Thursday, November 29, 2018

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.


On Twitter
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

On This Blog
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.....


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

Wednesday, November 28, 2018

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

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:

Tuesday, November 27, 2018

Sweetened drinks pose greater diabetes risk than other sugary foods

Recommended Reading
The Liver Meeting® 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.

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." 

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: