Provincial funding for hepatitis C drugs a game changer, health professionals say

CBC News Provincial funding for hepatitis C drugs a game changer, health professionals say
Changes spurred by development of minimally invasive drugs with extremely high cure rates

Mar 05, 2018
The Ontario government says it will cover the cost of medication for all hepatitis C patients, regardless of the severity of the disease, a move that's being touted as a game-changing decision by health professionals in the field.

Dr. Paul Marotta believes the changes mark a critical turning point for treatment of the disease.

He's a hepatologist and the medical director of the liver transplant program at the London Health Sciences Centre.

"This is probably — hopefully — the final piece of the puzzle," says Marotta.

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Meeting Coverage - Conference on Retroviruses and Opportunistic Infections CROI 2018

Conference on Retroviruses and Opportunistic Infections (CROI)
March 4 to March 7, 2018
Boston MA
Website

Abstracts from Press Conference

Links

NEJM
HIV and ID Observations.
Paul Sax is Clinical Director of the HIV Program and Division of Infectious Diseases at Brigham and Women’s Hospital and Professor of Medicine at Harvard Medical School.
Paul E. Sax, MD
March 11th, 2018
Really Rapid Review — CROI 2018, Boston

CROI clearly remains our best meeting, the only one that brings together so much high quality research from so many disciplines. Clinical, basic, and behavioral researchers all have a place here.

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National AIDS Treatment Advocacy Project NATAP
Coverage @ NATAP
Jules Levin, Executive Director

Our web site is read all over the world and is recognized as a leading reliable source of HIV and Hepatitis treatment information for doctors, patients, and others. The information on the site is scientifically oriented, abundant, and comprehensive in its coverage of both HIV and Hepatitis. The site is regularly updated with new articles, studies and highlights from various major conferences.

Merck to Present New Data from Studies of Investigational HIV Therapies Doravirine and MK-8591 at CROI 2018
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Healio
Coverage @  Healio
Healio brings you the highlights from the Conference on Retroviruses and Opportunistic Infections (CROI). Refer back to this page often for the latest news from CROI, perspectives and interviews with leading researchers and clinicians, and to review archives of past meetings.

CROI chair: HIV conference promises to be ‘exciting meeting’

March 4, 2018
BOSTON — CROI 2018 Chair Judith S. Currier, MD, professor of medicine and division chief of infectious diseases at…

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NAM
Coverage @ NAM aidsmap

We will be reporting on key research presented at the conference, publishing news online and sending out four conference news summary bulletins – three during the week of the conference and one the week after. The bulletins will be available in English, French, Spanish, Portuguese, Italian and Russian. You can sign up here to receive these email bulletins. (If you already receive NAM’s regular email bulletins, you will automatically receive our conference bulletins.)

Experimental antibody plus TLR7 agonist maintains viral suppression in monkeys

Liz Highleyman

Published: 05 March 2018
Treatment with a broadly neutralising antibody plus an immune-stimulating drug led to long-term viral remission after interrupting antiretroviral therapy in a monkey study, according to data presented at the 25th Conference on Retroviruses and Opportunistic Infections (CROI 2018) this week in Boston.

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Contagion 

Coverage @ Contagion

Contagion® will be providing exclusive coverage on the conference, and so, keep your eyes peeled for session coverage and interviews with some of the key presenters.

Harnessing the Power of International, Interdisciplinary Collaboration on the Quest to Cure HIV
International interdisciplinary collaboration will bring us that much closer to a cure for HIV.

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MedPage Today
Coverage @ MedPage Today

MedPage Today, a CE and CME accredited medical news service, provides free continuing education to healthcare professionals in addition to the latest news.

Sex in Late-Stage Pregnancy Tied to Higher HIV Risk Biological changes may increase HIV transmission in serodiscordant couples 

BOSTON -- The risk of HIV transmission per sex act increased steadily through pregnancy, and was highest during postpartum, researchers reported here. In two HIV prevent studies that included 2,571 African women living in HIV serodiscordant relationships (female partners did not have HIV), the risk of HIV infection was 2.97-fold higher during the second two trimesters of pregnancy (P=0.01) and 4.18-fold higher during the 6-month post partum period (P=0.01), according to Renee Heffron, PhD, of the University of Washington in Seattle, and colleagues.
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Clinical Care Options HIV

Coverage @ Clinical Care Options

Get up to date on the latest HIV data with rapid Capsule Summaries, downloadable slidesets, and live, expert-led Webinars covering key studies from Boston.

