Sunday, August 31, 2014

Weekend Reading: Evolution of Hepatitis C Virus Treatment

Evolution of Hepatitis C Virus Treatment

Good afternoon folks, welcome to this edition of weekend reading, we close out the month with a podcast from the August issue of Gastroenterology & Hepatology

Dr. Kuemmerle along with Dr. Fasiha Kanwal discuss SVR rates using first generation DAA therapies, current agents, and what we can expect in the future. In addition, access to treatment is examined with an emphasis on making HCV treatment more affordable to everyone.

Evolution of Hepatitis C Virus Treatment

  • An editorial in the August issue of CGH discusses changing treatment methods for Hepatitis C Virus infection over the last several years. Dr. Kuemmerle speaks to first author Dr. Fasiha Kanwal of Baylor College of Medicine.

Friday, August 29, 2014

TGIF - Hepatitis C Bloggers Corner

Hepatitis C: Bloggers Corner

Hello friends, its TGIF, finally the week comes to a close.

Today we have a lovely variety of articles written from a patients' perspective by bloggers devoted to helping people who are living with hepatitis C.  Thank you for continuing to keep us informed and full of hope.

Enjoy!

Solvitur Ambulando
By Rick Nash

It's Thursday, today. I had a routine MRI to check the state of my liver, the regenerative nodules, and if I have cancer. I just parked the car, and my phone rings. I answer the phone and put it on speaker. It was my doc again.
Continue reading...

Hepatitis C Is Curable
By Lucinda K. Porter, RN

Periodically, someone mistakenly tells me that hepatitis C is not curable. Most of the time, they are happy to learn that hepatitis C can be cured. However, some people just want to hang on to what they believe is true, even if it is wrong. There are still people who believe that the earth is flat and that a man never walked on the moon. There is no sense in arguing with people over beliefs.
Continue reading...

Hepatitis C and Your Future: Make Your Voice Loud and Clear
In my recent blog, The Latest Hepatitis C Recommendations: Who Decides Your Future?, I expressed my concern about the latest hepatitis C recommendations. For details, you can read my previous blog or the recommendations, but the short version is that patients with stage 1 or 0 fibrosis were assigned the lowest treatment priority.  Insurance companies, state Medicaid programs, and health maintenance organizations can use this to deny treatment to patients in early stages. To me, this is sort of like saying to someone who has stage 1 cancer, "Come back when you have stage 2--then we'll treat you."


Recovery from hep C treatment holds important questions and expectations. How long does recovery from hep C treatment take? Will I regain my life beyond recovery?

Continue reading....

Liver Cancer after Hepatitis C Treatment
By Karen Hoyt

Liver Cancer after Hepatitis C Treatment is not the norm, but it is a threat to those of us who have severe liver damage. Reading about Hepatocellular Carcinoma (HCC) and Hepatitis C can take your mind in a couple of different directions.
 Continue reading....

Fast Food Drive Thru with Low Sodium
By Karen Hoyt

It’s time to get smart about eating out! My life has been a blur of travel lately and there are times that I have to rely on the fast food drive thru. We have all heard the down side and nasty things said about fast food. But sometimes it is a reality that we are just going to be stuck in a situation where we are … driving thru!
Continue reading...

UPDATE—Patients First: The Right to Be Treated and Cured 

AASLD/IDSA recently released hepatitis C treatment guidelines that limit treatment of hepatitis C to those who are considered the most seriously ill. In this respect, people with debilitating fatigue are recommended as the “highest” in need of treatment along with those with advanced disease, other conditions or diseases in addition to having HCV, and HCV populations who are at high risk for transmitting HCV.

Continue reading.... 


Thursday, August 28, 2014

Hepatitis C - New Therapies Are Coming Soon: The Case To Wait

New Therapies Are Coming Soon:  The Case To Wait

Good morning folks, sit back and watch an entertaining webcast presented in a trial and jury format, which examines the "Treat Now Or Wait" scenario in patients with HCV.

The program was recently launched for your viewing pleasure over at CLDF, listen to the judge and expert witnesses discuss new HCV regimens under development with or without ribavirin in this light-hearted innovative presentation.

Click here..........

More On: Daclatasvir (Daklinza) for Chronic Hepatitis C Cleared in EU

Related News....

Daclatasvir (Daklinza) for Chronic Hepatitis C Cleared in EU
Medscape
The European Commission has approved daclatasvir (Daklinza, Bristol-Myers Squibb) to treat adults with chronic hepatitis C virus (HCV) infection in combination with other drugs, the company announced today.

The approval follows an endorsement in June by the European Medicines Agency Committee for Medicinal Products for Human Use.

Daclatasvir blocks the action of NS5A, a protein essential for HCV replication. It is indicated for adults infected with HCV genotypes 1, 2, 3, and 4.

In a news release, the company notes that oral daclatasvir in combination with oral sofosbuvir provided cure rates of up to 100% in clinical trials, including in patients with advanced liver disease, genotype 3, and those who have previously failed treatment with protease inhibitors.

Daclatasvir is the first NS5A complex inhibitor approved in the European Union (EU) and, in combination with other drugs, provides a "shorter treatment duration (12 or 24 weeks) compared to 48 weeks of treatment with interferon- and ribavirin-based regimens," the company says.

Across clinical studies, daclatasvir-based regimens have been generally well-tolerated, with low discontinuation rates. The most common adverse effects with daclatasvir when used in combination with other drugs are fatigue, headache, and nausea.

The safety of daclatasvir has been demonstrated in diverse patient populations that include elderly patients, patients with advanced liver disease, post–liver transplant recipients, and patients coinfected with HIV, the company says.

