Nine-year distribution pattern of hepatitis C virus (HCV) genotypes in Southern Italy

Nine-year distribution pattern of hepatitis C virus (HCV) genotypes in Southern Italy
Arnolfo Petruzziello , Rocco Sabatino, Giovanna Loquercio, Annunziata Guzzo, Lucia Di Capua, Francesco Labonia, Anna Cozzolino, Rosa Azzaro, Gerardo Botti
Published: February 20, 2019
https://doi.org/10.1371/journal.pone.0212033

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In conclusion, the epidemiological framework of Hepatitis C infection in Southern Italy, particularly interesting for the high prevalence of this virus in the general population, seems to highlight the "returning" role of the iatrogenic transmission as risk factor for the diffusion of HCV infection. Furthermore, the small increase of genotype 3a among young people should be more investigated, with a support of a phylogenetic analysis. At support of our hypothesis, some studies report small HCV outbreaks in Europe due to breaches in standards of health and safety practices among health-care workers [56]. Indeed, an interesting case–control study highlighted some unconventional routes of diffusion of Hepatitis C infection such as digestive endoscopy, beauty treatments and professional pedicure/manicure [57]. This suggest not only a necessary evaluation of the safety practices in surgery, but the fundamental importance of not lowering the safety levels, especially among all health-care professionals.

Abstract
Introduction
It has been greatly described that different hepatitis C virus (HCV) genotypes are strictly correlated to various evolution, prognosis and response to therapy during the chronic liver disease. Aim of this study was to outline the changes in the epidemiology of Hepatitis C genotypes in Southern Italy regions from 2006 to 2014.

Material/Methods
Prevalence of HCV genotypes was analyzed in 535 HCV-RNA positive patients with chronic Hepatitis C infection, selected during the period 2012–2014, and compared with our previous data, referred to periods 2006–2008 and 2009–2011.

Results
In all the three periods analyzed, genotype 1b is predominant (51.8% in 2006–08, 48.3% in 2009–11 and 54.4% in 2012–14) while genotype 2 showed an increase in prevalence (27.9% in 2006–08, 31.7% in 2009–11 and 35.2% in 2012–14) and genotypes 3a and 1a a decrease during the same period (6.8% in 2006–08, 4.7% in 2009–11 and 3.2% in 2012–14 and 7.9% in 2006–08, 4.7% in 2009–11 and 2.6% in 2012–14, respectively). Subtype 1b seems to be equally distributed between males and females (52.7% vs 56.6%) and the prevalence in the age range 31–40 years is significantly higher in the 2012–14 period than in both previous periods (53.8% vs. 16.6% in 2009–11, p< 0.001 and 13.4% in 2006–08, p < 0.001).

Conclusions
Genotype 1b is still the most prevalent, even if shows a significantly increase in the under 40 years old population. Instead, genotype 3a seems to have a moderate increase among young people. Overall, the alarming finding is the “returning” role of the iatrogenic transmission as risk factor for the diffusion of Hepatitis C infection.

Ribavirin Beneficial For Patients with Hepatitis C Genotype 3

Ribavirin Beneficial For Patients with Hepatitis C Genotype 3
NOVEMBER 29, 2018

Kenneth Bender, PharmD, MA

The addition of ribavirin to a regimen of sofosbuvir and velpatasvir (Epclusa) to treat hepatitis C virus (HCV) genotype 3 appeared to increase efficacy for patients with compensated cirrhosis, particularly in those with resistance-associated substitution (RAS), in a trial that sought to confirm the therapeutic strategy for this considered difficult-to-cure population.

Rafael Esteban, MD, of the Vall d'Hebron Hospital University, Spain, and colleagues conducted the comparison in patients with compensated cirrhosis to elaborate on earlier indications of ribavirin benefit from phase 2 studies, and from the ASTRA-4 study in patients with HCV genotype 3 and decompensated cirrhosis.
Read more:
https://www.mdmag.com/medical-news/ribavirin-beneficial-for-patients-with-hepatitis-c-genotype-3

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The Liver Meeting
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November 2018

"Treatment of Genotype 3 Cirrhotic patients with 12 weeks Sofosbuvir/Velpatasvir with or without ribavirin: Real life experience from Italy" 

On This Blog

2018 Articles

Review research articles with a focus on treating HCV according to genotype using FDA approved  medicines. Information is extracted from news articles, peer-reviewed journals, as well as liver meetings/conferences, research manuscripts and interactive learning activities.

Mavyret for HCV/HIV Coinfection and Genotype 3: A Report of Three Cases

Intern Med. 2018 Nov 19. doi: 10.2169/internalmedicine.1856-18.
[Epub ahead of print]

Glecaprevir and Pibrentasvir for Japanese Patients with Human Immunodeficiency Virus and Genotype 3 Hepatitis C Virus Coinfection: A Report of Three Cases
Takuya Sho1, Goki Suda1, Megumi Kimura1, Tomoe Shimazaki1, Osamu Maehara1, Taku Shigesawa1, Kazuharu Suzuki1, Akihisa Nakamura1, Masatsugu Ohara1, Machiko Umemura1, Takaaki Izumi1, Naoki Kawagishi1, Masaru Baba2, Masato Nakai1, Mitsuteru Natsuizka1, Kenichi Morikawa1, Koji Ogawa1 and Naoya Sakamoto1; for the NORTE Study Group

Abstract:
The efficacy and safety of glecaprevir and pibrentasvir in Japanese patients with human immunodeficiency virus (HIV) and/or genotype 3 hepatitis C virus (HCV) infection is yet to be clarified. This is because no or only a few patients have been included in Japanese phase 3 trials. We herein report for the first time the successful treatment of glecaprevir and pibrentasvir in three Japanese patients with HIV and genotype 3 HCV coinfection as well as hemophilia. Glecaprevir and pibrentasvir treatment is safe and effective for Japanese patients with genotype 3 HCV and HIV coinfection.

