Friday, November 16, 2018

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

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

Thursday, November 15, 2018

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...

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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.

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...

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Wednesday, November 14, 2018

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
Tweet @HepatitisCTrust
www.hepctrust.org.uk

Tuesday, November 13, 2018

8-week Maviret HCV genotype 1-6 & compensated cirrhosis:The EXPEDITION-8 Study

Meeting Coverage @ infohep Keith Alcorn / 14 November 2018
An 8-week course of the combination of glecaprevir and pibrentasvir (Maviret) is highly effective in curing hepatitis C in people with compensated cirrhosis, across a wide range of genotypes, Robert S. Brown of Weill Cornell Medical College reported at the AASLD Liver Meeting in San Francisco this week. Maviret is a highly effective combination of an HCV protease inhibitor (glecaprevir) and an NS5A inhibitor (pibrentasvir) that has been shown to cure hepatitis C in 98% of people without cirrhosis after eight weeks of treatment. A previous study showed that a 12-week course of the combination cured hepatitis C in 99% of people with compensated cirrhosis. The EXPEDITION-8 study was designed to test whether an 8-week treatment course was as effective in previously untreated people with compensated cirrhosis as the rate of cure achieved in the previous 12-week study.
High SVR12 rate suggests 8-week treatment could be used for this population
Read more: https://www.medpagetoday.com/meetingcoverage/aasld/76333
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Presented at the AASLD: The Liver Meeting®
Preliminary efficacy & safety of 8-week GLE/PIB in patients with #HCV genotype 1-6 infection & compensated cirrhosis: The EXPEDITION-8 Study 

LINK

Shared via @HenryEChang on twitter.





All adults should be screened for unhealthy alcohol use, new guidelines say

All adults should be screened for unhealthy alcohol use, new guidelines say
CNN
All adults should be screened for unhealthy alcohol use, new guidelines say. The negative consequences of too much alcohol include illness, injury, and death -- unhealthy alcohol use ranks as the third leading preventable cause of death in the US according to the task force. When pregnant women drink, birth defects and developmental problems in their children may follow.

By Susan Scutti, CNN
Updated 2:06 PM ET, Tue November 13, 2018
You can expect a "drinking checkup" when you visit the doctor. All adults, including pregnant women, should be screened for unhealthy alcohol use by their primary care physicians, the United States Preventive Services Task Force advises. For those patients who drink above the recommended limits, doctors should provide brief counseling to help them reduce their drinking, according to the new task force statement published Tuesday in the medical journal JAMA.

US Preventive Services Task Force Recommendation Statement 
November 13, 2018 
Screening and Behavioral Counseling Interventions to Reduce Unhealthy Alcohol Use in Adolescents and Adults
JAMA. 2018;320(18):1899-1909. doi:10.1001/jama.2018.16789
The USPSTF recommends screening for unhealthy alcohol use in primary care settings in adults 18 years or older, including pregnant women, and providing persons engaged in risky or hazardous drinking with brief behavioral counseling interventions to reduce unhealthy alcohol use. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening and brief behavioral counseling interventions for alcohol use in primary care settings in adolescents aged 12 to 17 years. (I statement)

AbbVie's MAVYRET™ (glecaprevir/pibrentasvir) Shows High Virologic Cure* Rates in Treatment-Naïve Hepatitis C Patients with Compensated Cirrhosis

The Liver Meeting® 2018
Meeting Updates 
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Related Links:
High SVR12 rate for 16 week glecaprevir/pibrentasvir regimen in HCV GT1

Today's Press Release
AbbVie's MAVYRET™ (glecaprevir/pibrentasvir) Shows High Virologic Cure* Rates in Treatment-Naïve Hepatitis C Patients with Compensated Cirrhosis

- EXPEDITION-8 is the first Phase 3b study evaluating 8 weeks of MAVYRET™ in treatment-naïve chronic hepatitis C virus (HCV)-infected patients with compensated cirrhosis across all major genotypes (GT1-6)[1] 

- In cohort one, 100 percent of genotype 1, 2, 4, 5 and 6 treatment-naïve chronic HCV patients with compensated cirrhosis achieved SVR[12] with 8 weeks of MAVYRET per protocol analysis[1]
- Cohort two of the study is ongoing, evaluating treatment-naïve genotype 3 (GT3) patients with compensated cirrhosis 

- MAVYRET is currently approved as an 8-week, pan-genotypic treatment for treatment-naïve patients without cirrhosis

NORTH CHICAGO, Ill., Nov. 13, 2018 /PRNewswire/ -- AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced new data for its pan-genotypic chronic hepatitis C virus (HCV) treatment, MAVYRET™ (glecaprevir/pibrentasvir), in treatment-naïve patients with compensated cirrhosis. Results from the Phase 3b EXPEDITION-8 study showed that with 8 weeks of MAVYRET, 100 percent (n=273/273) of genotype 1, 2, 4, 5 and 6 patients achieved a sustained virologic response 12 weeks after treatment (SVR12) per protocol analysis.1

These data are being presented today as a late-breaking, oral presentation at The Liver Meeting® 2018 organized by the American Association for the Study of Liver Diseases (AASLD) in San Francisco, California.

