February 6, 2014

Hepatitis C treatment shifts as new drugs emerge

Kim Painter, Special for USA TODAY 6:29 p.m. EST January 29, 2014

Treatment for liver-damaging virus is changing fast. Experts release new guidelines.

1391030010000-Sofosbuvir-bottle-with-pill-on-Gray

Sofosbuvir, with the brand name Sovaldi, is among new medications changing the treatment of hepatitis C.(Photo: Gilead Sciences Inc.)

John Billeris has tried and failed four grueling rounds of treatment for his chronic hepatitis C infection over the past 15 years. He is not convinced that his fifth try — with what he jokingly calls "magic medicine" — will be the charm. But he says the three-drug regimen he started on Christmas is definitely easier to take.

"I saw the doctor a couple of weeks ago… and I told him this (stuff) is not working because I don't feel anything," says the 59-year-old semi-retired real estate agent from Oyster Bay, N.Y. Since then, Billeris says, he's developed a familiar "anemic feeling," but still nothing like the persistent flu-like symptoms he has endured in the past.

That's because Billeris' new treatment does not include one drug that, until now, has been essential for patients like him: interferon, a medication known for causing fevers, headaches, fatigue, mood swings and other unpleasant and sometimes dangerous side effects. It does include two drugs approved by the Food and Drug Administration in late 2013, sofosbuvir from Gilead Sciences, Inc., and simeprevir from Janssen Therapeutics.

Those medications, and others the FDA is expected to consider soon, are part of what experts are calling a revolution in treatment for 3 million people in the USA chronically infected with hepatitis C, the nation's leading cause of liver cancer and liver transplants.

Changes in treatment are coming so fast that several medical groups on Wednesday took an unusual step: posting preliminary online treatment guidelines that will evolve as more medications become available.

Those medications could soon eliminate the need for interferon injections for most patients. They also are expected to make treatment faster, easier and more effective than older regimens, which last at least six months and succeed about 75% of the time, experts say.

"The ideal would be a single pill once a day, for eight or 12 weeks, with success rates of greater than 90%," says Donald Jensen, a liver disease specialist from the University of Chicago and co-chair of the committee behind the guidelines posted at HCVguidelines.org by the American Association for the Study of Liver Diseases, the Infectious Diseases Society of America and the International Antiviral Society-USA.

While single-pill therapies are not yet available and the FDA has not yet approved an interferon-free regimen for the majority of patients, the experts say doctors can combine drugs on the market to get faster, easier, more effective treatment for many patients who need care now. In some cases, that will mean using combinations not explicitly approved by the FDA — including the interferon-free cocktail Billeris is using. The guidelines say it is an option for hepatitis C patients with genotype 1 (the most common strain) who can't tolerate interferon or have certain conditions, including depression.

The guidelines don't carry the same weight as those that go through formal reviews to be published in medical journals, "but we are saying that if these were our patients, this is how we would handle them," says committee co-chair David Thomas, a liver specialist at Johns Hopkins School of Medicine, Baltimore.

The guidelines will be "enormously valuable" in convincing more insurers to cover the very expensive emerging treatments, says Douglas Dieterich, a liver specialist at Mount Sinai Hospital, New York. He says some have been refusing to pay for the combination of sofosbuvir, which costs $84,000 for 12 weeks, and simeprevir, which costs $66,000 for 12 weeks, according to manufacturers.

The prices for the new drugs, especially, sofosbuvir, at $1,000 a pill, also have drawn criticism from patient advocates who say high prices will limit access in the USA and worldwide.

"Gilead is exploiting the fact that this is essentially a cure for a deadly disease," says Michael Weinstein, president of the AIDS Healthcare Foundation.

Gilead believes the price of sofosbuvir "is fair, based on the value it represents" to patients, company president John Milligan said in a statement. Most private insurers are covering the drug in FDA-approved combinations, he says, and the company is working with Medicaid and Medicare to set terms for access under those plans. The company also has an assistance plan for uninsured patients and those who need help with co-pays.

The new expert guidelines "are not designed to address cost," Jensen says. "Our recommendations are based on what we think is best for patients."

The new guidelines also do not say which patients doctors should treat now and which patients can wait — a crucial issue since hepatitis C can cause varying degrees of harm and take decades to cause symptoms. A future version will address that issue, Thomas says.

Many people don't even know they have the infection. But the federal Centers for Disease Control and Prevention says it is so common among Baby Boomers that everyone born between 1945 and 1965 should be tested. The virus spreads through shared needles, birth and, sometimes, sex. About 5% of people with chronic infections eventually die of cancer or cirrhosis, the CDC says.

Getting tested is especially crucial now, Thomas says. "All the major advances in treatment are insignificant if a person doesn't even know they have the infection."

Of course, those advances in treatment still need to pass the test of real-world use — a test that some previous medical advances have failed. Billeris, for one, says, "I'm not optimistic — but I am hopeful."

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Some receive unnecessary prioritization for liver transplantation, says Penn Medicine study

PUBLIC RELEASE DATE: 5-Feb-2014

Contact: Lee-Ann Landis Donegan
leeann.donegan@uphs.upenn.edu
215-349-5660
University of Pennsylvania School of Medicine

Findings could influence process for allocation of scarce organ resources

(PHILADELPHIA) – Patients waiting for liver transplants who develop hepatopulmonary syndrome (HPS), a lung disorder associated with end-stage liver disease, are eligible to move up on the wait list. In a new paper published in Gastroenterology, however, Penn Medicine researchers argue the so-called "exception points" given to these patients award some HPS patients unnecessary priority over others on the list, which includes about 17,000 patients.

The current U.S. transplant allocation system prioritizes patients based on medical urgency using the Model for End Stage Liver Disease (MELD) score, which takes into account the expected three-month survival due to end-stage liver disease, but does not consider other, unrelated medical complications. As a result, a system that allows wait-list candidates with certain conditions, HPS among them, to be eligible for exception points to increase their waitlist priority has been developed.

