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

Full-text article:

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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

Recommended Reading

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 ..

On Twitter
Full-text article downloaded & shared via twitter by Henry E. Chang:

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.

Article:

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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?

Reviews
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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Article downloaded and  shared by Henry E. Chang via Twitter.

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" 

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.

HighTide Receives Fast Track Designation for new drug to treat NASH

[Rockville, Maryland, Nov. 27, 2018] — HighTide Therapeutics Inc., a clinical-stage biopharmaceutical company, announced that the U.S. FDA has granted Fast Track Designation to its investigational new drug, HTD1801, for the treatment of patients with nonalcoholic steatohepatitis (NASH).

Liping Liu, PhD, Chief Executive Officer of HighTide, commented, “NASH represents a rapidly developing field with potential therapeutic options in the pipeline, yet none have made it to the market. At the recent AASLD Liver Meeting, experts in the field generally agreed that modest clinical responses to date are likely to be improved by thoughtful combination approaches. HTD1801, a multifunctional oral therapeutic, was designed to address the complex nature of NASH, especially for patients with comorbid diabetes and/or dyslipidemia. We are pleased by the FDA’s decision and look forward to bringing this much needed solution to millions of patients suffering from this disease.”

“This represents another step forward in our development of HTD1801 for the treatment of liver diseases with no currently approved therapies. We are proceeding with parallel clinical development of HTD1801 for NASH as well as primary sclerosing cholangitis (PSC) for which HTD1801 already received Orphan Drug Designation and Fast Track Designation,” said Janice Soreth, M.D., Chief Strategy and Regulatory Officer of HighTide, former Associate Commissioner for Special Medical Programs at the FDA.

FDA’s Fast Track program is designed to facilitate the development and expedite the review of new drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs. An investigational drug that receives Fast Track Designation is eligible for more frequent communications between the FDA and the company relating to the development plan and clinical trial design, and may be eligible for priority review if certain criteria are met.

HighTide completed a first in human study of HTD1801 in healthy volunteers. A multi-center Phase 2 trial in adult patients with NASH is scheduled to enroll soon in the United States. A multi-center Phase 2 trial in adult patients with PSC is currently ongoing in the United States.

About HighTide Therapeutics and HTD1801
HighTide Therapeutics Inc., founded in 2011, is dedicated to the discovery and development of innovative therapeutics for people suffering from chronic liver diseases, gastrointestinal diseases and metabolic disorders with large and unsatisfied market needs.

HTD1801 is a new molecular entity being developed for the treatment of PSC and NASH.

About Nonalcoholic Steatohepatitis
Nonalcoholic steatohepatitis (NASH), a form of nonalcoholic fatty liver disease (NAFLD), is a chronic, complex liver disease characterized by hepatitis – inflammation of the liver – and liver cell damage, which can lead to fibrosis of the liver. NASH can lead to cirrhosis and liver cancer. Prevalence of NASH is on the rise and it may soon surpass hepatitis C as a cause for liver transplant. Currently, there are no approved therapies for NASH.

Balancing Efficacy With Toxicity Among the Agents for HCC

Balancing Efficacy With Toxicity Among the Agents for HCC
Catherine Frenette, MD

Published Online:Nov 29, 2018

Catherine Frenette, MD: The 2 groups of lenvatinib [Lenvima] versus sorafenib [Nexavar] in the REFLECT trial were not stratified by AFP [alpha-fetoprotein] level. They were also not stratified by their underlying cause of liver disease. The patients in the lenvatinib group did have a slightly higher AFP than the patients in the sorafenib group. This may actually have resulted in a favorable imbalance in the positive for sorafenib. Additionally, hepatitis C patients were more frequent in the sorafenib group as compared with the lenvatinib group. This may have given a benefit to sorafenib. The reason for this discussion is that we recall, in the SHARP trial, when they broke out a subgroup of patients who were treated with sorafenib and had hepatitis C, had quite a longer median survival. In the SHARP trial, the overall survival [OS] in the subgroup was 10.7 months. In the hepatitis C–treated population with sorafenib, there may have been a longer OS than would have been seen in patients who were stratified for that risk factor.....

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https://www.targetedonc.com/case-based-peer-perspectives/hepatocellular-carcinoma/frenette-unresectable-hcc/balancing-efficacy-with-toxicity-among-the-agents-for-hcc

Vaccination may reduce the severity of the flu in vaccinated but still infected patients

On This Blog
Flu Activity Updated Nov 28/News Articles Nov 28

Baby Boomers and the Flu

Vaccination may reduce the severity of the flu in vaccinated but still infected patients

Date: November 28, 2018

Study analyzes all severe influenza cases in 12 Catalan hospitals between the 2010-2011 and 2015-2016 campaigns

When influenza vaccination is ineffective in preventing the flu, it could have an additional effect reducing the severity of the infection, according to an epidemiological study which has the participation of members of the research group Epidemiology, Prevention and Control of Communicable Diseases led by Professor Angela Dominguez, from the Department of Medicine of the UB- and the Epidemiology and Public Health Networking Research Center (CIBERESP), from the Health Institute Carlos III.

The study, published in the scientific journal Eurosurveillance, also counts on the participation of researchers from the Public Health Agency of Catalonia, the Lleida Institute of Biomedical Research and the Barcelona Public Health Agency.

Fewer ICU admissions and deaths 
Each year, between 5 and 20 % of the world population catches the flu, which causes about between 3 and 5 million severe cases and between 300,000 and 500,000 deaths worldwide. The new study analyses the effectiveness of anti-influenza vaccines to reduce the most severe effects of the flu: ICU admissions and death of patients whose vaccine did not prevent them from getting infected. To do so, researchers study all severe cases of influenza in twelve Catalan hospitals during the influenza seasons in 2010-2011 and 2015-2016, a period during which 1,727 patients over eighteen entered the hospital, 591 being ICU admissions and 223 resulting in deaths.

Results show that, among those ICU admissions and deaths, vaccination was less frequent (21.2 % of the cases) than the rest of the patients with more benign symptomatology, 29.7 % of them being vaccinated. Therefore, the effectiveness of influenza vaccination to prevent ICU admissions or death among the total people in hospital for influenza was of 23 %, and in particular, a 44 % for the group of people aged 65. "We should add the effectiveness of the vaccine to prevent the flu to these percentages. These data highlight the need of an influenza vaccine for each season for those people who are more likely to show severe types of influenza, such as people over 65, and people with other diseases, for whom the influenza vaccine was not enough to prevent the infection from appearing," note the authors.

In the study, researchers note an explanation for these results would be the role the immune system plays. "People who were previously infected by the virus or who received anti-influenza vaccines would get benefits, at least, in the pre-existing cross-reactive memory of cytotoxic T lymphocytes, which would reduce the severity of the infection, even without protective antibodies," they conclude.

Story Source:
Materials provided by University of Barcelona. Note: Content may be edited for style and length.