"Current guidelines recommend a 12-week pan-genotypic regimen for people who have hepatitis C, are treatment-naïve and have compensated cirrhosis," said Robert S. Brown, Jr., M.D., the Gladys and Roland Harriman professor of medicine, Weill Cornell Medical College. "We are interested in investigating shorter treatment options, which may simplify care for patients with compensated cirrhosis while providing high cure rates."

This analysis is part of the ongoing Phase 3b EXPEDITION-8 study evaluating the safety and efficacy of MAVYRET in treatment-naïve chronic HCV patients with compensated cirrhosis across all major genotypes (GT1-6).1 The study includes two cohorts; cohort one with genotype 1, 2, 4, 5, 6 chronic HCV-infected patients, and cohort two with genotype 3 (GT3) chronic HCV-infected patients.1

"MAVYRET is already having a significant impact on people living with HCV. However, there are still groups of patients who may benefit from a shorter treatment option," said Janet Hammond, M.D., Ph.D., vice president, infectious diseases development, AbbVie. "We continue to investigate and understand the value of an 8-week treatment regimen for patients, something we recognize as an important step towards HCV elimination."

To date, no virologic failures have been reported in cohort one of the study and no patients have discontinued treatment due to adverse events.1 Adverse events (>5%) reported of the study populations include pruritus (9.6%), fatigue (8.6%), headache (8.2%) and nausea (6.4%).1 Six serious adverse events (2%) have occurred during the study, none of which were deemed to be related to glecaprevir/pibrentasvir.1 No new safety signals were identified in this study.

Data from the ongoing EXPEDITION-8 Phase 3b study will be presented as a late-breaking, oral presentation during the Late-breaking Abstract Oral Session II on November 13 at 8:30 a.m. PST.

MAVYRET is approved in the U.S. as a 12-week pan-genotypic treatment for treatment-naïve patients with compensated cirrhosis.2

*Patients who achieve a sustained virologic response at 12 weeks post treatment (SVR12) are considered cured of hepatitis C.

About the EXPEDITION-8 Study1
EXPEDITION-8 is an ongoing non-randomized, single arm, open-label, multicenter Phase 3b study evaluating the safety and efficacy of glecaprevir/pibrentasvir in treatment-naïve GT1-6 chronic HCV patients with compensated cirrhosis. The study investigated two cohorts of patients:
Cohort one: treatment-naïve genotype 1, 2, 4, 5, 6 patients with compensated cirrhosis (n=280)
Cohort two: treatment-naïve GT3 patients with compensated cirrhosis (n=60)

The primary endpoint is the percentage of patients achieving SVR12 in a per-protocol analysis and the secondary endpoints are on-treatment virologic failure and relapse rates. For cohort one, 280 patients were enrolled and seven patients were excluded from the SVR12 per-protocol analysis (n=273); five patients were lost to follow up, and two patients received less than 8 weeks of treatment (one of these two patients achieved SVR12).

Additional information on the clinical trials for MAVYRET is available at www.clinicaltrials.gov/.

About MAVYRET™ (glecaprevir/pibrentasvir)
MAVYRET™ is approved by the U.S. Food and Drug Administration (FDA) for the treatment of chronic hepatitis C virus (HCV) infection in adults across all major genotypes (GT1-6). MAVYRET is a pan-genotypic, once-daily, ribavirin-free treatment that combines glecaprevir (100mg), an NS3/4A protease inhibitor, and pibrentasvir (40mg), an NS5A inhibitor, dosed once-daily as three oral tablets, taken with food.

MAVYRET is an 8-week, pan-genotypic option for patients without cirrhosis and who are new to treatment, who comprise the majority of people living with HCV. MAVYRET is also approved as a treatment for patients with specific treatment challenges, including those (GT1) not cured by prior treatment experience to either a protease inhibitor or NS5A inhibitor (but not both), and in patients with limited treatment options, such as those with severe chronic kidney disease (CKD) or those with genotype 3 chronic HCV. MAVYRET is a pan-genotypic treatment approved for use in patients across all stages of CKD.