"HCV is a challenging virus to overcome," Michael P. Manns, MD, professor and chairman, Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Germany, said in the release. Daclatasvir, when combined with other compounds, "often results in cure among even the hardest-to-treat patients," he added.

Recommended regimens and treatment durations for daclatasvir-based regimens include:
  • For HCV genotype 1 or 4 without cirrhosis: daclatasvir plus sofosbuvir for 12 weeks. Consider prolongation to 24 weeks for patients with prior treatment, including a NS3/4A protease inhibitor.
  • For genotype 1 or 4 with compensated cirrhosis: daclatasvir plus sofosbuvir for 24 weeks. Consider shortening treatment to 12 weeks for previously untreated patients with cirrhosis and positive prognostic factors such as IL28B CC genotype and/or low baseline viral load. Consider adding ribavirin for patients with very advanced liver disease or with other negative prognostic factors, such as prior treatment experience.
  • For genotype 3 with compensated cirrhosis and/or treatment experienced: daclatasvir plus sofosbuvir plus ribavirin for 24 weeks.
  • For genotype 4: 24 weeks of daclatasvir plus 24 to 48 weeks of peginterferon alfa and ribavirin. If the patient has HCV RNA undetectable at both treatment weeks 4 and 12, all 3 components of the regimen should be continued for 24 weeks. If the patient achieves undetectable HCV RNA, but not at both treatment weeks 4 and 12, daclatasvir should be discontinued at 24 weeks and peginterferon alfa and ribavirin continued for a total duration of 48 weeks.
Daclatasvir monotherapy is not recommended. The Summary of Product Characteristics will be available online. Commercial availability of daclatasvir in the EU will be determined by individual member states.

Wednesday, August 27, 2014

Bristol-Myers Squibb’s Daklinza (daclatasvir), Approved By European Commission

European Commission Approves Bristol-Myers Squibb’s Daklinza (daclatasvir) Across Multiple Genotypes for the Treatment of Chronic Hepatitis C Infection

Daklinza, when used in combination with sofosbuvir, is an all-oral, once daily regimen that yields cure rates of up to 100%

Daklinza + sofosbuvir offers potential cure for a broad range of EU HCV patients, including those with advanced liver disease, genotype 3 and protease inhibitor failures

R&D News
Wednesday, August 27, 2014 5:00 am EDT
"The eradication of HCV is in sight, and with today’s approval, Daklinza, in combination with other agents, will be an important option to achieve cure across many HCV genotypes and patient types for those in the EU who are in dire need of new treatment choices"
PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) today announced that the European Commission has approved Daklinza (daclatasvir), a potent, pan-genotypic NS5A replication complex inhibitor (in vitro), for use in combination with other medicinal products across genotypes 1, 2, 3 and 4 for the treatment of chronic hepatitis C virus (HCV) infection in adults. Daklinza, when used in combination with sofosbuvir, is an all-oral, interferon-free regimen that provided cure rates of up to 100% in clinical trials, including patients with advanced liver disease, genotype 3 and those who have previously failed treatment with protease inhibitors. Daklinza is the first NS5A complex inhibitor approved in the European Union (EU) and will be available for use in combination with other medicinal products, providing a shorter treatment duration (12 or 24 weeks) compared to 48 weeks of treatment with interferon- and ribavirin-based regimens.

Today’s approval allows for the marketing of Daklinza in all 28 Member States of the EU. The marketing authorization for Daklinza follows an accelerated assessment by the Committee for Medicinal Products for Human Use (CHMP), a designation that is granted to new medicines of major public health interest.

“HCV is a challenging virus to overcome, requiring multiple modes of attack. With the approval of Daklinza, we have a new class of drug that disrupts the virus in two ways - by inhibiting both viral replication and assembly - and when combined with other compounds often results in cure among even the hardest-to-treat patients,” said Michael P. Manns, MD, Professor and Chairman, Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany.

Of the estimated nine million people living with HCV in the EU, genotype 1 is the most common genotype, though distribution varies across the region. The burden of liver disease and other morbidities from HCV infection is significant in Europe, where HCV accounts for 63% of liver transplants among patients with virus-related liver disease. Patient populations with high unmet needs include those with advanced liver disease, protease inhibitor failure, genotype 3, HIV co-infected patients and those who have undergone liver transplant.

“The eradication of HCV is in sight, and with today’s approval, Daklinza, in combination with other agents, will be an important option to achieve cure across many HCV genotypes and patient types for those in the EU who are in dire need of new treatment choices,” said Emmanuel Blin, Head of Worldwide Commercialization, Bristol-Myers Squibb. “We are proud to have discovered, developed and now brought to market this first-in-class NS5A replication complex inhibitor. We look forward to our continued work with EU health authorities to ensure Daklinza-based regimens are available to patients as quickly as possible.”
The approval of Daklinza is supported by data from multiple studies, including an open-label, randomized study of Daklinza with sofosbuvir in genotypes 1, 2, and 3, including patients with no response to prior therapy with telaprevir or boceprevir and patients with fibrosis. Results showed that a regimen of Daklinza with sofosbuvir achieved SVR12 (sustained virologic response 12 weeks after the end of treatment; a functional cure) in 99% of treatment-naïve patients with HCV genotype 1, 100% of patients with genotype 1 who had failed treatment with either telaprevir or boceprevir, 96% of those with genotype 2 and 89% of those with genotype 3.

In addition, the regimen resulted in low rates of discontinuation (<1%) due to adverse events (AEs). The rate of serious adverse events (SAEs) was low (4.7%). The most common adverse events were fatigue, headache and nausea. Across clinical studies, Daklinza-based regimens have been generally well tolerated with low rates of discontinuation across a range of patients. Ongoing and completedDaklinza studies have included more than 5,500 patients in a variety of all-oral regimens and with the current interferon-based standard of care.