Journal Reference: Pere Godoy, Arantxa Romero, Núria Soldevila, Nuria Torner, Mireia Jané, Ana Martínez, Joan A Caylà, Cristina Rius, Angela Domínguez. Influenza vaccine effectiveness in reducing severe outcomes over six influenza seasons, a case-case analysis, Spain, 2010/11 to 2015/16. Eurosurveillance, 2018; 23 (43) DOI: 10.2807/1560-7917.ES.2018.23.43.1700732

Australian experience shows high DAA uptake and rapid fall in rates of HCV viraemia among people who inject drugs

Australian experience shows high DAA uptake and rapid fall in rates of HCV viraemia among people who inject drugs

Michael Carter

Published: 28 November 2018

Providing hepatitis C virus (HCV) therapy with direct-acting antivirals (DAAs) to people who inject drugs can achieve rapid reductions in community prevalence of viraemia, according to Australian research published in the Journal of Hepatology. Uptake of HCV treatment increased from 10% to 41% after unrestricted access to DAAs was rolled out in March 2016, and the proportion of viraemic patients fell from 43% to 25%.

The authors believe their findings have significance for the World Health Organization (WHO) target of eliminating HCV as a public health threat by 2030.

Read More:

http://www.aidsmap.com/page/3394458/

Sweetened drinks pose greater diabetes risk than other sugary foods

Recommended Reading
The Liver Meeting® 2018

The incidence of diabetes, stroke and kidney disease falls after hepatitis C cure 

The incidence of some of the most serious extrahepatic health problems caused by hepatitis C declines sharply after the infection is cured by antiviral treatment, a review of people treated for hepatitis C in the Canadian province of British Columbia has found.

Healthy You 

Sweetened drinks pose greater diabetes risk than other sugary foods

The findings suggest that fruit and other foods containing fructose seem to have no harmful effect on blood glucose levels, while sweetened drinks and some other foods that add excess "nutrient poor" energy to diets may have harmful effects.

"These findings might help guide recommendations on important food sources of fructose in the prevention and management of diabetes," said Dr. John Sievenpiper, the study's lead author and a researcher in the Clinical Nutrition and Risk Factor Modification Centre of St. Michael's Hospital in Toronto, Canada. "But the level of evidence is low and more high quality studies are needed."

The role of sugars in the development of diabetes and heart disease attracts widespread debate and increasing evidence suggests that fructose could be particularly harmful to health.

Fructose occurs naturally in a range of foods, including whole fruits and vegetables, natural fruit juices and honey. It is also added to foods, such as soft drinks, breakfast cereals, baked goods, sweets, and desserts as 'free sugars'.

Current dietary guidelines recommend reducing free sugars, especially fructose from sweetened beverages, but it is unclear whether this holds for all food sources of these sugars.

So researchers based at St. Michael's and the University of Toronto in Canada analysed the results of 155 studies that assessed the effect of different food sources of fructose sugars on blood glucose levels in people with and without diabetes monitored for up to 12 weeks.

Results were based on four study designs: substitution (comparing sugars with other carbohydrates), addition (energy from sugars added to diet), subtraction (energy from sugars removed from diet), or ad libitum (energy from sugars freely replaced).

Outcomes were glycated haemoglobin or HbA1c (amount of glucose attached to red blood cells), fasting glucose, and fasting insulin (blood glucose and insulin levels after a period of fasting).

Studies were also assessed for bias and certainty of evidence. Overall, no serious risk of bias was detected, but the certainty of evidence was low.

The results show that most foods containing fructose sugars do not have a harmful effect on blood glucose levels when these foods do not provide excess calories. However, a harmful effect was seen on fasting insulin in some studies.

Analysis of specific foods suggest that fruit and fruit juice when these foods do not provide excess calories may have beneficial effects on blood glucose and insulin control, especially in people with diabetes, whereas several foods that add excess "nutrient poor" energy to the diet, especially sweetened drinks and fruit juice, seem to have harmful effects.

The low glycaemic index (GI) of fructose compared with other carbohydrates, and higher fibre content of fruit, may help explain the improvements in blood glucose levels, by slowing down the release of sugars, say the researchers.

They point to some limitations, such as small sample sizes, short follow-up periods, and limited variety of foods in some studies. However, strengths included an in-depth search and selection process and thorough assessment of evidence quality.

As such, they conclude: "Until more information is available, public health professionals should be aware that harmful effects of fructose sugars on blood glucose seem to be mediated by energy and food source." 

https://www.bmj.com/company/newsroom/sweetened-drinks-pose-greater-diabetes-risk-than-other-sugary-foods/

Research
Food sources of fructose-containing sugars and glycaemic control: systematic review and meta-analysis of controlled intervention studies
BMJ 2018; 363 doi: https://doi.org/10.1136/bmj.k4644 (Published 21 November 2018) Cite this as: BMJ 2018;363:k4644

Wall Street - Curing diseases like Hepatitis C just doesn’t pay

On This Blog
The controversy over expensive new drugs for hepatitis C
Link to a collection of current articles regarding the effectiveness and safety of generic hepatitis C medicines, addressing the high cost, insurance restrictions; private insurers/Medicaid and availability of generic versions/India, Egypt and other lower-income countries or through online "buyers clubs"

In The News

Wall Street Wants the Best Patents, Not the Best Drugs

Curing diseases like Hepatitis C just doesn’t pay.
By
Joe Nocera

‎November‎ ‎27‎, ‎2018‎ ‎8‎:‎00‎ ‎AM‎ ‎EST 

It’s probably unfair to start a column about the new drugs that are curing Hepatitis C by referencing Jonas Salk and the discovery of the polio vaccine, but I’m going to do it anyway. It’s worth remembering what the world used to look like as we contemplate what it looks like now.

In the late 1940s and early 1950s, there was nothing that scared American parents more than polio, a disease that a) caused partial paralysis, b) was easily transmitted, and c) primarily affected children. Salk, who had worked on flu vaccines during World War II, joined the University of Pittsburgh in 1947 and soon began working on a possible polio vaccine. In 1953, he announced — on a national radio broadcast, no less — that he had developed a vaccine that prevented the disease; two years later, once its efficacy had been proven, the country undertook a national inoculation program, paid for by the federal government.
Read More:

https://www.bloomberg.com/opinion/articles/2018-11-27/gilead-s-cures-for-hepatitis-c-were-not-a-great-business-model

In a Critical State: Ongoing Barriers to Treatment for Hepatitis C Virus (HCV)

Editorial

In a Critical State: Ongoing Barriers to Treatment for Hepatitis C Virus (HCV)

Jorge Mera, MD, Brigg Reilley, MPH, Jessica Leston, David Stephens, RN

DOI: https://doi.org/10.1016/j.amjmed.2018.10.031

The American Journal of Medicine

Publication History

Published online: November 24, 2018

Abstract 

Recent advances in Hepatitis C Virus HCV treatment could be described as revolutionary: for uncomplicated patients, treatment is nearly 100% effective, oral-only, has a low pill burden, minimal side effects, and results in a cure.1 Comparisons we have heard from clinicians are that HCV is now easier to treat than either diabetes or hypertension. Unfortunately for many patients, their state of residence is the decisive factor for whether they will receive lifesaving treatment. As part of a tribal telehealth network for HCV, we support several rural clinics successfully treating HCV and see this dilemma all too frequently.