Glecaprevir (GLE) was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors.

Full prescribing information can be found here.

Do Patients with Chronic Liver Disease Face Higher Drug-induced Liver Injury Risk?

Meeting Coverage > AASLD

Do Patients with Chronic Liver Disease Face Higher DILI Risk? 
by Molly Walker, Staff Writer, MedPage Today
November 12, 2018
Research suggests a link of which drug developers should be aware, expert says

SAN FRANCISCO -- Individuals with certain types of chronic liver disease may be particularly susceptible to drug-induced liver injury (DILI), and the pharmaceutical industry should take this population into account during drug development, an expert said here.

Indeed, some research suggested that drug-induced liver injury is linked with a higher risk of poor outcomes in patients with pre-existing liver disease, said Naga Chalasani, MD, of Indiana University School of Medicine in Indianapolis.
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DAA Treatment and Hepatic Fibrosis Improvement in HCV: What's the Link?

Abstract
Presented at AASLD The Liver Meeting 2018. Study number 0603.
Kommineni VT et al. Factors Associated with Lack of Improvement in Fibrosis Following HCV Treatment.

Monthly Prescribing Reference
DAA Treatment and Hepatic Fibrosis Improvement in HCV: What's the Link?
According to the results of a prospective cohort study, 57% of patients with hepatitis C virus (HCV) infection who achieved sustained virologic response (SVR) showed no improvement in hepatic fibrosis. The study, which took place at a tertiary liver center, aimed to determine whether direct-acting antiviral (DAA) therapy reduced fibrosis and assessed whether any predictors of treatment failure existed at 1-year follow-up. A total of 193 patients were divided into 2 groups: those who achieved SVR (N=143) and those who failed treatment or did not receive it (N=50). 

Conference Articles
By Cassandra Pardini, PharmD November 13, 2018 

Hepatitis C is detectable in rectal and nasal fluid

Conference Coverage @ infohep
Hepatitis C is detectable in rectal and nasal fluid

Keith Alcorn Published: 12 November 2018

High levels of hepatitis C virus (HCV) can be found in the rectal and nasal fluids of people with high hepatitis C viral loads even when blood is not present, Austrian researchers reported on Sunday at the 2018 AASLD Liver Meeting.

The findings reinforce the plausibility of HCV transmission through sharing up rolled-up bank notes or other equipment for snorting drugs.

The findings were presented by Dr David Chromy of the Medical University of Vienna on behalf of the Vienna HIV & Liver Study Group.


Conference Updates: infohep news
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The incidence of diabetes, stroke and kidney disease falls after hepatitis C cure

AASLD Liver Meeting news @ infohep
The incidence of diabetes, stroke and kidney disease falls after hepatitis C cure
Keith Alcorn Published: 12 November 2018 

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.

The findings were presented by Carmine Rossi of the British Columbia Centre for Disease Control at the 2018 AASLD Liver Meeting in San Francisco on Sunday.

Hepatitis C infection is associated with a higher incidence of chronic kidney disease, diabetes and cardiovascular disease. Although the mechanisms leading to an increased risk of these conditions in people with hepatitis C are not fully understood, liver damage caused by hepatitis C is known to disrupt glucose metabolism. Chronic hepatitis C infection affects the cardiovascular system in numerous ways and also damages the kidneys.


Conference Updates: infohep news 
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Sofosbuvir/ledipasvir cures most young children with hepatitis C

Sofosbuvir/ledipasvir cures most young children with hepatitis C
Liz Highleyman 
Published: 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 2018 AASLD Liver Meeting in San Francisco.

The prevalence of hepatitis C virus (HCV) infection is low among children in Europe and the US, though there is concern that the rate may be rising in the US as more young women become infected as a consequence of the burgeoning opioid epidemic. In some resource-limited countries such as Egypt, HCV among children is much more common.

The advent of direct-acting antiviral agents (DAAs) has revolutionised the treatment of hepatitis C for adults. These include Gilead Science's HCV polymerase inhibitor sofosbuvir (marketed alone as Sovaldi) and NS5A inhibitor ledipasvir, which are co-formulated in a 400/90mg once-daily tablet (Harvoni). 