"To examine the impact of HPS MELD exception points on outcomes, we examined the relationship between patients' blood oxygen levels and outcomes in a national cohort of patients who received HPS exception points, and compared survival in HPS vs. non-HPS patients," says David Goldberg, MD, MSCE, instructor of Medicine at the Perelman School of Medicine of the University of Pennsylvania and lead author on the study.

HPS is found in approximately 20 percent of patients awaiting liver transplant and is associated with a worse health-related quality of life. The condition is known to double the risk of death among patients evaluated for liver transplantation.

The Penn researchers looked at data from February 2002, the date the exception point program commenced, to December 2012. During this time, 973 patients on the liver transplant list received HPS exception points. While post-transplant survival was similar in HPS vs. non-HPS patients, post-transplant survival in HPS patients varied based on the severity of pre-transplant oxygen saturation levels.

The team found that patients with the poorest oxygen saturation levels (lower than 44 mm Hg) had a significantly lower three-year post-transplant patient survival rate.

Comparatively, significantly more non-HPS waitlisted patients, who did not receive exception points, died on the waitlist or within 90 days of waitlist removal, while a great proportion of HPS waitlist candidates were transplanted (73 percent vs. 43 percent). In addition, the study showed that only 49 percent of HPS transplant recipients had clear evidence of clinical indications for transplantation aside from HPS, as compared with 89 percent of non-HPS transplant recipients.

The findings refute recent reports and demonstrate an association between pre-transplant oxygen levels and post-transplant mortality, suggesting that the criteria for doling out exception points be adjusted based on patients' oxygenation, and suggesting an over-prioritization of all HPS patients in the current system.

This study represents the largest analysis of liver transplant waitlist candidates with HPS to date.

"These data, we hope, can provide some guidance to UNOS, as the exception point policy comes under revision," says Goldberg. "As organs are a scarce resource, we want to make it easier for the patients in the most urgent need to be prioritized as such, according to evidence-based criteria."

###

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 16 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $398 million awarded in the 2012 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; Chester County Hospital; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2012, Penn Medicine provided $827 million to benefit our community.

Source

Can-Fite Submitted Phase II Study Protocol with CF102 to Treat Patients with Advanced Liver Cancer

PRESS RELEASE February 6, 2014, 7:06 a.m. ET

CF102 has Orphan Drug Designation from U.S. FDA

Global Liver Cancer Drug Market is Expected to Exceed $2 Billion by 2015

PETACH TIKVA, Israel, Feb. 6, 2014 /PRNewswire/ -- Can-Fite BioPharma (TASE: CFBI), (OTC: CANFY), a biotechnology company with a pipeline of proprietary small molecule drugs that address inflammatory and cancer diseases, announced today that a Phase II study protocol for the treatment of advanced liver cancer with its CF102 drug candidate has been submitted.

The company plans to conduct the Phase II study in Israel, Europe and the US and will include 78 subjects (less than what has been reported previously since the company is treating a patient population with a more advanced disease) with second-line treatment of advanced hepatocellular carcinoma with Child-Pugh Class B cirrhosis. The study will investigate the efficacy and safety of CF102 vs. placebo. The protocol has been submitted to the ethics committee in Israel and the company intends to follow up with European and US submissions shortly. The study protocol was developed with the assistance of Dr. Keith Stuart, MD, Chairman, Department of Hematology and Oncology Professor of Medicine, Tufts University School of Medicine a well-known internationally expert in Liver Cancer.

The US Food and Drug Administration (FDA) has granted Orphan Drug designation for CF102, for the treatment of hepatocellular carcinoma.

According to Global Industry Analysts, the global liver cancer drug market is expected to exceed $2 billion by 2015.

The company reported earlier that data from the Phase I/II study was published recently in The Oncologist, one of the leading journals in this field, and was presented at the 18th World Congress on Advances in Oncology. The company reported that the Phase 1/II study data demonstrated that the trial objectives were successfully achieved, demonstrating a very favorable safety profile for CF102 in a patient population with hepatocellular carcinoma and Child-Pugh cirrhosis classes A and B. In addition, the median overall survival time was very encouraging given that most patients were treated in the second-line setting and some were Child-Pugh Class B. Another finding indicated that the A3 adenosine receptor, which is the target of CF102, can serve as a biomarker to predict the patients' reaction to treatment with CF102. Interestingly, one of the patients included in the Phase 1/II study has been treated for 4 years with CF102 and is continuing to be treated, with CF102.

About CF102

CF102 is a small orally bioavailable drug which binds with high affinity and selectivity to the A3 adenosine receptor. The latter is highly expressed in tumor cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug. In our pre-clinical and clinical studies, CF102 induces a robust anti-tumor effect via de-regulation of the Wnt signaling pathway, resulting in apoptosis of liver cancer cells.

About Can-Fite BioPharma Ltd.

Can-Fite BioPharma Ltd is an Israeli public company, the ordinary shares of which are traded on the Tel Aviv Stock Exchange (the "TASE") (TASE: CFBI). Level II American Depository Receipts of the Company currently trade on the NYSE MKT (NYSE MKT: CANF). Can-Fite, which commenced business activity in 2000, was founded by Pnina Fishman, Ph.D., researcher in the Rabin Medical Center, and Ilan Cohn Ph.D., patent attorney and senior partner at Reinhold Cohn Patent Attorneys in Israel. Dr. Fishman serves as the Chief Executive Officer of Can-Fite. Dr. Fishman founded Can-Fite on the basis of her scientific findings, and Can-Fite is focused on the development of small molecule orally bioavailable drugs, in particular, ligands that bind to the A3 adenosine receptor. Such drugs mediate anti-inflammatory and anti-cancer effects and the A3AR is developed as a biological predictive marker. Can-Fite's lead drug candidate, CF101, is in clinical development for the treatment of autoimmune inflammatory diseases including Rheumatoid Arthritis and Psoriasis. Can-Fite's CF102 drug candidate is being developed for the treatment of liver diseases and CF602 is being developed for the treatment of inflammation and sexual dysfunction. To date, more than 1000 patients have participated in clinical trials conducted by Can-Fite. Can-Fite previously spun off it's activity in the ophthalmic field to OphthaliX Inc., in which it holds 82%, and is currently listed on the U.S. Over-the-Counter Markets (OTCQB: OPLI).