Consider a patient with chronic HCV infection who presents with a recent history of marijuana use and has been late picking up hypertension medication. The patient has cirrhosis and is at high risk of HCV related mortality. He is enrolled in state Medicaid and highly motivated for treatment. What is the treatment plan? It depends on the state. A resident of New Mexico can start treatment without delay. If instead the patient lives in Montana, a state that determines treatment eligibility based on advanced liver fibrosis, documented sobriety, and compliance with existing medications, the consultation is effectively moot; treatment will be denied. Montana is far from alone in its HCV treatment restrictions. Patients in South Dakota, Oregon, and several other states we serve face similar hurdles …

View Full-Text Article Online:
https://www.amjmed.com/action/showFullTextImages?pii=S0002-9343%2818%2931072-6

Download PDF:
https://www.amjmed.com/article/S0002-9343(18)31072-6/pdf

Current Issue
November 2018
Volume 131, Issue 11 

Treatment of hepatitis C virus genotype 4 in the DAA era

Review Article

Treatment of hepatitis C virus genotype 4 in the DAA era 
Antonio Di Biagio Email author View ORCID ID profile , Lucia Taramasso and Giovanni Cenderello Virology Journal 201815:180
https://doi.org/10.1186/s12985-018-1094-4© The Author(s).

2018 Received: 22 November 2017 Accepted: 13 November 2018
Published: 22 November 2018

Abstract

The recently approved interferon-free DAA (direct antiviral agents) regimens have shown not only to be effective in terms of sustained virological response (SVR) rates (> 90%) but also well tolerated in most hepatitis C virus (HCV) infected patients. Nevertheless HCV genotypes are different and only a small percentage of trials consider genotype 4 (GT4), which was associated with lower rates of SVR compared with other genotypes before the arrival of the DAA’s. In this review, we discuss the efficacy of DAA therapy in GT4 HCV infection with specific reference to more recent studies, including those conducted in a ‘field-practice’ scenario. Overall, DAA-based regimens appear more effective also in the poorly-explored setting of patients with HCV GT4 infection. Despite an overall limited number of patients was evaluated, favorable results are being derived from studies on ombitasvir/paritaprevir/ritonavir, sofosbuvir and velpatasvir, whether or not in association with voxilaprevir, and with the new combined therapy glecaprevir + pibentasvir.

Read complete article online: https://virologyj.biomedcentral.com/articles/10.1186/s12985-018-1094-4

SVR in patients with HCV genotype 6 treated with ledipasvir+sofosbuvir or sofosbuvir+velpatasvir

Aliment Pharmacol Ther. 2018 Nov 22. https://doi.org/10.1111/apt.15043 . [Epub ahead of print]

Sustained virologic response rates in patients with chronic hepatitis C genotype 6 treated with ledipasvir+sofosbuvir or sofosbuvir+velpatasvir

Emily Nguyen Sam Trinh Huy Trinh Huy Nguyen Khanh Nguyen Aivien Do Brian Levitt Son Do My Nguyen Treta Purohit Eugenie Shieh Mindie H. Nguyen 

First published: 22 November 2018

View full article online: https://onlinelibrary.wiley.com/doi/full/10.1111/apt.15043

Abstract

BACKGROUND: 

Hepatitis C virus (HCV) genotype 6 (GT 6) is the predominant genotype among certain Asian populations. The availability of newer DAA options is limited in many parts of Asia.

AIM: 

To compare sustained virologic response (SVR-12) rates between ledipasvir and sofosbuvir (LDV+SOF) and velpatasvir+SOF (SOF+VEL) for patients with HCVGT6 infection.

METHOD: 

Retrospective study of consecutive adult HCVGT6 patients identified via ICD 9 code: 070.5 from United States treatment centers. Treatment was LDV+SOF or SOF+VEL for 8-24 weeks. A 1:1 propensity score matching (PSM) on HCV RNA, cirrhosis, alanine aminotransferase, aspartate aminotransferase, platelets, and fibrosis score was conducted among the treatment-naïve HCVGT6 patients to balance groups and isolate treatment effects.

RESULTS: 

After exclusion criteria, 149 patients remained (n = 135 treatment-naïve; n = 14 treatment-experienced). The mean age was 63.8 ± 10.2 years, 66.9% male, and 93.9% Vietnamese. In treatment-naïve arm, 52.2% LDV+SOF cohort were cirrhotic compared to 11.6% SOF+VEL cohort (P < 0.0001). SVR-12 for LDV+SOF was 96.4% and 100% for the SOF+VEL cohort (P = 0.22). SVR-12 for cirrhotic patients was 95.4% (n = 41/43) for LDV+SOF and 100.0% (n = 5/5) for SOF+VEL (P = 0.62). After PSM (n = 33 per group), LDV+SOF SVR-12 rate was 97.0% compared to SOF+VEL SVR-12 of 100% (P = 0.31). The treatment-experienced group (n = 14), were all treated with LDV+SOF-SVR-12 of 92.3%.

CONCLUSION: 

Whether treatment-naïve, treatment-experienced, or cirrhotic patients with HCV GT 6 residing in the US had excellent outcomes when treated with SOF+VEL or LDV+SOF. Since LDV+SOF is more readily available globally, our results may provide clinicians with a treatment option when cost and availability limit the treatment choice.

Full-Text Online:

https://onlinelibrary.wiley.com/doi/full/10.1111/apt.15043

In half of hepatitis C patients, DAA treatment can shortened to 6 weeks

Recommended 
Media
Hepatitis C treatment can be shortened in 50 percent of patients, study finds
Shorter treatment times could significantly reduce costs of the expensive therapy

Slides available online @ NATAP

Response-Guided Therapy with DAA Shortens Treatment Duration in 50% of HCV Treated Patients

AASLD The Liver Meeting 2018

Abstract

LB-34 Response-Guided Therapy with Direct-Acting Antivirals Shortens Treatment Duration in 50% of HCV Treated Patients

In half of hepatitis C patients, DAA treatment can shortened to 6 weeks

Last Updated: 2018-11-23
By Lorraine L. Janeczko

NEW YORK (Reuters Health) - In about half of patients with hepatitis C virus (HCV) infection, response-guided therapy with oral direct-acting antiviral agents (DAAs) can be reduced from the standard 12 weeks to as little as six weeks and still be effective, according to a new pilot study.

DAAs have revolutionized hepatitis C treatment, eliminating the virus and enabling a cure with minimal side effects in over 90% of patients treated. But the high cost, which can exceed $50,000 per patient, limits patient access and burdens the insurance industry, researchers write in a press release.

"Implementing response-guided therapy as standard of care may lead to significant cost savings on the expensive hepatitis C treatment," senior author Dr. Amir Shlomai of Beilinson Hospital in Petah-Tikva, Israel, told Reuters Health by email.

The team enrolled 22 HCV patients with compensated liver disease and genotypes 1 to 6, who were either treatment naive or interferon experienced. Participants were treated with one of four DAA regimens chosen by the investigators.