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Osteopontin: A new emerging role in HCV-related hepatocellular carcinoma

Published: 03 September 2018 in scientific reports; https://www.nature.com/articles/s41598-018-31421-6
https://doi.org/10.1038/s41598-018-31421-6

Osteopontin: A new emerging role in HCV-related hepatocellular carcinoma

Kanazawa University
Hepatitis C virus (HCV) infection is the major cause of hepatocellular carcinoma (HCC) and was estimated to be responsible for 745,000 deaths in 2012. Recently, highly efficient and direct-acting antiviral agents (DAAs) have been able to eliminate HCV from infected livers in more than 90% of cases. However, emergence of HCC at a rate of about 1% per year is now reported in HCV-infected livers. Therefore, new therapeutic strategies are needed to prevent HCV infection, HCC recurrence, and hepatocarcinogenesis.

Osteopontin (OPN) is a multifunctional cytokine and is involved in normal physiological processes, as well as in numerous pathological conditions, including inflammation, fibrogenesis, and carcinogenesis. In liver diseases, OPN plays an important role in acute liver injury, viral replication, liver repair, fibrosis, and HCC.

Recent work has identified CD44 as the most common marker for cancer stem cells (CSCs) in several human cancers. CD44 has a pivotal role in regulating the properties of CSCs, including their self-renewal, tumor initiation, metastasis, and chemoradioresistance, and OPN reportedly interacts with CD44.

In HCC, enrichment of several stem cell markers, including CD133, CD90, CD13, epithelial cell adhesion molecule (EpCAM), CD44, CD24, and oval cell marker OV6, is reported in certain side populations of CSCs. However, CSCs represent only a minor population of the cancer cells and there is currently no evidence for a role for CSCs in supporting HCV replication. Therefore, identifying the underlying mechanism of HCV pathogenesis and its relationship to CSCs is an important research challenge.

In this study, a group from Kanazawa University evaluated the significance of the OPN-CD44 axis for HCV replication in EpCAM+/CD44+ CSCs, and investigated the role of OPN in the regulation and maintenance of EpCAM+/CD44+ CSCs.

[Results]

EpCAM+/CD44+ CSCs showed marked HCV replication when compared with EpCAM?/CD44? cells. In addition, the levels of OPN mRNA and protein were higher in EpCAM+/CD44+ CSCs than in EpCAM?/CD44? cells. OPN significantly enhanced HCV replication in EpCAM+/CD44+ CSCs and markedly suppressed interferon (IFN)-stimulated gene expression. Glycogen synthase kinase-3β inhibitor 6-bromoindirubin-3-oxime increased the EpCAM+/CD44+ CSC population and OPN expression and impaired IFN signaling via signal transducer and activator of transcription 1 (STAT1) degradation. Furthermore, OPN regulated stemness of EpCAM+/CD44+ CSCs, which led to inactivation of IFN signaling and enhanced HCV replication.

[Significance and future prospects]

The Kanazawa University group focused its attention on CSCs, as HCC is proposed to develop from CSCs, even though they represent a small part of the HCC cell population. However, HCV replication in CSCs is still poorly understood. This study showed the significance of the OPN-CD44 axis for HCV replication in EpCAM+/CD44+ CSCs.

The results of the Kanazawa University group highlight a new role for OPN in supporting HCV replication in EpCAM+/CD44+ CSCs through a reduction in STAT1 activation. They also provide evidence that OPN has the potential to maintain CSC phonotypes, and identify the OPN-CD44 pathway as a potential target for regulating HCV replication and stemness in HCC cells. 

Monday, November 12, 2018

The Medicines Patent Pool Signs Licence With AbbVie to Expand Access to Key Hepatitis C Treatment, glecaprevir/pibrentasvir

The Medicines Patent Pool Signs Licence With AbbVie to Expand Access to Key Hepatitis C Treatment, glecaprevir/pibrentasvir 

SAN FRANCISCO, November 12, 2018 /PRNewswire/ --
Important collaboration will ensure affordable hepatitis C treatment options in low- and middle-income countries.

The Medicines Patent Pool (MPP) has today announced a new, royalty-free licence agreement with AbbVie for glecaprevir/pibrentasvir (G/P) - a World Health Organization (WHO)-recommended treatment for people living with chronic hepatitis C (HCV). The licence will enable quality-assured manufacturers to develop and sell generic medicines containing G/P in 99 low- and middle-income countries (LMICs) and territories at affordable prices, enabling access to and treatment scale-up with the most effective pan-genotypic regimens. The agreement was launched at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2018 in San Francisco.