Contact:

IRTH Communications, LLC

Robert Haag

canfy@irthcommunications.com

Forward-Looking Statements

This press release contains forward-looking statements, about Can-Fite's expectations, beliefs or intentions regarding, among other things, its product development efforts, business, financial condition, results of operations, strategies or prospects. In addition, from time to time, Can-Fite or its representatives have made or may make forward-looking statements, orally or in writing. Forward-looking statements can be identified by the use of forward-looking words such as "believe," "expect," "intend," "plan," "may," "should" or "anticipate" or their negatives or other variations of these words or other comparable words or by the fact that these statements do not relate strictly to historical or current matters. These forward-looking statements may be included in, but are not limited to, various filings made by Can-Fite with the U.S. Securities and Exchange Commission (the "SEC"), press releases or oral statements made by or with the approval of one of Can-Fite's authorized executive officers. Forward-looking statements relate to anticipated or expected events, activities, trends or results as of the date they are made. Because forward-looking statements relate to matters that have not yet occurred, these statements are inherently subject to risks and uncertainties that could cause Can-Fite's actual results to differ materially from any future results expressed or implied by the forward-looking statements. Many factors could cause Can-Fite's actual activities or results to differ materially from the activities and results anticipated in such forward-looking statements, including, but not limited to, the factors summarized in Can-Fite's filings with the SEC and in its periodic filings with the TASE. In addition, Can-Fite operates in an industry sector where securities values are highly volatile and may be influenced by economic and other factors beyond its control. Can-Fite does not undertake any obligation to publicly update these forward-looking statements, whether as a result of new information, future events or otherwise.

SOURCE Can-Fite BioPharma

/Web site: http://www.canfite.com/

Source

Gilead to license hepatitis C drug to lower-cost manufacturers in India

Thu Feb 6, 2014 4:28am IST

(Reuters) - Gilead Sciences plans to license its breakthrough hepatitis C drug Sovaldi to a number of Indian generic pharmaceutical manufacturers, allowing for lower-priced sales of the medication in that developing nation, according to the company.

Although prices for the drug have not been set, company spokesman Nick Francis said in an emailed statement on Wednesday that Gilead aims to establish "tiered pricing."

For example, the price discussed for 24 weeks of Sovaldi therapy would run about $2,500 for certain patients at public hospitals, community clinics and non-governmental agencies in India, the Hindu Business Line reported earlier this week.

"Providing treatment in resource-limited settings presents complex challenges, and we will work with partners in multiple sectors around the world to ensure our access program reaches as many patients as possible," Francis said.

Gilead said final details of the program in India will be announced in coming months. The company has a similar program in place for lower-cost versions of its HIV/AIDS drugs.

In the United States, where Sovaldi was approved by regulators in December, the drug costs $84,000 for 12 weeks of therapy or $1,000 for a daily pill.

The Foster City, California-based company has said the price is fair because the treatment offers a potential cure for the liver-destroying virus without injections of interferon, which can cause severe side effects that compromise patient outcomes.

Prices in Europe are also lower than in the United States. The cost for treatment in the United Kingdom is about $57,000 while the price in Germany is around $66,000, the company has said.

Analysts have estimated that the drug will eventually generate billions of dollars in annual sales. Sanford Bernstein has forecast sales this year alone of $6.7 billion.

But some have questioned whether that is achievable. Many patients including those in the United States, where more than half of hepatitis C patients are estimated to rely on public funding, could have difficulty securing reimbursement for such a high-priced drug.

Other companies including Johnson & Johnson, AbbVie and Merck & Co are also working to develop new hepatitis C treatments with some in advanced stages of clinical studies.

Gilead, which reported 2013 earnings on Tuesday, declined to include an estimate for hepatitis C sales in its 2014 sales forecast, saying only that Sovaldi sales so far have been strong and broadly based.

Sales of Sovaldi in the last three weeks of 2013 totaled more than $139 million.

The World Health Organization estimates that about three percent of the world's population has been infected with the hepatitis C virus and that more than 170 million chronic carriers are at risk of developing liver cirrhosis, liver cancer or both.

Shares of Gilead fell $3.87, or nearly five percent, to close at $78.15 in Nasdaq trading on Wednesday. Over the past two years, the stock has nearly tripled.

(Reporting By Deena Beasley; Editing by Diane Craft)

Source

Patient-important benefits of clearing the hepatitis C virus through treatment: a simulation model

Journal of Hepatology

Article in Press

Hamish Innes, David Goldberg, Geoffrey Dusheiko, Peter Hayes, Peter R. Mills, John F. Dillon, Esther Aspinall, Stephen T. Barclay,Sharon J. Hutchinson

Received 7 August 2013; received in revised form 20 January 2014; accepted 27 January 2014. published online 06 February 2014.
Accepted Manuscript

Abstract

Background & Aims

Given an appreciable risk of adverse-effects, current therapies for chronic hepatitis C virus (HCV) infection pose a dilemma to patients. We explored, via simulation modelling, patient-important benefits of attaining a Sustained Viral Response (SVR).

Methods

We created the HCV Individualised Treatment-decision model (the HIT-model) to simulate, on a per patient basis, the lifetime course of HCV-related liver disease according to two distinct scenarios: (i) SVR attained, and (ii) SVR not attained. Then, for each model subject, the course of liver disease under these alternative scenarios was compared. The benefit of SVR was considered in terms of two patient-important outcomes: (1) The percent-probability that SVR confers additional life-years; and (2) The percent-probability that SVR confers additional healthy life-years, where “healthy” refers to years spent in compensated disease states (i.e. the avoidance of liver failure).