Full-text article
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Hepatitis C - Vosevi safe, effective in ‘triple-infected’ patients with HCV, HBV, HIV

Vosevi safe, effective in ‘triple-infected’ patients with HCV, HBV, HIV

PHILADELPHIA – The direct-acting antiviral Vosevi demonstrated an average sustained virologic response rate of 87% among patients who were “triple-infected” with hepatitis C genotype 3, hepatitis B and HIV, as presented at the American College of Gastroenterology Annual Meeting.

“Chronic hepatitis C treatment is no longer challenging in the era of DAAs with an SVR of up to 97%. However, triple infection treatment with HCV, HIV and hepatitis B has not been explored in real life situations,” Nimy John, MD, from the University of Massachusetts Medical School, said during her presentation.

Read the article: 
https://www.healio.com/gastroenterology/hepatitis-c/news/online/%7B48f981a3-e83f-4e70-8c39-4acd467af6f7%7D/vosevi-safe-effective-in-triple-infected-patients-with-hcv-hbv-hiv

Healio Coverage:

American College of Gastroenterology Annual Meeting 
October 5, 2018 - October 10, 2018
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Hepatitis C virus genotype 3: clinical features, current and emerging viral inhibitors, future challenges

Ann Gastroenterol. 2018 Sep-Oct;31(5):541-551. doi: 10.20524/aog.2018.0281. Epub 2018 Jun 4.

REVIEW ARTICLE
Hepatitis C virus genotype 3: clinical features, current and emerging viral inhibitors, future challenges
Vahe Shahnazariana, Daryl Ramaia,b, Madhavi Reddya, Smruti Mohantyc

Download full article: http://www.annalsgastro.gr/files/journals/1/earlyview/2018/ev-06-2018-01-AG_3988-0281.pdf
Article available online: Europe PMC (Open Access)

Abstract
Hepatitis C virus (HCV) represents a global burden on healthcare that affects over 150 million people worldwide. In the past, HCV genotype 3 was considered difficult to treat relative to other genotypes. Genotype 3 has been associated with a higher rate of complications, including fatty liver disease, fibrosis, hepatocellular carcinoma and mortality. However, with the advent of first- and second-generation direct-acting antivirals, genotype 3 can be treated effectively. Additionally, these new drugs are well tolerated by patients and have significantly fewer side effects compared to ribavirin and interferon-based regimens. However, while great strides have been made in overcoming biological barriers, our next challenge lies in overcoming economic and financial obstacles if we are to eradicate HCV genotype 3. Herein, we review the clinical features associated with HCV genotype 3, current and emerging treatment regimens, and challenges associated with treatment.

Keywords Hepatitis C, genotype 3, sustained viral response, direct acting antivirals, treatment Ann Gastroenterol 2018; 31 (4): 1-11

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Challenges and perspectives of direct antivirals for the treatment of hepatitis C virus infection

Journal of Hepatology
Challenges and perspectives of direct antivirals for the treatment of hepatitis C virus infection

JohannesVermehren, James S. Park, Ira Jacobson, StefanZeuzem

https://doi.org/10.1016/j.jhep.2018.07.002

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Abstract

Treatment of chronic hepatitis C virus (HCV) infection has been revolutionized with the development of direct-acting antiviral agents (DAAs). Eight to twelve weeks of all-oral, once-daily treatments is now the standard of care and viral eradication can be achieved in >95% across different patient populations. Despite these advances, several unresolved issues remain, including treatment of HCV genotype 3, chronic kidney disease, and in patients in whom DAA therapy has failed. Glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) are the most recently approved DAA regimens. Given the overwhelming success of modern DAA-based therapies, GLE/PIB and SOF/VEL/VOX are also likely to represent the last DAAs to be approved. Both are pangenotypic, once-daily, all-oral DAA combinations that have the potential to close the gaps in the current DAA treatment portfolio. Here, we review the challenges associated with current DAAs and how these two regimens may be implemented in existing treatment algorithms.

Continue to article: https://jumpshare.com/v/UyqlFMHW9EjHQW9vWFYJ

Of Special Interest
Commentary
Hepatitis C Management Simplification From Test to Cure:A Framework for Primary Care Providers
SOF/VEL or GLE/PIB), both highly tolerated and effective for all genotypes.

Sofosbuvir and Ledipasvir is Associated with High Sustained Virologic Response and Improvement of Health-Related Quality of Life in East Asian Patients with Hepatitis C Virus Infection
In summary, our data clearly show the superiority of IFN-free RBV-free LDV/SOF in East Asian patients with chronic HCV genotype 1 infection. The advantages of that regimen are related not only to its high efficacy and excellent tolerability but also to significantly better quality of life during treatment and after achieving SVR. These data provide evidences up porting the comprehensive benefit of LDV/SOF for eligible patients which should inform all stakeholders, including providers, payers, and policy makers in East Asian countries

Absolute Insurer Denial of Direct-Acting Antiviral Therapy for Hepatitis C: A National Specialty Pharmacy Cohort Study

Absolute denials of DAA regimens by insurers in the U.S. have remained high & increased over time, regardless of type of insurance.

Sofosbuvir/velpatasvir and Resistance-associated Substitutions in HCV genotype 3

SOF/VEL and Resistance-associated Substitutions in HCV GT3

Alimentary Pharmacology & Therapeutics, June 21, 2018
J. von Felden; J. Vermehren; P. Ingiliz; S. Mauss; T. Lutz; K. G. Simon; H. W. Busch; A. Baumgarten; K. Schewe; D. Hueppe; C. Boesecke; J. K. Rockstroh; M. Daeumer; N. Luebke; J. Timm; J. Schulze zur Wiesch; C. Sarrazin; S. Christensen

Does the presence of resistance-associated substitutions impact the efficacy of therapy with sofosbuvir/velpatasvir with or without ribavirin in patients with HCV genotype 3?
Medscape - Full Text

Abstract and Introduction
Abstract
Background Twelve weeks of the pangenotypic direct–acting antiviral (DAA) combination sofosbuvir/velpatasvir (SOF/VEL) was highly efficient in patients with hepatitis C virus (HCV) genotype 3 (GT3) infection in the ASTRAL–3 approval study. However, presence of resistance–associated substitutions (RASs) in the HCV nonstructural protein 5A (NS5A) was associated with lower treatment response.

