Monday, August 31, 2015

Articles in Press - Liver Toxicity Associated with Sofosbuvir, an NS5A Inhibitor and Ribavirin Use

Journal of Hepatology
Articles in Press

Liver Toxicity Associated with Sofosbuvir, an NS5A Inhibitor and Ribavirin Use
Jessica K Dyson, John Hutchinson, Laura Harrison, Olorunda Rotimi, Dina Tiniakos, Graham R Foster, Mark A Aldersley, Stuart McPherson

Published Online: August 29, 2015

Abstract 

Hepatitis C (HCV) is a major cause of end-stage liver disease and hepatocellular carcinoma. There have been rapid advances in HCV treatment with the development of oral direct acting antivirals (DAAs). Studies have shown sustained virological response rates above 90% with combinations of DAAs, including patients with compensated cirrhosis. Thus far, significant drug toxicity has not been seen with these agents, but there is limited experience of using DAAs in decompensated HCV cirrhosis. This report describes the first experience of serious drug-induced hepatotoxicity with the new DAAs. The mechanism underlying these drug reactions is currently unknown. Few patients with decompensated cirrhosis have been treated with DAAs, so the exact pharmacokinetics in this population have not been characterised. In both cases patients were taking or had recently taken other drugs. It is possible that an unknown interaction or reaction to the drug combination caused the hepatotoxicity. Although the association with the DAAs is not proven these cases indicate that patients with advanced liver disease need close monitoring while on DAA therapy and if there is a significant unexplained deterioration in liver function the DAAs should be discontinued.

Friday, August 28, 2015

TGIF HCV Rewind: A Week In Review With A Spotlight On Don Crocock and Greg Jefferys

TGIF HCV Rewind: A Week In Review With A Spotlight On Don Crocock and Greg Jefferys

Hello everyone, we made it through another week, only a few day's until September, where does the time go?

Did you all see the article from "People" on Pamela Anderson? After living with HCV for over sixteen years she has decided to start therapy.

Its always great when hepatitis C is in the news, especially when a celebrity is involved, Anderson's announcement may reach more people over the next week than a year of "advocacy programs" designed to raise HCV awareness and testing, here is the statement.

After Living with Hepatitis C for 16 Years, Pamela Anderson Now Says 'I Could Be Cured Within a Month'
After experimenting with various alternative medicines, Anderson recently decided to try the new anti-viral medication. The Baywatch actress says, "I could be Hep C free within the month."
Lovely Pamela is not alone, close to 130-170 million people worldwide have HCV and those numbers do not include people who have no idea they are infected. The good news is that we have a cure, the bad news is the cost. Here is an article written by Lucinda K. Porter on the sad reality....

Creating a World Free of Hepatitis C
Lucinda K. Porter, RN
Hepatitis C Treatment is Worth Fighting for
Aug 20
Hepatitis C infection is curable. Unfortunately, a hepatitis C diagnosis is not an automatic qualifier for getting the medication. Many people are engaged in what seems like an endless fight for the newest hepatitis C drugs. Insurance companies were happy to approve treatment in the past, when treatments were difficult, risky, and less successful. Now that the drugs are costly, insurance companies are denying, denying, denying.....

Despite everything you hear, sometimes there is no fight at all. This is from a reader:
I am currently taking Harvoni (after having Hep C for 40 years) and here’s how I was able to get it – FOR FREE!

To learn more about FDA approved treatments for hepatitis C, start here, to read patient friendly newsletters published by our devoted HCV community, click here.

In The Spotlight

Today the spotlight shines brightly on two familiar HCV advocates, both men may not be Hollywood celebrities, but they sure are famous in my book. Don Crocock and Greg Jefferys have waged a campaign using Twitter and Facebook offering information and support to anyone battling hepatitis C.

Don Crocock
I have great admiration for Don, his years of zealous work to increase HCV awareness to me is simply outstanding. 

HCV survivor takes advocacy to social media to help other patients and spread awareness

Don Crocock: The Hepatitis C Dragon Slayer
BY CARLY SZABO, ASSISTANT EDITOR
Don Crocock was not ashamed of his hepatitis C diagnosis in September 2008. Shocked, yes. Shaken, yes. But not ashamed. For many, a diagnosis of hepatitis C virus (HCV) comes with a sense of embarrassment due to the disease’s stigma of being “dirty.” But for Crocock, the news came with a sense of empowerment and a deep desire to share information about the virus with others in order to prevent further spread of the disease.
Read more

Connect with Dan on Facebook or Twitter.

Greg Jefferys
Greg Jefferys, a blogger at "Hep Blogs" is featured in an August article published online at "ABC." The author writes about Mr. Jefferys incredible journey to India in search of an affordable generic version of Gilead's Sovaldi (Sofosbuvir), 

Hepatitis C sufferer imports life-saving drugs from India, takes on global pharmaceutical company
By Michael Atkin and Joel Keep
Mr Jefferys was so sick from hepatitis C last year that he was unable to get out of bed some days.

He dropped out of his university PhD studies and quit many of his hobbies, including kayaking and fishing.

He desperately needed a drug called Sovaldi, manufactured by US pharmaceutical giant Gilead, but could not afford it without selling his house.
Read more

Mr. Jefferys has documented his trip to India, and so much more here on his website.
Connect with Greg on Facebook.

Next up we have a few editorials, a new "learning activity," an inspiring patient video, plus a collection of great articles written by your favorite bloggers, followed by research and news.

Editorials

World Journal of Hepatology
Three decades of hepatitis B control with vaccination
It is now 50 years since the discovery of the hepatitis B virus (HBV). Effective vaccines have been available since the 80s and vaccination has proved to confer lifelong protection against hepatitis B and was highly successful in reducing the disease burden. However, the occurrence of breakthrough infections, the immunological effect of natural boosting and the effectiveness of universal hepatitis B vaccination remains a challenge. The fight against HBV is not over
Clinical Liver Disease
Hepatitis C treatment: Back to the warehouse
Like many physicians that specialize in hepatitis C virus (HCV) treatment, I have spent the last few years advising many of my patients with chronic HCV infection to defer treatment and wait for new therapies. For those without advanced fibrosis or an extraintestinal manifestation of HCV, this process of “warehousing” patients for future HCV treatment made perfect sense.
Read more

Medscape
HCV: The Best Cure Possible or the Best Possible Cure?
Is a regimen combining interferon (IFN) with a highly effective direct-acting antiviral agents (DAA) still an acceptable choice in 2015? The ultimate goal for society as a whole is to obtain what is best for each individual, but in doing so, it should aim not towards the best possible cure, but the best cure possible.
Read more

HCV Treatment: What Can I Do Now? What's Coming Next?
The development of direct-acting antivirals represents a significant improvement in HCV treatment. New combinations of drugs have led to improved response rates, even in patients with characteristics previously associated with having lower response rates: African American, high viral load, concomitant cirrhosis, infection with genotype 1a, and failed treatment with other anti-HCV drugs.

HEPATITISC.NET
Expert Answers – Should people who use injection drugs be treated?
By Editorial Team
Injection drug use is the most common means of hepatitis C transmission. It’s estimated 70-90% of current and former injection drug users are infected with hepatitis C. Many in the community debate whether injection drug users should be treated.
Read more

Healio
Recent Approval Holds Promise for Genotype 3, but Hurdles Anticipated
HCV Next, August 2015
Genotype 3 accounts for 10% to 15% of patients with hepatitis C in the United States, but has been estimated to be the second most prevalent genotype…
Read more

Learning Activity

From Medscape Education Gastroenterology

Initiating Antiviral Therapy for HCV Infection in a New Era of Care: Treatment Vignette CME
A new CME was recently launched over at "Medscape" for physicians, and other healthcare professionals examining follow up care after HCV diagnosis. Although the "CME questions or post test" may not be of interest or patient friendly, a fictitious patient video vignette in the CME is worth watching for anyone considering treatment. The scenario is that of a newly diagnosed HCV patient at a two week follow up appointment.  In this "Treatment Vignette" liver heath, lifestyle changes, HCV testing of family members, adherence to treatment and follow up blood tests is examined.