New Data from CROI 2018

Expert faculty members summarize key studies from this important annual conference.

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ViralEd

Expert Review @ ViralEd

ViralEd, Inc. is a physician-directed medical education company whose mission is to provide thought-provoking, effective, and evidence-based CME to help improve health care provider knowledge and professional development. For over a decade, ViralEd's team of dedicated professionals have specialized in using a blended learning approach that combines innovative technology with live programming to provide programs and medical education content that is unique, timely, and of high quality.

3/12 and 3/13 - CME Webcasts - CROI 2018 Expert Review

The ARV Therapies and Therapeutic Strategies program is a comprehensive, independent review of the 25th Conference on Retroviruses and Opportunistic Infections (CROI 2018). This program consists of three components: (1) CME Internet Symposium: CROI 2018 Expert Review: a 1.5 hour Internet symposium that features an overview and discussion of key presentations and posters, selected by the expert faculty discussants; (2) Rapid-Fire Review of CROI 2018: a podcast that provides a brief, audio summary of the most essential data presented at the conference; and (3) From Conference to Clinic: Reviewing and Applying Data From CROI 2018: case-based dinner meetings during which the key data are reviewed, discussed and applied to patient care.

The CME Internet Symposium: CROI 2018 Expert Review will feature a panel of HIV experts reviewing and discussing key presentations on antiretroviral therapy presented at CROI 2018. The review and discussion will focus on HIV therapeutic options and developments, including: current treatment and management strategies, algorithms and recommendations, therapies in development, epidemiology, and diagnosis and clinical management of specific patient populations. This activity will enable participating health care providers caring for HIV-infected patients to become aware of and understand the data presented at this important conference and appropriately utilize those data to improve patient care. All online components of the program can be accessed at www.viraled.com.

This program is produced by the Postgraduate Institute for Medicine and ViralEd, Inc. It is not a session created by or presented at CROI 2018 and it is not sanctioned by the organizers of CROI 2018.

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Norah A. Terrault, MD - Managing HBV Infection Following Liver Transplant: Expert Q&A

Jasenka Piljac Žegarac, PhD
March 05, 2018

Managing HBV Infection Following Liver Transplant: Expert Q&A
In an interview with Infectious Disease Advisor, Norah A. Terrault, MD, MPH, professor of medicine and director of the Viral Hepatitis Center at the University of California, San Francisco (UCSF), discussed the recent advances and remaining challenges in managing HBV infection in patients undergoing liver transplantation.

Infectious Disease Advisor: What is the primary indication for liver transplantation in patients with HBV infection?

Norah A. Terrault, MD, MPH: In our transplant center at UCSF, as in others throughout the United States, the majority of patients with HBV have liver cancer as the primary indication for liver transplantation.7 The other group of patients in whom we perform liver transplants are patients with acute liver failure due to hepatitis B and those with decompensated cirrhosis. For those with decompensated cirrhosis, these are frequently patients with HBV who present very late to care and who have been undiagnosed and untreated for a very long time. However, anyone who is engaged in care and having their hepatitis B appropriately managed is generally at low risk of getting decompensated cirrhosis, because current guidelines recommend that patients who have cirrhosis and HBV continue with antiviral therapy for life. Long-term suppressive antiviral therapy would be expected to prevent progression of cirrhosis and decompensated liver disease.

Continue reading.......

Of Interest
Developing a New Combination Treatment for HBV Infection
NVR3–778, a capsid assembly modulator, reduces serum levels of hepatitis B virus (HBV) DNA and HBV RNA in mice with humanized livers and stable HBV infection, researchers report in the February issue of Gastroenterology. The combination of NVR3–778 and interferon prevented viral replication and HBV RNA particle production to a greater extent than either compound alone or entecavir.