Aim To assess the efficacy and safety of SOF/VEL ± ribavirin (RBV) and the impact of NS5A RASs and RBV use on treatment outcome in HCV GT3 infection in a real–world setting.

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SVR 24 Two Weeks After a Tripled Dose of Daclatasvir in an HCV Genotype 3 Patient (Case Report)

Case Report

Ann Hepatol. 2018 July - August ,;17(4):661-664. doi: 10.5604/01.3001.0012.0950.

SVR 24 Achievement Two Weeks After a Tripled Dose of Daclatasvir in an HCV Genotype 3 Patient.
Lo Menzo S1, Biagi E1, Di Nuzzo M1, Grilli A1, Contini C1.

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Abstract

Directly-acting antivirals (DAA) have changed the chronic hepatitis C virus (HCV) infection therapeutic scenario allowing virus eradication in more than 95% of patients, independently from the genotype, with 12 to 24-week treatment regimens. We describe a 51-year-old Pakistani man with a chronic HCV-genotype 3 (GT3a) infection with moderate liver fibrosis, who achieved sustained virological response (SVR) 24 after a tripled dose of Daclatasvir (DCV) taken erroneously associated to Sofosbuvir (SOF). The patient had a concomitant intestinal TB infection whose treatment had been delayed in order to firstly eradicate HCV to reduce the liver toxicity of anti-mycobacterial drugs. Thanks to the cultural mediator support, we explained to the patient the correct posology of each drug to take during the day consisting of 12 week SOF (400 mg daily) plus DCV (60 mg daily) regimen. He returned 13 days after for a programmed visit and we were surprised to learn that he had taken 3 pills of DCV (180 mg/daily) instead of one, thus ending DCV assumption after only 9 days while SOF was taken correctly. He complained no symptoms. We immediately performed blood test that showed alteration of lactate dehydrogenase, creatine phosphokinase, and creatin kinase MB activity. At day 15 we stopped SOF closely monitoring the patient. Blood test alterations returned normal after one week of treatment suspension, HCV viremia remained suppressed after 4, 12 and 24 weeks proving HCV eradication. If confirmed, these data could suggest that higher doses of DCV, if tolerated, might be employed in short-time HCV-GT3 treatment.

PMID: 29893709 DOI: 10.5604/01.3001.0012.0950 

Download full-text article:

 http://annalsofhepatology.com/revista/numeros/2018/HP184-18-SRV24%20(F_120618m)_PROTEGIDO.pdf

Eight weeks of treatment with Epclusa cured almost all people receiving opioid substitution therapy

Conference news @infohep
Eight weeks of treatment with Epclusa cured almost all people receiving opioid substitution therapy
Keith Alcorn
Published: 12 April 2018
An eight-week course of sofosbuvir/velpatasvir (Epclusa) cured almost all people with hepatitis C genotype 3 without cirrhosis receiving treatment alongside opioid substitution therapy through community pharmacies or prisons in the Greater Glasgow area, Alison Boyle of Gartnavel Hospital, Glasgow, reported at the 2018 International Liver Congress in Paris on Thursday. Genotype 3 is especially common in people who inject drugs and former drug users. It has been considered 'harder to cure' although recent studies of newer agents in people with genotype 3 have shown high cure rates.
Continue reading......

Slides @ NATAP
8 weeks sofosbuvir/velpatasvir in genotype 3 patients with significant fibrosis: Highly effective amongst an OST cohort - (04/13/18)

New @infohep
New Hepatocellular carcinoma (HCC)
EASL updates liver cancer guidelines at International Liver Congress
Liz Highleyman / 7 hours ago
The European Association for the Study of the Liver (EASL) presented updated clinical practice guidelines for the management of hepatocellular carcinoma (HCC) during a special session at the 2018 International Liver Congress yesterday

New NAFLD
Cenicriviroc treatment improves liver fibrosis in people with NASH
Liz Highleyman / 7 hours ago
Cenicriviroc, a drug that blocks both CCR5 and CCR2 receptors on immune cells, continued to show an anti-fibrotic effect in people with non-alcoholic steatosis (NASH) after two years of follow-up, according to a

New Treatment for people who use drugs
Eight weeks of treatment with Epclusa cured almost all people with HCV receiving opioid substitution therapy
Keith Alcorn / 18 hours ago
An eight-week course of sofosbuvir/velpatasvir (Epclusa) cured almost all people with hepatitis C genotype 3 without cirrhosis receiving treatment alongside opioid substitution therapy through community pharmacies or prisons in the Greater Glasgow area...

Pan-genotypic regimens
New affordable hepatitis C combination shows 97% cure rate
Keith Alcorn / 12 April 2018
The combination of sofosbuvir and the new NS5A inhibitor ravidasvir cured 97% of people with hepatitis C in a study carried out in Malaysia, and could provide a safe and

Begin here.....

Sweden-Introduction of second-generation direct-acting antivirals in HCV:Register-based Study

Introduction of the second-generation direct-acting antivirals (DAAs) in chronic hepatitis C: a register-based study in Sweden

P. Frisk, K. Aggefors T. Cars N. Feltelius S. A. LoovB. Wettermark O. Weiland

First Online: 09 April 2018

The conditions for introducing the first six of the second-generation direct-acting antivirals for chronic hepatitis C infection in Sweden were outlined in a national introduction protocol. The overall cure rate was estimated to 96%, with some variation between genotypes. Despite regional variation in other cost containment strategies, the high level of adherence to recommendations among prescribers and similar introduction rates in the regions indicate that the protocol contributed considerably to a rapid uptake and equal distribution of DAAs in Sweden.