Nancy Reau, MD

CME Released: 08/24/2015 

For Your Viewing Pleasure 

Hepatitis C Patient Journey: Coping With Drug Side Effects
In part four, Jim Wilson, RPh, MBA, president of WilsonRx, discusses the difficulties he faced during treatment from interferon therapy following his liver transplant.

Wilson was infected with an acute case of Non-A/Non-B hepatitis in 1975 due to a tainted blood supply but was not diagnosed with the disease until 1999. After receiving a liver transplant in 2006, he was finally cured of HCV in 2012 after enrolling in a 12-week clinical trial of the drug Harvoni.
PUBLISHED WEDNESDAY, AUGUST 26, 2015



Source

Blogger Updates

Lucinda K. Porter, RN @ Hep blogs
Aug 24
Surprising Updates to the HCV Guidelines
The HCV Guidelines added the combination of Daklinza/Sovaldi for 12 weeks for genotype 3 patients without cirrhosis or 24 weeks with/without ribavirin for those with cirrhosis.

What I did not anticipate was that the panel would make off-label recommendations for daclatasvir. Off-label use allows physicians to prescribe approved drugs according to their clinical judgment, regardless of the indication the FDA has approved for the drug.
Read more

Greg Jefferys
Did I sound a bit angry in my last post?
That's because I was. I was angry because every day I get emails from people who are desperate to begin treatment with these new antiviral drugs and they go to their doctor and the doctor refuses to write them a prescription.
Or their specialist sneers at them and asks,
"How do you know what is in these India drugs? How do you know they are safe?"

An Unintended, but Necessary Hepatitis C Advocacy
So take the interferon treatment, with a 50% possibility of a cure and a high chance of permanent organ damage but don't use Indian generics because there is a possibility they might be sub standard (or not). Go figure that out!

Rick Nash
Aug 19
Why Harvoni and Sovaldi failed me. They are amazing new drugs with high efficacy, but they may not be best for your situation..

View all blog updates at Hep Blogs , here.

Hepatitis C Research Center Blog
HCV Drug Costs: A Treatment Access Barrier
Posted on August 27, 2015
In a newly published, thought-provoking article in the journal Clinical Infectious Diseases, Stacey B. Trooskin and colleagues discuss how the high cost of newer hepatitis C therapies has become a major treatment access barrier in the US (Trooskin SB, et al. Clin Infect Dis. 2015 Aug 12 [Epub ahead of print]). Controversial insurance coverage restrictions and treatment rationing has resulted in national patient advocacy mobilization, US Congressional inquiry, and legal challenges. Authors of this article state that the establishment of a federal program, analogous to the successful AIDS Drug Assistance Programs (ADAP), would substantially reduce access barriers and facilitate focused price negotiations between pharmaceutical companies and payers.
Read more

AGA Journals BlogAug 28
Kristine Novak
Public Health Officials Call for Wider Access to HCV Drugs
Experts from the Public Health Service and President Obama’s Advisory Council on HIV/AIDS are calling on federal and state Medicaid officials to widen access to prescription drugs that could cure tens of thousands of people with hepatitis C virus (HCV) infection. They say restrictions on the drugs imposed by many
Read more

Aug 26
Is Nonceliac Gluten Sensitivity Real?
When patients with nonceliac gluten sensitivity (NCGS) unknowingly ingested small amounts of gluten for 1 week, they developed more severe abdominal pain and bloating that patients who ingested a matched placebo, researchers report in the September issue of Clinical Gastroenterology and Hepatology. The study provides evidence for a form of

Aug 19
Can we Reduce Muscle Cramps in Patients with Cirrhosis?
L-carnitine appears to be safe and effective for reducing muscle cramps in patients with cirrhosis, researchers report in the August issue of Clinical Gastroenterology and Hepatology. Many patients with cirrhosis develop frequent muscle cramps, which reduce their quality of life. L-carnitine (L-beta-hydroxy-gamma-N-trimethyl aminobutyric acid) is an amino acid that transports
Read more

Aug 12
What Causes Different Types of Fatty Liver Disease?
Hepatic steatosis and steatohepatitis are increasing in prevalence, and can progress to histologically identical, more severe liver disease. They are associated with 3 main factors: alcohol, obesity or metabolic syndrome, and exposure to toxins. Researchers review the similarities, differences, and pathogenic mechanisms of alcohol-associated steatohepatitis (ASH), nonalcoholic steatohepatitis (NASH), and toxicant-associated fatty liver

Aug 10
Does Weight Loss Resolve Fatty Liver Disease?
Two separate studies in the August issue of Gastroenterology show that weight loss, via diet or bariatric surgery, reduce features of non-alcoholic steatohepatitis (NASH). Eduardo Vilar-Gomez et al associated extent of weight loss, produced by lifestyle changes, with level of improvement in histologic features of NASH. The highest rates of NASH reduction
Read more

NEJM
Aug 20
When to Start HCV Treatment: The Intersection of Guidelines and Real-World Practice
By Kelly Eagen, MD
Treatment for hepatitis C virus (HCV) infection is changing at a pace almost too rapid for the average physician to keep up with. Until recently, HCV treatment required weekly interferon injections plus oral ribavirin for up to a year and
Read more

HIV and ID Observations
Aug 23
Post-Exposure Prophylaxis for HCV Can’t Be Cost-Effective — But We Might End Up Recommending It Anyway
An email query from a colleague:
Hi Paul,
Just got a call from one of our surgeons who got a needlestick from a suture needle, small amount of blood. Patient is HCV +. Any post-exposure prophylaxis recommended?
Thanks,
Dan
Read more

Research

Interferon-free regimens overcome the effects of portal hypertension on virological responses in Hep C
Aug 28
September's publication of the Alimentary Pharmacology & Therapeutics investigated the effects of portal pressure on virological responses in hepatitis C patients treated with interferon-free regimens.
Read more

Resistance-Associated Gene Variants Found In Hep C Patients Who Received First-Generation DAAs
First-generation triple therapies for hepatitis C virus (HCV) infection are being phased out in favor of next-generation interferon-free direct-acting antiviral agents (DAAs).
Read more..

Mechanisms of Non-response to Hepatitis C Therapy
Liver International, August 28, 2015
Since the introduction of interferon-based therapy for hepatitis C virus (HCV) infection, predictors of response have been carefully evaluated to determine which patients are more likely to respond and why. While many of these factors were identified and explained, the presence of cirrhosis remains one of the well established yet least understood conditions that complicate HCV therapy.[1] In this review, we aim to shed light on the various and likely multifactorial mechanisms responsible for impaired responses in patients with cirrhosis.
Read more

Fatty Liver and Diabetes Increase Liver Fibrosis Risk
The combination of diabetes and nonalcoholic fatty liver disease increase the risk for liver fibrosis more than fivefold, according to a large prospective cohort study published online July 14 in Hepatology.

"These findings underline the significant role of these — potentially modifiable — risk factors in liver fibrosis and stress the importance of early targeting insulin resistance and/or [diabetes mellitus]," write Edith M. Koehler, MD, from the Erasmus MC University Hospital Department of Gastroenterology and Hepatology in Rotterdam, the Netherlands, and associates. "[They also] suggest that [nonalcoholic fatty liver disease] may be an important determinant of clinically relevant fibrosis in a population that has a very low prevalence of viral hepatitis."
Read more

Interferon-free regimens for the treatment of hepatitis C virus in liver transplant candidates or recipients
Treatment against hepatitis C virus has dramatically improved with the novel direct-acting antivirals (DAAs). The currently available DAAs are sofosbuvir, simeprevir, daclatasvir, ledipasvir/sofosbuvir, paritaprevir/ombitasvir and dasabuvir. IFN-free combinations of these novel DAAs with or without ribavirin give excellent sustained virological response in patients with decompensated cirrhosis awaiting liver transplantation and those with recurrence of hepatitis C post liver transplantation. More data regarding the safety and efficacy of these new DAAs are needed, but ongoing clinical trials and real life data will clarify better these issues.
Read more

Prevalence of Insomnia and Sleep Patterns among Liver Cirrhosis Patients
Few studies are available regarding the prevalence of sleep disturbance in cirrhotic patients without overt hepatic encephalopathy. This study aimed to assess the prevalence of insomnia in stable liver cirrhosis patients who are attending the outpatient clinics at King Abdulaziz Medical City, Riyadh (KAMC-KFNGH).

