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Hepatitis C: Genotype 3 Infection
Hello everyone, hope your day is going as planned. Today the focus is on genotype 3 infection, a difficult genotype to treat, especially in persons with cirrhosis.
After visiting "NATAP" this morning I was inspired to provided a comprehensive summary of articles evaluating characteristics and evolving therapies in genotype 3 infection, using information extracted from peer-reviewed journals, as well as online interactive learning activities.
This summary will offer insight into the following common questions about HCV genotype 3;
Is the rate of fibrosis progression faster when compared with non-3 genotypes? What about a higher grade of steatosis, or higher incidence of hepatocellular carcinoma? Is treating HCV genotype 3 more difficult than treating other genotypes?
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Articles 2015
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We begin with an article published yesterday over at Medscape.
Hepatitis C: 25 Years Old, and Fading
A wave of new antiviral drugs and novel treatment strategies are heralding a future in which hepatitis C may be globally eradicated -- but some obstacles still remain.
A wave of new antiviral drugs and novel treatment strategies are heralding a future in which hepatitis C may be globally eradicated -- but some obstacles still remain.
Link - All-Oral Treatment With Daclatasvir and Sofosbuvir
Nelson and colleagues[15] reported the results of a phase 3 trial of an all-oral, RBV-free combination of DCV and SOF in patients with genotype 3 infection. Treatment-naive and treatment-experienced patients received open-label DCV + SOF once daily for 12 weeks. Responses to prior treatments included relapse, null response, partial response, and other forms of nonresponse or interferon intolerance.
All patients completed 12 weeks of treatment, and SVR12 was achieved in 86% of patients. All prior null and partial responders and interferon-intolerant patients responded. SVR12 rates were higher in patients without cirrhosis and those with the IL28B CC genotype. Treatment failure occurred in seven patients: five prior PEG/RBV recipients and two patients who had relapse after prior treatment with SOF/RBV. Of the two patients with prior relapse, one had cirrhosis with grade 1 steatosis and one had a FibroTest score of F3, grade 2 steatosis, and a baseline NS5A-Y93 resistance-associated variant.
The most frequent adverse events were fatigue, headache, nausea, and arthralgia, but there were no serious adverse events. Thus, this well-tolerated, all-oral 12-week combination of DCV + SOF achieved high SVR12 rates in previously treated patients with genotype 3 HCV.
Link - Direct-Acting Antiviral Therapy Improves the Metabolic Syndrome
Chronic HCV infection has been linked to insulin resistance and the development of the metabolic syndrome. Does viral eradication reduce the risk?
Pedersen and colleagues[22] evaluated the effect of direct-acting HCV antiviral therapy on components of the metabolic syndrome in a prospective cohort study of monoinfected chronic HCV patients who initiated treatment with a SOF- or SIM-containing regimen. Consecutively enrolled patients received one of the following regimens: PEG + SOF + RBV, SOF + RBV, or SOF + SIM. Concomitant metabolic syndrome parameters before treatment were hypertension, diabetes, and hyperlipidemia.
End-of-treatment response (ie, undetectable HCV RNA) was 98%. At the end of treatment, significant reductions in BMI; systolic blood pressure; diastolic blood pressure; and total, high-density lipoprotein, and low-density lipoprotein cholesterol levels were noted in the entire cohort. In subgroup analysis, patients with cirrhosis had significant reductions in BMI; systolic blood pressure; and total cholesterol, high-density lipoprotein cholesterol, and triglyceride levels. Patients receiving non–interferon-containing regimens had significant reductions in BMI, systolic blood pressure, diastolic blood pressure, and total cholesterol level. The investigators concluded that direct-acting antiviral therapy for HCV improves individual components of the metabolic syndrome.
Full article available, here....
June 2015
HCV Genotypes
Alan Franciscus, Editor-in-Chief
This month’s column is about hepatitis C (HCV) genotypes. I will present a brief overview of genotypes 1, 2, 3, 4, and 6. You will notice that I am not discussing genotype 5, which is discussed more in-depth later in this issue, and Genotype 7, which is very rare.