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Abstract

Purpose Introduction of the direct-acting antivirals (DAAs) for treatment of chronic hepatitis C (CHC) infection has been challenging in all health systems. In Sweden, a national protocol for managed introduction was developed. It was optional, but all county councils agreed to implement and follow it. The purpose of this study was to study (a) cure rates among all patients initiated on treatment in 2014–2015, (b) prescribers’ adherence to the drug recommendations and treatment eligibility criteria in the protocol, and (c) introduction rate in the six Swedish healthcare regions.

Method
A cross-sectional study where national data from the Prescribed Drug Register and the quality register InfCare Hepatitis defined the study population, and clinical data from the Patient Register and InfCare Hepatitis were used to monitor outcomes. Descriptive statistics were used.

Results
A total of 3447 patients were initiated on treatment during 2014–2015. The overall cure rate, based on data from 85% of the cohort, was 96%, with variation between genotypes. Adherence to drug recommendations increased over time and varied between 43.2 and 94.2%. Adherence to the treatment eligibility criteria was initially 80% and increased to 87% when treatment restrictions were widened. The introduction rate differed initially between the regions and reached stable levels 15–18 months after the launch of the first DAA.

Conclusion
The estimated overall cure rate was 96%, with some variations between genotypes. A high level of adherence to the introduction protocol as well as similar introduction rates in the health care regions indicate that the introduction protocol, alongside with other measures taken, contributed considerably to a rapid uptake and equal distribution of DAAs in Sweden.

Continuer reading online: https://link.springer.com/article/10.1007%2Fs00228-018-2456-y

Prevalence and genotype distribution of hepatitis C virus infection among patients with type 2 diabetes mellitus.

Med Princ Pract. 2018 Apr 5. doi: 10.1159/000488985. [Epub ahead of print]

Published online: April 05, 2018

Prevalence and genotype distribution of hepatitis C virus infection among patients with type 2 diabetes mellitus.
Farshadpour F, Taherkhani R, Ravanbod MR, Eghbali SS.

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Conclusion:
In this study, the prevalence of HCV infection in the diabetic patients in southern Iran was high and it was not associated with the biochemical measurements. Genotype 3a was the only genotype found in the diabetic population of this study, and all the HCV-infected diabetic patients were unaware of the infection due to asymptomatic nature of chronic HCV infection. Therefore, screening of all diabetic patients for HCV infection should be recommended to prevent the serious consequences associated with the coexistence of these two chronic diseases in a long run.

As Noted In The Study: After genotype 1a, genotype 3a is the most prevalent genotype in Iran, which is frequently observed among young Iranian patients and intravenous drug users; while genotypes 2 and 4 are uncommon in Iran [11, 27]. Overall, it is not obvious whether HCV genotype 3a observed in the present study is responsible for the occurrence of DM or whether it merely follows the predominant genotypic pattern of HCV in the region. However, this specific genotypic pattern of HCV infection in the diabetic patients of the present study is unlikely to be ascribable to chance alone and, therefore, merits further attention.

Abstract

This study was conducted to determine the prevalence and genotype distribution of HCV infection among patients with type 2 diabetes mellitus (DM).

Materials (Subjects) and Methods

A total of 556 consecutive patients with confirmed type 2 DM attending the diabetic clinic of Bushehr University of Medical Sciences and 733 non-diabetic subjects as control group were included in this study. Levels of FBS, ALT, AST, TCH and TG were measured by enzymatic colorimetric method, and the presence of anti-HCV antibodies were determined by ELISA. Semi-nested RT-PCR followed by sequencing was performed for all the anti-HCV seropositive samples. The data were analyzed using the Statistical Package for the Social Sciences 17.

Results:

Seroprevalence of HCV in diabetic patients was 1.98% (11/556), which was higher than HCV prevalence among the non-diabetic controls (4/733, 0.54%) (P=0.032). No significant differences in ALT, AST, FBS, TG and TCH levels were found between HCV seropositive and seronegative diabetic patients, although HCV seropositive diabetic patients tended to have higher ALT, AST and TCH levels but lower TG and FBS levels than seronegative patients. In the logistic regression analysis, only AST level was significantly associated with HCV seropositivity. Hence, AST level of 41-80 IU/L was the only significant predictive variable for HCV seropositivity in the diabetic patients (odds ratio, 4.89; 95% CI: 1.06-22.49; P= 0.041). Of 11 HCV seropositive diabetic patients, 10 (91%) had HCV viremia with genotype 3a.

Conclusion:

Patients with type 2 DM had a higher prevalence of HCV infection than controls, and this HCV seropositivity was independent of biochemical parameters.

Continue reading: https://www.karger.com/Article/Pdf/488985

Hepatitis C genotype 3 - 12 weeks of SOF/VEL safe and highly efficient across a diverse patient population

In conclusion, we confirm an overall very high efficacy and safety of 12 weeks of SOF/VEL in patients with HCV GT3 infection in a real-world setting. While the prevalence of clinically relevant NS5A RASs was low, our data indicate that their impact may be of less importance than previously expected. Thus, addition of RBV may only be required in certain subgroups, including patients with previous DAA-experience and/or decompensated cirrhosis.

Alimentary Pharmacology and Therapeutics

High efficacy of sofosbuvir/velpatasvir and impact of baseline resistance‐associated substitutions in hepatitis C genotype 3 infection

J. von Felden J. Vermehren P. Ingiliz S. Mauss T. Lutz K. G. Simon H. W. Busch A. Baumgarten K. Schewe D. Hueppe C. Boesecke J. K. Rockstroh M. Daeumer N. Luebke ...