Hepatitis C in the UK 2015 report

Hot Topic

One in Four Hepatitis C Patients Denied Initial Approval for Drug Treatment
New Haven, Conn. -- Nearly one in four patients with chronic hepatitis C (HCV) are denied initial approval for a drug therapy that treats the most common strain of the infection, according to a Yale School of Medicine study. The finding, published Aug. 27 in PLOS ONE, identifies a new barrier to caring for patients with this severe condition.


A Look At This Week's Headlines

Hepatitis C: Meet the Meds
By Roger Pebody
From TheBody.com
August 28, 2015
Hepatitis C treatment used to have a terrible reputation. Until very recently, it consisted of weekly injections with pegylated interferon and daily tablets of ribavirin.

Not everyone did badly, but a significant number of people had debilitating side effects from the injections, including fever, tiredness and depression. Treatment usually lasted six months to one year. Worse, it didn't get rid of hepatitis C in everyone.

The new generation of hepatitis C treatments are different. You only need to take pills, and often just for 12 weeks (three months).

Oysters harbor, transmit human norovirus: Avoid raw ones
American Society for Microbiology
Washington DC - August 28, 2015 - Oysters not only transmit human norovirus; they also serve as a major reservoir for these pathogens, according to research published August 28 in Applied and Environmental Microbiology, a journal of the American Society for Microbiology. "More than 80 percent of human norovirus genotypes were detected in oyster samples or oyster-related outbreaks," said corresponding author Yongjie Wang, PhD.

FDA warns of severe joint pain risk with DPP-4 diabetes drugs
- A class of diabetes drugs that include Merck & Co Inc's Januvia have been linked with severe joint pain, the U.S. Food and Drug Administration said on Friday.

Harvoni Sees Near-Perfect Cure Rate for Hep C Genotype 4
Gilead Sciences’ Harvoni (ledipasvir/sofosbuvir) cured almost all people with genotype 4 of hepatitis C in a small trial.

Health ministry approves new hepatitis C drug under insurance scheme
A health ministry panel has added a new highly effective, but expensive, hepatitis C virus drug to the national health insurance scheme, giving high hopes for patients who have had to endure painful interferon injections. 

Wider Reach Is Sought for Costly New Hepatitis C Treatments
WASHINGTON — Federal and state Medicaid officials should widen access to prescription drugs that could cure tens of thousands of people with hepatitis C, including medications that can cost up to $1,000 a pill, health care experts have told the White House.

Hepatitis C - Liver Damage Significantly Underestimated and Underreported
The number of hepatitis C patients suffering from advanced liver damage may be grossly underestimated and underdiagnosed, according to a study led by researchers at Henry Ford Health System and the U.S. Centers for Disease Control and Prevention.

Of Interest

August 2015
Summary report: Hepatitis C Good Practice Roadshow, London
This report provides a summary of the good practice hepatitis C roadshow held by HCV Action and Public Health England on 26th June 2015. The roadshow was aimed at sharing good practice around hepatitis C and instigating local action to address the virus. The report includes summaries of the talks and workshops held on the day, as well as suggested next steps to be taken in order to tackle hepatitis C more effectively in the capital. 

August 2015
Developed by the Hepatitis C Coaltiion on the basis of interviews with patient and clinical experts, as well as drawing upon the expertise within the Hepatitis C Coalition’s membership, this fact-sheet provides an overview of the linkages between hepatitis C and alcohol-related liver disease. As well as detailing the interactions between the two conditions, it also details the health impact, as well as the latest relevant policy developments.

View Complete List Of August Reports @ HCV Action.

Enjoy the upcoming weekend.
Tina

Thursday, August 27, 2015

A new virus in liver cancer

A new virus in liver cancer
25.08.2015

More than a cause of a simple infection, viruses are often involved in the development of serious diseases. Such is the case with liver cancer, which often develops in an organ that has been weakened by hepatitis B or C virus. Researchers at Inserm, the Paris Public Hospitals (AP-HP), Paris Descartes University, Paris 13 University (USPC), and Paris Diderot University have just identified the role of a new virus, hitherto unsuspected, in the occurrence of a rare type of liver cancer.

This study, based on follow-up and observation of 193 patients, is published in the 24 August issue of Nature Genetics.

With over 8,000 new individuals diagnosed annually, liver cancer mainly affects men, and is a major cause of death worldwide. Among the different types of liver cancer, hepatocellular carcinoma usually occurs in a liver that has already been damaged by illness. The liver may, for example, have been weakened by excessive alcohol consumption, obesity, or chronic viral infection by hepatitis B or C viruses, which causes irreversible liver lesions leading to cirrhosis.

Cirrhosis patients generally undergo regular tests to detect cancer. However, in 5% of cases, liver cancer occurs in patients who had not reported cirrhosis, and the reason for developing the cancer remains to be identified.

Jessica Zucman-Rossi and her staff at Inserm Unit 1162, “Functional Genomics of Solid Tumors,” focused on these patients to determine the risk factors that had contributed to the development of their cancer.

In the genome of tumour cells of 11 patients, the scientists observed the insertion of a viral DNA segment from adeno-associated virus type 2, known as AAV2. This virus has been considered non-pathogenic for humans until now. In order to confirm the virus’s involvement in the cancer, the research team compared tumour tissues with normal tissues. They thus confirmed their hypothesis: the integration of viral DNA was found more often in tumour cells than in healthy cells in these 11 patients. Moreover, 8 of these patients did not have cirrhosis, and 6 of them presented no known risk factors for liver cancer.


Hierarchical clustering analysis of the data of nominal chip expression of liver cancer DNA genes. ©Inserm/Zucman-Rossi, Jessica

By studying these malignant cells in greater detail, they discovered that the virus, when inserting its DNA into the genome of the patient’s cells, targets genes that are important in cell proliferation. Jessica Zucman-Rossi and her colleagues have shown that AAV2 leads to excessive expression of these genes which, according to the researchers, may favour tumour development.

By this work, the researchers have identified the involvement of AAV2 virus, previously thought to be harmless, in the occurrence of hepatocellular carcinoma, particularly in the rare cases of cancer that develop in the absence of cirrhosis and without an identified cause.These results also call for caution: “AAV2 is often used as a vector in gene therapy. Although the insertion of its DNA into tumour promoting genes is rare, and probably a chance event, precautions must be taken regarding the use of this virus,” explain the authors.

This work was supported by the French National Cancer Institute (INCa) via ICGC and PAIR-CHC NoFLIC (with the participation of ARC Foundation) and the French National Cancer League. Tumour sequencing was performed by IntegraGen, in its laboratories located at Genopole, Evry.

Press release – Inserm press room – A new virus in liver cancer

Link :
http://presse-inserm.fr/en/a-new-virus-in-liver-cancer/20276/

Seattle Children’s Bellevue clinic warns of potential infection risk

Seattle Children’s Bellevue clinic warns of potential infection risk
Originally published August 26, 2015 at 2:59 pm Updated August 27, 2015 at 7:01 am

Hospital staff are sending out warnings to patients and their families and asking the patients to come in for blood tests for diseases, including hepatitis B and C and HIV.