Results

The benefit of SVR varied strikingly. It was lowest for patients aged 60 years with initially mild fibrosis; 1.6% (95% CI: 0.8-2.7) and 2.9% (95% CI: 1.5-4.7) probability of gaining life-years and healthy life-years, respectively. Whereas it was highest for patients with initially compensated cirrhosis aged 30 years; 57.9% (95%CI: 46.0-69.0) and 67.1% (95%CI: 54.1-78.2) probability of gaining life-years and healthy life-years, respectively.

Conclusions

For older patients with less advanced liver fibrosis, SVR is less likely to confer benefit when measured in terms of averting liver failure and premature death. These data have important implications. Foremost, it may inform the contemporary patient dilemma of immediate treatment with existing therapies (that have poor adverse effect profiles) versus awaiting future regimens that promise better tolerability.

Abbreviations: HCV, Hepatitis C Virus, SVR, Sustained Viral Response, HIT model, Hepatitis-C Individual-based Treatment-decision model,HCC, Hepatocellular Carcinoma, NSS, Number need to attain SVR, NNT, Number needed to treat, SA, Sensitivity Analysis

Keywords: Hepatitis C, Chronic Hepatitis C, Patient-centred, Patient-important outcomes, Markov model, Simulation model, Antiviral treatment,Adverse effects, Risk-benefit ratio

Source

The Relationship of Hepatitis C Virus Infection with Diabetes in the United States Population

Hepatology

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Original

Constance E. Ruhl M.D., Ph.D.1,*, Andy Menke Ph.D.1, Catherine C. Cowie Ph.D.2,  James E. Everhart M.D., M.P.H.2

DOI: 10.1002/hep.27047

Copyright © 2014 American Association for the Study of Liver Diseases

Publication History
Accepted manuscript online: 5 FEB 2014 10:25AM EST
Manuscript Accepted: 31 JAN 2014
Manuscript Revised: 5 DEC 2013
Manuscript Received: 20 SEP 2013

Keywords: insulin resistance; alanine aminotransferase;  gamma glutamyltransferase;  National Health and Nutrition Examination Survey;  epidemiology

ABSTRACT

An association of hepatitis C virus (HCV) infection with diabetes has been reported in many studies, but few have been population-based and applied standard criteria for diabetes diagnosis. We examined this relationship using recent population-based data from the U.S. National Health and Nutrition Examination Survey. 15,128 adult participants in the 1999-2010 surveys had data on diabetes status and serum HCV antibody (anti-HCV) or HCV RNA. Using American Diabetes Association criteria, diabetes was defined as a health care provider diagnosis, serum hemoglobin A1C (A1C) ≥6.5%, or fasting plasma glucose (FPG) ≥126 mg/dL; pre-diabetes as A1C 5.7%-<6.5% or FPG 100-<126 mg/dL; and normal glucose as A1C <5.7% and FPG <100 mg/dL. Odds ratios (OR) for diabetes and pre-diabetes, comparing persons with HCV infection to those without, were adjusted for demographics, BMI, C-reactive protein, smoking, drinking, and blood transfusion before 1992. Among participants without diabetes, we compared mean insulin resistance, estimated using homeostasis model assessment (HOMA-IR), by HCV status. The overall prevalence of anti-HCV+ was 1.7%, of HCV RNA+, 1.1%, of diabetes, 10.5%, and of pre-diabetes, 32.8%. The prevalence of diabetes and pre-diabetes did not differ by HCV status. In multivariate-adjusted analysis, diabetes remained unassociated with anti-HCV (OR=1.0, 95% confidence interval (CI), 0.6-1.7) or with HCV RNA (OR=1.1, 95% CI, 0.6-1.9). In contrast, elevated alanine aminotransferase and gamma glutamyltransferase activities were associated with diabetes regardless of HCV status. HOMA-IR was not associated with HCV markers in unadjusted or multivariate-adjusted analyses (p>0.05). Conclusion. In the U.S. population, HCV was not associated with diabetes, or with insulin resistance among persons with normal glucose. Previously reported relationships of HCV with diabetes were possibly attributable to the effect of elevated liver enzymes. (Hepatology 2014;)

Source

February 5, 2014

Injection behaviors among injection drug users in treatment: The role of hepatitis C awareness - Does HCV+ Awareness Among IDUs Reduce Needle Sharing

Provided by NATAP

Download the PDF here

Does HCV+ Awareness Among IDUs Reduce Needle Sharing? This study found NO - ."In adjusted analysis (Table 2), recent syringe/needle sharing was more likely among those who reported they were HCV-positive compared with those who were HCV negative/unaware (aOR 2.37 [95% CI 1.15, 4.88]), and among IDUs obtaining needles from the street, using any opioids, marijuana, or injected crack cocaine; sharing was less likely among males and participants with some college education......More HCV-positive IDUs reported recent syringe/needle sharing compared with those with HCV negative/unknown status (44.6% vs. 38.5%, p = .131), though this was not statistically significant"

from Jules: with the advent & revolution of new HCV oral & interferon-free therapy it will be important to provide education to at-risk patients about the risks for-re-infection with HCV. It is important to provide treatment to IDUs as persons but also for society. All too often now treatment for IDUs is withheld for a number of reasons including because IDUs are at risk for continuing risky behavior, sharing unclean needles & getting re-infected. Instead treatment for IDUs should be viewed as important for the patient, for prevention, ad for society & treatment should be viewed as an opportunity to provide education about preventing re-infection, why & how the patient should not be re-infected. Often this means addressing the patient's risky behavior, which could be sharing used/unclean syringes for the IDU or continued risky sexual & drug behavior for MSM. In recent studies in NYC & in London re-infection was cited among MSM due to continued unsafe drug & sex behavior, in fact re-infection was reported to occur 2-3 times after successful treatment for some individuals. In recent studies re-infection among IDUs has been found often. With treatment & cure of HCV comes a responsibility that these at-risk individuals, IDUs or a history of IDU, are educated not to be re-infected. Resources are scarce and should not be wasted particularly in the developing & undeveloped world but also in Europe, the USA & the Western world, its possible that retreatment may be denied by government or payers.