First published: 14 March 2018 https://doi.org/10.1111/apt.14592

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Summary Background
Twelve weeks of the pangenotypic direct‐acting antiviral (DAA) combination sofosbuvir/velpatasvir (SOF/VEL) was highly efficient in patients with hepatitis C virus (HCV) genotype 3 (GT3) infection in the ASTRAL‐3 approval study. However, presence of resistance‐associated substitutions (RASs) in the HCV nonstructural protein 5A (NS5A) was associated with lower treatment response.

Aim
To assess the efficacy and safety of SOF/VEL ± ribavirin (RBV) and the impact of NS5A RASs and RBV use on treatment outcome in HCV GT3 infection in a real‐world setting.

Methods
In this multicentre cohort study, GT3 patients from ten treatment centres across Germany were included. Sustained virological response was assessed 12 weeks after end‐of‐treatment (SVR12) in modified intention‐to‐treat (mITT) and per‐protocol analysis (PP). NS5A RASs were tested by population‐based sequencing.

Results
A total of 293 GT3 patients were included. The median age was 48 years, 70% were male, 25.3% were cirrhotic, 9.2% were HCV/HIV co‐infected and 21.8% were treatment‐experienced, including 4.1% with DAA experience. Baseline NS5A RASs (Y93H, A30K, L31M) were detected in 11.2%. RBV was added in 5% of noncirrhotic and 58.9% of cirrhotic patients, respectively. SVR12 rates for SOF/VEL±RBV were 95.9% (mITT) and 99.5% (PP), respectively. Only 1 virological relapse occurred in a cirrhotic patient previously treated with SOF/RBV. No treatment‐related major adverse events occurred.

Conclusion
Twelve weeks of SOL/VEL±RBV was safe and highly efficient in HCV GT3 across a diverse patient population. Baseline NS5A RASs were rarely observed and presence did not seem to impact SVR, regardless of the use of RBV.

Full article:
https://onlinelibrary.wiley.com/doi/full/10.1111/apt.14592

Patient To Patient Video - Treating HCV according to genotype with a focus on HCV genotype 3

Patient To Patient Video 
Happy Saturday folks, here is a new patient friendly video launched by Hepatitis C activist Greg Jefferys, with a look at current therapies used to treat the hepatitis C virus across all HCV genotypes.

Website
Generic Hepatitis C Drugs
Greg is the founder of Hepatitis C Buyers Club, formed to help people buy generic Harvoni or Epclusa. Visit his website and watch treatment videos, learn about symptoms or possible treatment side effect. Finally, make sure to read Greg's latest articles over at HepMag.

On This Blog

2018 HCV Genotypes and Treatment
Offered on this page is research updates with a focus on treating HCV according to genotype using FDA approved and investigational medicines. Information is extracted from news articles, peer-reviewed journals, as well as liver meetings/conferences, research manuscripts and interactive learning activities.

Drugs Used To Treat Hep C
The following HCV Guidelines offer treatment recommendations using current HCV medications based on HCV Genotype and history of treatment. Which include treatment-naive patients (patients who have never used HCV medications to treat the virus) and treatment-experienced patients (patients who have previously taken HCV medications).

The following pages include guidance for management of treatment-naive patients.
Genotype 1
Genotype 2
Genotype 3
Genotype 4
Genotype 5 or 6

The following pages include guidance for management of treatment-experienced patients.
Genotype 1
Genotype 2
Genotype 3
Genotype 4
Genotype 5 or 6

Stay current with all guideline updates, "click here."

Enjoy your weekend, thank you Mr. Jefferys!
Tina

HCV infection and liver cirrhosis - Predictors of functional benefit of hepatitis C therapy in a ‘real-life’ cohort

World J Gastroenterol. Feb 21, 2018; 24(7): 852-861
Published online Feb 21, 2018. doi: 10.3748/wjg.v24.i7.852

Retrospective Study

Predictors of functional benefit of hepatitis C therapy in a ‘real-life’ cohort

Niels Steinebrunner, Kerstin Stein, Catharina Sandig, Thomas Bruckner, Wolfgang Stremmel, Anita Pathil

Therapeutic regimens for patients with chronic hepatitis C virus (HCV) infection have substantially improved over the last few years. However real-life data in patients with cirrhosis are still limited, and predictors of functional benefit of direct-acting antivirals are not well defined. We analysed data from patients with HCV infection and liver cirrhosis to evaluate predictors of functional benefit for identifying patients profiting most from antiviral therapy beyond HCV eradication.

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Abstract
AIM
To define predictors of functional benefit of direct-acting antivirals (DAAs) in patients with chronic hepatitis C virus (HCV) infection and liver cirrhosis.

METHODS
We analysed a cohort of 199 patients with chronic HCV genotype 1, 2, 3 and 4 infection involving previously treated and untreated patients with compensated (76%) and decompensated (24%) liver cirrhosis at two tertiary centres in Germany. Patients were included with treatment initiation between February 2014 and August 2016. All patients received a combination regimen of one or more DAAs for either 12 or 24 wk. Predictors of functional benefit were assessed in a univariable as well as multivariable model by binary logistic regression analysis.

RESULTS
Viral clearance was achieved in 88% (175/199) of patients. Sustained virological response (SVR) 12 rates were as follows: among 156 patients with genotype 1 infection the SVR 12 rate was 90% (n = 141); among 7 patients with genotype 2 infection the SVR 12 rate was 57% (n = 4); among 30 patients with genotype 3 infection the SVR 12 rate was 87% (n = 26); and among 6 patients with genotype 4 infection the SVR 12 rate was 67% (n = 4). Follow-up MELD scores were available for 179 patients. A MELD score improvement was observed in 37% (65/179) of patients, no change of MELD score in 41% (74/179) of patients, and an aggravation was observed in 22% (40/179) of patients. We analysed predictors of functional benefit from antiviral therapy in our patients beyond viral eradication. We identified the Child-Pugh score, the MELD score, the number of platelets and the levels of albumin and bilirubin as significant factors for functional benefit.