By Sandi Doughton
Seattle Times science reporter

Up to 12,000 children and young adults treated at Seattle Children’s Bellevue Clinic and Surgery Center since 2010 could be at risk of infection from surgical instruments that may not have been properly sterilized.

The hospital is sending out warnings to patients and their families, offering free tests for blood-borne viruses, including hepatitis B and C and HIV, said hospital Chief Executive Officer Dr. Jeff Sperring.

Health ministry approves new hepatitis C drug under insurance scheme

Health ministry approves new hepatitis C drug under insurance scheme
Kyodo
Aug 27, 2015
Article history

A health ministry panel has added a new highly effective, but expensive, hepatitis C virus drug to the national health insurance scheme, giving high hopes for patients who have had to endure painful interferon injections.

The tablet drug Harvoni, developed by U.S.-based Gilead Sciences Inc., is expected to revolutionize the treatment of patients with hepatitis C genotype 1, which accounts for about 70 percent of all hepatitis C patients in Japan.

A daily dose of one pill set at ¥80,171 will starting Monday be covered by the insurance, limiting the patient cost to about ¥20,000 a month.

The decision was made at a meeting of The Central Social Insurance Medical Council on Wednesday.

Read more

Wednesday, August 26, 2015

One in Four Hepatitis C Patients Denied Initial Approval for Drug Treatment

Here is a link to the PLOS ONE study; http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0135645

One in Four Hepatitis C Patients Denied Initial Approval for Drug Treatment
Published: August 26, 2015.
Released by Yale University

New Haven, Conn. -- Nearly one in four patients with chronic hepatitis C (HCV) are denied initial approval for a drug therapy that treats the most common strain of the infection, according to a Yale School of Medicine study.

The finding, published Aug. 27 in PLOS ONE, identifies a new barrier to caring for patients with this severe condition.

Prior to the FDA approval of novel antiviral therapies for HCV in 2014, treatment options for patients were limited, requiring weekly injections of interferon-based therapy that caused severe side effects. The new regimens revolutionized treatment and offered patients an oral therapy with cure rates exceeding 90%. However, the high cost of care led insurers to impose new restrictions on drug authorization.

In light of the new restrictions, the study authors hypothesized that while most patients would be able to access antiviral therapy, some would experience delays in approval and others would be denied. Led by Joseph K. Lim, M.D., associate professor of medicine and director of the Yale Viral Hepatitis Program, the investigators reviewed records of 129 patients who were prescribed a combination of two drugs (sofosbuvir and ledipasvir, or SOF/LED) between October and December 2014.

"The first key finding is that upon initial request for treatment, approximately one in four patients are denied," said Albert Do, M.D., internal medicine resident and co-first author with Yash Mittal, M.D. "That proportion is surprising."

The researchers also found that certain subsets of patients were more likely to receive initial approval, including those with advanced liver disease such as cirrhosis and those on public insurance, either Medicare or Medicaid. "It is significant that factors beyond disease state and medical necessity now affect one's likelihood of accessing HCV treatment," said Mittal.

While most patients in the study eventually received approval for treatment through the insurance appeals process, the delays are concerning, said Lim, as time is critical for patients on the verge of developing cirrhosis or liver failure. "It could make the difference for those who can be treated and remain stable long-term, versus those who have gone past the point of no return and will require liver transplantation or succumb to their illness," he noted.

This study adds to a growing body of literature on the hepatitis C "cascade of care," in which attrition occurs at every step from diagnosis, confirmation, linkage to care, and treatment, Lim explained. He hopes the study triggers further research and discussion about this new barrier to HCV care.

"Delay in access may further challenge our ability to cure hepatitis C in this country," Lim said. "Some patients are told they must wait until they have advanced liver disease before they can undergo potentially curative treatment. We hope these data may help inform national policy discussions on promoting more rational, patient-centered approaches to HCV treatment access."

The above story is based on materials provided by Yale University.

Fatty Liver and Diabetes Increase Liver Fibrosis Risk

Medscape Medical News 

Fatty Liver and Diabetes Increase Liver Fibrosis Risk
Tara Haelle

The combination of diabetes and nonalcoholic fatty liver disease increase the risk for liver fibrosis more than fivefold, according to a large prospective cohort study published online July 14 in Hepatology.

"These findings underline the significant role of these — potentially modifiable — risk factors in liver fibrosis and stress the importance of early targeting insulin resistance and/or [diabetes mellitus]," write Edith M. Koehler, MD, from the Erasmus MC University Hospital Department of Gastroenterology and Hepatology in Rotterdam, the Netherlands, and associates. "[They also] suggest that [nonalcoholic fatty liver disease] may be an important determinant of clinically relevant fibrosis in a population that has a very low prevalence of viral hepatitis."

The researchers performed abdominal ultrasounds on 3041 Dutch adults aged 45 years and older, with a mean age of 66 years, and used transient elastography to scan their livers between January 2011 and September 2013 in Rotterdam. The researchers also collected blood samples, anthropometric measurements, and data on demographics, medical history, comorbid conditions, smoking history, drug use, and alcohol consumption.

Slightly more than a third (35.5%) of the participants had presence of steatosis on abdominal ultrasound. A liver stiffness measurement of at least 8 kPa denoted clinically relevant fibrosis, and was found in 5.6% of participants.

The odds of fibrosis doubled with each decade of age, going from an incidence of 1.4% in those aged 50 to 60 years, to 3.4% among those aged 60 to 70 years, to 5.5% among those aged 70 to 80 years, to 9.9% in those older than 80 years (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.72 - 3.36; P < .001). In addition, 0.6% had a liver stiffness measurement greater than 13.0 kPa, indicating likely advanced fibrosis or cirrhosis.

The two largest risk factors for fibrosis were presence of hepatitis B or hepatitis C and combined presence of diabetes mellitus and steatosis. Odds for liver stiffness at least 8 kPa or higher were more than five times greater with hepatitis B surface antigen or anti–hepatitis C positivity (OR, 5.38; 95% CI, 1.60 - 18.0; P = .006) and for combined diabetes and nonalcoholic fatty liver disease (OR, 5.20; 95% CI, 3.01 - 8.98; P < .001 for combined presence).

Smoking conferred 77% greater odds of fibrosis (OR, 1.77; 95% CI, 1.16 - 2.70; P = .008), and abnormally high levels of alanine aminotransferase, defined as higher than 40 U/L for men and 30 U/L for women, carried 24% greater odds (OR, 1.24; 95% CI, 1.12 - 1.38; P < .001). An enlarged spleen, defined as greater than 12 cm, increased the odds of fibrosis by 23% (OR, 1.23; 95% CI, 1.09 - 1.40, P = 0.001).

"To date, limited studies have been performed focusing on the prevalence of, and risk factors for liver fibrosis in the general population, as data are mainly derived from autopsy studies or biopsy studies in selected populations," the authors write. Biopsies are invasive, however, and healthy volunteers for the procedure would not likely be representative of the general population, Dr Koehler's team notes, which led the researchers to rely on transient elastography.

"Transient elastography is a very good non-invasive way to measure how much swelling is in the liver, the degree of fibrosis," said David Bernstein, MD, chief of the Division of Hepatology at North Shore University Hospital in Manhasset, New York. The modality was only approved by the US Food and Drug Administration in April 2013, however, and it is not yet widely available, Dr Bernstein added. Therefore, a data set like that in this study would be unusual in the United States.

"I really think that this study probably underestimates the problem that we have in the US because the Dutch are a thinner, healthier population than Americans," he added.

"We have a much higher prevalence of diabetes and obesity, and both are linked to nonalcoholic fatty liver disease" he explained. He noted that approximately 90% of type 2 diabetics have fatty liver disease, and that the US population has a higher proportion of type 2 diabetics than the Dutch population has.

