpretation of fold resistance data against the NS5A inhibitors was done with the help of earlier published phenotypic data. Baseline resistance variants associated with high resistance (1000-50,000-fold) was found in three patients: Q30H or Y93N in genotype 1a patients and further Y93H in a genotype 3a patient.
Using this method, baseline resistance can be examined and the data could have a potential role in selecting the optimal and cost-efficient treatment for the patient.
PubMed ID
25851241 View in PubMed
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Treatment of hepatitis C virus infection for adults and children: updated Swedish consensus guidelines 2017.

https://arctichealth.org/en/permalink/ahliterature295492
Source
Infect Dis (Lond). 2018 08; 50(8):569-583
Publication Type
Consensus Development Conference
Journal Article
Review
Date
08-2018
Author
Martin Lagging
Rune Wejstål
Ann-Sofi Duberg
Soo Aleman
Ola Weiland
Johan Westin
Author Affiliation
a Department of Infectious Diseases , Institute of Biomedicine at Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden.
Source
Infect Dis (Lond). 2018 08; 50(8):569-583
Date
08-2018
Language
English
Publication Type
Consensus Development Conference
Journal Article
Review
Keywords
Antiviral Agents - adverse effects - therapeutic use
Female
Hepacivirus - drug effects - genetics - physiology
Hepatitis C - drug therapy - pathology
Humans
Male
Practice Guidelines as Topic
Sweden
Abstract
Following the approval of two new therapeutic combinations within the European Union in 2017, the former Swedish recommendations for the treatment of hepatitis C virus (HCV) infection from 2016 were deemed in need of updating.
An expert meeting to this end was held in Stockholm, Sweden in October 2017.
An interferon-free combination of direct-acting antiviral agents is now recommended for all patients with chronic HCV infection, regardless of liver fibrosis stage, in order to limit morbidity and spread of the disease. An extended discussion of treatment for people who inject drugs in order to diminish transmission is included.
PubMed ID
29495923 View in PubMed
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Treatment of hepatitis C virus infection: updated Swedish Guidelines 2016.

https://arctichealth.org/en/permalink/ahliterature284886
Source
Infect Dis (Lond). 2017 Aug;49(8):561-575
Publication Type
Article
Date
Aug-2017
Author
Martin Lagging
Rune Wejstål
Gunnar Norkrans
Olle Karlström
Soo Aleman
Ola Weiland
Maria Castedal
Johan Westin
Source
Infect Dis (Lond). 2017 Aug;49(8):561-575
Date
Aug-2017
Language
English
Publication Type
Article
Keywords
Antiviral Agents - administration & dosage - pharmacology - therapeutic use
Drug Resistance, Viral
Genotype
Hepacivirus - drug effects - genetics - pathogenicity
Hepatitis C - drug therapy - genetics - physiopathology - virology
Humans
Practice Guidelines as Topic
Sweden
Abstract
In a recent expert meeting, Swedish recommendations for the treatment of hepatitis C virus (HCV) infection were updated. An interferon-free combination of direct-acting antiviral agents is considered and indicated for all patients with chronic HCV infection, but the ability to treat all is limited primarily by high cost of medication. The group of patients prioritized for therapeutic intervention has been extended to also include fertile women desiring to become pregnant. A more thorough discussion of treatment for people who inject drugs (PWIDs) in order to diminish transmission is included, and the clinical significance of baseline NS5A resistance associated variants (RAVs), also known as resistance associated substitutions (RASs), for the treatment of HCV genotype 1a or 3 infection is discussed.
PubMed ID
28293974 View in PubMed
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[Treatment of hepatitis C with peginterferon and ribavirin in Iceland from 2002-2012].