Viral load was measured at baseline, at day 2, and at weeks 1, 2, and 4 after the start of treatment. The primary endpoint was the proportion of patients with sustained virologic response at 12 weeks (SVR12) post-treatment, with undetectable HCV RNA (<15 IU/mL).

The researchers presented the preliminary proof-of-concept results in a late-breaking abstract poster session on November 12 at The Liver Meeting 2018, the annual meeting of the American Association for the Study of Liver Diseases (AASLD), in San Francisco.

Participants averaged roughly 50 years of age, 11 were female and 9% had METAVIR scores of F3-4. The most common genotypes were G1b (59%) G3 (27%), G1a (9%), and G2 (5%).

The drug combinations sofosbuvir/velpatasvir, elbasvir/grazoprevir, sofosbuvir/ledipasvir and glecaprevir/pibrentasvir were administered to 41%, 31%, 23% and 5% of participants, respectively.

Mathematical modeling of viral kinetics was performed during weeks 2-4 to project time to cure, and model projections were used to individualize each participant's treatment duration.

Modeling predicted that treatment duration could be shortened to 10 weeks in one patient (5%), eight weeks in eight (36%) and six weeks in two (9%).

Of the 19 participants who completed therapy, 100% had undetectable viral load at the end of treatment. Of those, 18 (95%) remained HCV-undetectable four weeks after treatment.

Of the 15 patients who reached post-treatment week 12, 14 (93%) achieved SVR12.

One treatment-naive G3 patient with F1 fibrosis who was treated with sofosbuvir/velpatasvir for six weeks relapsed. Virus sequencing did not detect resistance-associated substitutions at baseline or in response to treatment, and no significant side effects were found among the DAA-treated patients.

"A shorter treatment may lead to improved compliance to treatment, especially in special populations, including hepatitis C patients with limited health insurance benefits," Dr. Harel Dahari of Loyola University Chicago in Maywood, Illinois, who also worked on the study, told Reuters health by email.

Dr. Dahari estimates that the shorter treatment may potentially decrease the cost of HCV drugs by up to 20%.

Now that the proof-of-concept pilot study has shown that response-guided therapy can potentially reduce treatment times, a large multicenter trial to validate the results is underway in Israel, the authors say.

Clalit Health Services in Israel and the United States National Institutes of Health helped support the study. The authors state that they have no conflicts of interest.

http://www.chronicliverdisease.org/reuters/article.cfm?article=20181123Other134843869

SOURCE: LB-34 Response-Guided Therapy with Direct-Acting Antivirals Shortens Treatment Duration in 50% of HCV Treated Patients

AASLD The Liver Meeting 2018.

Blogging About Liver Disease: Reasons To Be Grateful

Happy Thanksgiving! This year, and every year, I am grateful for a small group of talented bloggers who continue to keep us informed about all types of viral hepatitis.

In the spirit of the holiday, each blog has featured many reasons to be thankful this year; from curing HCV to improving the treatment of HIV.

Latest Articles 

Some of the following blogs are published by support organizations, healthcare professionals or physicians, while others are written from a patients perspective, offering us healthy tips about each stage of liver disease.

New @ HIV and ID Observations

HIV and HCV Treatment, Shorter Antibiotic Courses, Malaria-Sniffing Dogs, and Other ID and HIV Reasons To Be Grateful, 2018 Edition 

Paul E. Sax, MD

As noted here before, I’m a big fan of Thanksgiving, a great excuse to get together with family and friends, and to eat a gargantuan amount of food.*

Hepatitis B Foundation

Holidays with Hepatitis B: How to Tell Your Family

hepbtalk

As the holidays approach, families are planning parties and dinners and preparing to spend time with their loved ones. In such a merry atmosphere, the idea of discussing hepatitis B – whether its a recent diagnosis or the first time that you are ready to disclose your status – may be intimidating. However, it doesn’t have to be! In honor of National Family Health History Day – which falls on Thanksgiving – we put together some tips to help you start the conversation.

Joseph Galati, M.D.
Tips for a Healthier Holiday
Ahh, the holidays. A time to celebrate all the good that has come our way during the previous year. First up: Thanksgiving. What better way to begin the year-end wrap-up than to sit down at a hearty meal with family and friends? But the holidays are arguably the toughest time of the year to eat..

Hep Blogs

Finding Gratitude in Sickness, Health and Hepatitis 
By Lucinda K. Porter, RN
Some good news in the hepatitis C realm, plus a look at the practice of gratitude.

Mavyret versus Epclusa

By Greg Jefferys
Both Mavyret and Epclusa give cure rates above 97% for all genotypes of Hepatitis C except for G3 where both give a cure rate of around 95%.

The End Times

By Grace Campbell
Who gave cirrhosis such a catchy generic title? End stage liver disease. There’s a name sure to invoke confidence.

Liver Meeting 2018 Wrap-Up: Vaccines, Diet, and an Increasing Liver Menace 
By Lucinda K. Porter, RN
Ending the week with summaries of research from the 2018 Liver Meeting. I cover hepatitis B vaccination, diet and alcoholic liver disease.

HepatitisC.net
Options for Treatment with Liver Cancer
By Karen Hoyt
After my diagnosis of liver cancer, I had to find out what options for treatment were available.

ADRLF (Al D. Rodriguez Liver Foundation)

Liver-Healthy Thanksgiving Feast Ideas

Who says a fantastically delicious Thanksgiving spread can’t be healthy? This year, make your Thanksgiving feast even more special with these liver-healthy options that won’t give you or your family that post-holiday guilt; nor will they keep you stuck in the kitchen for hours on end! Check out these appetizing recipes for a healthy, scrumptious, easy-to-prep (or time-saving) Thanksgiving meal!

Finding Hope in Affordable Hepatitis Screening
Screening remains to be the best defense against detecting the hepatitis virus in its earliest stages, and potentially developing life-threatening complications, later down the line. Dubbed as the “silent killer,” hepatitis doesn’t exhibit obvious symptoms in many people, who may live, comfortably, with the virus for years and only discover their condition at its advanced, acute stage. Noting the importance of the timeliness of testing, Texas-based Link2Labs is making affordable hepatitis C tests available to uninsured and underinsured people.

HCV News
Weekly Review
Catch up on what you missed this week, read HepCBC's - Weekly Bull.

FYI - Lettuce Recall 

The CDC tells people to stop eating romaine lettuce — again — after another E. coli outbreak sickens at least 32 people in 11 states

GI and Hepatology News
U.S. death rates from chronic liver disease continue to rise

“I believe it’s all related to a big increase in obesity and type 2 diabetes in this country,” lead study author Zobair M. Younossi, MD, MPH, said in an interview in advance of the annual meeting of the American Association for the Study of Liver Diseases. “Those two risk factors drive NAFLD and its progressive type, nonalcoholic steatohepatitis (NASH). That accounts for at least part of the increase in mortality related to liver disease.”

AGA Journals - Blog

Hazards of Very Hot Coffee

Dr. Kristine Novak

Persistent drinking of very hot coffee can cause exfoliative esophagitis due to thermal injury, researchers report in the November issue of Clinical Gastroenterology and Hepatology. Florian Schertl et al describe the case of a 55-year-old woman with new retrosternal pain upon swallowing. She had been receiving continuous and successful proton pump inhibitor.