Despite these successes, genotype 3 hepatitis C, particularly those with cirrhosis who have failed prior therapy, remains a population in need of additional strategies to achieve SVR.
Sofosbuvir plus pegylated interferon/ribavirin is highly effective for people with hard-to-treat genotype 3 hepatitis C
When hepatitis C virus (HCV) genotyping became available, I learned that I had genotype 1a. Until recently, genotype 1 hepatitis C was the hardest to treat. However,genotype 1 is quite easy to treat now with the latest approved HCV drugs. Genotype 2 has always been fairly easy to treat too. Genotype 3 is the one causing problems. In this blog, I discuss genotype 3, review the current hepatitis C genotype 3 treatment recommendations, and look at what is ahead.
Global Distribution & Prevalence of HCV Genotypes (GT3) - (06/15/15)
HCV genotype 3 is the next most common and is estimated to account for 54.3 million (30.1%) cases globally, approximately three-quarters of which occur in south Asia. Genotypes 2, 4, and 6 are responsible for the majority of the remaining cases of HCV worldwide, with an estimated 16.5 million (9.1%), 15.0 million (8.3%), and 9.8 million (5.4%) cases, respectively. East Asia accounts for the greatest numbers of genotype 2 and genotype 6 HCV cases, while North Africa and the Middle East have the largest number of genotype 4 cases. We estimate genotype 5 to be responsible for the fewest HCV cases globally (1.4 million, <1% of all HCV cases), the great majority of which occur in Southern and Eastern sub-Saharan Africa.
Genotype 3 Numbers in USA - (06/15/15)
NATAP: Conference Reports
EASL 2015 - HCV Genotype 3 Treatment
EASL: Cohort Studies at EASL 2015 - (05/14/15)
EASL: Sofosbuvir Plus Peg-IFN/RBV for 12 Weeks vs Sofosbuvir/RBV for 16 or 24 Weeks in Genotype 3 HCV-Infected Patients and Treatment-Experienced Cirrhotic Patients With Genotype 2 HCV: The BOSON Study - (04/27/15)
APASL: All-Oral 12-Week Combination Treatment With Daclatasvir and Sofosbuvir in Patients Infected With HCV Genotype 3: ALLY-3 Phase 3 Study - (03/18/15)
Clinical Pharm of HIV & Hepatitis Population Viral Kinetic Modeling: SVR Prediction in HCV GT-3 Cirrhotic Patients With 24 Weeks of Daclatasvir + Sofosbuvir Administration - (05/29/15)
EASL: DACLATASVIR PLUS SOFOSBUVIR WITH OR WITHOUT RIBAVIRIN IN PATIENTS WITH HCV GENOTYPE 3 INFECTION: INTERIM ANALYSIS OF A FRENCH MULTICENTER COMPASSIONATE USE PROGRAM - (04/24/15)
Alan Franciscus, Editor-in-Chief
This month’s column is about hepatitis C (HCV) genotypes. I will present a brief overview of genotypes 1, 2, 3, 4, and 6. You will notice that I am not discussing genotype 5, which is discussed more in-depth later in this issue, and Genotype 7, which is very rare.
May 2015
Genotype 3:One of the Remaining Challenges for Hepatitis CDespite these successes, genotype 3 hepatitis C, particularly those with cirrhosis who have failed prior therapy, remains a population in need of additional strategies to achieve SVR.
April - EASL 2015
March 2015
February 2015
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Learning Activities
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June 2015
Next we have a learning activity updated today by "Hepatitis C Online" a free educational web site from the University of Washington.
Module 5 - Treatment of HCV Genotype 3
Lesson 3: Treatment of HCV Genotype 3
Contents: Introduction
Genotype 3: Initial Treatment
Genotype
Genotype 3: Retreatment of Patients in whom Prior Therapy Failed
Genotype
Genotype 3: Future Treatment Options
Summary Points
References
Figures
May 2015
Clinical Care Options
Audio - HCV Experienced Patients: Resistance testing, Cirrhosis and Genotype 3 Infection
Topics Include;
HCV therapy in the setting of renal impairment, resistance testing in DAA experienced patients, and the best approach to treat patients with cirrhosis or experienced patients who have genotype 3 infection.