CONCLUSION
Our data may contribute to the discussion of potential risks and benefits of antiviral therapy with individual patients infected with HCV and with advanced liver disease.

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Glecaprevir–Pibrentasvir for 8 or 12 Weeks in HCV Genotype 1 or 3 Infection

Glecaprevir–Pibrentasvir for 8 or 12 Weeks in HCV Genotype 1 or 3 Infection
Stefan Zeuzem, M.D., Graham R. Foster, Ph.D., Stanley Wang, M.D., Armen Asatryan, M.D., Edward Gane, M.D., Jordan J. Feld, M.D., M.P.H., Tarik Asselah, M.D., Ph.D., Marc Bourlière, M.D., Peter J. Ruane, M.D., Heiner Wedemeyer, M.D., Stanislas Pol, Ph.D., Robert Flisiak, M.D., Ph.D., Fred Poordad, M.D., Wan-Long Chuang, M.D., Ph.D., Catherine A. Stedman, M.B., Ch.B., Ph.D., Steven Flamm, M.D., Paul Kwo, M.D., Gregory J. Dore, Ph.D., M.P.H., Gladys Sepulveda-Arzola, M.D., Stuart K. Roberts, M.D., Ruth Soto-Malave, M.D., Kelly Kaita, M.D., Massimo Puoti, M.D., John Vierling, M.D., Edward Tam, M.D., Hugo E. Vargas, M.D., Rafi Bruck, M.D., Francisco Fuster, M.D., Seung-Woon Paik, M.D., Franco Felizarta, M.D., Jens Kort, M.D., Ph.D., Bo Fu, Ph.D., Ran Liu, Ph.D., Teresa I. Ng, Ph.D., Tami Pilot-Matias, Ph.D., Chih-Wei Lin, Ph.D., Roger Trinh, M.D., M.P.H, and Federico J. Mensa, M.D.et al.

Full Text Article

https://jumpshare.com/v/9GtWUYi3hENIx8GnabyH

Article shared and downloaded via Twitter by Henry E. Chang 

Abstract
Background
Glecaprevir and pibrentasvir are direct-acting antiviral agents with pangenotypic activity and a high barrier to resistance. We evaluated the efficacy and safety of 8-week and 12-week courses of treatment with 300 mg of glecaprevir plus 120 mg of pibrentasvir in patients without cirrhosis who had hepatitis C virus (HCV) genotype 1 or 3 infection.

Methods
We conducted two phase 3, randomized, open-label, multicenter trials. Patients with genotype 1 infection were randomly assigned in a 1:1 ratio to receive once-daily glecaprevir–pibrentasvir for either 8 or 12 weeks. Patients with genotype 3 infection were randomly assigned in a 2:1 ratio to receive 12 weeks of treatment with either glecaprevir–pibrentasvir or sofosbuvir–daclatasvir. Additional patients with genotype 3 infection were subsequently enrolled and nonrandomly assigned to receive 8 weeks of treatment with glecaprevir–pibrentasvir. The primary end point was the rate of sustained virologic response 12 weeks after the end of treatment.

Results
In total, 1208 patients were treated. The rate of sustained virologic response at 12 weeks among genotype 1–infected patients was 99.1% (95% confidence interval [CI], 98 to 100) in the 8-week group and 99.7% (95% CI, 99 to 100) in the 12-week group. Genotype 3–infected patients who were treated for 12 weeks had a rate of sustained virologic response at 12 weeks of 95% (95% CI, 93 to 98; 222 of 233 patients) with glecaprevir–pibrentasvir and 97% (95% CI, 93 to 99.9; 111 of 115) with sofosbuvir–daclatasvir; 8 weeks of treatment with glecaprevir–pibrentasvir yielded a rate of 95% (95% CI, 91 to 98; 149 of 157 patients). Adverse events led to discontinuation of treatment in no more than 1% of patients in any treatment group.

Conclusions
Once-daily treatment with glecaprevir–pibrentasvir for either 8 weeks or 12 weeks achieved high rates of sustained virologic response among patients with HCV genotype 1 or 3 infection who did not have cirrhosis. (Funded by AbbVie; ENDURANCE-1 and ENDURANCE-3 ClinicalTrials.gov numbers, NCT02604017 and NCT02640157.)

View full text article: https://jumpshare.com/v/9GtWUYi3hENIx8GnabyH

Ira M. Jacobson MD: 8-week therapy for patients with HCV infection

Clinical Care Options 

How New Data From AASLD 2017 Inform the Use of 8-Week Regimens for HCV
Ira M. Jacobson MD - 1/9/2018
Several studies presented at the 2017 AASLD meeting in Washington, DC, assessed 8-week therapy for patients with HCV infection. In this commentary, I discuss how key data from these studies may have an impact on management of patients with HCV infection.

Studies discussed:

8-Week GZR/EBR for Treatment-Naive, Noncirrhotic Patients With Genotype 1b HCV Infection
GLE/PIB for Treatment-Naive Genotype 3 HCV
8-Week LDV/SOF for Acute Genotype 1 or 4 HCV and HIV Coinfection

Free registration required
https://www.clinicaloptions.com/Hepatitis.aspx

New At Clinical Care Options 
New Insights on NAFLD/NASH From AASLD 2017
Philip Newsome PhD, FRCPE - 1/8/2018
Here’s my take on how new data from AASLD 2017 on noninvasive imaging modalities and emerging investigational agents may affect the NAFLD/NASH patient management landscape.

How Injection Drug Use Affects HCV Treatment
Norah Terrault MD, MPH - 1/3/2018
Here’s my take on why colocalization of HCV treatment with other medical and social services may be ideal for persons who inject drugs. 