Fatty Liver Disease
Canadian Liver Foundation
It Happened To Me | My Fatty Liver Journey
Melanie was all too familiar with fatty liver disease, with her husband being diagnosed 5 years earlier. But, she never thought it would happen to her.

The Flu & You

Canadian Liver Foundation
What’s intended to help shouldn’t hurt
Before you head to the cabinet for medication, there are a few things you should know to ensure that what you take will help, not hurt.

One Medical blog

Our definitive guide to cold and flu

So you’ve come down with a nasty bug that’s been making the rounds.

This Blog
Flu Activity Updated Nov 10/News Articles Nov 16
Weekend Reading - Baby Boomers and the Flu

Recommended Blogs

HepatitisC.net

Hep Blogs
Lucinda K. Porter
Life Beyond Hepatitis C | Real Hope for Life with Hepatitis C
I Help C
AGA Journals - Blog
Hepatitis B Foundation - Blog
ADRLF (Al D. Rodriguez Liver Foundation)
HIV and ID Observations
Joseph Galati, M.D.
Canadian Liver Foundation - Blog

Questions About The Liver

Dr Paul Gow talks all things the liver and answers call-in questions on ABC Nightlife 

Source - Hepatitis Victoria

On Twitter

Hep C Calculator: an online tool for cost-effectiveness analysis of DAAs

Shared by @HenryEChang 

Just Because

Answers to every Thanksgiving question you've ever had

Matthew Kaskavitch

CU Anschutz Medical Campus experts share Thanksgiving health insights

Thanksgiving is almost here, and that means two things: 1) time spent with family and friends around the television watching football, and 2) eating turkey. Lots and lots of turkey. At this time of year, we often overindulge and loosen our belt and wonder how we fit all that stuffing and gravy into our stomach. Don’t worry. We asked leading health experts from the University of Colorado Anschutz Medical Campus a few of the Thanksgiving questions you’ve always wanted to know the answer to.

Happy Thanksgiving!

Opioid use more common in chronic liver disease than other chronic diseases

VIDEO: Opioid use more common in chronic liver disease than other chronic diseases
Healio

SAN FRANCISCO — In this exclusive video perspective from The Liver Meeting 2018, Monica Konerman, MD, director of the Michigan Medicine NAFLD Clinic, discusses results of a study that found opioid use to be twice as common among patients with chronic liver disease compared with other common chronic diseases.

Continue reading...…

See more from The Liver Meeting @ Healio

HCV epidemic continues to rise among young adults

Of Interest 
AASLD 2018 The Liver Meeting®:

People with Hepatitis C Who Actively Inject Illegal Drugs Have High Rates of Hepatitis C Treatment Adherence and Cure 

“Our data demonstrate that people who inject drugs can achieve SVR at comparable rates to non-drug using populations, even if adherence is imperfect,”

We Cured Hepatitis C - Now The Work Begins: Finding Neglected Patients  

One Health System's Efforts to Eliminate Hepatitis C

Real-World Data Show Rising HCV Epidemic Among Young Adults

Cassandra Pardini, PharmD

Results from the largest real-world study analyzing hepatitis C virus (HCV) screening practices determined that, although HCV antibody (AB) screening and confirmatory RNA testing rates are improving, the HCV epidemic continues to rise among young adults.

The study included 17,149,480 patients obtained from 2 national laboratory datasets who were screened between 2013 and 2016 based on an AB test. The study authors defined an active HCV infection as having an HCV RNA+ result following a positive AB test. The study authors added, "AB screening rates, AB+ rates, RNA follow-up testing rates, and RNA+ rates were assessed descriptively by year and stratified by baby boomers 48-71 years old and young adults 18-39 years old, to reflect the evolving disease epidemiology."

Read More: https://www.empr.com/news/hepatitis-c-virus-screening-diagnosis-rates-united-states-rna-testing-antibody/article/815299/

Reference: Abstract
Sulkowski MS, Marx S, Manthena SR, Strezewski J, Chirikov VV. National Estimates for HCV Screening and Diagnosis Rates in the United States (2013-2016) Based on Large Real-World Dataset. Presented at AASLD The Liver Meeting 2018. Study number 1565.

Full-Text Article

First published: 6 November 2018 - In Hepatology

Estimating Prevalence of Hepatitis C Virus Infection in the United States, 2013‐2016

View Slides: National Estimates for HCV Screening and Diagnosis Rates in the United States (2013-2016) Based on a Large Real-World Dataset

Kansas Agrees To Cover Potentially Life-Saving Drugs For Patients With Chronic Hepatitis C

Kansas Agrees To Cover Potentially Life-Saving Drugs For Patients With Chronic Hepatitis C 

By Dan Margolies
Kansas has agreed to cover the cost of drugs to treat Medicaid patients with chronic hepatitis C without subjecting them to a lengthy list of requirements.

A legal settlement, which awaits final court approval, resolves a class action lawsuit alleging the state made it too difficult for hepatitis C patients to receive the potentially life-saving treatments.

The parties first notified the court in July that they had resolved the case after mediation. On Tuesday, the court set deadlines for approval of a final settlement.

“Essentially, the agreement is that all hep C patients who use Medicaid to get their drugs will be entitled to Mavyret or Harvoni, the two curative drugs, regardless of their fibrosis score,” said Lauren Bonds, legal director of the ACLU of Kansas, which along with the Shook Hardy & Bacon law firm, sued Kansas officials over the state's hep C treatment guidelines in February.

Fibrosis scores measure the health of the liver. Scores range from F0, referring to mild or no scarring of the liver, to F4, referring to significant liver damage or cirrhosis. Kansas’ privatized Medicaid program, known as KanCare, had limited coverage to patients with a fibrosis score of F3 or F4. 

Read More: http://www.kmuw.org/post/kansas-agrees-cover-potentially-life-saving-drugs-patients-chronic-hepatitis-c

On Twitter 

Hep C Calculator: an online tool for cost-effectiveness analysis of DAAs 

Shared by @HenryEChang

On This Blog

The controversy over expensive new drugs for hepatitis C
Link to a collection of current articles regarding the effectiveness and safety of generic hepatitis C medicines, addressing the high cost, insurance restrictions; private insurers/Medicaid and availability of generic versions/India, Egypt and other lower-income countries or through online "buyers clubs"

The Revolution in Treatment of Hepatitis C

Medical Clinics
January 2019 Volume 103, Issue 1, Pages 43–55 

The Revolution in Treatment of Hepatitis C

Jordan Mayberry, PA-C, William M. Lee, MD

View Article Online:
https://www.medical.theclinics.com/article/S0025-7125(18)30098-1/fulltext?rss=yes
Download PDF:
https://www.medical.theclinics.com/article/S0025-7125(18)30098-1/pdf

Key points

•Hepatitis C infection typically goes unrecognized at onset and develops into a chronic infection that can lead to cirrhosis, liver failure and liver cancer.
•Novel treatments that are safe, without significant side effects and nearly 100% effective became available in the last 5 years.
•Sustained viral response (SVR--no virus detectable 12 weeks after end of treatment) is synonymous with life-long cure.
•SVR patients with cirrhosis require ongoing surveillance for liver cancer.
•Remaining challenges include identifying those who are not aware but have infection and providing treatment for those lacking funding.