The safety of Daklinza for the treatment of hepatitis C has been demonstrated in diverse patient populations that include elderly patients, patients with advanced liver disease, post-liver transplant recipients and patients co-infected with HIV. No unique safety concerns have been identified in patients who were treated withDaklinza across clinical studies and in the early access program. Several of these studies are ongoing.

Recommended regimens and treatment duration for Daklinza combination therapy include:
HCV genotype and patient populationTreatmentDuration
Genotype 1 or 4 without cirrhosis
Daklinza + sofosbuvir
12 weeks
Consider prolongation of treatment to 24 weeks for patients with prior treatment including a NS3/4A protease inhibitor (see sections 4.4 and 5.1).
Genotype 1 or 4 with compensated cirrhosisDaklinza + sofosbuvir24 weeks
Shortening treatment to 12 weeks may be considered for previously untreated patients with cirrhosis and positive prognostic factors such as IL28B CC genotype and/or low baseline viral load.
Consider adding ribavirin for patients with very advanced liver disease or with other negative prognostic factors such as prior treatment experience.
Genotype 3 with compensated cirrhosis and/or treatment experiencedDaklinza + sofosbuvir + ribavirin24 weeks
Genotype 4Daklinza + peginterferon alfa + ribavirin24 weeks of Daklinza in combination with 24-48 weeks of peginterferon alfa and ribavirin.
If the patient has HCV RNA undetectable at both treatment weeks 4 and 12, all 3 components of the regimen should be continued for a total duration of 24 weeks. If the patient achieves HCV RNA undetectable, but not at both treatment weeks 4 and 12, Daklinza should be discontinued at 24 weeks and peginterferon alfa and ribavirin continued for a total duration of 48 weeks.
Daklinza monotherapy is not recommended. The Summary of Product Characteristics will be available at www.ema.europa.eu. Commercial availability of Daklinza in the EU will be determined by individual Member States.

Investment Commentary

Bristol-Myers gets the approval Gilead didn't want: Daklinza + Sovaldi for hep C
And here's where it gets more interesting. We know Gilead will be leaning on its Sovaldi + ledipasvir pill, which is up for FDA approval by Oct. 10. AbbVie's three-drug option is under FDA review for a December decision. Bristol-Myers might want to tout the Daklinza + Sovaldi option when (and if) its FDA nod comes through in November.
But the FDA didn't allow the company to turn in that Sovaldi-Daklinza data with its current app. The approval would be for Daklinza and another BMS drug, Sunvepra (asunaprevir)--and that combo hasn't performed quite as well as the Daklinza-Sovaldi team in trials. Sustained virological response--a common measure in hep C trials--for the latter duo approached 100% in some patients, as Bristol-Myers noted in its E.U. announcement.....
Continue reading... 

Medscape

More On: Daclatasvir (Daklinza) for Chronic Hepatitis C Cleared in EU

"HCV is a challenging virus to overcome," Michael P. Manns, MD, professor and chairman, Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Germany, said in the release. Daclatasvir, when combined with other compounds, "often results in cure among even the hardest-to-treat patients," he added.
Continue reading..... 

MSF urges BMS to make daclatasvir accessible in low-and middle-income countries
Ramesh Shankar, Mumbai
Saturday, August 30, 2014, 08:00 Hrs [IST]

Even as the European Commission (EC) and European Medicines Agency (EMA) approved the new direct-acting antiviral (DAA) daclatasvir to treat hepatitis C, the international medical humanitarian organization Médecins Sans Frontières (MSF) has asked the Bristol-Myers Squibb (inventor of daclatasvir) to ensure that people living with hepatitis C in low- and middle-income countries can actually access this important drug, so that it can have the greatest impact on hepatitis C globally in helping to cure people.

Welcoming the EMA's approval of daclatasvir on August 27, 2014, the MSF said that the BMS must rapidly register daclatasvir in those countries with a high burden of hepatitis C, especially in those countries with a high prevalence of genotype 3. It also urged BMS to ensure daclatasvir is affordable in those countries with a high burden of hepatitis C.

“Intellectual property barriers for daclatasvir, unless they are overcome, could keep affordable versions out of reach of people and may also prevent the development of an optimal fixed-dose combination that can provide simple, highly effective treatment for all people with hepatitis C, regardless of genotype”, said Dr Jennifer Cohn, medical director, MSF Access Campaign.

“Patent barriers that prevent affordable access to daclatasvir and the new DAAs must be addressed by governments to promote robust generic competition, which will enable price reductions, facilitate the development of a pan-genotypic combination, and accelerate availability in all developing countries that are bearing the brunt of the hepatitis C epidemic,” Dr Cohn further said.

On 27 August 2014, the EC and the EMA became the second regulatory authority (after Japan in July) to approve new direct-acting antiviral (DAA) daclatasvir, used to treat hepatitis C. Daclatasvir is the third DAA - a new class of oral drugs used to treat hepatitis C – to be approved.

The approval of daclatasvir is medically significant, as it, in combination with other hepatitis C drugs including other DAAs, results in high cure rates; clinical trials have also shown it to be well tolerated by people. In addition, combining two DAAs is critical to simplifying treatment in developing countries, and combinations which include daclatasvir, such as sofosbuvir+daclatasvir, have pan-genotypic potential; daclatasvir has shown to be effective for genotype 3, which has proven difficult to treat with other DAAs and is highly prevalent among people living with hepatitis C in India and Pakistan.