High incidence of hepatitis C virus reinfection within a cohort of injecting drug users - (10/13/13)

HCV Reinfection - (10/11/13)

HCV superinfection and reinfection - Review - (10/10/13)

HCV reinfection incidence and treatment outcome among HIV-positive MSM in London - (06/17/13)

---------------------------

Injection behaviors among injection drug users in treatment: The role of hepatitis C awareness

Highlights

->38.5% of 244 IDUs seeking treatment reported sharing needles/syringes. ->Only 46.9% of IDUs always used a sterile needle/syringe. ->37.7% of IDUs reported being HCV positive. ->HCV awareness was associated with increased risky injection behaviors. ->New HCV prevention interventions are needed for IDUs seeking treatment.

"one's belief about one's HCV status is conceptually more closely related to injection behaviors than biologically confirmed HCV status......IDUs may adopt more of a fatalistic attitude toward risky injection practices. Indeed, a recent synthesis of qualitative studies of HCV risk among IDUs identified risk ubiquity as a common theme, supporting a perception of HCV as "a risk accepted rather than avoided.....The observed multivariable association between knowledge of HCV status and syringe/needle sharing may reflect overall greater drug use severity among those who become HCV-infected rather than a causal pathway toward increased risky behaviors. Regardless, the association highlights the role of HCV awareness as a marker for IDUs in particular need of harm reduction interventions.....The observed association between HCV-awareness and increased needle/syringe sharing may reflect a complex cluster of characteristics among HCV-aware IDUs in this cross-sectional study. Our data support that HCV awareness is likely a marker for IDUs with greater addiction severity (e.g., increased heroin injection and methadone maintenance among HCV-aware), addiction duration (older age among HCV-aware), and increased opportunities for HCV testing (e.g., increased needle exchange program use among HCV-aware, many of which offer HCV testing)."

"Risky injection practices persist among IDUs, with rates in the current study consistent with those of other recent studies (Booth et al., 2011 and Centers for Disease Control and Prevention, 2009) and may partially explain persistently high HCV incidence among IDUs.......In adjusted analysis (Table 2), recent syringe/needle sharing was more likely among those who reported they were HCV-positive compared with those who were HCV negative/unaware (aOR 2.37 [95% CI 1.15, 4.88]), and among IDUs obtaining needles from the street, using any opioids, marijuana, or injected crack cocaine; sharing was less likely among males and participants with some college education......More HCV-positive IDUs reported recent syringe/needle sharing compared with those with HCV negative/unknown status (44.6% vs. 38.5%, p = .131), though this was not statistically significant......The majority of IDUs in the present study obtained needles from safe sources, including pharmacies and syringe exchange programs, as corroborated in surveys of IDUs in other U.S. cities with policies that increase availability of sterile needles and syringes......Despite this, fewer than half of IDUs reported always using a clean needle or consistently cleaning needles, indicating that needle re-use and lack of needle cleaning are common. Even among the minority of IDUs reporting consistent needle cleaning, sterilization techniques other than use of bleach were frequently employed, suggesting that renewed efforts are needed to promote harm reduction techniques among IDUs.......Participants who reported they were HCV positive differed in several important behaviors compared with their counterparts. HCV positive IDUs more frequently exhibited harm reduction behaviors such as obtaining needles from a syringe exchange program, cleaning needles with bleach, and avoiding drinking alcohol to intoxication, suggesting that awareness of HCV status may confer increased adoption of some protective behaviors. HCV positive IDUs, however, were also more likely to inject heroin and, in multivariable analysis, to share needles."

"This finding contrasts with a sero-survey of street-recruited IDUs in Denver from 1998 to 1999, where those with a previous HCV positive test reported less receptive syringe/needle sharing, sharing of drug paraphernalia, and safer injecting practices compared with those with unknown status who tested HCV-positive during the study (Kwiatkowski et al., 2002). It is possible that in populations where higher proportions of IDUs are aware they are HCV-positive, IDUs may adopt more of a fatalistic attitude toward risky injection practices. Indeed, a recent synthesis of qualitative studies of HCV risk among IDUs identified risk ubiquity as a common theme, supporting a perception of HCV as "a risk accepted rather than avoided" (Rhodes, Singer, Bourgois, Friedman, & Strathdee, 2005). This is consistent with findings from a multicenter study of Swedish IDUs, in which 74% of those HCV-aware shared needles compared with 68% of those with unknown status (Norden et al., 2009)."

Author's CONCLUSIONS: This study highlights the need for broadly implemented HCV prevention interventions for all IDUs seeking addiction treatment, and suggests such interventions might particularly decrease transmission behaviors by those aware of their HCV infection and prevent HCV infection in those HCV-negative/unaware. Research which prospectively studies the effect of HCV testing and notification on risk behavior could help further clarify the association between HCV awareness and risk behaviors. Interventions that could improve services for IDUs include those that explicitly and repeatedly educate IDUs about safer injection practices and the treatability of HCV, and those that integrate HCV testing and treatment with addiction treatment services. As HCV screening and treatment options advance, community based treatment programs have a greater opportunity to play a central role in reducing HCV transmission and engaging HCV-infected IDUs in treatment.

-------------------------------

Injection behaviors among injection drug users in treatment: The role of hepatitis C awareness

Addictive Behaviors April 2012

P. Todd Korthuis a,, Daniel J. Feaster b, Zoilyn L. Gomez b, Moupali Das c,d, Susan Tross e, Katharina Wiest f, Antoine Douaihy g, Raul N. Mandler h, James L. Sorensen c, Grant Colfax d, Dennis McCarty a, Stephanie E. Cohen d, Patricia E. Penn i, Diane Lape a, Lisa R. Metsch b
a Department of Medicine and Department of Public Health and Preventive Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
b Department of Epidemiology and Public Health, University of Miami Miller School of Medicine, 1425 Northwest 10th Ave, 3rd floor, Miami, FL 33136, USA c University of California, San Francisco, 1001 Potero Ave., San Francisco, CA 94110, USA
d San Francisco Department of Public Health, 356 7th St., San Francisco, CA 94103, USA
e HIV Center For Clinical and Behavioral Studies, NYS Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USA
f CODA, 1027 East Burnside St., Portland, OR 97214, USA
g University of Pittsburgh School of Medicine, 3811 O'Hara St # 1059, Pittsburgh, PA 15213, USA
h National Institute on Drug Abuse, National Institutes of Health, 6001 Executive Blvd., Bethesda, MD 20892, USA
i La Frontera Arizona, 504 W. 29th St., Tucson, AZ 85713, USA

Abstract

Background

Injection drug use (IDU) is a primary vector for blood-borne infections. Awareness of Hepatitis C virus (HCV) infection status may affect risky injection behaviors. This study determines the prevalence of risky injection practices and examines associations between awareness of positive HCV status and risky injection behaviors.