Article Outline
Key points
Introduction
Epidemiology
Risk factors for hepatitis C
Natural history
Virology
Acute hepatitis C
Chronic hepatitis C
Cirrhosis
Pretreatment testing
Current treatment options for hepatitis C
Eight-week treatment options
Hepatitis B screening
Special patient populations
Renal disease
Decompensated liver disease
Post-treatment laboratory studies and follow-up
Barriers to treatment

References

Treatment of hepatitis C with interferon therapy produced some cures early on, but was associated with significant side effects. Because of further advances in the molecular understanding of hepatitis C, by 2014 effective treatments became available that far surpassed all prior interferon-based regimens in efficacy, tolerability, and safety. This led to rapid transformation of a hard-to-treat disease to simple, safe, and effective treatment offered to anyone. This article focuses on hepatitis C epidemiology; the clinical impact and consequences; discussion of past hepatitis C treatments; and a review of current recommendations for screening, diagnosis, and treatment of this ubiquitous virus.
https://www.medical.theclinics.com/article/S0025-7125(18)30098-1/fulltext?rss=yes

Expert opinion on managing chronic HCV in patients with cardiovascular disease

Navigate this blog 
Sift through current research articles on the extrahepatic manifestations of hepatitis C, in particular an association between HCV and cardiovascular conditions.

Review

Expert opinion on managing chronic HCV in patients with cardiovascular disease

Cristina Vassalle1, Salvatore Petta2, Alessia Pepe3, Antonio Craxi2, Mark Bondin4, Patrice Cacoub

Abstract

Extrahepatic manifestations of chronic HCV infection include cardiovascular diseases and an increase in cardiovascular mortality. The pathogenic mechanisms by which HCV contributes to cardiovascular disease are not well defined, however, it is likely that systemic inflammation, and the promotion of other metabolic diseases are involved. In this Review, the evidence for HCV infection as a non-traditional risk factor for cardiovascular disease is evaluated. Furthermore, practical advice to evaluate cardiovascular disease risk and disease in chronic hepatitis C patients are included for help in daily clinical practice. Despite the advances in therapies for the treatment of HCV, there remains a need for increased awareness among specialists so that patients are more likely to obtain the treatment required to mitigate disease progression.

Full Text

PDF (978 KB)

Conclusions

HCV has a complex role in the atherosclerotic process, although the association between HCV and CVD has not been clearly defined. In particular, the biological significance of this association remains undefined. Thus, a pathogen resident in an atherosclerotic plaque may simply represent a ‘bystander’ rather than a ‘culprit’ or a diseased vessel may simply be more vulnerable to pathogens, including HCV. In any case, it would be superficial to consider as irrelevant a hypothesis that is reinforced by multiple lines of evidence, and by the involvement of systemic inflammation and the autoimmune response, which are both critical in HCV infection and atherosclerosis.

Currently, HCV-infected patients are not generally recognized as a high priority for cardiovascular assessment and/or treatment owing to the lack of definitive conclusions on the role of HCV in CVD. In view of present available evidence, it is important that clinicians begin to consider HCV as a non-traditional risk factor for CVD. Evidence of a beneficial effect of SVR after antiviral treatment on cardiovascular risk is encouraging, especially with the introduction of new IFN-free combinations that are more effective and better tolerated than IFN-based therapies. In this context, from a pathophysiological point of view, the observation that some patients with chronic HCV infection remained free of atherosclerosis, while others develop extensive disease, represents a challenging point that merits further investigation. Thus, it remains crucial for clinicians to consider their patients as a whole, and evaluate correlated factors and diseases that place the chronic HCV infection patient at risk for HCV-related extra-hepatic complications, including CVD. Specifically, it is critical for clinicians to recognize the multilevel dimensions of HCV disease and its natural history, in the attempt to optimize treatment, apply general guidelines, avoid adverse events and improve the quality of life for each patient. In this context, the assessment of additional factors and comorbidities (for example, steatosis, diabetes) or biomarkers (for example, inflammatory, lipids) might be helpful to eventually identify subgroups of patients at higher risk of developing atherosclerosis.

It is conceivable that all patients with chronic HCV infection would benefit from a detailed assessment of their cardiovascular status, whereas patients with CVD would benefit from the screening for HCV and other HCV-related parameters. In this scenario, a close collaboration between hepatologists and cardiologists is also desirable to correctly interpret patient-specific data and make the best recommendation for each patient.

Full-Text: https://www.intmedpress.com/journals/avt/article.cfm?id=3248&pid=88&sType=AVT

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
Download PDF: https://www.jstage.jst.go.jp/article/internalmedicine/advpub/0/advpub_1856-18/_pdf/-char/en

Targeted Hepatitis C testing misses substantial number of cases in correctional setting

Targeted Hepatitis C testing misses substantial number of cases in correctional setting

Researchers recommend routine testing for all incarcerated individuals upon arrival

Results from a new study led by Boston Medical Center (BMC) found routine Hepatitis C testing identified a significant number of cases that would have been missed by targeted testing among a population of individuals in Washington State prisons. Published in the American Journal of Preventive Medicine, the authors recommend routine testing in correctional facilities to best identify and treat the disease as part of the national strategy to eliminate Hepatitis C transmission.

It is estimated that 30 percent of the total Hepatitis C (HCV) infected population in the United States passes through the prison system annually, yet there is no widely accepted approach to HCV testing in correctional settings. Approximately 40 percent of state prison facilities, including Washington State, routinely test for HCV. Other facilities employ the Centers for Disease Control and Prevention (CDC) recommendation of targeted or risk-based testing, which tests individuals born between 1945 and 1965 as well as those with a history of injection drug use.

Researchers looked at data from Washington State prison HCV testing results to determine whether routine or targeted testing was most effective in identifying cases of disease. From 2012 to 2016, more than 24,000 people were tested for HCV; 20 percent of those people were infected and close to 2,000 people had chronic infections. Of those with chronic infections, nearly a quarter had at least moderate liver disease, putting them at risk for complications.

Infections were more prevalent in individuals born between 1945 and 1965, however nearly 35 percent of infections would have been missed if only targeted testing was performed. With routine testing, five individuals had to be tested to identify a case of HCV, compared to three individuals with targeted testing. This remains a small number in contrast with other infectious diseases, such as HIV, that require testing a large number of incarcerated individuals to identify a single case.

"These data build upon existing evidence supporting the implementation of routine testing for all individuals when entering a correctional facility," said Sabrina Assoumou, MD, MPH, an infectious diseases physician at BMC and lead author of the study. "Coupled with treatment, routine testing would identify and cure many cases of HCV, preventing the substantial burden of future liver disease."