However, the MSF expressed its concern about the potential lack of affordable access to daclatasvir, and patent barriers that could prevent the development of effective and affordable combinations.

Development and testing of sofosbuvir/daclastavir combination treatment was delayed when Gilead (owner of sofosbuvir) stopped collaboration with Bristol-Myers Squibb (owner of daclatasvir) in favour of Gilead's proprietary sofosbuvir/GS-5816 combination. Only now is BMS able to undertake phase III trials of this combination with commercially available sofosbuvir. Further, BMS has not yet announced any access plans for low- and middle-income countries, where the majority of the hepatitis C burden lies.

Tuesday, August 26, 2014

Chronic hepatitis C and liver fibrosis

Chronic hepatitis C and liver fibrosis

Good afternoon folks, today on the blog the focus in on liver fibrosis and noninvasive methods to estimate liver fibrosis in chronic hepatitis C infection.

An article published online in the August issue of World Journal of Gastroenterology offers an updated review of liver fibrosis associated with HCV, with an in-depth look at noninvasive testing used currently in clinical practice to assess liver fibrosis.

The clinical article is written using medical terminology that only a professional in the industry could understand, after five minutes of reading I was on ARRP's website researching ways to improve my brain function. Which is so hypocritical, considering I refuse to join any organization for people fifty and over. However, I did read an article about Cher while I was there, which by the way is highly entertaining.

In any event, after reading the entire article; Chronic hepatitis C and liver fibrosisyou should come away understanding the importance of using noninvasive testing to manage chronic hepatitis C, and the likely course of the disease. In addition, as noted by the authors; to monitor the regression of liver fibrosis in response to antiviral therapy.

FibroScan® Noninvasive test to measure liver inflammation and fibrosis

Essentially, most people are familiar with FibroScan®, FDA approved in 2013, with that said, before you read the article, Stuart Gordon, M.D., Director of Hepatology at Henry Ford Hospital explains FibroScan® in simple terms;

Using FibroScan ®, the skin in the area of the liver is first coated with a water-based gel. The doctor then passes an ultrasound sensor over the area to take 10 consecutive readings. The sensor produces vibrations that create a low-frequency seismic wave sent between the ribs and into the liver. The speed of the wave as it passes through the liver is used to determine the hardness or stiffness of the organ – the faster the wave, the harder the tissue.
The data collected during the readings are collected and analyzed in the console connected to the sensor, and provides immediate results on the presence and severity of liver fibrosis.

For people who have utilized the test, information understanding results or stage of fibrosis can be confusing. On the website, a scoring card is available, making it easier to convert test results into grading systems that are used to determine "liver biopsy" results. 

What is liver fibrosis?

HCV Advocate has an array of current fact sheets at your disposal explaining liver fibrosis, please consider reading; What is liver fibrosis and Use of Fibroscan in medical practice, both updated within the last two months. Lucinda K. Porter, RN., who writes for HCV Advocate and hepmag.com., recently published; Hepatitis C: Some Good News for a Change, which offers a few facts about fibrosis.

Role of magnetic resonance elastography in compensated and decompensated liver disease

Research into the natural history of HCV suggest the disease usually evolves slowly, how quickly liver damage develops depends on a number of factors; older age at infection, gender, diabetes, obesity, hepatic steatosis, alcohol use, and co-infection with HBV or HIV. 

For example, a 50-year old who has been infected with HCV for 30 years is likely to have a higher HCV-related morality risk, even when the above cofactors are not present, in relation to a 30-year old with 5 to 10 years of infection and several cofactors. 

Therefore people who did not achieve SVR,  ( never treatednatural history of HCV) and were infected with HCV in the 1970s and 1980s, also a time before Direct-acting antiviral therapies were available, are at a greatest risk for disease progression, including cirrhosis and liver cancer.

This brings us to another noninvasive test for accessing liver damage in persons with cirrhosis called magnetic resonance elastography or MRE. In the article; Role of magnetic resonance elastography in compensated and decompensated liver disease, by Dr. Sumeet Asrani from Baylor University, the good doctor discusses the role of MRE used to predict the progression of cirrhosis from compensated to decompensated disease. View a video summarizing the article, here, or the article found in May 2014 issue of Journal of Hepatology.

Finally, check out the article published online in World Journal of Gastroenterology

See you soon, stay well.

Tina

Missing the point: Clean needles can control the added health risks of drug users

Missing the point: Clean needles can control the added health risks of drug users 
By Eric Boodman / Pittsburgh Post-Gazette

“Rural counties suddenly have high rates of hepatitis C, and it’s a very expensive disease to treat,” says Alice Bell, a coordinator at Prevention Point Pittsburgh, a needle exchange program that disperses clean needles. “It’s going to bankrupt the local health departments.”
Ms. Bell has heard many stories like Mr. Stamerra’s. The people who come into the needle exchange often report being turned away from pharmacies. Some people -- especially in small towns -- are afraid to go in and ask for syringes because of the stigma surrounding heroin addiction. But for those who do go in, the sale often depends on how you look.


Read more... 


Monday, August 25, 2014

Clinical evidence and bioinformatics characterization of potential hepatitis C virus resistance pathways for Sofosbuvir

Data suggests that Sofosbuvir (SOF) has a high barrier to resistance; however, low frequency NS5B substitutions associated with treatment failure were identified that may contribute to resistance of this important drug for chronic hepatitis C virus (HCV) infection.
 
