Beyond interferon side effects: What residual barriers exist to DAA hepatitis C treatment for people who inject drugs?

Beyond interferon side effects: What residual barriers exist to DAA hepatitis C treatment for people who inject drugs? 
Annie Madden, Max Hopwood, Joanne Neale, Carla Treloar
Published: November 30, 2018 https://doi.org/10.1371/journal.pone.0207226

Abstract
Recent advances in the efficacy and tolerability of hepatitis C treatments and the introduction of a universal access scheme for the new Direct Acting Antiviral (DAA) therapies in March 2016, has resulted in a rapid increase in the uptake of hepatitis C treatment in Australia. Despite these positive developments, recent data suggest a plateauing of treatment numbers, indicating that more work may need to be done to identify and address ongoing barriers to hepatitis C treatment access and uptake. This paper aims to contribute to our understanding of the ongoing barriers to DAA therapies, with a focus on people who inject drugs. The paper draws on participant interview data from a qualitative research study based on a participatory research design that included a peer researcher with direct experience of both hepatitis C DAA treatment and injecting drug use at all stages of the research process. The study’s findings show that residual barriers to DAA treatment exist at personal, provider and system levels and include poor venous access, DAA treatments not considered ‘core-business’ by opioid substitution treatment (OST) providers, and patients having to manage multiple health and social priorities that interfere with keeping medical appointments such as childcare and poor access to transport services. Further, efforts to increase access to and uptake of DAA hepatitis C treatment over time will require a focus on reducing stigma and discrimination towards people who inject drugs as this remains as a major barrier to care for many people.

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Hepatitis C: How resistance-associated substitutions evolved after DAA treatment failures

Full-text article available online @ Medscape, free registration may be required. 

This study investigated how resistance-associated substitutions evolved after DAA treatment failures in HCV-infected patients, and assessed the effect of those substitutions on viral fitness.

J Viral Hepat. 2018 Nov;25(11):1251-1259. doi: 10.1111/jvh.12932. Epub 2018 Jun 13.
Evolution and persistence of resistance-associated substitutions of hepatitis C virus after direct-acting antiviral treatment failures.
Jeong Y1,2, Jin B1,2, Lee HW2,3, Park HJ2, Park JY2,3, Kim DY2,3, Han KH1,2,3,4, Ahn SH1,2,3, Kim S2,3,4,5.

Abstract

Daclatasvir plus asunaprevir (DCV+ASV) treatment is an all-oral direct-acting antiviral (DAA) therapy for the genotype 1b HCV-infected patients. In this study, we investigated how resistance-associated substitutions (RASs) evolved after treatment failures and assessed the effect of those substitutions on viral fitness. Sequencing of NS5A and NS3 revealed typical RASs after treatment failures. Interestingly, the RASs of NS3 reverted to the wild-type amino acid within 1 year after treatment failures. However, the RASs of NS5A were stable and did not change. The effect of NS5A and NS3 RASs on viral RNA replication was assessed after mutagenic substitution in the genotype 1b HCV RNA. Among single substitutions, the effect of D168V was more substantial than the others and the effect of the triple mutant combination (D168V+L31V+Y93H) was the most severe. The RAS at NS5A Y93 affected both viral RNA replication and virus production. Finally, the effect of trans-complementation of NS5A was demonstrated in our co-transfection experiments and these results suggest that such a trans-complementation effect of NS5A may help maintain the NS5A RASs for a long time even after cessation of the DAA treatment. In conclusion, the results from this investigation would help understand the emergence and persistence of RASs.