Read more

Cancer stem cells, allies of the tumor and enemies of the patient

Cancer stem cells, allies of the tumor and enemies of the patient
University of Extremadura

The scientists of the UEx Molecular Biology of Cancer Research Group have a very clear objective. They want to uncover the physiological mechanisms of the cancer stem cell, the arch-enemy of the patient because it is responsible for the progression of the tumour. With that in mind, they are working on identifying new cell proteins which control cellular differentiation. Cancer stem cells possess the capacity to adopt highly undifferentiated states, characteristic of pluripotent cells, which very possibly contribute to the progression and maintenance of the different cells that form the tumour, in the same way that a healthy stem cell can give rise to different cell phenotypes. "These cancer stem cells are more resistant to the attack of chemotherapeutic agents, they are capable of regenerating the tumour and helping the tumour cells to spread to other organs", explains Pedro Fernández Salguero, lead researcher on the project.

The deregulation of cellular differentiation plays a very important role from an oncological point of view because it fosters the development of more undifferentiated and aggressive tumours, whose prognosis is worse. "Therefore, we want to identify which proteins within the cells are involved in retaining the undifferentiated characteristics of the tumour, which would allow it to be attacked more successfully, or, on the contrary, those leading to differentiated characteristics which reduce tumour development", adds Fernández Salguero.

The dioxin receptor, implicated in hepatocellular carcinoma and melanoma

One specific protein might contribute to keeping the tumour in a more highly undifferentiated state that could affect its metastatic capacity and its response to therapy. In fact, this group of researchers has already observed how a certain cell protein, the dioxin receptor (Ahr), participates in this process of cellular differentiation. "We have studied lines of cancer stem cells derived from patients and analysed tumour markers of potential clinical interest in animal models. The results obtained from both models have been validated in biopsies from patients with hepatocellular carcinoma and melanoma at the Infanta Cristina Hospital, in Badajoz (Spain). In this validation, the investigators found different values for this protein within the tumour and in the non-cancerous tissue from the same patients, and in turn, that the protein changes its expression in advanced stages, compared with stages prior to the development of the tumour (hepatic cirrhosis or hepatitis, in the case of hepatocellular carcinoma).

Thus, the results point to a therapeutic value for this protein (Ahr) because controlling it might repress the pluripotency of the cancer stem cell and reduce the malignity of the tumour. Indeed, different naturally-occurring molecules have been identified that modulate the activity of this protein in specific ways. In addition, the dioxin receptor might also facilitate the development of tools for the prognosis and evolution of the types of cancer in the study, hepatocellular carcinoma and melanoma.

Liver cancer
Hepatocellular carcinoma is a primary liver cancer, which is distinct from hepatic metastases originated by other tumours, highly aggressive and generally with poor prognosis. Further, its incidence is rising because this tumour usually appears as a consequence of an alcoholic liver cirrhosis or an infection by hepatitis B or C. At the moment, those suffering from liver cancer have few therapeutic opportunities, one of the few alternatives being a liver transplant. Tools for molecular prognosis and therapeutic targets are very scarce and the current survival rate for patients with advanced hepatocellular carcinoma is below 10%. As a consequence, it is necessary to identify new molecules and therapeutic options which complement the use of surgical resection and the transplant.
https://www.eurekalert.org/pub_releases/2018-03/uoe-csc030518.php

Minireview - DAAs and the occurrence or recurrence of HCC among patients with HCV related liver disease

Minireviews
World J Hepatol. Feb 27, 2018; 10(2): 267-276
Published online Feb 27, 2018.
doi: 10.4254/wjh.v10.i2.267

Impact of direct acting antivirals on occurrence and recurrence of hepatocellular carcinoma: Biologically plausible or an epiphenomenon?
Amna Subhan Butt, Fatima Sharif, Shahab Abid

The ground breaking discovery of the new group of direct acting antiviral agents (DAAs) had led to a paradigm shift in the management of chronic hepatitis C (CHC) which is the most common cause of hepatocellular carcinoma (HCC) in Japan, Pakistan, United States and many European countries[1,2]. With annual incidence of HCC ranging from 1% to 7% in patients with HCV related cirrhosis, (HCC) is a leading cause of morbidity and the second most common cause of cancer related deaths worldwide[3,4]. Besides contribution of several host and viral factors in the pathogenesis of disease progression, achieving sustained virologic response (SVR) has been found as the single most important factor in reducing HCV associated HCC incidence[5].

The novel DAAs not only provided a potent, oral alternative to injectable interferons, but also had a shorter duration of treatment, better efficacy with over 90% achievement of SVR and a more favorable side effect profile[6]. However, since 2016, concerns were raised regarding the effect of DAAs on progression to HCC[7]. In addition, their long-term benefits including impact on HCC have been questioned in the context of specific populations and subgroups which were not included in the landmark trials investigating DAA based therapy[3].