Audio - HCV Experienced Patients: Resistance testing, Cirrhosis and Genotype 3 Infection
Topics Include;
HCV therapy in the setting of renal impairment, resistance testing in DAA experienced patients, and the best approach to treat patients with cirrhosis or experienced patients who have genotype 3 infection.
March 2015
Web-based CME activity
Weekend Reading: Current options for treating HCV genotypes 1-4
Although this learning activity is clinical in nature and directed at physicians, anyone living with HCV and considering treatment has an opportunity to learn more about disease management, testing, methods used to assess fibrosis, current options for treating HCV genotypes 1-4, and more.
Weekend Reading: Current options for treating HCV genotypes 1-4
Although this learning activity is clinical in nature and directed at physicians, anyone living with HCV and considering treatment has an opportunity to learn more about disease management, testing, methods used to assess fibrosis, current options for treating HCV genotypes 1-4, and more.
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Research
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Over at NATAP executive director Jules Levin has posted a collection of articles on the subject of liver cancer in HCV genotype 3 infection, published in the following journals; Hepatology 2014, and Journal of Viral Hepatitis 2011.
HCV genotype 3 is associated with a higher hepatocellular carcinoma incidence in patients with ongoing viral C cirrhosis - (06/15/15)
"In this retrospective study of a large cohort of patients with HCV cirrhosis and persistent viral replication prospectively screened for HCC, we observed that infection with a genotype 3 was associated with an increased risk of HCC occurrence either in univariate or in multivariate analysis taking in account the most commonly recognized risk factors.
Data show that viral genotype 1 may increase the risk of cirrhosis and hepatocellular carcinoma (HCC) compared to genotype 2 in patients with chronic hepatitis C virus (HCV) infection. However, the effect of HCV genotype 3 on cirrhosis and HCC risk is uncertain.
Global Distribution & Prevalence of HCV Genotypes (GT3) - (06/15/15)
HCV genotype 3 is the next most common and is estimated to account for 54.3 million (30.1%) cases globally, approximately three-quarters of which occur in south Asia. Genotypes 2, 4, and 6 are responsible for the majority of the remaining cases of HCV worldwide, with an estimated 16.5 million (9.1%), 15.0 million (8.3%), and 9.8 million (5.4%) cases, respectively. East Asia accounts for the greatest numbers of genotype 2 and genotype 6 HCV cases, while North Africa and the Middle East have the largest number of genotype 4 cases. We estimate genotype 5 to be responsible for the fewest HCV cases globally (1.4 million, <1% of all HCV cases), the great majority of which occur in Southern and Eastern sub-Saharan Africa.
Genotype 3 Numbers in USA - (06/15/15)
Approximately 75% of Americans with HCV have genotype 1 of the virus (subtypes 1a or 1b), and 20-25% have genotypes 2 or 3, with small numbers of patients infected with genotypes 4, 5, or 6......
Genotypes, Genotype 3 (GT3) in VA, Global - (06/15/15)
VA
A total of 88,348 patients (79.9%) had HCV genotype 1, 13,077 (11.8%) genotype 2, 8,337 (7.5%) genotype 3, and 1,082 (0.9%) patients had genotype 4 infection. There were significant demographic and clinical differences among the HCV genotype groups (Table 1). Patients with genotype 3 were younger (mean age, 50.2 years, SD 6.4 years) whereas those with genotype 2 were older (mean age 52.7 years, SD 7.5 years) than patients with genotype 1 infection (mean age, 51.9 years, SD 6.6 years) (P<0.0001). Genotype 3 patients were more likely to have served in the post-Vietnam era (31.4%) compared to HCV genotype 1 (25.3%) and 2 patients (22.6%) (P<0.0001). Both genotype 2 and 3 patients were more likely to be white non-Hispanic compared to genotype 1 patients. HCV genotype 3 patients were less likely to have diabetes, HIV coinfection, and had lower BMIthan genotype 1 patients. As expected, significantly more patients with HCV genotypes 2 and 3 received antiviral treatment and achieved SVR compared to genotype 1 patients. HCV genotype 4 patients were more likely to be Hispanics and diabetics than HCV genotype 1 patients.