KEYWORDS:

asunaprevir; daclatasvir; hepatitis C virus; resistance-associated substitution; viral fitness

View full-text article: http://www.medscape.com/viewarticle/904724

Combination interventions for Hepatitis C and Cirrhosis reduction among people who inject drugs: An agent-based, networked population simulation experiment

Combination interventions for Hepatitis C and Cirrhosis reduction among people who inject drugs: An agent-based, networked population simulation experiment
Bilal Khan, Ian Duncan, Mohamad Saad, Daniel Schaefer, Ashly Jordan, Daniel Smith, Alan eaigus,

Don Des Jarlais, Holly Hagan, Kirk Dombrowski 

Published: November 29, 2018

https://doi.org/10.1371/journal.pone.0206356 

Fig 1. Finite state diagram of the HCV model used in the experiments.
Once infected, agents face a series of stochastic and enforced progressions through a series of ever worsening liver function. Throughout the simulation, infected agents who have reached a chronic state (non-acute HCV infected agents) face a small but regular chance of moving directly to cirrhosis, decompensated cirrhosis, or hepatocellular carcinoma. In addition, their Metavir fibrosis level is incremented yearly, moving them gradually from early stage fibrosis to cirrhosis. Once in any of the three severe liver stages, agents face an increasing probability of death due to HCV infection, incremented on a five year basis.
https://doi.org/10.1371/journal.pone.0206356.g001

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Abstract

Hepatitis C virus (HCV) infection is endemic in people who inject drugs (PWID), with prevalence estimates above 60% for PWID in the United States. Previous modeling studies suggest that direct acting antiviral (DAA) treatment can lower overall prevalence in this population, but treatment is often delayed until the onset of advanced liver disease (fibrosis stage 3 or later) due to cost. Lower cost interventions featuring syringe access (SA) and medically assisted treatment (MAT) have shown mixed results in lowering HCV rates below current levels. However. little is known about the potential cumulative effects of combining DAA and MAT treatment. While simulation experiments can reveal likely long-term effects, most prior simulations have been performed on closed populations of model agents—a scenario quite different from the open, mobile populations known to most health agencies. This paper uses data from the Centers for Disease Control’s National HIV Behavioral Surveillance project, IDU round 3, collected in New York City in 2012 to parameterize simulations of open populations. To test the effect of combining DAA treatment with SA/MAT participation, multiple, scaled implementations of the two intervention strategies were simulated. Our results show that, in an open population, SA/MAT by itself has only small effects on HCV prevalence, while DAA treatment by itself can lower both HCV and HCV-related advanced liver disease prevalence. More importantly, the simulation experiments suggest that combinations of the two strategies can, when implemented together and at sufficient levels, dramatically reduce HCV incidence. We conclude that adopting SA/MAT implementations alongside DAA interventions can play a critical role in reducing the long-term consequences of ongoing HCV infection.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0206356

Perinatal Exposure to HCV Leads to Earlier Cirrhosis

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Liver Meeting 2018 

Sofosbuvir/ledipasvir cures most young children with hepatitis C
Liz Highleyman / 13 November 2018
Almost all young children ages 3 to 6 years with chronic hepatitis C achieved sustained virological response after 12 weeks of treatment using sofosbuvir/ledipasvir oral granules, according to findings presented at the ..

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Safety & efficacy of LDV-SOF with or without RBV for chronic hepatitis C in children ages 6-11.

Perinatal Exposure to HCV Leads to Earlier Cirrhosis
Samantha DiGrande
A recent retrospective review of patients who contracted hepatitis C (HCV) in childhood found that those with perinatal infection developed cirrhosis earlier than other risk groups.

A recent retrospective review of patients who contracted hepatitis C (HCV) in childhood found that those with perinatal infection developed cirrhosis earlier than those in other risk groups.
Read more:
https://www.ajmc.com/newsroom/perinatal-exposure-to-hcv-leads-to-earlier-cirrhosis

Abstract

Modin L, Arshad A, Wilkes B, et al. Epidemiology and natural history of hepatitis C virus infection among children and young people [published online November 26, 2018]. J Hepatol. doi: 10.1016/j.jhep.2018.11.013.