Current estimates suggest that at least 60 million people in the United States have nonalcoholic fatty liver disease, Dr Bernstein said. "You're talking about a tremendous number, and it's only growing because, for the first time in our history, we have a really overweight and obese population of young people who are likely to develop diabetes. This is a problem we're going to have for a long time."

"Most doctors think that fatty liver is benign," he said. "We know now that fatty liver is not benign. The vast majority of people with fatty liver will have no problem, but 2% to 4% will develop cirrhosis, and people with fatty liver are at greater risk of developing cancer."

It is estimated that fatty liver disease will soon overtake hepatitis C as the leading indication for liver transplantation in the United States, said Dr Bernstein.

The research was funded by Erasmus MC University Medical Center, Erasmus University Rotterdam, Netherlands Organization for Scientific Research, Netherlands Organization for Health Research and Development, Research Institute for Diseases in the Elderly, Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission, the Municipality of Rotterdam, and the Foundation for Liver Research.

Hepatology. Published online July 14, 2015. Abstract
As direct-acting antivirals continue to show success in HCV, the possibility for treatment expands to an even greater number of patient groups.

Medscape Gastroenterology
The HIV/HCV Outbreak in Indiana 
An Indiana outbreak of HIV/HCV coinfection serves as a cautionary tale to other regions of the United States.

Tuesday, August 25, 2015

Wider Reach Is Sought for Costly New Hepatitis C Treatments

Wider Reach Is Sought for Costly New Hepatitis C Treatments
By ROBERT PEAR
AUG. 25, 2015

WASHINGTON — Federal and state Medicaid officials should widen access to prescription drugs that could cure tens of thousands of people with hepatitis C, including medications that can cost up to $1,000 a pill, health care experts have told the White House.

The experts, from the Public Health Service and President Obama’s Advisory Council on H.I.V./AIDS, said that restrictions on the drugs imposed by many states were inconsistent with sound medical practice, as reflected in treatment guidelines issued by health care professionals and the Department of Veterans Affairs.



HCV Treatment: What Can I Do Now? What's Coming Next?

Medscape Gastroenterology

COMMENTARY
HCV Treatment: What Can I Do Now? What's Coming Next?
Rowen K. Zetterman, MD

Treating an Underdiagnosed Disease
Approximately 170-200 million persons worldwide are infected with hepatitis C virus (HCV), including 3.2 million in the United States.[1] Many lack symptoms and are clinically unrecognized.[2]

Outcomes of HCV infection include chronic hepatitis; cirrhosis; hepatocellular carcinoma; and a need for orthotopic liver transplantation owing to complications, such as cirrhosis or cancer.[3] Estimating the quantity of fibrosis in a liver biopsy specimen from patients with HCV may help determine the risk for decompensation[4] and the need for HCV therapy. Approximately 40% of patients awaiting liver transplantation have underlying HCV infection, and recurrent HCV infection of the transplant allograft is virtually assured.[5] Eradication of HCV from infected patients improves survival of all patients, even if they have advanced liver disease.[6,7]

There are six major genotypes of HCV.[8] Genotype 1 accounts for approximately 75% of HCV infections in the United States, of which two thirds are genotype 1a and one third are genotype 1b. Genotype 1b is less likely to develop resistance during therapy, resulting in better cure rates with treatment than genotype 1a. Approximately 16% of HCV-infected patients have genotype 2; 12% have genotype 3; and 1% each have genotype 4, 5, and 6.

The development of direct-acting antivirals represents a significant improvement in HCV treatment. New combinations of drugs have led to improved response rates, even in patients with characteristics previously associated with having lower response rates: African American, high viral load, concomitant cirrhosis, infection with genotype 1a, and failed treatment with other anti-HCV drugs.[9]

Continue reading @ Medscape

Treating an Underdiagnosed Disease
Surveying the Current Treatment Landscape
Emerging Drugs
Options for Difficult-to-Treat Patients


Hepatitis C treatment: Back to the warehouse

Hello folks, the August issue of Clinical Liver Disease is available online, here.
An excerpt of this months editorial is included below followed by the August index.

This journal is an official digital educational resource from the American Association for the Study of Liver Diseases. Along with full text access, each article includes a video presentation and author interview.

Clinical Liver Disease
Special Issue: Editorial, Palliative Care & Non-Viral Liver Infections
Volume 6, Issue 2, pages 27–29, August 2015

Hepatitis C treatment: Back to the warehouse
John P. Rice M.D

Article first published online: 24 AUG 2015
DOI: 10.1002/cld.490

Hepatitis C treatment: Back to the warehouse
Like many physicians that specialize in hepatitis C virus (HCV) treatment, I have spent the last few years advising many of my patients with chronic HCV infection to defer treatment and wait for new therapies. For those without advanced fibrosis or an extraintestinal manifestation of HCV, this process of “warehousing” patients for future HCV treatment made perfect sense. Why undergo interferon-based therapy, with all of the side effects and marginal results, when it was becoming clear that highly efficacious, interferon-free therapy was close to becoming a reality? Patients, advocacy groups, and physicians closely followed the development of sofosbuvir (Sovaldi), simeprevir (Olysio), sofosbuvir/ledipasvir (Harvoni), and paritaprevir/ritonavir/ombitasvir/dasabuvir (Viekira Pak) among others in eager anticipation of US Food and Drug Administration (FDA) approval and, for most patients, the possibility of a cure of their HCV infection.
Watch a video presentation of this article

Index
Hepatitis C treatment: Back to the warehouse (pages 27–29)
Overview of palliative care and hospice services (pages 30–32)
Issues in the end-stage liver disease patient for which palliative care could be helpful (pages 33–36)
Working with palliative care services (pages 37–40)
Amebic liver abscess (pages 41–43)
Recognizing clonorchiasis: A foodborne illness leading to significant hepatobiliary disease (pages 44–46)
Hepatosplenic candidiasis (pages 47–50)
Pyogenic liver abscess (pages 51–54)



Interferon-free regimens for the treatment of hepatitis C virus in liver transplant candidates or recipients

World J Gastroenterol. 2015 August 28; 21(32): 9526-9533.
Published online 2015 August 28. doi: 10.3748/wjg.v21.i32.9526.

Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.

Interferon-free regimens for the treatment of hepatitis C virus in liver transplant candidates or recipients

Evangelos Cholongitas, 4th Department of Internal Medicine, Medical School of Aristotle University, Hippokration General Hospital of Thessaloniki, 54642 Thessaloniki, Greece
Chrysoula Pipili, Division of Nephrology, Royal Infirmary of Edinburgh, Scotland EH16 4SA, United Kingdom
George Papatheodoridis, Department of Gastroenterology, Athens University Medical School, Laiko General Hospital of Athens, 11527 Athens, Greece
Author contributions: Cholongitas E and Pipili C performed the literature search, wrote the first draft of the manuscript and approved the final version; Papatheodoridis GV wrote and edited the final draft of the manuscript and approved the final version.

Core tip: Treatment against hepatitis C virus has dramatically improved with the novel direct-acting antivirals (DAAs). The currently available DAAs are sofosbuvir, simeprevir, daclatasvir, ledipasvir/sofosbuvir, paritaprevir/ombitasvir and dasabuvir. IFN-free combinations of these novel DAAs with or without ribavirin give excellent sustained virological response in patients with decompensated cirrhosis awaiting liver transplantation and those with recurrence of hepatitis C post liver transplantation. More data regarding the safety and efficacy of these new DAAs are needed, but ongoing clinical trials and real life data will clarify better these issues.