"G/P is a priority therapy for licensing for the MPP, so this agreement with AbbVie is very good news for public health," said Dr Marie-Paule Kieny, Chair of the MPP Governance Board. "It is a really important new option for a significant proportion of HCV patients throughout the world. As with previous MPP licences, we look forward to facilitating access to generic versions of this product as quickly as possible in as many territories as possible."

Globally, 71 million people are currently living with chronic HCV, many of them in LMICs. By the end of 2015, only 20 percent had been diagnosed and a mere seven percent of them had received treatment. In February 2017, the MPP issued its annual report on priority medicines for in-licensing. Given its favourable clinical profile and high potential in LMICs, G/P was listed as a key priority treatment.

G/P is an all-oral, once-daily, pan-genotypic combination regimen and was originally approved in 2017. It has achieved high cure (SVR12) rates of 98 per cent in treatment-naïve non-cirrhotic patients across all six genotypes of the virus. It is recommended by the WHO as a first-line treatment for eight weeks in treatment- naïve non-cirrhotic patients. Treatment-naïve patients with compensated liver cirrhosis require a 12-week treatment course.

Further, the regimen is also indicated for use in HCV patients with any degree of renal impairment, including patients on dialysis. Globally between five and ten percent of all people living with chronic HCV infection are estimated to be living with kidney disease and this treatment will be very helpful for them.

There are 95 countries and four territories included in the MPP/AbbVie licence for G/P at this point.

Hepatitis C treatment can be shortened in 50 percent of patients, study finds

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

Loyola University Health System

MAYWOOD, IL - Hepatitis C drugs cure more than 90 percent of patients, but can cost more than $50,000 per patient.

Findings from a new study could lead to significant cost savings. Preliminary data from the study, co-led by a theoretical modeling researcher from Loyola University Chicago Stritch School of Medicine and Loyola Medicine, found that in 50 percent of patients, the standard 12-week treatment regimen could be shortened to as little as six weeks without compromising efficacy.

"There's a potential to save up to 20 percent of the costs of hepatitis C drugs," said Loyola researcher Harel Dahari, PhD, co-first author of the study along with Ohad Etzion, MD, of Soroka University Medical Center in Israel. Senior author is Amir Shlomai, MD, PhD, of Beilinson Hospital in Israel.

The study was presented November 12 during the annual meeting of the American Association for the Study of Liver Diseases in San Francisco.

Dr. Dahari is co-director of the Program for Experimental and Theoretical Modeling (PETM) in the division of hepatology of Loyola Medicine and Loyola University Chicago Stritch School of Medicine. Two other Loyola authors are Susan Uprichard, PhD, co-director of PETM and an associate professor in the department of microbiology and immunology and Scott Cotler, MD, head of Loyola Medicine's division of hepatology and a professor in the department of medicine of Loyola University Chicago Stritch School of Medicine.

Hepatitis C is an infection caused by a virus spread through contaminated blood. It can lead to liver damage, liver failure and liver cancer. An estimated 70 million people worldwide, including about three million in the United States, are chronically infected with hepatitis C.

A class of oral medications called direct acting anti-virals (DAA) has revolutionized the treatment of hepatitis C. In more than 90 percent of patients, the medications eliminate the virus and cure the patient, with minimal side effects. But the high cost limits access and is a substantial financial burden on Medicare, Medicaid and private insurers.

"Treatment currently is standardized to be given for a set period of time, usually 12 weeks, rather than being tailored to the individual patient," Dr. Cotler said.

In the new study, researchers used a personalized medicine technique called modeling-based response-guided therapy to reduce treatment times when possible. After patients had undergone treatment for a few weeks, researchers measured how much hepatitis C virus levels had decreased. They used mathematical modeling to estimate how long it would take to completely eliminate the virus.

The study has included 22 patients so far. Mathematical modeling predicted that treatment could be shortened to 10 weeks in one patient (five percent of the total patients), eight weeks in eight patients (36 percent) and six weeks in two patients (nine percent). The other 11 patients (50 percent) needed to be treated for the standard 12 weeks.

Twenty-one patients remained virus-free. The only patient who relapsed had the most difficult-to-treat form of the hepatitis C virus, known as genotype 3.

The proof-of-concept pilot study showed that using response-guided therapy to reduce treatment times is feasible. To validate the results, a large multicenter trial is underway in Israel.

Dr. Dahari said that in addition to cutting costs, shorter treatment regimens would make it easier to treat hepatitis C patients who have limited health insurance benefits.