Clinical evidence and bioinformatics characterization of potential hepatitis C virus resistance pathways for Sofosbuvir

Eric F. Donaldson*, Patrick R. Harrington, Julian J. O’Rear andLisa K. Naeger
DOI: 10.1002/hep.27375


ABSTRACT
Sofosbuvir (Sovaldi™, SOF) is a nucleotide analog prodrug that targets the hepatitis C virus (HCV) NS5B polymerase and inhibits viral replication. High sustained virologic response rates are achieved when SOF is used in combination with ribavirin with or without pegylated interferon in subjects with chronic HCV infection. Potential mechanisms of HCV resistance to SOF and other nucleos(t)ide analog NS5B polymerase inhibitors are not well understood. SOF was the first FDA-approved antiviral drug for which genotypic resistance analyses were based almost entirely on next generation sequencing (NGS), an emerging technology that lacks a standard data analysis pipeline. The FDA Division of Antiviral Products developed an NGS analysis pipeline and performed independent analyses of NGS data from 5 SOF clinical trials.

Additionally, structural bioinformatics approaches were used to characterize potential resistance-associated substitutions. Using protocols we developed, independent analyses of the NGS data reproduced results that were comparable to those reported by Gilead Sciences, Inc. Low frequency treatment-emergent substitutions occurring at conserved NS5B amino acid positions in subjects who experienced virologic failure were also noted and further evaluated.

The NS5B substitutions, L159F (sometimes in combination with L320F or C316N) and V321A, emerged in 2.2-4.4% of subjects who failed SOF treatment across clinical trials. Moreover, baseline polymorphisms at position 316 were potentially associated with reduced response rates in HCV genotype 1b subjects. Analyses of these variants modelled in NS5B crystal structures indicated that all 4 substitutions could feasibly impact SOF anti-HCV activity.

Conclusion: SOF has a high barrier to resistance; however, low frequency NS5B substitutions associated with treatment failure were identified that may contribute to resistance of this important drug for chronic HCV infection. (Hepatology 2014;)

Liver inflammation is a Risk Factor for Prediabetes in At-Risk Latinos with and without Hepatitis C Infection

Liver International
Accepted Articles, Accepted manuscript online: 23 AUG 2014
(Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Liver inflammation is a Risk Factor for Prediabetes in At-Risk Latinos with and without Hepatitis C Infection

Blaire E Burman1, Peter Bacchetti2, Claudia E. Ayala1, Nicholas Gelman1, Jennifer Melgar1 and
Mandana Khalili1,3,*

DOI: 10.1111/liv.12676
Abstract

Background and Aims

Early recognition of prediabetes can lead to timely clinical interventions to prevent type 2 diabetes. Both Latino ethnicity and chronic hepatitis C (HCV) have been identified as diabetic risk factors. We aimed to investigate predictors of impaired fasting glucose (IFG), a common prediabetic state, among Latinos with and without HCV.

Methods

One hundred Latino adults with no history of diabetes or cirrhosis underwent clinical, laboratory, and metabolic evaluation, including oral glucose tolerance testing (OGTT) and insulin suppression testing to quantify directly measured insulin resistance (IR). Isolated IFG was defined as fasting glucose ≥100mg/dL and <140mg/dL at 2 hours with normal glucose tolerance during OGTT.

Results

Overall subject characteristics included median age 44 years, 64% male, 40% HCV-positive, and 32% with isolated IFG. Factors associated with isolated IFG included subject age (OR 2.42 per decade, 95%CI 1.40-3.90, p=0.001), HCV infection (OR 4.0, 95%CI 1.71-9.72, p=0.002), and alanine aminotransferase (ALT) (OR 2.35 per doubling, 95%CI 1.46-3.77, p<0.0001). Multipredictor logistic regression analysis identified ALT (OR 2.05 per doubling, p=0.005, 95% CI 1.24-3.40) and age (OR 2.20 per 10 years, p=0.005, 95%CI 1.27-3.80) as factors independently associated with IFG. While HCV was associated with 4-fold higher odds of IFG, this entire effect was mediated by ALT.

Conclusions

We found strong evidence that liver inflammation is a risk factor for prediabetes among Latinos with and without HCV. Among HCV-infected individuals, early antiviral therapy could mitigate the effect of inflammation and represent an important intervention to prevent diabetes in this at-risk population.

Saturday, August 23, 2014

HCV Weekend Reading: Fatty Liver Disease

HCV Weekend Reading: Fatty Liver Disease 

Good afternoon folks, welcome to this edition of weekend reading, today the topic is fatty liver disease.

So sit back and listen to Dr. Joe Galati, interview NY Times reporter, Anahad O’Connor about this serious liver disease and the detrimental effect it has on the liver.

If you haven't read it yet, an article written by O'Connor for the NY Times offers a clear understanding of the condition, including the rise of fatty liver disease in children.

Also in today's post, is an interesting research paper which examines if Non-Alcoholic steatohepatitis (NASH) is associated with HCV disease progression in persons afflicted with both conditions. Finally, an update on Galectin Therapeutics’ drug GR-MD-02 to treat NASH.

In addition, an article over at Healio, published in the July/August issue of "HCV Next" written by Alia Hasham, MD and Thomas C. Mahl, MD., discuss factors associated with fibrosis progression  in persons with fatty liver and HCV.

The Patient with NAFLD and Chronic HCV
In the absence of significant alcohol consumption, non-alcoholic fatty liver disease is now becoming a more frequent, concomitant diagnosis in HCV patients, and insulin resistance has emerged as a key underlying pathogenic feature. NAFLD includes a spectrum of disease, ranging from nonalcoholic steatohepatitis (NASH) to steatosis, with a prevalence of approximately 10% and 30% respectively, in the general population.
The cumulative effects of HCV and NAFLD could have important clinical implications and may accelerate fibrosis progression, increase risk for hepatocarcinogenesis and impair response to antiviral therapy. However, with the introduction of newer anti-HCV agents, including direct-acting antivirals (DAAs), the presence of hepatic steatosis may have less impact on treatment response, and interventions directed at lifestyle modifications, with improvements in insulin sensitivity, could represent an important therapeutic focus. 
Read the article here...