One of the current barriers to routine testing is the high cost of HCV treatment. Even without treatment, those who receive a diagnosis of HCV may make lifestyle changes that can reduce transmission.

Researchers also note that it is unclear how these findings will generalize to other U.S. prison populations, and believe more research should be done to determine the effectiveness of routine HCV testing across the country. 

Journal American Journal of Preventative Medicine

https://www.eurekalert.org/pub_releases/2018-11/bmc-thc111918.php

We Cured Hepatitis C - Now The Work Begins: Finding Neglected Patients

Conference Coverage:
MedPage Today
Twitter @medpagetoday

Video
IDSA Video Conference Reporter: AASLD 2018
Watch exclusive comments from study authors and discussants at AASLD 2018

One Health System's Efforts to Eliminate Hepatitis C
Douglas Dieterich, MD



Topics Of Interest 
Treatment for Non-alcoholic Fatty Liver Disease
Emerging Therapies in Ongoing NASH Studies

What a Clinician is Looking for in New NASH Tx

View All Video Comments:
https://www.medpagetoday.com/video/meetingcoverage/aasld/idsa-video-conference-reporter-aasld-2018/191/2622

HCV Re-infection in People with High-risk Behavior Low

AGA Reading Room 

11.15.2018 

HCV Re-infection in People with High-risk Behavior Low

Widespread treatment should be offered to people who inject drugs

by Pippa Wysong

Contributing Writer, MedPage Today 

The overall number of people re-infected with hepatitis C (HCV) after successful treatment with direct-acting agents (DAAs) was small in a large population-based study from Canada, providing more evidence to offer widespread treatment to high-risk populations.

But the key to eliminating HCV is to get treatment to HCV-infected people who have high-risk behaviors quickly to reduce the number of people living with infection. This in turn would reduce the passing on of the disease to others who have cleared the virus from treatment, said Naveed Janjua, PhD, senior scientist with the British Columbia Centre for Disease Control.

In fact, the study, published in the Journal of Hepatology, found evidence that people who inject drugs (PWID) who continued to use opiate agonist therapy after successful cure with direct-acting antiviral therapies (DAAs) had lower re-infection rates than PWID who had no opiate-agonist therapy or supports.
Read More: https://www.medpagetoday.com/reading-room/aga/lower-gi/76361

In Older Hep B Patients, Carcinoma Surveillance Is Advised

Medscape Medical News > Conference News > AASLD 2018
In Older Hep B Patients, Carcinoma Surveillance Is Advised
Laird Harrison

November 15, 2018 

SAN FRANCISCO — Surveillance for hepatocellular carcinoma (HCC) should continue in patients older than 50 years, even after they have undergone 5 years of therapy for chronic hepatitis B, according to an analysis of the PAGE-B cohort.

But the risk for the cancer is low enough in younger patients — except for those with cirrhosis — that surveillance might not be warranted, said George Papatheodoridis, MD, PhD, from Athens University Medical School in Greece.

"It will save monitoring in some patients," he told Medscape Medical News.

Long-term monotherapy with entecavir (Baraclude, Bristol-Myers Squibb) or tenofovir disoproxil fumarate (Viread, Gilead) suppresses the hepatitis B virus and improves liver lesions, so the survival rate in patients without compensated cirrhosis is comparable to that in the general population, Papatheodoridis explained here at The Liver Meeting 2018...

Read More: https://www.medscape.com/viewarticle/904951

Free registration may be required

Meeting Coverage

Medscape 

Twitter @Medscape

Recommended Coverage 

Updates on this blog (LINK), recommended coverage elsewhere (LINK). 

Albertans are dying at alarming rates from opioid overdoses

Personal drug use should be decriminalized, addictions expert says

Sarah Rieger · CBC News · Posted: Nov 15, 2018

Doctor says removing barriers to help saves lives — but not all agree

"Personal drug use needs to be decriminalized and the possession of small amounts of substances needs not to result in people going to jail."

Virani spoke at an expert forum hosted by the Alberta Liberals in northwest Calgary Wednesday evening. The party, and the doctor, are calling on the federal government to amend the criminal code.

Read more: https://www.cbc.ca/news/canada/calgary/drug-decriminalization-health-1.4906365

Managing DAA Failures When Treating Hepatitis C Virus Infections

Norah Terrault, MPH, MD: 

Managing DAA Failures When Treating Hepatitis C Virus Infections

NOVEMBER 14, 2018

Krista Rossi

Patient nonadherence to treatment is an ongoing issue that physicians from all specialties face. It is particularly prevalent among patients who are infected with hepatitis C virus. Gaps in treatment of any infection or condition can have deleterious effects on patient outcomes; however, new research has revealed that gaps in treatment for hepatitis C virus is no longer a deal-breaker in terms of achieving sustained viral response (SVR), including in patients who abuse drugs.

We sat down with Norah Terrault, MPH, MD, director of the Viral Hepatitis Center at University of California, San Francisco, at the 2018 American Association for the Study of Liver Diseases (AASLD) Liver Meeting, November 9-13, 2018, in San Francisco, California, to discuss gaps in treatment in people who are infected with hepatitis C virus and what steps clinicians should take when treating these patients...

Watch video or read the transcript; https://www.mdmag.com/conference-coverage/aasld-2018/norah-terrault-mph-md-managing-daa-failures-when-treating-hepatitis-c-virus-infections

Meeting Coverage 

MD Magazine 

Twitter - @MDMagazine

Recommended Coverage

View updates on this blog (LINK), recommended coverage (LINK).

Hepatitis C in the UK – the path to elimination

Rachel Halford
Chief Executive
The Hepatitis C Trust
Tweet @HepatitisCTrust
www.hepctrust.org.uk

Hepatitis C in the UK – the path to elimination
14th November 2018
Following an 11% fall in hepatitis C-related deaths between 2016 and 2017, Rachel Halford makes the case for a national strategy to eliminate hepatitis C in the UK.

In May 2016, the UK joined 193 other countries in committing to eliminate viral hepatitis C globally by 2030, as part of the World Health Organization’s Global Health Sector Strategy on Viral Hepatitis. This commitment marked a watershed moment in the fight against hepatitis C, a blood-borne virus which primarily affects the liver. Earlier this year, NHS England went even further and announced a target of elimination of hepatitis C in the UK by 2025.

Globally, it is estimated that 71 million people are infected with chronic hepatitis C, including around 210,000 in the UK. Hepatitis C disproportionately affects disadvantaged and marginalised communities in the UK, including injecting drug users, homeless people, prisoners and certain migrant communities.
Opportunities and challenges in the fight against hepatitis C in the UK

To monitor the UK’s progress towards eliminating hepatitis C as a major public health threat, Public Health England produces an annual ‘Hepatitis C in the UK’ report. The latest edition, released in August 2018, highlighted some positive developments, with an 11% fall in hepatitis C-related deaths between 2016 and 2017, following on from a 3% fall in deaths the previous year. More people are accessing treatment for hepatitis C in the UK than ever before, with 14,348 accessing treatment in the UK in 2017/18, more than double pre-2015 levels.

This encouraging progress follows the arrival in 2014 of the new direct acting antiviral (DAA) treatments for hepatitis C, which offer a significant improvement on the old, interferon-based treatments. Whereas the old treatments required a course of injections over a 48-week period and had significant side effects and low cure rates, the new DAA treatments are taken orally for 8-12 weeks, have very few side effects and cure around 95% of patients.

The new treatments have revolutionised hepatitis C care, making treatment both more effective and accessible.

However, in other regards the 2018 ‘Hepatitis C in the UK’ report made less encouraging reading. The report revealed no significant reduction in overall prevalence of hepatitis C or in numbers of new infections, which suggests that the WHO target of reducing new cases of chronic hepatitis C by 30% by 2020 and 80% by 2030 represents a significant challenge for UK hepatitis C prevention and treatment services

In addition to the lack of progress in reducing prevalence and incidence rates, it is estimated that around 40-50% of those infected with chronic hepatitis C in the UK remain undiagnosed. As the ‘Hepatitis C in the UK’ report notes, meeting the WHO goal of a 65% reduction in mortality from hepatitis C depends on sustaining the current improvements in the numbers of people accessing treatment, which in turn is dependent on capacity to find and treat those who remain undiagnosed, and to re-engage those diagnosed but not treated.

Addressing these ongoing issues will require a range of actions, and it is The Hepatitis C Trust’s view that a comprehensive, written national hepatitis C elimination strategy is needed to co-ordinate the various actors and actions needed to achieve elimination by 2030 at the latest, a view shared by the All-Party Parliamentary Group on Liver Health, leading clinicians, patient organisations and industry. Such a strategy should cover the approach to raising awareness of hepatitis C, preventing new infections, and increasing testing and treatment rates, with some of the key issues that must be addressed outlined below.
We must boost awareness

It is vital that awareness of hepatitis C transmission risks is increased among at-risk groups and the wider public. A government-led awareness campaign, comparable to the approach taken to HIV in the 1980s, could help to raise awareness of hepatitis C among the general public. The use of peer programmes, whereby former patients deliver talks and provide support to those with a background similar to their own, are a particularly effective way of increasing awareness among at-risk groups, and The Hepatitis C Trust is actively involved in delivering peer support in substance misuse services and prisons. Increasing awareness of hepatitis C transmission risks is a vital tool in both preventing new infections and finding undiagnosed patients.

As well as increasing awareness among at-risk groups and the wider public, more needs to be done to increase knowledge of hepatitis C among healthcare professionals. The Hepatitis C Trust’s helpline still too often hears stories of patients going years without being diagnosed, despite presenting to their GP with symptoms that should have led to the offer of a hepatitis C test. To support efforts to increase awareness of hepatitis C among key healthcare professionals, The Hepatitis C Trust co-ordinates HCV Action, a network for hepatitis C professionals, which holds roadshows and public health meetings, produces resources and circulates examples of best practice. However, other measures could help to further support professional knowledge of hepatitis C, such as the circulation of key hepatitis C-related information and resources by Public Health England and clinical commissioning groups and ongoing hepatitis C training opportunities for healthcare professionals.
We must strengthen prevention efforts

Preventing new infections of hepatitis C is also key to achieving the elimination goal. Whilst increased awareness of hepatitis C transmission risks can support prevention efforts, there is also a need for greater harm reduction services for those at risk. For example, the provision of sterilised injecting equipment and support transitioning to opioid substitution treatment (OST) is crucial in reducing transmission between injecting drug users, which accounts for around 95% of new hepatitis C infections in the UK. With the 2018 ‘Hepatitis C in the UK’ report highlighting suboptimal provision of clean injecting equipment across the UK, a greater emphasis on harm reduction is key to preventing new infections and must be supported in the commissioning and funding of services for injecting drug users.

Innovative approaches to preventing new infections should also be explored. Drug consumption rooms, for example, offer the opportunity to support injecting drug users with harm reduction and have been successfully implemented in a number of European countries. Another innovative prevention strategy is the ‘treatment as prevention’ approach, which involves treating large numbers of actively injecting drug users and others still engaged in risky behaviours to halt further transmissions. This approach is currently being trialled by NHS Tayside in Scotland, with models indicating that a reduction of hepatitis C among those injecting drugs from over 30% to below 10% would result in a corresponding decline in transmission from 10% to below 1%, leading to effective elimination of the virus. Should such an approach be proved to be effective, it should be implemented across the UK.
We must improve and prioritise testing and diagnosis

A rapid expansion of testing will also be needed to ensure sufficient numbers of patients are diagnosed and enrolled into treatment. There are a number of measures that can be taken to improve the approach to testing in key settings. For example, ‘opt-out’ testing of clients should be introduced in substance misuse services, with monitoring systems and targets for test offers and uptake included in commissioning contracts. In prisons, another high-prevalence setting, an opt-out testing policy is already in place, but more needs to be done to ensure effective implementation, including guidance and training for prison healthcare teams. Just as importantly, re-testing must take place regularly in high-prevalence settings, to ensure new infections are picked up.

There are a number of other settings in which hepatitis C testing should be prioritised, including pharmacies, homeless hostels, mosques and A&E departments. Pharmacies are a particularly important setting, with many current or former injecting drug users accessing them to collect clean needle and syringes or OST. Interim results from an ongoing pilot project by the London Joint Working Group on Substance Use and Hepatitis C have shown community pharmacies to be an effective setting for finding those with an undiagnosed infection of hepatitis C, with results from the first six weeks of testing in six London pharmacies showing a 50% hepatitis C antibody positive rate among those tested, with 47% of these previously undiagnosed.
We must expand access to treatment

As the ‘Hepatitis C in the UK’ report notes, achieving the WHO target of a 65% reduction in hepatitis C deaths by 2030 will depend upon sustaining current improvements in numbers accessing treatment. With most patients in touch with services having now been treated, there is a pressing need to find undiagnosed patients so that they can receive treatment. In support of its target of elimination by 2025, NHS England is currently engaged in negotiations with industry to agree a new funding approach to hepatitis C treatments. If agreed, such a deal is expected to cap the cost of treatments to the NHS above a certain threshold and include a role for industry in case finding. This is a positive step, but The Hepatitis C Trust believes that there must be central co-ordination to ensure a strategic and equitable approach to case finding and treatment.

Engaging more patients in treatment will also require treatment to be made available in settings most convenient to patients. Making treatment available in community settings such as pharmacies, substance misuse services, sexual health clinics, homeless hostels and GP surgeries supports patients to engage with treatment and can be particularly beneficial for patients who traditionally have difficulty accessing secondary care services.

Elimination is possible, but more action is needed

Considerable progress has been made in relation to hepatitis C in recent years. Achieving elimination by 2030 (or even by 2025) is feasible, but it will require the mobilisation and co-ordination of a range of actors. Despite this, the government maintains that it has no plans to publish an elimination strategy. With the prospect of a new funding deal offering the opportunity to treat many more patients, it essential that a national strategy is developed and implemented to ensure the opportunity to eliminate hepatitis C as a public health threat in the UK is seized.

Rachel Halford
Chief Executive
The Hepatitis C Trust
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