Highlights
• HCV infection in UK children - IV drug use 53%; blood products 24%; perinatal 11%
• Cirrhosis in 32% of patients at median of 33 years irrespective of infection route.
• Treatment impact on disease progression better if started before cirrhosis.
• Anti-HCV therapy should be available in childhood to prevent long-term liver disease.
Read more:
https://www.journal-of-hepatology.eu/article/S0168-8278(18)32545-5/fulltext

HIV, HCV and HBV: A Review of Parallels and Differences

Infect Dis Ther. 2018 Dec;7(4):407-419. doi: 10.1007/s40121-018-0210-5. Epub 2018 Sep 4.

HIV, HCV and HBV: A Review of Parallels and Differences.
Leoni MC1,2, Ustianowski A3,4, Farooq H3, Arends JE5.

Abstract
Elimination of the three blood-borne viruses-human immunodeficiency virus (HIV), hepatitis B (HBV) and hepatitis C (HCV)-as public health issues may be plausible in the near future. Spectacular advances have been made with the introduction of highly effective antiviral agents into clinical practice, and prevention strategies are available for all three infections. Effective disease control, laid out by WHO global strategies, is currently feasible for all three viruses. However, for worldwide elimination of these viruses, effective vaccines are required that are currently only available for HBV. In this review differences and parallels among HIV, HCV and HBV will be discussed with a focus on virologic and therapeutic issues, and prospects for the future of HBV will be presented.

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https://link.springer.com/article/10.1007%2Fs40121-018-0210-5

Hepatitis C Screening And New Treatments Allow Baby Boomers To Escape “The Kiss of Death”

Hepatitis C Screening And New Treatments Allow Baby Boomers To Escape “The Kiss of Death”
By Katherine O'Brien

November 29, 2018 

Finding out you have stage 3 hepatitis C (HCV) might not be most people’s idea of luck, but Ron Shean feels fortunate. Despite the damage to his liver, his disease was caught before it progressed to cancer.

Shean, who had planned to donate a kidney to his uncle, found out about his condition from the Kidney Foundation. “I got so lucky [that] I backed right into it,” says the 62 year old, who surmises that his “demise would have come sooner than expected” had the foundation not asked him for bloodwork.

When he first heard the news, though, Shean felt more devastated than grateful. “The only thing I’d heard about hep C was that it was referred to as ‘the kiss of death’ so there’s a bit of shock that comes with that,” he says.

Read more:

https://www.youareunltd.com/2018/11/29/hepatitis-c-screening-and-new-treatment-options-allow-baby-boomers-to-escape-the-kiss-of-death/

Hepatitis C: is eradication possible?

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Hepatitis C: is eradication possible? 
Andrea Lombardi Mario U. Mondelli ESCMID Study Group for Viral Hepatitis (ESGVH)

First published: 25 November 2018
https://doi.org/10.1111/liv.14011 

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. 

Please cite this article as doi: 10.1111/liv.14011

Abstract

Hepatitis C has a relevant global impact in terms of morbidity, mortality and economic costs, with more than 70 million people infected worldwide. In the resolution “Transforming our world: the 2030 Agenda for Sustainable Development” was included as a focus area in the health‐related goal with world leaders pledging to ‘combat’ it by 2030. In response, WHO drafted the Global Viral Hepatitis Strategy carrying the ambitious targets to reduce the number of deaths by two thirds and to increase treatment rates up to 80%. Despite the availability of highly effective therapeutic regimens based on direct acting antivirals many barriers to HCV eradication still remain. They are related to awareness of the infection, linkage to care, availability of the therapeutic drug regimens and reinfection. Overall, if an effective prophylactic vaccine will not be available, HCV eradication appears difficult to achieve in the future....

Key points:
DAA availability increased hope of HCV elimination and WHO defined that as a goal to be achieved by 2030. 

DAAs proved to efficiently eliminate HCV in specific settings/populations, but economical and logistic reasons make extremely difficult to apply this approach globally. 

A therapeutic vaccine is considered essential to reliably target HCV eradication.

Download Full Article: https://jumpshare.com/v/itrPCpIw4R33Hf1593sO

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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

Recommended Reading
The Liver Meeting
San Francisco

November 2018

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

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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.