Your Health First Radio

 
In order to gain a better perspective of fatty liver disease; Non-alcoholic fatty liver disease (NAFLD) and Non-Alcoholic steatohepatitis (NASH) an overview is provided by; The Canadian Liver Foundation

What is a fatty liver?

A fatty liver is the result of the excess fat in liver cells. Fatty tissue slowly builds up in the liver when a person’s diet exceeds the amount of fat his or her body can handle. A person has a fatty liver when fat makes up at least 5% of the liver 1. Simple fatty liver can be a completely benign condition and usually does not lead to liver damage. However, once there is a buildup of simple fat, the liver becomes vulnerable to further injury, which may result in inflammation and scarring of the liver 2.

What is Non-alcoholic fatty liver disease (NAFLD)?


NAFLD is a progressive complex of liver disease which starts with fat accumulation in the liver without excessive alcohol consumption. It is strongly associated with metabolic syndrome (obesity + insulin resistance + dyslipidemia)

What is NASH?

NASH stands for Non-Alcoholic steatohepatitis and it represents the more severe end of the spectrum of non-alcoholic fatty liver disease. Steatohepatitis means fatty liver with inflammation, in other words, ongoing damage similar to alcoholic liver disease but in this case it occurs in people who do not drink alcohol or drink minimally 13.

NASH differs from the simple accumulation of fat in the liver, which is a completely benign condition. Up to 20% of adults with NASH develop cirrhosis and up to 11% may experience liver-related deaths. Many individuals develop chronic liver failure and require liver transplantation. The prevalence of NASH is 2-6% in the general population.

Fatty Liver Disease and Hepatitis C
Fatty liver disease has become a serious health problem in the last decade, affecting close to 20 percent of Americans and is estimated to surpass hepatitis C as the leading case of liver transplants by 2020.

A research article published in the current issue of Journal Of Hepatitis Research, titled; Non-Alcoholic Steatohepatitis (NASH) Influences the Disease Progression of Chronic Hepatitis C (CH-C): Histopathological Study of Liver Biopsies in 400 Cases with CH-C., authored by Matsumoto T, Fukuhara K, Yaginuma R, Ikejima K, Morizane T, suggest NASH, the more severe form of NAFLD,  may have an influence on disease progression in people who also have chronic hepatitis C.

In short the authors wrote;
The liver biopsies were performed in Juntendo Hospital or Juntendo University Nerima Hospital. The examined cases were 400 Japanese adults (229 males and 171 females) with ages ranging from 21 to 78 years (mean: 51 years). None of the cases had a past history taking alcohol.

A histological study of the association of NASH in Chronic Hepatitis C (CH-C) in a large number of cases has been performed to date in three studies, including the present study, and the present study involves the largest number of examined cases. The incidence of NASH in CH-C ranged from 9 to 18.3% in the studies (Table 6). These results indicate that the incidence of NASH in CH-C is about 10 to 20%.



The previous two studies [2-4], and the present study showed that patients with NASH had a more advanced stage than those without NASH. In the present study, the likelihood ratio for stage (fibrosis) indicated that, when being NASH-positive, the odds of having a more progressed stage is 1.76 times higher than on being NASH-negative.

Thus, the possibility of an increase in fibrosis due to the association of NASH was considered. However, we thought that this hypothesis needs to be investigated by the examination of repeated liver biopsies in the same patients, but such a study had not been published. Thus, we performed the evaluation of liver changes in the cases of Chronic Hepatitis C (CH-C) with NASH in repeated liver biopsies. Subsequently, three cases of advanced stages (F3 or F4) of CH-C with NASH showed increasing fibrosis from early (F1) to advance (F3) stages in long intervals (9, 12, and 18 years). This indicated that the association of NASH causes an increase of fibrosis with long intervals.

On the other hand, one case with a short interval (2 years) was in an advanced stage (F3) in the first liver biopsy. Thus, the change in liver fibrosis by the association of NASH in short intervals could not be clarified in the present study.

Although the proportion of the increase of fibrosis by CH-C or NASH in CH-C cases with NASH has not been studied, the present study demonstrated that the increase occurred in the same proportion by both CH-C and NASH in two cases, and, in one case, the increase mainly occurred due to CH-C and partly due to NASH.

These indicated that the importance of treatment of both CH-C and NASH in CH-C cases with NASH. Our previous study reported that hepatic steatosis is a predictor of a poor response to interferon α-2b and ribavirin therapy in patients with CH-C [9]. So, we think that a new treatment method is needed in patients with CH-C with NASH.

As an interesting finding in this study, the two cases (case no. 2 and 4) with disease progression from early to advanced stages had fibrosis due to both CH-C and NASH, but no association of NASH was found in the initial biopsy. Until now, it has been reported that chronic infection of HCV leads to NASH [10-12]. Thus, in the two cases, HCV induced NASH and disease progression occurred due to the interaction between HCV infection and the NASH state induced by HCV.

In conclusion, the present study confirmed that the association of NASH influences the disease progression of CH-C, and it is the first to demonstrate that the disease progression is caused by both CH-C and NASH equally or CH-C mainly. These findings are useful for the treatment of CH-C with NASH.