Genotypes, Genotype 3 (GT3) in VA, Global - (06/15/15)
VA
A total of 88,348 patients (79.9%) had HCV genotype 1, 13,077 (11.8%) genotype 2, 8,337 (7.5%) genotype 3, and 1,082 (0.9%) patients had genotype 4 infection. There were significant demographic and clinical differences among the HCV genotype groups (Table 1). Patients with genotype 3 were younger (mean age, 50.2 years, SD 6.4 years) whereas those with genotype 2 were older (mean age 52.7 years, SD 7.5 years) than patients with genotype 1 infection (mean age, 51.9 years, SD 6.6 years) (P<0.0001). Genotype 3 patients were more likely to have served in the post-Vietnam era (31.4%) compared to HCV genotype 1 (25.3%) and 2 patients (22.6%) (P<0.0001). Both genotype 2 and 3 patients were more likely to be white non-Hispanic compared to genotype 1 patients. HCV genotype 3 patients were less likely to have diabetes, HIV coinfection, and had lower BMIthan genotype 1 patients. As expected, significantly more patients with HCV genotypes 2 and 3 received antiviral treatment and achieved SVR compared to genotype 1 patients. HCV genotype 4 patients were more likely to be Hispanics and diabetics than HCV genotype 1 patients.
2015
NATAP: Conference Reports
Summary from EASL 2015 for Hepatitis C All oral HCV DAA therapy on its way to optimization: still much to learn. - Jurgen K. Rockstroh M.D., Professor of Medicine University of Bonn, Germany (05/22/15)
EASL: Cohort Studies at EASL 2015 - (05/14/15)
EASL: Sofosbuvir Plus Peg-IFN/RBV for 12 Weeks vs Sofosbuvir/RBV for 16 or 24 Weeks in Genotype 3 HCV-Infected Patients and Treatment-Experienced Cirrhotic Patients With Genotype 2 HCV: The BOSON Study - (04/27/15)
APASL: All-Oral 12-Week Combination Treatment With Daclatasvir and Sofosbuvir in Patients Infected With HCV Genotype 3: ALLY-3 Phase 3 Study - (03/18/15)
Clinical Pharm of HIV & Hepatitis Population Viral Kinetic Modeling: SVR Prediction in HCV GT-3 Cirrhotic Patients With 24 Weeks of Daclatasvir + Sofosbuvir Administration - (05/29/15)
EASL: DACLATASVIR PLUS SOFOSBUVIR WITH OR WITHOUT RIBAVIRIN IN PATIENTS WITH HCV GENOTYPE 3 INFECTION: INTERIM ANALYSIS OF A FRENCH MULTICENTER COMPASSIONATE USE PROGRAM - (04/24/15)
Begin here.....
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June 2015
Effects of delaying Hepatitis C treatment
Begin here....
See you all soon
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Of Interest
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June 2015
Effects of delaying Hepatitis C treatment
Now that better and more effective treatments exist for Hepatitis C (HCV), should all – not just the sickest – patients be eligible for these therapies? David Rowlands’ latest poll examines the issues around treating earlier or waiting.
Begin here....
2014
Begin here....
2014
The Challenge of Genotype 3
For many clinicians, genotype 3 now presents the greatest challenge in the treatment and management of patients with hepatitis C virus.
In a recent paper published in the Journal of Viral Hepatology, HCV Next Editorial Board member Nezam H. Afdhal, MD, and Elliot B. Tapper, MD, from Beth Israel Deaconess Medical Center, called genotype 3 “potentially the most difficult-to-treat genotype and an area of intense research for new drug development.”
For many clinicians, genotype 3 now presents the greatest challenge in the treatment and management of patients with hepatitis C virus.
In a recent paper published in the Journal of Viral Hepatology, HCV Next Editorial Board member Nezam H. Afdhal, MD, and Elliot B. Tapper, MD, from Beth Israel Deaconess Medical Center, called genotype 3 “potentially the most difficult-to-treat genotype and an area of intense research for new drug development.”
Begin here....
See you all soon
Tina
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