Showing posts with label geno3. Show all posts
Showing posts with label geno3. Show all posts

Thursday, June 14, 2018

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 

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Friday, April 13, 2018

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

Tuesday, April 10, 2018

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.

Full-Text

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

Friday, April 6, 2018

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.

Thursday, March 29, 2018

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

Saturday, March 10, 2018

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

Friday, February 9, 2018

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.


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.

Full Text

Thursday, January 25, 2018

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

Thursday, January 11, 2018

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


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. 

Saturday, January 6, 2018

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.

Friday, December 1, 2017

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.

Monday, November 27, 2017

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   

Wednesday, November 22, 2017

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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https://jumpshare.com/v/7WGwhBE2O7flSReyq4y7

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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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Friday, November 17, 2017

Effectiveness of current and future regimens for treating genotype 3 hepatitis C virus infection: a large-scale systematic review

Effectiveness of current and future regimens for treating genotype 3 hepatitis C virus infection: a large-scale systematic review
Hosnieh Fathi, Andrew Clark, Nathan R. Hill and Geoffrey Dusheiko

BMC Infectious Diseases BMC series – open, inclusive and trusted 201717:722 https://doi.org/10.1186/s12879-017-2820-z©

View Full Text Article Online

Received: 24 May 2017
Accepted: 6 November 2017
Published: 16 November 2017

Abstract
Background
Six distinct genetic variants (genotypes 1 − 6) of hepatitis C virus (HCV) exist globally. Certain genotypes are more prevalent in particular countries or regions than in others but, globally, genotype 3 (GT3) is the second most common. Patients infected with HCV GT1, 2, 4, 5 or 6 recover to a greater extent, as measured by sustained virological response (SVR), following treatment with regimens based on direct-acting antivirals (DAAs) than after treatment with older regimens based on pegylated interferon (Peg-IFN). GT3, however, is regarded as being more difficult to treat as it is a relatively aggressive genotype, associated with greater liver damage and cancer risk; some subgroups of patients with GT3 infection are less responsive to current licensed DAA treatments. Newer DAAs have become available or are in development.

Methods
According to PRISMA guidance, we conducted a systematic review (and descriptive statistical analysis) of data in the public domain from relevant clinical trial or observational (real-world) study publications within a 5-year period (February 2011 to May 2016) identified by PubMed, Medline In-Process, and Embase searches. This was supplemented with a search of five non-indexed literature sources, comprising annual conferences of the AASLD, APASL, CROI, EASL, and WHO, restricted to a 1-year period (April 2015 to May 2016).

Results
Of the all-oral regimens, the efficacy (SVR12 ≥ 90%) of sofosbuvir plus daclatasvir- and velpatasvir-based regimens in clinical trials supports and reinforces their recommendation by guidelines. Other promising regimens comprise grazoprevir + elbasvir + sofosbuvir, and ombitasvir + paritaprevir/ribavirin + sofosbuvir. Newer regimens incorporating pibrentasvir + glecaprevir or grazoprevir + ruzasvir + MK-3682 (uprifosbuvir), offer all-oral, ribavirin-free SVR12 rates consistently greater than 95%. Observational studies report slightly lower overall SVR rates but reflect corresponding clinical trial data in terms of treatments most likely to achieve good responses.

Conclusions
On the basis of SVR12, we established that for treating GT3 infections (i) regimens incorporating newer DAAs are more effective than those comprising older DAAs, and (ii) ribavirin may be of less benefit in newer DAA regimens than in older DAA regimens. The analysis provides evidence that DAA regimens can replace Peg-IFN-based regimens for GT3 infection.

Keywords
Hepatitis C virus Genotype 3 Direct-acting antiviral Cirrhosis Co-infection Systematic literature review
https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-017-2820-z

For Patients
HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C
This version of the guidance has been updated to reflect several important developments, including the recent approvals of glecaprevir/pibrentasvir and sofosbuvir/velpatasvir/voxilaprevir. Updated recommendations reflecting these approvals are provided throughout the guidance

New Treatment-Naïve & Treatment-Experienced
The following pages include guidance for management of treatment-naive patients.
The following pages include guidance for management of treatment-experienced patients.
Stay current with all guideline updates, "click here."