Download The Full Text Article, here

Research
New Mouse Model Points to Therapy for Liver Disease 
Aug 19, 2014

Of Interest

PBAC decisions – a mixed bag for Australians living with Hepatitis C

Media statement released, 22 August 2014: Download PDF Here

PBAC decisions – a mixed bag for Australians living with Hepatitis C 

 simeprevir (Olysio) 

 Hepatitis Australia today welcomed the recommendation to add simeprevir (Olysio) to the Pharmaceutical Benefits Scheme (PBS) for the treatment of genotype 1 chronic hepatitis C.

 CEO of Hepatitis Australia, Helen Tyrrell, said: “The use of simeprevir as an addition to pegylated interferon and ribavirin to treat people with genotype 1 hepatitis C is an important step forward in the evolution of hepatitis C treatment. “Simeprevir will make the treatment process both safer and better tolerated than current regimens. This therapy must now be listed on the PBS as soon as possible.”

 sofosbuvir (Sovaldi) 

 Responding to the PBAC decision to reject an application to subsidise the antiviral medication sofosbuvir (Sovaldi), Ms Tyrrell said “it’s a sad day when access to game-changing therapy is denied. This is a bad outcome for people living with hepatitis C”.

 Hepatitis Australia called on both the Federal Government and Gilead Sciences to “work together to ensure this curative hepatitis C treatment is made broadly available as soon as possible”.

 “We have nationally approved treatment targets and need to get on with the job of increasing treatment in order to avert a liver disease crisis,” she said. “The well-being of people with hepatitis C should not be jeopardised by blocking access to a cure which is available in other countries. This is plainly unacceptable.  “In the interim, we need a mechanism to fund treatment for Australians with serious liver disease who can’t wait any longer for bureaucratic wheels to turn,” Ms Tyrrell said.

Parliamentary Briefing on new Hepatitis C treatments Hepatitis Australia will now join with Senator Dean Smith and Senator Lisa Singh to convene a Parliamentary Breakfast Briefing on 23 September to brief politicians on ‘Costly Cures? The Case for Action on Hepatitis C Treatment’.

Independent of commercial interests, the briefing will include addresses from World Hepatitis Alliance President Charles Gore and Dr Alex Thompson, Director Gastroenterology Department, St Vincent’s Hospital, Melbourne, as well as people living with hepatitis C. “It’s important that politicians understand exactly what the Government is being asked to subsidise.

There’s no question these therapies come with a sizeable price tag, but investment now will save considerable downstream costs and halt the death toll associated with serious liver disease,” Ms Tyrrell said. For further information or to arrange an interview, please contact Fiona Beveridge at Ethical Strategies – 02 8904 7335 / 0405 902 826.


Friday, August 22, 2014

Keeping an Eye on Hepatitis C Virus Drug Approvals

Related - An index of articles pointing the reader to the current controversy over the high price of Sovaldi.

Keeping an Eye on Hepatitis C Virus Drug Approvals

Lee Goldberg, MBA Published Online: Wednesday, August 20, 2014

This article was originally published on the Specialty Pharmacy Times website.

With the recent approval of new hepatitis C treatments, payers are increasingly concerned with controlling costs in this category through policies that may affect treatment decisions. Given the recent evolution of hepatitis C virus (HCV) treatment, starting with the 2011 introduction of Incivek and Victrelis and continuing with the late 2013 approval of Olysio and Sovaldi, it’s no surprise that payers now consider the HCV category nearly as important a management priority as cancer, rheumatoid arthritis (RA), or multiple sclerosis (MS) (Online Table 1).

These are all high-spend disease states, and have become more so recently. They are all recipients of recent approvals with novel mechanisms of action, oral routes of administration, and improved clinical outcomes. In each category, payers have more to think about with greater financial consequences riding on each treatment decision.

Table 1: Payer Specialty Category Priorities Percentile Ranking: Trend


But just because payers prioritize the management of therapeutic categories for similar reasons doesn’t mean they’ll end up managing them similarly. Access restrictions in cancer look nothing like those in RA. Patients with HIV do not face the same hurdles as patients with MS. Utilization management is not a unilateral pursuit. It’s an ongoing negotiation among payers, doctors, specialty pharmacies, and manufacturers that takes place within limits set by the FDA label and best clinical practices.

As researchers at Zitter, we wanted to find out how these parties would react to the expected steady, almost rhythmic approval of hepatitis C agents expected between 2014 and 2018. In January of this year, we began by surveying 100 payer representatives about their attitudes and management expectations for the category. We also surveyed 150 specialist physicians and 50 primary care doctors to gather their attitudes and reactions to the new entrants and payer decisions. Finally, we conducted interviews with a handful of practice managers at infectious disease and gastroenterology practices to get the story behind how payer policies impact treatment decisions and day-to-day operations.

To start, we were surprised at the speed with which payers developed their formal, final policies for Olysio and Sovaldi, approved within 2 weeks of each other between November and December of 2013. By the end of January 2014, 36% of plans already had written policies. By the end of July 2014, another 32% expected to be finished (Online Table 2). Surprisingly, the rate of policy adoption has been even faster. Our analysis of prior authorization (PA) policies from commercial plans covering 190 million lives shows 75% of plans developed Sovaldi policies within 6 months of launch and 80% created documents for Olysio. In contrast, at 6 months after launch only 48% had policies in place for Xeljanz. Payers were likely in a hurry because they expected patients who deferred treatment to arrive, en masse, at the beginning of the 2014 plan year. Recently, UnitedHealth Group announced it spent “multiple” times what it had expected in Q1 to cover Sovaldi.