Therefore, this review aims to explore existing molecular studies as well as clinical observations in order to determine whether there is an association between the use of DAAs and the occurrence or recurrence of HCC among patients with HCV related liver disease. We also aim to evaluate whether there is a subset of the population in which this phenomenon has been observed.

Full text review: https://www.wjgnet.com/1948-5182/full/v10/i2/267.htm
Download PDF

Of Interest
Clinical Care Options

How I Manage HCC Risk Following HCV Cure
Paul Y. Kwo MD - 2/14/2018
Which patients, who have achieved a sustained virologic response with HCV treatment, need to be screened for hepatocellular carcinoma? Here’s my approach.

On This Blog
Risk Of Developing Liver Cancer After HCV Treatment

This page offers an index of links to current data investigating the possible risk of developing liver cancer (hepatocellular carcinoma, or HCC) during and after direct-acting antiviral therapy in patients with hepatitis C.

Healio

Liver cancer incidence after HCV therapy linked to risk factors, not treatment
Li DK, et al. Hepatol. 2017;doi:10.1002/hep.29707.

Direct-acting antiviral treatment for hepatitis C did not correlate with an increased risk for hepatocellular carcinoma in a large cohort study of both treated and untreated patients with or without cirrhosis. Those with incident HCC after DAA treatment had higher risk factors at baseline. “There was no increased risk for HCC as a result of having received DAA therapy whatsoever,” Raymond T. Chung, PhD, director of Hepatology and Liver Center at Massachusetts General Hospital, told Healio Gastroenterology and Liver Disease. 

Outcomes - HCV psoriatic patients using Pegylated Interferon plus Ribavirin compared to new Direct-Acting Antiviral agents

World J Hepatol. Feb 27, 2018; 10(2): 329-336
Published online Feb 27, 2018. doi: 10.4254/wjh.v10.i2.329

Outcomes assessment of hepatitis C virus-positive psoriatic patients treated using pegylated interferon in combination with ribavirin compared to new Direct-Acting Antiviral agents
Giovanni Damiani, Chiara Franchi, Paolo Pigatto, Andrea Altomare, Alessia Pacifico, Stephen Petrou, Sebastiano Leone, Maria Caterina Pace, Marco Fiore

Core tip: Psoriasis is a chronic inflammatory disease affecting approximately the 2% of population in Europe and North America. The hepatitis C virus (HCV) infection affects approximately the 3% of the world population with an estimated prevalence of 5 million people in the United States. Up to 0.06% of people in the United States suffer from both psoriasis and HCV. Psoriatic patients with HCV are excluded by randomized controlled clinical trials. Therefore, no data is currently available concerning the concomitant administration of biological disease modifying drugs and the new Direct-Acting Antiviral agents (DAAs) medications approved for the treatment of HCV infection. The aim of this study is to evaluate the outcomes in biological treatment and quality of life of psoriatic patients with HCV infection treated with DAAs compared to the previous standard therapy of Pegylated Interferon plus Ribavirin.

Full Text
Online
PDF

AIM
To evaluate the outcomes in biological treatment and quality of life of psoriatic patients with chronic hepatitis C (CHC) treated with new Direct-Acting Antiviral agents (DAAs) compared to pegylated interferon-2α plus ribavirin (P/R) therapy.

METHODS
This is a retrospective study involving psoriatic patients in biological therapy who underwent anti-hepatitis C virus (HCV) treatment at the Department of Dermatology Galeazzi Orthopaedic Institute Milan, Italy from January 2010 to November 2017. The patients were divided into two groups: patients that underwent therapy with DAAs and patients that underwent HCV treatment with P/R. Patients were assessed by a dermatologist for psoriasis symptoms, collecting Psoriasis Area Severity Index (PASI) scores and the Dermatology Quality of Life Index (DLQI). PASI and DLQI scores were evaluated 24 wk after the end of HCV treatment and were assumed as an outcome of the progression of psoriasis. Switching to a different bDMARD was considered as an inadequate response to biological therapy. The dropout of HCV therapy and sustained virological response (SVR) were considered as outcomes of HCV therapy.

RESULTS
Fifty-nine psoriatic patients in biological therapy underwent antiviral therapy for CHC. Of this, 27 patients were treated with DAAs and 32 with P/R. After 24 wk post treatment, the DLQI and the PASI scores were significantly lower (P < 0.001 and P < 0.005, respectively) in the DAAs group compared with P/R group. None of the patients in the DAAs group (0/27) compared to 8 patients of the P/R group (8/32) needed a shift in biological treatment.

CONCLUSION
DAAs seem to be more effective and safe than P/R in HCV-positive psoriatic patients on biological treatment. Fewer dermatological adverse events may be due to interferon-free therapy.

Full Text : https://www.wjgnet.com/1948-5182/full/v10/i2/329.htm

Cochrane Review Of HCV Drugs - The Controversy Continues

The Backstory
In the summer of 2017 a Cochrane Review concluded that achieving SVR (cure) for patients using hepatitis C direct-acting antivirals (DAAs) doesn't correlate with any long term benefits; reduce risks for HCV-related morbidity or all-cause mortality. Later that year, as we entered into November, Cochrane group’s conclusions changed, somewhat. Check out a quick overview, here.

Twitter & Mr. Chang
Henry E. Chang provided this blog with the above mentioned links, and kept the HCV community updated throughout the ongoing controversy by documenting each rebuttal on twitter, here is nice collection of his tweets: "Reactions from Hepatitis C Community on a Recent Cochrane Review of DAAs."

The Controversy Continues
On Twitter today an update from @HenryEChang

Authors of Cochrane HCV DAA review respond to AmJGastro Red Section commentary with their uncompromising worship for "well-designed & - executed RCTs to assess the utility of DAA treatment"→https://t.co/goqSWn2rC2

The Front Lines Of The Hepatitis C Crises
Patients, advocates, and physicians who have been on the front lines of the hepatitis C crises (for decades) understand first hand the damage Cochrane group’s irresponsible conclusions caused individuals living with HCV.

The Damage Is Done
Soon after the Cochrane Review was published, patients were hit with this horrendous headline in the media; "Hepatitis ‘wonder drug’ may be clinically ineffective, say experts." Leaving innocent patients confused and frightened, we'll never know how many people decided to forgo testing or treatment that summer, we can only surmise.

The New Era Of Hepatitis C Drugs
Today we have effective drugs to cure HCV, across all six HCV genotypes, including direct-acting antiviral therapy for people with severe liver damage, such as compensated cirrhosis, or kidney disease. HCV eradication is associated with the reversal of fibrosis, improvement of fibrosis and quality of life, as well as overall reduction of liver cancer, liver failure, risk of liver transplant, and liver-related mortality, including extrahepatic manifestations of HCV in patients who achieve SVR.

Do you think those Cochrane people, authors, men or women, even know the damage they have caused?

I do, and I am not alone.

Stay aware, stay healthy
Tina

Viral hepatitis: not just a silent killer but also a silencer

Viral hepatitis: not just a silent killer but also a silencer
BMC Blogs - 01 March 2018
Raquel Peck 
On Zero Discrimination Day (March 1st), the World Hepatitis Alliance (WHA) is encouraging the hepatitis community to challenge misconceptions and speak out about the devastating impact of stigma and discrimination across the globe.

Stigma and discrimination around viral hepatitis has long prevented people from speaking openly about their illnesses. For those brave enough to disclose their status, their reward, more often than not, may be social exclusion, diminished employment opportunities or unjust barriers to receiving healthcare. This harsh reality can have a devastating impact on an individual’s personal life and psychological well-being and prevent people from accessing much-needed diagnostics and treatment. There is no doubt that stigma and discrimination further perpetuate the epidemic of viral hepatitis.

We recently launched our Holding Governments Accountable: World Hepatitis Alliance Civil Society Survey Global Findings Report, which surveyed civil society organisations from 72 countries to better understand experiences of stigma and discrimination across the world. The findings confirmed and quantified what we had long suspected: stigma is felt in almost every corner of the globe (people from 93% of countries surveyed reported stigma and discrimination to some degree) and its impact is far-reaching (respondents reported on average 6 different types of stigma and discrimination).

Continue to full article: http://blogs.biomedcentral.com/on-health/2018/03/01/viral-hepatitis-not-just-a-silent-killer-but-also-a-silencer/