Of Interest
September 29,2017
Merck Discontinues MK-3682B and MK-3682C Development Programs
Merck announced its strategic decision to discontinue the development of the investigational combination regimens MK-3682B (grazoprevir/ruzasvir/ uprifosbuvir) and MK-3682C (ruzasvir/uprifosbuvir) for the treatment of chronic hepatitis C virus (HCV) infection. This decision was made based on a review of available Phase 2 efficacy data and in consideration of the evolving marketplace and the growing number of treatment options available for patients with chronic HCV infection

Wednesday, November 1, 2017

Challenges in Treating Genotype 3 Hepatitis C Virus


Challenges in Treating Genotype 3 Hepatitis C Virus
Sustained virological response (SVR), defined as "an HCV RNA level below the threshold of quantification,"4 sustained for 12 to 24 weeks after treatment ends, is considered predictive of cure. In clinical trials of the DAA agent sofosbuvir plus ribavirin, only 30% to 60% of patients with GT3 had SVR after 12 to 16 weeks of therapy compared with 95% of patients with GT2.2,3 Data have shown patients with GT3 HCV have faster progression of fibrosis and higher rates of cirrhosis, severe steatosis, and hepatocellular carcinoma.2,4 Steatosis is associated with higher viral loads, and cirrhosis predicts a lower likelihood of cure in treatment-naive patients, which may help explain the worse SVR rates in patients with GT3 relative to other HCV genotypes.4 Indeed, when SVR in patients with GT3 is stratified according to the presence of compensated cirrhosis or prior treatment failure, previously untreated patients and patients without cirrhosis are much more likely to achieve SVR with DAA therapy...

Monday, October 23, 2017

The Liver Meeting® 2017 - Is Ribavirin Really Needed for Patients With HCV Genotype 3 on Sofosbuvir/Velpatasvir 

Is Ribavirin Really Needed for Patients With HCV Genotype 3 on Sofosbuvir/Velpatasvir
By Andrew D. Bowser
The findings add new perspective to the ongoing discussion among researchers and clinicians as to whether adding ribavirin might prevent a relapse in patients with HCV genotype 3, particularly if they were previously treated.

Results of the current study represent “real world” experience with patients with HCV genotype 3 treated at 9 sites in Germany, according to Stefan Christensen, MD, Department of Infectious Diseases, Center for Interdisciplinary Medicine, Muenster, Germany.

“We could confirm the high SVR12 rates [sustained virologic response at 12 weeks] from the clinical phase 3 studies with sofosbuvir/velpatasvir, [but] in our cohort, it seems like the addition of ribavirin in cirrhotic patients did not have further benefit for those patients,” he said.
Read the article @ FirstWord Pharma

Of Interest - FirstWord Pharma

The Liver Meeting® 2017 - Mavyret (Glecaprevir/Pibrentasvir) for Treatment-Naive Patients With HCV Genotype 3

NAM Publications
An integrated analysis of clinical trial data showed that glecaprevir/pibrentasvir taken for 8 weeks cured 98% of people without cirrhosis with hard-to-treat genotype 3, while a 12-week course cured 100% of people with genotype 3 with cirrhosis. A related analysis showed that the combination taken for 12 or 16 weeks cured 96% of people with compensated cirrhosis across all genotypes.

Steven Flamm of Northwestern Feinberg School of Medicine in Chicago and colleagues performed an integrated analysis of efficacy and safety data from phase 2 and 3 clinical trials of glecaprevir/pibrentasvir for previously untreated people with HCV genotype 3, either without cirrhosis or with compensated cirrhosis.
Read the article @ aidsmap

aidsmap coverage
Conference news: The Liver Meeting

NATAP
WASHINGTON, DC -- October 23, 2017 -- Glecaprevir/pibrentasvir was well-tolerated and resulted in high virologic response rates in treatment-naive patients with hepatitis C virus (HCV) genotype 3 infection, according to a study presented here at The Liver Meeting, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).
Read the article @ FirstWord Pharma

Of Interest - HCV Genotype 3
Of Interest - FirstWord Pharma
By Andrew D. Bowser
The findings add new perspective to the ongoing discussion among researchers and clinicians as to whether adding ribavirin might prevent a relapse in patients with HCV genotype 3, particularly if they were previously treated.

Results of the current study represent “real world” experience with patients with HCV genotype 3 treated at 9 sites in Germany, according to Stefan Christensen, MD, Department of Infectious Diseases, Center for Interdisciplinary Medicine, Muenster, Germany.