Some portion of that spend is attributable to the combination use of Sovaldi with Olysio. Taken together, the drugs obviate the need for treatment with interferon. However, neither is FDA approved for use with the other (although Janssen, the manufacturer of Olysio, recently applied). Early analysis of PA policies and a survey of payers without extant policies at the time revealed a focus on preventing this particular off-label use. Forty-four percent of payers (representing 35% of covered lives) explicitly forbade combination use of Olysio and Sovaldi (Table 3). Among payers that had not yet written a formal policy, fully three-fourths thought there was no likelihood at all or that it was more unlikely than likely that their organization would cover the 2 together (Table 4). In the end, this is not how coverage played out at all.



On January 29, 2014, the American Association for the Study of Liver Diseases (AASLD) released treatment guidance for use of the new agents. Somewhat surprisingly, it endorsed the concomitant use of Sovaldi and Olysio for patients intolerant to interferon. Practically overnight, payers reversed their existing prohibitions and those writing new policies were not so eager to implement utilization management counter to the AASLD’s recommendation (Table 3).

As new drugs enter the market in the next 6 to 12 months, the AASLD will continue to update its treatment recommendations. A recent, quick pulse check of payers (n = 21) that participated in our original research indicates that plans intend to follow along (Online Table 5). Analogies to the role the National Comprehensive Cancer Network’s guidelines play in influencing payer management of oncology come to mind. But unlike oncology’s situation, the new direct-acting antiviral agents to treat HCV promise a cure. And unlike the majority of oncology subtypes, the market will soon see multiple, directly competitive therapeutic options.



By the time 3 of these new options receive approval, payers expect contracting for preferential treatment to evolve in the market. More specifically, payers believe it’s more likely than not that contracting will evolve at the genotype level, allowing them the option to circumscribe utilization tightly while limiting their contractual exposure with manufacturers (Online Figure 6). Of course, stakeholders’ ability to contract will rest on the breadth of treatment options endorsed by the AASLD, or, conversely, payers’ willingness to define best practices more narrowly. Finally, manufacturers will have to want to participate as well.



Perhaps surprisingly, specialists are on board with (or maybe resigned to) preferential contracting as a determinant of access. Of specialists surveyed in January, 73% were okay with payer/manufacturer contracting as long as 3 options were on the market, and a majority (53%) were satisfied with 2 choices (Table 7).

Doctors are more critical, however, of some common criteria within payers’ prior authorization policies. Specialists indicated that reauthorization timelines within the recommended treatment duration or liver biopsy requirements would be most burdensome to them (Table 8). Recent analysis of PA documents shows both have already found their way into Olysio and Sovaldi policies.


The processing and administration fall predominantly to practice managers and nurses. Conversations with practices located in New Jersey, New York, Florida, and Texas (so far) uncovered wide consistencies about how practices will navigate the treatment advances and the associated payer policy updates.

Universally, each of the offices has a strong relationship with 1 or 2 specialty pharmacies (SPs). These nearly personal connections have developed over years, built on the backs of attentive customer service by the pharmacies starting at the account management level. Practices rely on their SPs for benefits verification, PA submission, PA appeal, patient assistance support, patient education, and adherence initiatives, among other services. Moreover, practices are dedicated to using their preferred SP without regard to network status. Each practice told us that if their preferred pharmacy finds itself out of network, it simply determines the closest in-network pharmacy and forwards the prescription. Inasmuch as the prior authorization process creates an administrative burden for the practice, for each of these 4 offices it is a burden shared more than equally by the specialty pharmacy.


Assuming the 3 near-term treatments from Gilead, Bristol-Myers Squibb, and AbbVie win approval over the next 12 months, hepatitis C may become payers’ top management priority. With multiple options to play off each other, it is likely payers will try to move just as quickly as they did initially to firmly define the boundaries of appropriate utilization. But with 3 interferon-free treatments, it is arguable that the role of the AASLD will be even more important than it was in January. Ultimate responsibility for managing the category may fall by proxy first to the AASLD and then rest on manufacturers’ willingness to contract for position (should the treatment guidance permit). The only definite here is that the category will stay interesting and dynamic for a while longer. SPT

For further information on the HCV Zitter study, please contact Michala Jeberg, mjeberg@zitter.com.


About the Author
Lee Goldberg MBA, is director, syndicated research, at Zitter Health Insights. He previously worked as a senior financial analyst at Medco. Lee earned a Master of Business Administration in finance from Rutgers, The State University of New Jersey-Rutgers Business School.


Thursday, August 21, 2014

Patients First: Cost–Benefit Considerations in HCV Therapy

Mark S. Sulkowski, MD
Patients First: Cost–Benefit Considerations in HCV Therapy

Hello folks, with all this controversy over the high price of Gilead's Sovaldi, it was refreshing, and informative to watch a video presentation where the focus is on the HCV patient, and not only on drug cost.

This month Clinical Care Options launched a new 35 minute video module addressing the cost issue of new hepatitis C drugs. Interestingly enough, in comparison to the high cost of overall care needed to manage HCV patients, it appears these new drugs are more cost effective. But we all knew that, didn't we.


The program is hosted by Nancy Reau, MD, and Mark S. Sulkowski, MD,. from Johns Hopkins.

Topics include
  • Benefits of achieving SVR with HCV therapy
  • Impact of HCV on the healthcare system
  • Considering immediate cost vs deferred savings
  • Using cost per SVR to determine value of therapy
  • Importance of selecting the best therapy first 
*Free registration is required to view the program.

Clinical Focus: Clinical Outcomes and Cost–Benefit Considerations in HCV Therapy
Nancy Reau, MD, and Mark S. Sulkowski, MD, provide a clinical perspective on the debate over economic aspects of HCV therapy and explore whether new therapies increase or decrease overall HCV patient care costs.

Stay well, and safe.

Tina