https://arctichealth.org/en/permalink/ahliterature283174
Source
Laeknabladid. 2017 Mars;103(3):125-128
Publication Type
Article
Author
Benedikt Fridriksson
Ottar Mar Bergmann
Sigurdur Olafsson
Source
Laeknabladid. 2017 Mars;103(3):125-128
Language
Icelandic
Publication Type
Article
Keywords
Adolescent
Adult
Aged
Antiviral Agents - adverse effects - therapeutic use
Drug Therapy, Combination
Female
Genotype
Hepacivirus - drug effects - genetics
Hepatitis C - diagnosis - drug therapy - virology
Hospitals, University
Humans
Iceland
Interferons - adverse effects - therapeutic use
Liver Cirrhosis - virology
Male
Medical Records
Middle Aged
Polyethylene Glycols - adverse effects - therapeutic use
Retrospective Studies
Ribavirin - adverse effects - therapeutic use
Sustained Virologic Response
Time Factors
Treatment Outcome
Young Adult
Abstract
Hepatitis C is a major cause of chronic liver disease and cirrhosis in Western countries. Its treatment aims at eradicating the virus and patients are considered cured if the virus is undetectable by PCR in blood 12-24 weeks after end of treatment (sustained virological response, SVR). The aim of this study is to investigate the results of treating hepatitis C in Iceland during the period 2002-2012.
Retrospective study including all patients with hepatitis C receiving treatment with peginterferone and ribavirin at Landspitali University hospital during the period 2002-2012. Patients who had been treated previously were excluded. Information was obtained from medical records and the hospital pharmacy.
A total of 207 patients were included, 136 (66%) males and 71 (34%) females. Mean age was 38 years (range 17-66). Genotyping revealed that 71 (34%) patients had genotype 1, 135 (65%) genotype 3 and one genotype 2. A total of 147 (71%) patients achieved SVR. The rate of SVR was 77.8% for genotype 3 and 57.7% for genotype 1. 9 patients (4%) had cirrhosis and 3 of them had SVR. Of 161 patients who finished treatment per protocol, 87.5% and 77.1% with genotypes 3 and 1 respectively had SVR.
The study demonstrates higher rates of SVR in clinical practice in Iceland compared to controlled clinical trials. The improved effectiveness may be explained by younger patient population, low rate of cirrhosis and close follow-up of patients. Key words: Hepatitis C, peg-interferon, sustained virological response. Correspondence: Sigurdur Olafsson, sigurdol@landspitali.is.
PubMed ID
28262630 View in PubMed
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[When and how should hepatitis C be treated?].

https://arctichealth.org/en/permalink/ahliterature144101
Source
Duodecim. 2010;126(1):41-8
Publication Type
Article
Date
2010
Author
Martti Färkkilä
Author Affiliation
HYKS, medisiininen tulosyksikkö, Gastroenterologian klinikka, HUS.
Source
Duodecim. 2010;126(1):41-8
Date
2010
Language
Finnish
Publication Type
Article
Keywords
Age Factors
Antiviral Agents - administration & dosage
Drug Administration Schedule
Drug Therapy, Combination
Finland
Hepacivirus - drug effects - genetics
Hepatitis C - drug therapy
Humans
Interferons - administration & dosage - therapeutic use
Patient Selection
Protease Inhibitors - administration & dosage - therapeutic use
Ribavirin - administration & dosage
Treatment Outcome
Abstract
Treatment results of hepatitis C have improved markedly during the last years with the combination pegylated interferons and ribavirin. The indications for evaluation for therapy is positive HCV-PCR and lack of contraindications for treatment. Liver biopsy is considered only for those with suspicion of other concomitant liver disease or in patients, where retreatment is considered. The length of therapy is individualised and based on rapid virological response in both genotype 2/3 and in genotype 1. Patients with genotype 2/3 with negative HCV-PCR at week 4 and younger than 40 years are treated for 12 weeks only with 80-90 % response rate. In Finland some 70 % of the patients with genotype 2/3 can successfully be treated with 12 weeks therapy. In genotype 1 patients with rapid virological response, regardless of age are treated for 24 weeks. Treatment is discontinued for those, who are still positive at week 24. Early intervention with tailored combination therapy before cirrhosis has developed improves treatment results, patient's overall prognosis and reduces cost of medication and surveillance. New protease inhibitors, telaprevir and boceprevir combined with PEG-interferons and ribavirin might be a future option for those not achieving early virological response.
PubMed ID
20405608 View in PubMed
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9 records – page 1 of 1.