INTRODUCTION
Chronic hepatitis C (CHC) has infected approximately 3% of the world population[1]. Patients with hepatitis C virus (HCV) infection can develop cirrhosis and hepatocellular carcinoma (HCC)[2,3], while CHC is considered the leading cause for liver transplantation (LT) in many Western countries[4]. The combination of pegylated interferon-α (pegIFN) and ribavirin (RBV) in patients with CHC had relatively low rates of sustained virological response (SVR)[5,6], but during the last years several direct acting antiviral agents (DAAs) have increased the efficacy of antiviral therapy[7].
The first approved DAAs (boceprevir and telaprevir) were associated with high rates of clinical complications, particularly among cirrhotic patients with serum albumin levels ≤ 3.5 g/dL and platelet counts ≤ 100000/mm3[8]. Very recently, newer DAAs have been licensed by the European Medicines Agency and Food and Drug Administration to be used mainly as part of IFN-free combinations offering high SVR rates (> 95%), short treatment duration and excellent safety profiles. These agents include sofosbuvir (Sovaldi, Gilead), the first nucleotide analogue NS5B polymerase inhibitor[9], simeprevir (Olysio, Janssen), a second-wave NS3/4A protease inhibitor (achieving SVR in 77%-92% of genotype 1 CHC patients, compared to 46% under pegIFN plus RBV)[10], daclatasvir (Dankliza, Bristol-Myers Squibb)[11], a NS5A inhibitor, the co-formulation of the NS5A inhibitor ledipasvir with sofosbuvir (Harvoni, Gilead)[12], the co-formulation of a ritonavir boosted NS3/4A protease inhibitor, paritaprevir, with the NS5A inhibitor ombitasvir (Viekirax, Abbvie) and dasabuvir (Exviera, Abbvie), a non-nucleos(t)ide NS5B polymerase inhibitor[13] (Table1). They are all given as one tablet daily, except for paritaprevir/ombitasvir (two tablets once daily) and dasabuvir (1 tablet twice daily). The purpose of this review is to summarize the recent findings concerning the use of the new IFN-free regimens in LT candidates or recipients with CHC.

Sunday, August 23, 2015

AASLD/IDSA Update - HCV guidance for Cost, Reimbursement and Cost-Effectiveness Considerations



The American Association for the Study of Liver Diseases (AASLD), in partnership with the Infectious Diseases Society of America (IDSA) and in collaboration with the International Antiviral Society-USA (IAS-USA), created Recommendations for Testing, Managing, and Treating Hepatitis C in 2014. an online living document with ever evolving guidelines to aid practitioners treating patients infected with hepatitis C virus (HCV). An update to the HCV guidance for Cost, Reimbursement and Cost-Effectiveness Considerations was recently published online, here.

OVERVIEW OF COST, REIMBURSEMENT, AND COST-EFFECTIVENESS CONSIDERATIONS FOR HEPATITIS C TREATMENT REGIMENS
The Hepatitis C Guidance describes how to diagnose, link to care, and treat most groups of patients with HCV. (AASLD/IDSA/IAS-USA, 2015) However, a common challenge is reduced access to treatment caused by restrictions on drug reimbursement. This section summarizes the US payer system, explains the concepts of cost, price, cost-effectiveness, value, and affordability, and reviews current evidence of the cost-effectiveness of strategies to improve access to treatment. Although these may sound similar and are often confused, the following discussion will seek to clarify these terms with regard to HCV therapy. To be clear, this section is informational. As explained below, actual costs are rarely known. Accordingly, the HCV Guidance does not utilize cost-effectiveness analysis to guide recommendations at this time.

Continue reading, here.... 

Drug which cures hepatitis C given the go-ahead by NHS

Drug which cures hepatitis C given the go-ahead by NHS 
By Sophie Goodchild for The Mail on Sunday

A cure for the deadly hepatitis C virus has finally been granted NHS funding after ‘an inexcusable wait’ that has seen patients with the disease fall ill unnecessarily, say campaigners.

The once-a-day tablet called sofosbuvir – branded Sovaldi – could help thousands of people including those infected through contaminated blood transfusions. Charities say the fact that patients can now access the drug for free could also effectively help eradicate this chronic disease in the UK.

The go-ahead comes after months of delays and campaigning by patients and charities for the NHS to approve funding for sofosbuvir.

Health chiefs have been accused of deliberately delaying the drug because of its cost – £35,000 for a 12-week course.

It was officially approved by the drugs regulator the National Institute for Health and Care Excellence (Nice) in January this year.

Until now, only patients at a chronic stage of illness – about 500 – were eligible to have the breakthrough drug. But this month, health chiefs finally agreed to make funding available so that all health trusts can offer it. Patients will now have access to the drug, which will be prescribed in combination with other treatments.
Continue reading...





Saturday, August 22, 2015

HCV: The Best Cure Possible or the Best Possible Cure?

Journal of Viral Hepatitis

HCV: The Best Cure Possible or the Best Possible Cure?

L. Craxí; C. Cammá; A. Craxí
Disclosures

J Viral Hepat. 2015;22(8):627-629. 

 Is a regimen combining interferon (IFN) with a highly effective direct-acting antiviral agents (DAA) still an acceptable choice in 2015? The ultimate goal for society as a whole is to obtain what is best for each individual, but in doing so, it should aim not towards the best possible cure, but the best cure possible. This basic assumption is essential, even though it often leads to a conflict with the desires and aspirations of individuals, especially because immediate access to information about new and potentially effective treatments is available to anyone. In some instances, the high price tag on treatments and devices is unquestionably related to industrial costs (research, development, licensing, production and distribution), while in others finding any kind of justification is extremely hard. In the instance of HCV treatment, Are we really sure that IFN-free therapies cannot be both the best possible cure and the best cure possible for everyone?[2] These therapies are unquestionably more effective than the others, and the only obstacle towards a sustainable generalized distribution is their extremely high cost, which looks artificially inflated even considering the high R&D costs. The cost of fabricating all the new DAAs does not exceed 300 $ for a 12 weeks course of treatment, a more than 200-fold difference from their retail price.

Progress in medicine goes along with an exponential growth of the cost of drugs and devices. While any person has the right to obtain the best possible benefit from medical care, a state needs to strike a balance between granting the optimal personal benefit to each individual and the needs of the society as a whole. Health systems in all countries therefore are facing a huge problem of distributive justice, as while they should guarantee individual rights, among which the right to health in its broader sense, including physical, psychological and social well-being (therefore not limited to healing, but extending to compliance and quality of life), they must also grant equal access to the healthcare resources and keep the distribution system sustainable.

The new generation of highly effective direct acting antivirals (DAAs) to treat HCV infection brings major promises to infected patients in terms of exceedingly high rates of sustained virological response (SVR) but also of tolerability, allowing even the sickest patients to be treated.[1] However in most countries throughout the world, the exceedingly high prices of DAAs are hampering their integration into the HCV treatment programmes. A similar situation arose at the outset of the HIV/AIDS epidemics until the availability of generic compounds removed the price obstacle. The current costs of DAA combinations active against HCV mean that on a global level far less patients than needed are being treated and that no population-wide public health benefit can be expected for some of the most heavily affected countries.[2]

Direct acting antivirals in all-oral regimens need to be used in combination to get SVR rates beyond 90%, except for the easiest to treat patients such as those with HCV genotype 2, where sofosbuvir with ribavirin will suffice. A need to prolong therapy to 24 weeks when treatment is given to patients with cirrhosis emerged at least with some regimens. Need for combination and longer treatment duration will cause a further rise of costs, in a context where the prices of DAAs are already deemed to be exceedingly high.[3] Although in an ideal world everybody would like to get rid of interferon and of its complications and inherent limitations, its relatively low price tag still keeps it as an option to partner with one DAA to reduce costs while still obtaining high SVR rates, at least among patients without cirrhosis. Another currently popular option is to allow IFN-free DAA treatment only in patients with advanced fibrosis or cirrhosis, while keeping on hold persons with lesser stages of liver disease (so-called 'informed deferral' policies).[4] The net balance of these attitudes has never been quantified.