“We could confirm the high SVR12 rates [sustained virologic response at 12 weeks] from the clinical phase 3 studies with sofosbuvir/velpatasvir, [but] in our cohort, it seems like the addition of ribavirin in cirrhotic patients did not have further benefit for those patients,” he said.
Read the article @ FirstWord Pharma

FirstWord Pharma

Tuesday, October 17, 2017

The changing HCV treatment cascade

Pharmacology Consult
The changing HCV treatment cascade
Infectious Disease News, October 2017
Jocelyn Mason, PharmD; Kimberly D. Boeser, PharmD, MPH, BCPS, AQ-ID
The rapid development of DAA combinations provides simplified regimens, shorter durations, improved efficacy and greater tolerability, unlike the previous interferon and ribavirin cornerstone regimens. Although the IDSA/AASLD guidelines provide the map to managing HCV, they do not identify the ideal interferon-free regimen to begin with, nor have they given a clear path to treating genotype 3 and those with decompensated cirrhosis. This ever-changing field will require collaboration among health care providers, including those specializing in infectious diseases, hepatology and gastroenterology, as well as pharmacists, to optimize treatment strategies. As the landscape of HCV continues to update with new literature and new medications, this subspecialty continues to be dynamic.
Continue to article - https://www.healio.com/infectious-disease/hepatitis-c/news/print/infectious-disease-news/%7B87b74536-f358-43d3-a804-f37a98402b0b%7D/the-changing-hcv-treatment-cascade

Friday, September 22, 2017

HCV Guidance Updates - Recommendations Reflecting Vosevi and Mavyret


HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C
The American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) with the International Antiviral Society developed a living document with ever evolving guidelines to treat HCV.

The guidelines have a complex algorithm for practitioners around the country to follow and see what's the right treatment, for the right patients, for the right about of time. The document is beneficial for patients as well living with or treating HCV. When new HCV drugs are approved, and new real world data is established, the guidelines are updated.

What’s New, Updates, and Changes to the Guidance
Thursday, September 21, 2017
This version of the guidance has been updated to reflect several important developments, including the recent approvals of glecaprevir/pibrentasvir and sofosbuvir/velpatasvir/voxilaprevir. Updated recommendations reflecting these approvals are provided throughout the guidance.

Updated references have been provided throughout the guidance.

In addition to updates to all the sections, the following new sections have been added to the guidance:
Genotype 1 & 3
New Treatment-Naïve & Treatment-Experienced
The following pages include guidance for management of treatment-naive patients.
The following pages include guidance for management of treatment-experienced patients.
Stay current with all guideline updates, "click here."

Complete Guidance
Download the PDF
Version: September 21, 2017

Wednesday, September 20, 2017

Glecaprevir/Pibrentasvir for HCV Genotype 3 Patients with Cirrhosis and/or Prior Treatment Experience

Hepatology. 2017 Sep 19. doi: 10.1002/hep.29541. 

Glecaprevir/Pibrentasvir for HCV Genotype 3 Patients with Cirrhosis and/or Prior Treatment Experience: A Partially Randomized Phase III Clinical Trial.
Wyles D1, Poordad F2, Wang S3, Alric L4, Felizarta F5, Kwo PY6, Maliakkal B7, Agarwal K8, Hassanein T9, Weilert F10, Lee SS11, Kort J3, Lovell SS3, Liu R3, Lin CW3, Pilot-Matias T3, Krishnan P3, Mensa FJ3.

Full Text Article
View online @ NATAP

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.

Abstract
BACKGROUND:
This study assessed the efficacy and safety of ribavirin (RBV)-free coformulated glecaprevir/pibrentasvir (G/P) in patients with hepatitis C virus (HCV) genotype (GT) 3 infection with either prior treatment experience and/or compensated cirrhosis, a patient population with limited treatment options.

METHODS:
SURVEYOR-II, Part 3 was a partially-randomized, open-label, multicenter, phase 3 study. Treatment-experienced (prior interferon (IFN) or pegIFN ± ribavirin or SOF plus ribavirin ± pegIFN therapy) patients without cirrhosis were randomized 1:1 to receive 12 or 16 weeks of G/P (300 mg/120 mg) once daily. Treatment-naïve 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 post-treatment week 12 (SVR12). Safety was evaluated throughout the study.

RESULTS:
There were 131 patients enrolled and treated. Among treatment-experienced patients without cirrhosis, SVR12 was achieved by 91% (20/22; CI 72-97) and 95% (21/22; 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; CI 87-99) of treatment-naïve patients treated for 12 weeks, and 96% (45/47; CI 86-99) of patients with prior treatment experience treated for 16 weeks. No adverse events (AEs) led to discontinuation of study drug and no serious AEs were related to study drug.

CONCLUSIONS:
Patients with HCV GT3 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.

Full Text Article Available Online @ NATAP

http://onlinelibrary.wiley.com/doi/10.1002/hep.29541/abstract
© 2017 by the American Association for the Study of Liver Diseases.
This article is protected by copyright. All rights reserved.