Methods

We surveyed individuals seeking treatment for substance use at 12 community treatment programs as part of a national HIV screening trial conducted within the National Drug Abuse Treatment Clinical Trials Network. Participants reported socio-demographic characteristics, substance use, risk behaviors, and HCV status. We used multivariable logistic regression to test associations between participant characteristics and syringe/needle sharing.

Results

The 1281 participants included 244 (19.0%) individuals who reported injecting drugs in the past 6 months and 37.7% of IDUs reported being HCV positive. During the six months preceding baseline assessment, the majority of IDUs reported obtaining sterile syringes from pharmacies (51.6%) or syringe exchange programs (25.0%), but fewer than half of IDUs always used a sterile syringe (46.9%). More than one-third (38.5%) shared syringe/needles with another injector in the past 6 months. Awareness of positive HCV vs. negative/unknown status was associated with increased recent syringe/needle sharing (aOR 2.37, 95% CI 1.15, 4.88) in multivariable analysis.

Conclusions

Risky injection behaviors remain prevalent and awareness of HCV infection was associated with increased risky injection behaviors. New approaches are needed to broadly implement HCV prevention interventions for IDUs seeking addiction treatment.

1. Introduction

Injection drug use (IDU) is the primary driver for Hepatitis C virus (HCV) transmission, accounting for the majority of chronic HCV infections in the U.S. (Alter, 1999 and Armstrong et al., 2006). Across multiple U.S. studies, 35-65% of current IDUs report risky injection behaviors such as syringe/needle sharing (Bailey et al., 2007, Booth et al., 1998, Centers for Disease Control and Prevention, 2009 and Golub et al., 2007).

Knowledge of harboring a transmissible infection such as HCV may influence risky behaviors. Prior studies of the effects of HCV-infection awareness on risky behaviors demonstrate mixed results. In a serosurvey of out-of-treatment IDUs, those who reported awareness of HCV-infection engaged in fewer risky behaviors compared with those who were unaware (Kwiatkowski, Fortuin Corsi, & Booth, 2002). HCV-aware IDUs may also "sero-sort," or preferentially engage in risky injection behaviors with others they know to be similarly HCV-infected (Burt, Thiede, & Hagan, 2009). Other studies, however, suggest that HCV awareness is insufficient to change injection risk behaviors (Norden et al., 2009). Little is known about the influence of HCV awareness on IDUs engaged in substance use treatment-information that might improve HCV prevention services in addiction treatment settings.

The purpose of this analysis was to 1) assess the prevalence and correlates of drug use practices among patients presenting for addiction treatment and 2) compare risky behaviors in those reporting HCV-infection with those who reported negative or unknown HCV status.

2. Methods

2.1. Design and setting

The primary study was a National Drug Abuse Treatment Clinical Trials Network (CTN) trial comparing the effectiveness of strategies to increase HIV testing (Metsch et al., in press). Between January and May 2009, the trial randomized 1281 individuals receiving addiction treatment at 12 geographically diverse, community-based addiction treatment programs. After providing informed consent, participants completed an audio computer assisted self interview recording substance use behaviors.

2.2. Participants

Participants receiving addiction treatment were eligible for enrollment if they were 1) ³ 18 years old, 2) reported unknown or negative HIV status, and 3) had not been tested and received results for HIV within the last 12 months. The current analysis was restricted to the 244 participants who reported IDU in the six months preceding the study baseline assessment.

2.3. Measures

Participants were asked about injection risk behaviors over the prior six months using items from Project Inspire (Purcell et al., 2004) and the NIDA Risk Behavior Assessment survey (Needle et al., 1995) including source of syringes, needle cleaning practices, how they cleaned their needles, and recent syringe/needle sharing (the main dependent variable). Participants reported injection and non-injection drug use and drinking alcohol to intoxication in the past 6 months (Colfax et al., 2004).

The independent variable was self-reported HCV infection awareness. Patients were asked, "Have you ever been diagnosed with hepatitis C (yes, no, don't know)?" Because there was no difference in syringe/needle sharing between participants who reported they were HCV-negative and those who did not know their HCV status, we dichotomized this variable as HCV-positive vs.

HCV-negative/unknown. Covariates included age, gender, race/ethnicity, employment, education, court-mandated treatment, opioid replacement treatment, and whether or not the patient had been jailed in the last 6 months.

2.4. Analysis

Descriptive statistics characterized participant socio-demographics, and substance use behaviors. We assessed bivariate and multivariable associations between participant characteristics and any syringe/needle sharing using logistic regression. Variables were included in the multivariable logistic regression model if associated with syringe/needle sharing in univariate analyses (p < .20), or on the basis of a priori hypotheses. Potential interactions were assessed.

3. Results

3.1. Participant characteristics

Of 244 recent IDUs, 60.7% were men, 66.0% white, 14.3% Hispanic, and 10.2% Black race/ethnicity, with a mean age of 39.3 (SD = 11.0) years. Twenty percent were employed, 36.2% had attained at least some college education, 30.3% had been recently incarcerated, 20.1% were receiving court-mandated treatment and 46.7% opioid replacement therapy. Ninety-two IDU (37.7%) reported being positive for HCV, 55 (22.5%) HCV-negative, and 97 (39.8%) unknown HCV status. Compared with those who were HCV negative/unaware, HCV positive IDUs were older (45.3 vs. 35.6 years, p < .001), more likely to be women (52.2% vs. 31.6%, p = .001) or enrolled in opioid replacement programs (68.5% vs. 33.6%, p < .001) and less likely to be recently incarcerated (21.7% vs. 35.5%, p = .023).