###
The study was conducted with David Yardeni, MD, Anat Nevo-Shor, MD, Daniela Munteanu, MD, and Naim Abufreha, MD, of the Department of Gastroenterology and Liver Diseases, Soroka University Medical Center, Beesheba, Israel; Assaf Issachar, MD, Michal Cohen-Naftaly, MD, Orly Sneh Arbib, MD, and Marius Braun, MD, of the Liver Institute, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel; and Orna Mor, PhD, of the Central Virology Laboratory, Ministry of Health, Sheba Medical Center, Israel.

The study is titled, "Response-Guided Therapy with DAA Shortens Treatment Durations in 50 Percent of HCV-Treated Patients."

The study was supported in part by Clalit, a health service organizaton in Israel and the U.S. National Institutes of Health. 

High SVR12 rate for 16 week glecaprevir/pibrentasvir regimen in HCV GT1

Combo HCV Pill Effective in Certain Refractory Patients
High SVR12 rate for 16 week glecaprevir/pibrentasvir regimen in HCV GT1 patients
by Molly Walker, Staff Writer, MedPage Today November 11, 2018 
November 11, 2018
A 16-week treatment course had a SVR 12 of 95%, including 94% in non-cirrhotic patients and 97% in cirrhotic patients who had failed prior treatment containing NS5A inhibitors, with no virologic failure among those with HCV genotype 1b infection, reported Mark S. Sulkowski, MD, of Johns Hopkins Hospital in Baltimore.

He said that glecaprevir/pibrentasvir was approved by the FDA in 2017 for treatment of NS5A inhibitor-experienced patients with genotype 1 infection and no NS3/4A protease inhibitor therapy.

A 16-week course of treatment was approved based on a small group of 17 patients in a trial where 16 of 17 achieved SVR12, Sulkowski explained at a press conference at the annual Liver Meeting, sponsored by the American Association for the Study of Liver Diseases (AASLD).

But that wasn't enough for the AASLD/Infectious Diseases Society of America (IDSA) guidelines panel, which labeled the therapy an "alternative regimen" and did not put it in the recommended category for treatment for this population, with "concerns based on the small number of human beings treated."
Read More: https://www.medpagetoday.com/meetingcoverage/aasld/76266
Website MedPage Today Twitter @medpagetoday

Coverage > Liver Meeting
Mavyret SVR high in patients with Sovaldi, NS5A inhibitor experience
November 11, 2018
SAN FRANCISCO — Mavyret was highly effective and well-tolerated in patients with chronic hepatitis C genotype 1 who had experience with a combination of Sovaldi, NS5A inhibitor and ribavirin, according to data presented at The Liver Meeting 2018.

“The context of this study was that the FDA granted approval in August 2017 for [Mavyret] for 16 weeks in persons who failed an NS5A-containing regimen that did not also contain a protease inhibitor,” Mark S. Sulkowski, MD, from Johns Hopkins Hospital in Maryland, said during a press conference presentation.
Website Healio - Twitter @HealioHep

Combined Glecaprevir/Pibrentasvir Highly Effective in HCV Patients Who Have Failed Other Therapies 
SAN FRANCISCO – Data from a new study presented this week at The Liver Meeting® – held by the American Association for the Study of Liver Diseases – found the combination of glecaprevir and pibrentasvir is highly effective and well tolerated in patients with chronic hepatitis C virus (commonly called HCV) genotype-1 infections who have prior treatment experience with sofosbuvir/NS5A inhibitor.

Meeting Updates 
View all updates on this blog, (LINK), coverage elsewhere, (LINK).

Abstract
American Association for the Study of Liver Diseases
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AASLD Poster Roundup: Factors that Impact Cirrhosis Diagnosis

Meeting Coverage > AASLD
AASLD Poster Roundup: Factors that Impact Cirrhosis Diagnosis
Selections from poster sessions at the annual Liver Meeting
Nov 11
by Elizabeth Hlavinka, Staff Writer, MedPage Today
SAN FRANCISCO -- Over 40,000 people die of cirrhosis and chronic liver disease per year, and determining which factors increase the risk of this illness is important for implementing prevention and treatment methods.

This issue was explored in poster presentations at the annual Liver Meeting, sponsored by the American Association for the Study of Liver Diseases (AASLD).