Mavyret (glecaprevir/pibrentasvir) for HCV genotype 3 patients with cirrhosis and/or prior treatment experience: A partially randomized phase 3 clinical trial

In case you missed it

Glecaprevir/pibrentasvir for hepatitis C virus genotype 3 patients with cirrhosis and/or prior treatment experience: A partially randomized phase 3 clinical trial
Authors David Wyles, Fred Poordad, Stanley Wang, Laurent Alric, Franco Felizarta, Paul Y. Kwo, Benedict Maliakkal, Kosh Agarwal, Tarek Hassanein, Frank Weilert, Samuel S. Lee, Jens Kort, Sandra S. Lovell, Ran Liu, Chih-Wei Lin, Tami Pilot-Matias, Preethi Krishnan, Federico J. Mensa

First published: 4 January 2018
DOI: 10.1002/hep.29541

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Abstract
This study assessed the efficacy and safety of ribavirin-free coformulated glecaprevir/pibrentasvir (G/P) in patients with hepatitis C virus genotype 3 infection with prior treatment experience and/or compensated cirrhosis, a patient population with limited treatment options. SURVEYOR-II, Part 3 was a partially randomized, open-label, multicenter, phase 3 study. Treatment-experienced (prior interferon or pegylated interferon ± ribavirin or sofosbuvir plus ribavirin ± pegylated interferon therapy) patients without cirrhosis were randomized 1:1 to receive 12 or 16 weeks of G/P (300 mg/120 mg) once daily. Treatment-naive or treatment-experienced patients with compensated cirrhosis were treated with G/P for 12 or 16 weeks, respectively. The primary efficacy endpoint was the percentage of patients with sustained virologic response at posttreatment week 12 (SVR12). Safety was evaluated throughout the study. There were 131 patients enrolled and treated. Among treatment-experienced patients without cirrhosis, SVR12 was achieved by 91% (20/22; 95% confidence interval [CI], 72-97) and 95% (21/22; 95% CI, 78-99) of patients treated with G/P for 12 or 16 weeks, respectively. Among those with cirrhosis, SVR12 was achieved by 98% (39/40; 95% CI, 87-99) of treatment-naive patients treated for 12 weeks and 96% (45/47; 95% CI, 86-99) of patients with prior treatment experience treated for 16 weeks. No adverse events led to discontinuation of study drug, and no serious adverse events were related to study drug. Conclusion: Patients with hepatitis C virus genotype 3 infection with prior treatment experience and/or compensated cirrhosis achieved high SVR12 rates following 12 or 16 weeks of treatment with G/P. The regimen was well tolerated.

(Hepatology 2017)

In summary, SURVEYOR-II Part 3 enrolled and treated some of the most difficult-to-cure HCV patients: those with GT3 infection and prior treatment experience and/or cirrhosis. Overall, the fixed-dose combination of once-daily RBV-free G/P was well tolerated and demonstrated high SVR12 rates (≥95%) in treatment-naive patients with cirrhosis treated for 12 weeks and treatment-experienced patients with or without cirrhosis treated for 16 weeks. Therefore, G/P provides an efficacious and well-tolerated once-daily RBV-free treatment option for patients with HCV genotype 3 and prior treatment experience and/or cirrhosis.

Continue to article: http://onlinelibrary.wiley.com/doi/10.1002/hep.29541/full

Summary from AASLD 2017 for Hepatitis C HCV: Game over?

Conference Reports from NATAP

Summary from AASLD 2017 for Hepatitis C HCV: Game over?
Jurgen K. Rockstroh M.D., Professor of Medicine
Department of Medicine I, University Hospital Bonn, Bonn, Germany

Introduction
The AASLD Liver Meeting was held in October from 20-24th, 2017 in Washington DC, USA. Many regular AASLD attendees will still remember the completely packed late breaker sessions from recent years, full of phase II and III new direct acting antiviral (DAA) combination trials in varying patient populations. At this year AASLD Liver Meeting, no new DAA combination study results were presented in these sessions but rather were replaced by new drug trials for treatment of NASH or primary sclerosing cholangitis. Indeed, the only two new dual and triple DAA combinations, which were presented at the meeting, were accompanied by press releases from the respective companies Merck and Janssen, which announced the termination of their DAA development programs (1-2). Nevertheless, important new findings from the HCV research space were reported including issues around HCV screening, how to improve linkage to care, and treatment results from many different patient populations and real-life cohorts as well as post HCV cure monitoring. Reassuringly, the high success rates of all oral DAA therapy was further confirmed from a wealth of data particularly from somewhat more challenging HCV patient populations including: PWIDs, patients with concomitant advanced kidney disease, patients before and after kidney or liver transplantation, HCV genotype 3 infection and patients with unfavorable HCV disease characteristics, including compensated and decompensated cirrhosis (3-11). However, there was also data on shorter treatment durations for patients with more favorable HCV disease characteristics such as for non-cirrhotic GT1b patients (12). In addition, there was also new data around retreatment of previous DAA failures (with documented resistance development) with new DAA combinations (13-14). In the area of HIV-coinfection, clearly outcomes of the ACTG trial on treatment of acute hepatitis C in HIV-seropositive individuals for eight weeks with ledipasvir/sofosbuvir (LDV/SOF) were also new and noteworthy (15). Of interest were also reports on the increases in acute HCV infections among HIV-seropositive men who have sex with men (MSM) and the high risk of reinfection in particular patient populations (16-17). Further data was also presented on the question whether there is an increased risk for hepatocellular carcinoma in DAA treated patients from large real-life cohorts and what impact SVR has on clinical endpoints under continued follow-up (18-22).

The following AASLD summary report tries to capture the major new findings and results presented around the topics raised above, as well as to outline some of the status reports of HCV treatment implementation on a global level. Clearly, the successes of modern HCV DAA combination therapy still have not reached all in need for these treatments.