The most commonly used substances were injected opioids (71.17%), drinking alcohol to intoxication (70.9%), non-injection opioids (66.4%), marijuana (48.8%), crack cocaine (45.1%), and cocaine (30.7%). The majority of IDUs (81.1%) injected more than one substance at a time. HCV positive IDUs were less likely to drink alcohol to intoxication (57.6% vs. 78.9%, p < .001) but more likely to inject heroin (68.5% vs. 55.3%, p = .041) compared with HCV negative/unaware.

3.2. Injection risk behaviors

More than one third (38.5%) of IDUs reported syringe/needles sharing in the past 6 months (Table 1). IDUs obtained needles mostly from pharmacies, syringe exchange programs, and diabetic supplies. Less than half always used a clean needle. Among IDUs who cleaned their needles, cleaning with bleach was the most common method, but many used more ineffective sterilization methods including soap and water. More HCV-positive IDUs reported recent syringe/needle sharing compared with those with HCV negative/unknown status (44.6% vs. 38.5%, p = .131), though this was not statistically significant. There was no difference in recent syringe/needle sharing between those who reported being HCV negative vs. unknown status (36.4% vs. 34.0%, p = .771). HCV positive IDUs more frequently obtained needles from a syringe exchange program and used bleach if they cleaned needles.

In adjusted analysis (Table 2), recent syringe/needle sharing was more likely among those who reported they were HCV-positive compared with those who were HCV negative/unaware (aOR 2.37 [95% CI 1.15, 4.88]), and among IDUs obtaining needles from the street, using any opioids, marijuana, or injected crack cocaine; sharing was less likely among males and participants with some college education.

4. Discussion

Risky injection practices persist among IDUs, with rates in the current study consistent with those of other recent studies (Booth et al., 2011 and Centers for Disease Control and Prevention, 2009) and may partially explain persistently high HCV incidence among IDUs (Mehta et al., 2011). In a survey of IDUs in 23 U.S. cities from 2005 to 2006, 31.8% of IDUs reported sharing needles (Centers for Disease Control & Prevention, 2009). Among IDUs enrolling in a behavioral intervention trial (2-session HIV/HCV counseling vs. therapeutic alliance vs. treatment as usual) at residential detoxification centers from 2004 to 2006, 61% reported sharing needles, works, or drug solution (Booth et al., 2011). More widespread adoption of interventions demonstrated to reduce risky injection practices, and development of new, more effective interventions, are urgently needed for patients enrolling in community-based treatment programs.

The majority of IDUs in the present study obtained needles from safe sources, including pharmacies and syringe exchange programs, as corroborated in surveys of IDUs in other U.S. cities with policies that increase availability of sterile needles and syringes (Golub et al., 2005 and Khoshnood et al., 2000) - policies that decrease HIV transmission and likely decrease HCV transmission, as well (Des Jarlais et al., 1996 and Des Jarlais et al., 2000). Despite this, fewer than half of IDUs reported always using a clean needle or consistently cleaning needles, indicating that needle re-use and lack of needle cleaning are common. Even among the minority of IDUs reporting consistent needle cleaning, sterilization techniques other than use of bleach were frequently employed, suggesting that renewed efforts are needed to promote harm reduction techniques among IDUs. Interventions that promote needle cleaning such as peer-based (Hawkins et al., 1999 and Rietmeijer et al., 1996), pharmacy-based (Romanelli, Smith, & Pomeroy, 2000), and provider-based (Carlson, Wang, Siegal, & Falck, 1998) interventions, continue to be relevant for IDUs engaged in community-based treatment. At the same time, renewed efforts to increase availability of clean syringe/needles are urgently needed to decrease HCV transmission.

Participants who reported they were HCV positive differed in several important behaviors compared with their counterparts. HCV positive IDUs more frequently exhibited harm reduction behaviors such as obtaining needles from a syringe exchange program, cleaning needles with bleach, and avoiding drinking alcohol to intoxication, suggesting that awareness of HCV status may confer increased adoption of some protective behaviors. HCV positive IDUs, however, were also more likely to inject heroin and, in multivariable analysis, to share needles. The observed association between HCV-awareness and increased needle/syringe sharing may reflect a complex cluster of characteristics among HCV-aware IDUs in this cross-sectional study. Our data support that HCV awareness is likely a marker for IDUs with greater addiction severity (e.g., increased heroin injection and methadone maintenance among HCV-aware), addiction duration (older age among HCV-aware), and increased opportunities for HCV testing (e.g., increased needle exchange program use among HCV-aware, many of which offer HCV testing).

This finding contrasts with a sero-survey of street-recruited IDUs in Denver from 1998 to 1999, where those with a previous HCV positive test reported less receptive syringe/needle sharing, sharing of drug paraphernalia, and safer injecting practices compared with those with unknown status who tested HCV-positive during the study (Kwiatkowski et al., 2002). It is possible that in populations where higher proportions of IDUs are aware they are HCV-positive, IDUs may adopt more of a fatalistic attitude toward risky injection practices. Indeed, a recent synthesis of qualitative studies of HCV risk among IDUs identified risk ubiquity as a common theme, supporting a perception of HCV as "a risk accepted rather than avoided" (Rhodes, Singer, Bourgois, Friedman, & Strathdee, 2005). This is consistent with findings from a multicenter study of Swedish IDUs, in which 74% of those HCV-aware shared needles compared with 68% of those with unknown status (Norden et al., 2009).

The current study confirms the importance of certain demographic and drug use characteristics previously associated with syringe/needle sharing including younger age, female gender, lower educational attainment, and use of opiates, and crack cocaine. While greater addiction severity is associated with riskier injection behaviors, the current study is among the first to identify an association between marijuana use and risky injection behaviors. Marijuana use in IDUs may be a marker of risk-taking personality or chronically decreased motivation to protect oneself, as hypothesized to explain similar findings in a study of Russian IDUs (Walley et al., 2008). Further research is required to assess the nature of this association.