Meeting Coverage
Website MedPage Today
Twitter @medpagetoday

Adolescents HCV Geno 1 or 4 -.Ombitasvir/Paritaprevir/Ritonavir With or Without Dasabuvir and With/Without Ribavirin

In Case You Missed It
Hepatol Commun. 2018 Nov; 2(11): 1311–1319.
Published online 2018 Oct 5. doi: [10.1002/hep4.1250]

Ombitasvir/Paritaprevir/Ritonavir With or Without Dasabuvir and With or Without Ribavirin for Adolescents With HCV Genotype 1 or 4.
Daniel H. Leung, 1 Stefan Wirth, 2 Betty B. Yao, 3 Rolando M. Viani, 3 , 13 Regino P. Gonzalez‐Peralta, 4 , 14 Maureen M. Jonas, 5 Steven J. Lobritto, 6 Michael R. Narkewicz, 7 Etienne Sokal, 8 Clàudia Fortuny, 9 Evelyn K. Hsu, 10 Antonio Del Valle‐Segarra, 11 Jiuhong Zha, 3 Lois Larsen, 3 Li Liu, 3 Diana L. Shuster, 3 , 15 Daniel E. Cohen, 3 and Philip Rosenthal 1

Abstract
In adults, treatment of hepatitis C virus (HCV) infection with ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) with or without dasabuvir (DSV) and ±ribavirin (RBV) results in high rates of sustained virologic response (SVR). However, these regimens have not been investigated in adolescents. This ongoing, open‐label, phase 2/3 study evaluated the pharmacokinetics, safety, and efficacy of OBV/PTV/r+DSV±RBV treatment for 12 weeks in adolescents infected with HCV genotype (GT) 1 without cirrhosis (part 1) and the safety and efficacy of OBV/PTV/r±DSV±RBV treatment for 12 or 24 weeks in adolescents infected with GT1 or GT4 without cirrhosis or with compensated cirrhosis (parts 1 and 2). Patients were 12‐17 years of age and treatment naive or interferon experienced. Treatment regimens were based on HCV GT and cirrhosis status. Endpoints were SVR at posttreatment week 12 (SVR12), adverse events (AEs), and pharmacokinetic parameters. Thirty‐eight adolescents were enrolled, 66% were female patients, and 76% were White; 42%, 40%, and 18% of patients had HCV GT1a, GT1b, and GT4 infections, respectively. Median age was 15 years (range, 12‐17 years), and 1 patient had cirrhosis. The SVR12 rate was 100% (38/38; 95% confidence interval [CI], 90.8%‐100%). No treatment‐emergent grade 3 or 4 laboratory abnormalities were reported. No serious AEs occurred on treatment, and no AEs led to study drug discontinuation. The most common AEs were headache (21%), fatigue (18%), nasopharyngitis (13%), pruritus (13%), and upper respiratory tract infection (11%). Intensive pharmacokinetic results showed OBV, PTV, DSV, and ritonavir drug exposures were comparable to those seen in adults. Conclusion: Treatment with OBV/PTV/r±DSV±RBV was well tolerated and highly efficacious in adolescents with HCV GT1 or GT4 infection.

Sunday, November 11, 2018

Tracking addiction: New treatments appear to be working

Tracking addiction: New treatments appear to be working
By Matt Bise
It has been almost a year since Gov. Henry McMaster called opioid and heroin addiction a statewide public health emergency. The declaration of a health emergency gives public health agencies and law enforcement new powers to act and respond on a much larger scale.

In October the Kennedy Center in Berkeley County started offering a new medical option for addicts who commit to counseling, and treatment for opioid or heroin addiction has shown that it can work when it’s accessible.

Meantime as new treatments make their way into rural communities, where the crisis takes root, another health concern is surfacing from the scourge — hepatitis C...


Hepatitis C Transmission
The great majority of HCV infections are found among people with a history of drug injection, including people who have been incarcerated. HCV is easily transmitted among drug injectors by sharing syringes or other injection paraphernalia (such as cookers, filters). Hepatitis C is easier to transmit through shared injection equipment than HIV, and HCV is usually the first blood borne virus IDUs acquire. As a result, as many as 50-90% of IDUs have been infected with HCV.

The Liver Meeting® - Nonalcoholic Fatty Liver Disease Patients Have Higher Rates of All Non-Liver-Related Cancers

Updated Nov 12, 2018
Meeting Coverage @ infohep
People with fatty liver disease are at greater risk for multiple cancers
Liz Highleyman / 12 November 2018
People with non-alcoholic fatty liver disease (NAFLD) were found to have higher rates of cancer, with the greatest increase observed for gastrointestinal cancers, according to findings presented yesterday at the 2018 AASLD Liver
Read More: http://www.infohep.org/People-with-fatty-liver-disease-are-at-greater-risk-for-multiple-cancers/page/3365838/

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Meeting Coverage @ Healio 
Fatty liver imposes 91% higher risk for cancer 
Nov 11, 2018
“The risk of malignancy was higher in NAFLD vs. controls ... 91% higher than the general population when we take all cancers into account,” Alina M. Allen, MD, of Mayo Clinic, Rochester, Minn., said during her presentation. “Obesity is associated with a higher risk of cancer only in those with NAFLD and not in those without.”
Read More: 

Meeting Updates
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Nonalcoholic Fatty Liver Disease Patients Have Higher Rates of All Non-Liver-Related Cancers
November 9, 2018
Data from a new study presented this week at The Liver Meeting® found that rates of malignancy occurring outside of the liver were higher in adults with nonalcoholic fatty liver disease than among adults across most types of cancers.