Continue reading... http://www.natap.org/2017/AASLD/AASLD_148.htm

Dramatic response of HCV patients with genotype 3 to sofosbuvir-based therapies in Punjab, Pakistan: A prospective study

World J Gastroenterol. Nov 28, 2017; 23(44): 7899-7905
Published online Nov 28, 2017. doi: 10.3748/wjg.v23.i44.7899

Dramatic response of hepatitis C patients chronically infected with hepatitis C virus genotype 3 to sofosbuvir-based therapies in Punjab, Pakistan: A prospective study
Sajjad Iqbal, Muhammad Haroon Yousuf, Muhammad Iftikhar Yousaf

Received: June 12, 2017
Peer-review started: July 12, 2017
First decision: August 10, 2017
Revised: September 6, 2017
Accepted: September 13, 2017
Article in press: September 13, 2017
Published online: November 28, 2017

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Core tip: Previously, hepatitis C was treated with interferon-based therapies. Intolerable side effects, prolonged treatment duration and unsatisfactory response rates were the major droughts of those therapies. The introduction of sofobuvir (SOF) was claimed as a highly responding oral drug for hepatitis C patients, with minimal side effects in different trials; thus, it was important to assess its efficacy in our population. We found an outstanding response rate of SOF in hepatitis C patients infected with genotype 3 of hepatitis C virus. These findings revealed that with SOF we may eliminate hepatitis C from our population.

Abstract

AIM

To prospectively evaluate the efficacy of sofobuvir (SOF) in hepatitis C patients infected with hepatitis C virus (HCV) genotype 3 in Pakistan.

METHODS
The present study was performed with the coordination of gastroenterology and pathology departments of Shalamar Hospital Lahore from August 2014 to May 2016. The total number of patients included in this study was 1375 and all of them were infected with HCV genotype 3. On the basis of drug combinations, all the patients were separated into two groups. The first group of patients was treated for 24 wk with SOF (Sovaldi^® by Gilead Sciences) plus ribavirin (RBV) [Ribazol^® by Getz Pharma Pakistan (PVT) Ltd], while the patients of the second group were treated with SOF + RBV + pegylated-interferon (pegIFN) alfa-2a (Ropegra by Roach) for 12 wk. HCV genotyping and viral load measurement were performed on fully automated Abbott Real-Time PCR system (Abbott m24sp automated nucleic acid extraction system and Abbott m2000rt amplification system; abbott Molecular, Des Plaines, IL, United States). For the assessment of sustained virological response (SVR), all HCV RNA negative patients were followed for 12 weeks after the treatment completion. Any patient with less than 12 IU/mL viral load after 12 wk of treatment completion was considered as a sustained virological responder (SVR-12).

RESULTS
A total of 1375 patients chronically infected with HCV genotype 3 were treated with two drug combinations SOF + RBV and SOF + RBV + pegIFN alfa-2a. On the basis of these drug combinations, patients were divided into two groups (first and second). Overall SVR-12 was excellent in both groups (99.17% and 97.91%). Older patients (> 40 years) of second group showed lower SVR-12 (93.46%) compared to first group older patients (98.79%), while in the younger patients of both groups, the SVR-12 rate was almost the same (99.54% in first group and 99.05% in second group). No such difference regarding SVR-12 rate was seen in males and females of first group patients (99.68% and 98.88%, respectively), while in second group the males were found to be better responders compared to females (98.96% and 95%). The SVR-12 rate in previously treated patients of first group was better (99.34%) than second group (93.70%), while naïve patients of second group were marginally better responders (99.25%) than first group (97.80%). Rapid viral response at week-4 was found to be a very effective predictor for assessing the SVR rate at this stage of therapy in both groups. Headache, anemia and fatigue were common side effects in both groups either treated with SOF + RBV or SOF + RBV + pegIFN alfa-2a, while the overall percentage of the side effects was higher in second group.

CONCLUSION
The remarkable SVR response rate of HCV genotype 3 infected patients to SOF provided a new way to look forward to eliminate hepatitis C from our region.

Key Words: Sofosbuvir, Sustained virological response, Pakistan

Continue reading article: https://www.wjgnet.com/1007-9327/full/v23/i44/7899.htm   

Intrapatient viral diversity & treatment outcomes in patients with genotype 3a HCV infection on SOF-containing regimens

Journal of viral hepatitis
Intrapatient viral diversity & treatment outcomes in patients with genotype 3a HCV infection on SOF-containing regimens
Neeru Bhardwaj, Manon Ragonnet-Cronin, Ben Murrell, Krishna Chodavarapu,  Ross Martin, Silvia Chang, Michael D. Miller, Jordan J. Feld, Mark Sulkowski, Alessandra Mangia, Joel O. Wertheim, Anu Osinusi, John McNally, Diana Brainard, Hongmei Mo, Evguenia S. Svarovskaia

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Abstract
Treatment with the direct-acting antiviral agent (DAA) sofosbuvir (SOF), an NS5B inhibitor, and velpatasvir (VEL), an NS5A inhibitor, demonstrates viral cure rates of ≥95% in hepatitis C virus (HCV) genotypes (GT) 1-6. Here we investigated intrapatient HCV diversity in NS5A and NS5B using Shannon entropy to examine the relationship between viral diversity and treatment outcome. At baseline, HCV diversity was lowest in patients infected with HCV GT3 as compared to the other GTs, and viral diversity was greater in NS5A than NS5B (p<0.0001). Treatment outcome with SOF/VEL or the comparator regimen of SOF with ribavirin (RBV) was not correlated with baseline diversity. However, among persons treated with SOF/VEL, a decrease in diversity from baseline was observed at relapse in the majority virologic failures, consistent with a viral bottleneck event at relapse. In contrast, an increase in diversity was observed in 27% of SOF+RBV virologic failures. We investigated whether the increase in diversity was due to an increase in the transition rate, one mode of potential RBV-mediated mutagenesis; however, we found no evidence of this mechanism. Overall, we did not observe that viral diversity at baseline influenced treatment outcome, but the diversity changes observed at relapse can improve our understanding of RBV viral suppression in vivo.

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