In this issue of JVH, Pho et al.[5] perform a cost–utility analysis aimed to quantify the trade-offs of immediate, interferon-containing therapy versus delayed, interferon-free therapy for interferon-eligible patients with HCV genotype 1 chronic infection. The evaluation, addressing a lifelong time horizon, was performed using a decision-analytic approach, and the natural history of progression of chronic hepatitis C was projected by Markov's model. Using grouped data derived from phase III studies, Pho et al. have tested the incremental cost-effectiveness ratio (ICER) of four different antiviral treatment scenarios stratified by the presence or absence of cirrhosis: (i) no treatment, (ii) immediate, one-time treatment with sofosbuvir interferon-containing regimen, (iii) immediate treatment as above with the opportunity for retreatment in patients who fail to achieve sustained virologic response with interferon-free therapy in 1 year and (iv) delayed therapy with interferon-free therapy in 1 year. They found that waiting 1 year for interferon-free therapy resulted in superior health benefits compared with one-time immediate therapy with interferon. This superiority in health benefits was however lost when the wait-time for an interferon-free therapy was >3 years. Time dependency of this choice was consistent across a broad range of disease variables, and more evident in subjects without cirrhosis. As a message, HCV-infected patients facing the decision of whether to accept to be treated immediately, with a less costly IFN-containing (but still sofosbuvir based) regimen, or wait until more relaxed rules and reduced costs will allow them to be eligible for an IFN-free treatment should opt for the IFN-containing regimen if they have severe disease (but not severe enough to prevent the use of IFN) if the projected waiting time for IFN-free DAAs exceeds 1 year.

The issue tackled by Pho et al.[5] is of practical relevance, given that due to costs, many countries are unable to effectively deliver this innovation.[2] One wonders however how large will be the reduction of costs, given that sofosbuvir, a highly priced drug except in Egypt and in some non-Western countries, is still the backbone of the regimen. If new DAA combos are priced in the same fascia of sofosbuvir, the advantage of an IFN-containing combination becomes far less relevant. Moreover, the indirect costs generated by the use of IFN (growth factors, EPO, transfusions, medical care) could offset the sparing obtained.[6] Also, the option of using only PEG IFN and ribavirin in patients with a high likelihood of response[7] as a way to reduce costs has not been explored in the model.

Albeit Pho's analysis is conducted rigorously, its conclusions cannot be fully transferred to clinical practice without considering some methodological issues. Decision models are often designed using summary data hampering more detailed treatment comparisons that could be achieved with a prognostic model using individual patient data. These summary results describe only between-population, not between-patient, variation because they reflect group averages rather than individual data. Therefore, conventional quality-adjusted life years (QALYs) are population-level tools and fail to take into account important interindividual differences that might affect the value of a particular intervention.[8] The choice that maximizes the population's health or has the best cost/effectiveness overall is not always the same as the best choice for a specific individual. Moreover, the best choices may differ for different individuals. There is thus interest in how to modify the ICER concept for applications in individual decision-making.[9] While for any person it would be more desirable to receive immediately a highly effective IFN-free regimen, at a societal level, it is important to know that an informed deferral strategy, to be carefully agreed with the patient, allows waiting 1 year for interferon-free therapy with superior health benefits as compared to one-time immediate therapy with interferon. According to Aronsohn,[4] deferring treatment is justifiable and appropriate for many patients, and an informed deferral is needed considering risks related to inaccurate staging of liver disease, inability to predict progression of fibrosis and comorbidity changes over time. Obviously, the clinical value and ethical impact of treatment or deferral should not be compromised by any economic analysis.

Moreover, in a prognostic setting, predictions are used to plan therapeutic choices based on the risk of a specific outcome, and estimates of probabilities are seldom based on a single predictor. In fact, physicians naturally integrate several patient's characteristics and symptoms to make a prediction. Prediction is therefore inherently multivariable.[9] Although deterministic and probabilistic analyses try to take these aspects into consideration, these analyses often fail to capture the full complexity of the clinical decision on the individual patient. In this setting, more detailed treatment comparisons could be achieved by combining the different variables affecting the achievement of SVR using multivariate risk modeling.[10] Pho's model adopts the same expected SVR rate regardless of the type of patient to be treated (naïve or P/R experienced, a relevant issue when dealing with IFN-based regimens).

In the end, a major question mark remains: Is a regimen combining IFN with a highly effective DAA still an acceptable choice in 2015? The ultimate goal for society as a whole is to obtain what is best for each individual, but in doing so, it should aim not towards the best possible cure, but the best cure possible. This basic assumption is essential, even though it often leads to a conflict with the desires and aspirations of individuals, especially because immediate access to information about new and potentially effective treatments is available to anyone. In some instances, the high price tag on treatments and devices is unquestionably related to industrial costs (research, development, licensing, production and distribution), while in others finding any kind of justification is extremely hard. In the instance of HCV treatment, Are we really sure that IFN-free therapies cannot be both the best possible cure and the best cure possible for everyone?[2] These therapies are unquestionably more effective than the others, and the only obstacle towards a sustainable generalized distribution is their extremely high cost, which looks artificially inflated even considering the high R&D costs. The cost of fabricating all the new DAAs does not exceed 300 $ for a 12 weeks course of treatment, a more than 200-fold difference from their retail price.[11] Even allowing for other industrial costs, this rate of amplification is totally unheard in any field of medical care. The basics of modern free market economics dictate that pharmaceutical industries have the right to set the price they like and seek the profit they deem appropriate, while facing supply and demand dynamics. But, Are we sure that both the parties in the negotiation game are playing by the same rules? Are pharmaceutical industries (private, profit-driven enterprises) and public healthcare services really peers? Can we really consider drugs market a free market when it has the dynamics of a monopoly or a cartel? The focal point therefore is increasing the state's negotiating power, which originates from the state's economic force and from the raw number of potential users. It is utterly absurd that despite the focus on European community, and on international trade treaties at large, each individual state negotiates the price of drugs and treatments individually based on its numerical needs. States could and most surely should join forces to apply more pressure on the industry. Possible means of pressure are generic drugs, treatment scale up and chiefly drugs patenting, which has often seen the granting of patents for drugs whose originality and potential benefits wee questionable to say the least. Last, but not the least, health technology assessment should give a strict guidance on the margins of negotiation available to provide the therapy to everyone.

In conclusion, an assessment of the possible timing of deferral of IFN-free treatments without prejudice for a patient's health is a useful tool, but cannot be used to justify the status quo and the adoption of a double track for treatment.
Source

Of Interest
In The News


Thursday, August 20, 2015

Hepatitis C sufferer imports life-saving drugs from India, takes on global pharmaceutical company

Hepatitis C sufferer imports life-saving drugs from India, takes on global pharmaceutical company

By Michael Atkin and Joel Keep

It is straight from the script of Hollywood movie Dallas Buyers Club — an Australian hepatitis C sufferer has taken on a global pharmaceutical company, accusing them of failing to provide a life-saving medication at an affordable cost.

"The only difference between me and the guy in Dallas Buyers Club is I'm not running it as a business and I'm not making any money out of it, as much as I like to see him with his big wads of dollar bills," Greg Jefferys told 7.30.

Mr Jefferys was so sick from hepatitis C last year that he was unable to get out of bed some days.

He dropped out of his university PhD studies and quit many of his hobbies, including kayaking and fishing.

He desperately needed a drug called Sovaldi, manufactured by US pharmaceutical giant Gilead, but could not afford it without selling his house.

How to pay the bill for hepatitis C

How to pay the bill for hepatitis C
By D. STEVEN FOX, JEFFREY S. MCCOMBS

How long should you wait to treat a possibly fatal but curable disease?

That's a question with major implications for millions of patients and for insurers and government programs that have to pay for the treatment.

In the last year this question has focused on hepatitis C, a viral infection of the liver that, left untreated, can lead to cirrhosis, cancer, liver failure and death. Hepatitis C is the leading cause for liver transplants in the United States.