SAN FRANCISCO – Preliminary data from a new study presented this week at The Liver Meeting® – held by the American Association for the Study of Liver Diseases – found that rates of malignancy occurring outside of the liver were higher in adults with nonalcoholic fatty liver disease than among adults across most types of cancers.

Nonalcoholic fatty liver disease (commonly called NAFLD or fatty liver disease) is used to describe liver complications that arise from the buildup of excess fat in the liver. NAFLD is estimated to affect more than 80 million Americans.

Malignancy is among the most common causes of death in patients with NAFLD. To examine whether increased malignancy risk is similar across all types of cancers, researchers at the Mayo Clinic in Rochester, Minn. conducted a study to determine the rates of cancer diagnoses among NAFLD patients compared to other adults in the United States of similar age and sex.

“Population-based studies such as this one can offer important epidemiologic data regarding the important threats to the health of a community,” explains Alina M. Allen, MD, assistant professor of medicine, Mayo Clinic, and the study’s co-author. “While it is known that individuals with NAFLD are at higher risk to develop cancers, it was not clear which type of cancer and how much higher their risk is, in reference to the general population. Such data would enable appropriate counseling and could inform screening policies.”

The researchers identified 4,782 NAFLD patients and compared them to 14,441 age- and sex-matched controls living in Olmsted County, Minn., between 1997 and 2016 using the Rochester Epidemiology Project database. They calculated age- and sex-adjusted incidence ratios of common cancers per 100,000 person-years between these two patient groups. The median age of the NAFLD patients was 54, and 54 percent were women. Median follow-up time was eight years. Overall, 788 (16 percent) of NAFLD patients and 1,752 (12 percent) of controls were diagnosed with malignancies during the study’s timespan.

Rates of malignancy were higher for NAFLD compared to controls for most types of cancers. The increased malignancy rate for NAFLD patients was highest for liver cancer, followed by stomach cancer, pancreatic cancer, and uterine cancer. Overall, breast, prostate and colon cancers were the three most common malignancies among NAFLD patients.

“These data provide an important “hierarchical” overview of the top most important malignancy risks associated with NAFLD. Liver cancer had the highest increase in relative risk, and this was not a surprising finding,” says Dr. Allen. “However, the 2.5-fold higher risk of stomach and pancreatic cancer are novel data that the medical community should be aware of. Future studies should further examine this association to determine if screening methods should be implemented in this population.”

Editor’s note: This press release contains updated data that is not reflected in the published abstract but will be presented at The Liver Meeting®.

Dr. Allen will present these findings at AASLD’s press conference in Room 312-314 at the George R. Moscone Convention Center in San Francisco on Saturday, November 10 from 4:00 PM – 5:30 PM. The study entitled “The Incidence of Extrahepatic Malignancies in Nonalcoholic Fatty Liver Disease(NAFLD)” will be presented on Sunday, November 11 at 8:30 AM in Room 24/25. The corresponding abstract (number 0031) can be found in the journal, HEPATOLOGY

About AASLD 
AASLD is the leading organization of clinicians and researchers committed to preventing and curing liver disease. The work of our members has laid the foundation for the development of drugs used to treat patients with viral hepatitis. Access to care and support of liver disease research are at the center of AASLD’s advocacy efforts.
Read the press release and additional information about AASLD are available online at www.aasld.org.

Daily Clinical Clips Of The Liver Meeting 2018 - ‘What you need to know in 5-minutes’

Hot Topics In HCV
Practice Point is once again launching daily clinical clips reviewing hot topics in HCV presented each day at the meeting. Although the activity is intended for physicians and health care professionals, anyone, especially patients can benefit from each 5-minute review as well, check it out:

In this video series, Dr. Saab will present ‘what you need to know in 5‐minutes’ regarding today's presentations from AASLD 2018 in San Francisco, CA

Free "registration" is required, once accomplished:
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Index of recommended sites offering meeting coverage.