In July the California Department of Health Care Services ordered a new protocol that will mean many thousands of Medi-Cal patients will have to wait for treatment. But far from jeopardizing lives, the department is helping to lead the way out of the hepatitis C conundrum with a sensible policy: Treat everyone who needs it, but not until treatment is necessary...

Tuesday, August 18, 2015

While Washington Tackles Opioid Abuse Epidemic, Hepatitis C Treatment Remains Unaffordable

While Washington Tackles Opioid Abuse Epidemic, Hepatitis C Treatment Remains Unaffordable

If Washington wants to do something about the public health issues left behind by the opioid abuse epidemic, it might have to start doing something about prescription-drug costs.
August 18, 2015 

Big names in Washington are increasingly joining the fight to combat the rise of opioid and heroin abuse, but the conversation around the issue is missing half the problem.

On Monday, the White House announced an initiative to curb heroin use by addressing it as both a public-safety and public-health issue, pairing law enforcement with access to treatment for addicts. This builds on momentum within Congress and talk among 2016 presidential hopefuls surrounding the reduction of national opioid drug addiction.

But largely excluded from the discussion is what to do about those living with the consequences of their addiction and the public health concern that presents. For many, access to treatment for disease contracted through drug use is unaffordable. Although there is medication on the market to treat hepatitis C—a disease common among drug users—its cost often makes it unavailable to the sick.



Can we Reduce Muscle Cramps in Patients with Cirrhosis?

Can we Reduce Muscle Cramps in Patients with Cirrhosis?
Kristine Novak

L-carnitine appears to be safe and effective for reducing muscle cramps in patients with cirrhosis, researchers report in the August issue of Clinical Gastroenterology and Hepatology.

Many patients with cirrhosis develop frequent muscle cramps, which reduce their quality of lifeL-carnitine (L-beta-hydroxy-gamma-N-trimethyl aminobutyric acid) is an amino acid that transports long-chain fatty acids across the mitochondrial membrane, and has been proposed to provide energy for skeletal muscle. Hiroyuki Nakanishi et al evaluated its effects on muscle cramps in a prospective study.

Consecutive patients with cirrhosis and muscle cramps were given L-carnitine (300 mg) 3 times/day (900 mg/day total, n = 19) or 4 times/day (1200 mg/day total, n = 23) for 8 weeks. The frequency of muscle cramps was assessed by questionnaires, and the degree of muscle cramping was assessed by the visual analogue scale (VAS).

The VAS is a horizontal, 100 mm line with word descriptors at each end (left, totally without pain and right, unbearable pain). Patients mark points on the line the point that best indicates their current state. The VAS score is then determined by measuring millimeters from the left end of the line to the marked points.

At the end of the 8 week study period, muscle cramps decreased in 88.1% of all subjects; 28.6% of patients had no cramps at al.

Overall VAS scores decreased significantly, from a mean value of 69.9±22.5 at baseline to 26.2±29.1 after 8 weeks.

Muscle cramps were reduced in 43.5% of patients in the 1200 mg/day group and 10.5% in the 900 mg/day group. At the end of the 8-week study period, mean VAS scores were 9.9±13.5 in the 1200 mg/day group and 39.6±31.9 in the 900 mg/day group (see figure).

Nakanishi et al did not observe any adverse events.


VAS scores before and after 8 weeks of L-carnitine. Black lines indicate the 1200 mg group, gray the 900 mg group. (A) Overall, the mean VAS score was reduced significantly from 69.9 ± 22.5 to 26.2 ± 29.1 after 8 weeks of therapy. (B) VAS scores after 8 weeks were significantly lower in 1200 mg group than in 900 mg group

Why do patients with cirrhosis develop cramps, and why might L-carnitine reduce them? An analysis of skeletal muscle biopsies from patients with cirrhosis and found reductions in ATP, phosphocreatine, and total adenine nucleotides. Deficiencies in ATP result in insufficient dissociation of myosin from actin, and thereby prolonged muscle contraction and cramping.

Carnitine transports long-chain acyl groups from fatty acids into the mitochondrial matrix, so they can be broken down through β-oxidation to acetyl CoA to obtain usable energy via the citric acid cycle.

This process provides ATP for heart and skeletal muscles. Nakanishi et al propose that some patients with cirrhosis could have carnitine deficiency. Larger, randomized, controlled studies are necessary to further evaluate the efficacy of L-carnitine in reducing muscle cramps in patients with cirrhosis and other disorders.


Hepatitis C - Liver Damage Significantly Underestimated and Underreported

Liver Damage in Hepatitis C Patients Significantly Underestimated and Underreported, says Henry Ford Hospital Study

Aug. 18, 2015

DETROIT – The number of hepatitis C patients suffering from advanced liver damage may be grossly underestimated and underdiagnosed, according to a study led by researchers at Henry Ford Health System and the U.S. Centers for Disease Control and Prevention.

The findings, recently published in the American Journal of Gastroenterology, were the result of a study of nearly 10,000 patients suffering from hepatitis C. The results could have a significant effect on patient care and healthcare policy regarding the chronic disease.

“Knowledge of the prevalence of liver damage will help decision making regarding screening for the effects of hepatitis C, when to start anti-viral therapy, and the need for follow-up counseling,” says Stuart Gordon, M.D., lead researcher and Director of Hepatology at Henry Ford Hospital.

The Chronic Hepatitis Cohort Study is an analysis of records from a large, geographically and racially diverse group of 9,783 patients receiving care at four large U.S. health systems: Henry Ford Health System in Detroit; Kaiser Permanente Northwest in Portland, Oregon; Kaiser Permanente in Honolulu and Geisinger Health System in Danville, Pennsylvania.

The records analyzed by the researchers indicated evidence of liver damage, or cirrhosis, in 29% or 2,788 of the hepatitis C patients included in the study. But surprisingly, 1727 of those 2,788 patients, or 62% of those suffering from liver damage, had no formal documentation in their medical records that they had cirrhosis.

The results suggest cirrhosis may be underdiagnosed in a large segment of the population, he added. Clinicians typically rely on liver biopsies to diagnose cirrhosis. But in the hepatitis C patients studied, only 661 patients were diagnosed with cirrhosis through a liver biopsy.

“Our results suggest a fourfold higher prevalence of cirrhosis than is indicated by biopsy alone,” says Gordon.

The researchers discovered highly likely signs of liver damage by calculating the patients’ liver enzymes, platelet counts and age in a previously validated test called a FIB-4 score.

“It’s an under-appreciated, easily obtained and, widely available test done through lab work that can point out there’s a problem,” says Dr. Gordon. “It’s a simple test not routinely used by clinicians. A lot of patients in our study had cirrhosis and probably didn’t know they had cirrhosis. In addition, electronic medical record reports may not be a reliable indicator of just how many hepatitis C patients may be suffering from cirrhosis.”

Hepatitis C is a viral infection that causes inflammation and infection of the liver. The U.S. Centers for Disease Control and Prevention’s Division of Viral Hepatitis estimates 2.7 to 3.9 million people in the United States currently suffer from chronic hepatitis C. Without treatment, the virus over time can cause liver cancer or cirrhosis, which can lead to liver failure.

“Sometimes the clues of liver damage or cirrhosis are very subtle – a dropping platelet count, a spleen size that is slightly increased on an ultrasound,” says Dr. Gordon. “It is not unusual for patients with hepatitis C to come in and they have liver cancer, and they didn’t even know that they had cirrhosis that led to their cancer.”

The results could have wide impact on the treatment of those with hepatitis C, a disease now curable in many cases with oral antivirals.

“People with hepatitis C need to find out the severity of their underlying liver disease, because they may not realize that they have cirrhosis,” says Dr. Gordon. “Obviously, treatment can slow down the progression.”

Patients seeking a medical consultation can make an appointment for the Henry Ford Health System Liver Disease Center by calling 1-800-HENRYFORD (800-436-7936).

MEDIA CONTACT: Tammy Battaglia

Tbattag1@hfhs.org

248-881-0809