This study has limitations. First, our study population was recruited from individuals seeking or actively engaged in treatment in community-based treatment programs. Findings may not be generalizable to IDUs in other settings. Second, HCV status was assessed by self-report and likely underestimates the actual prevalence of HCV. However, one's belief about one's HCV status is conceptually more closely related to injection behaviors than biologically confirmed HCV status. Third, we were unable to assess sero-sorting in the current study, so increased sharing among HCV may have been with other known HCV-positive IDU, as was observed in one prior study (Burt et al., 2009). Finally, the current study's cross-sectional design limits our ability to infer causality. The observed multivariable association between knowledge of HCV status and syringe/needle sharing may reflect overall greater drug use severity among those who become HCV-infected rather than a causal pathway toward increased risky behaviors. Regardless, the association highlights the role of HCV awareness as a marker for IDUs in particular need of harm reduction interventions.

5. Conclusions

This study highlights the need for broadly implemented HCV prevention interventions for all IDUs seeking addiction treatment, and suggests such interventions might particularly decrease transmission behaviors by those aware of their HCV infection and prevent HCV infection in those HCV-negative/unaware. Research which prospectively studies the effect of HCV testing and notification on risk behavior could help further clarify the association between HCV awareness and risk behaviors. Interventions that could improve services for IDUs include those that explicitly and repeatedly educate IDUs about safer injection practices and the treatability of HCV, and those that integrate HCV testing and treatment with addiction treatment services. As HCV screening and treatment options advance, community based treatment programs have a greater opportunity to play a central role in reducing HCV transmission and engaging HCV-infected IDUs in treatment.

Role of funding source

This work was supported by the National Institute on Drug Abuse which supported the design, distribution, collection and analysis of the clinical trial. The final version of the manuscript was reviewed and approved by the NIDA Clinical Trials Network publications committee.

Source

Patient Advocate Foundation Announces Co-Pay Relief (CPR) Support for Patients Living with Hepatitis C

logo-prn-01_PRN

The launch of the CPR Silo for Hepatitis C Patients Will Provide Financial Assistance to Patients in Need

HAMPTON, Va., Feb. 5, 2014 /PRNewswire-USNewswire/ -- Patient Advocate Foundation (PAF) announced today the expansion of its Co-Pay Relief (CPR) program with the opening of the Hepatitis C disease silo. Supported through a generous donation of5 million dollars, this CPR program silo providers financial support for pharmaceutical co-payments for insured patients who are facing financial distress and are unable to afford their costs associated with treatment for the virus. "Management of Hepatitis C is extremely challenging for patients as most need ongoing medication to reduce their chance of liver damage or liver cancer.  It is in these cases that a patient's survival and overall health can be jeopardized if he or she is unable to access pharmaceutical treatment and therapies required to control the virus," said Alan Balch, PhD,  CEO of PAF. "We are grateful for the significant support we have received for the Hepatitis C silo which allows us to expand our Co-Pay Relief Program in such a meaningful way."  The donation allows PAF to provide financial support to Hepatitis C patients ensuring their access to the treatments that can restore balance to their health and markedly improve their quality of life.  Qualified patients whose applications are approved, are eligible for up to $3,000 per year in copayment assistance through the program.

PAF is a pioneer in the field of copayment support programs, providing more than $190 million in financial assistance to more than 95,000 patients who would have been otherwise unable to afford their pharmaceutical co-payments since 2004. The program provides this support to insured patients who financially and medically qualify including those covered by government sponsored insurance programs such as Medicare, Medicaid or Tricare.  

For more information about PAF's Co-Pay Relief program and the options for assistance for Hepatitis C patients, visit http://www.copays.org/diseases/hepatitis-c or call 866-512-3861.

About the Patient Advocate Foundation (PAF) Co-Pay Relief Program (CPR)

The Co-Pay Relief Program, a division of Patient Advocate Foundation, provides direct financial support for pharmaceutical co-payments to insured patients who financially and medically qualify.

The program offers innovative technology tools for patients, providers and pharmacy representatives including 24 hour web based application portals, electronic signature, document upload and bar code fax routing capabilities, increasing the speed with which an approval can be granted and expenditure can be paid.  Keeping with Patient Advocate Foundation's emphasis on patient-centric service, the program also offers individualized assistance to all patients through trained, professional staff who personally guide them through the enrollment process. 

For more information or to contact Patient Advocate Foundation's Co-Pay Relief program visit www.copays.org or 1-866-512-3861

SOURCE Patient Advocate Foundation

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February 4, 2014

Gilead Sciences' CEO Discusses Q4 2013 Results - Earnings Call Transcript

These are two very interesting excerpts from todays Earnings Conference Call. There was a lot of talk about Sovaldi as well other HCV drugs in trials. I have pulled 2 very interestiong quoted pieces from the call, the first concerning European pricing and the second concerning new Research and Development (R&D). I would encourage everyone to go to read the entire transcript which is available at Seeking Alpha. It is very informative as well as enlightening.

“I would like to talk a little bit about the rest of the pricing for Europe. We have now listed our price in the U.K. The price in the U.K. is almost UK35,000, so that’s about $57,000. And I think, as a benchmark for the majority of Europe, that would be a good price point for you going forward. So I’ll say that again. About UK35,000, this is the 12-week course of treatment, or about $57,000.

And I also mentioned the German pricing. The German pricing is almost EUR49,000, or $66,000. So Germany typically is a little bit higher. And my final comment on European pricing is just to say that these are significant differences to the telaprevir pricing. And the [unintelligible] that we’ve taken for Sovaldi, we believe, is very justified according to cost effectiveness data, and the premium is very comparable to the premium that we took on Sovaldi versus the original price of telaprevir in the United States.”

---------------------------------

“Thanks for asking an R&D question. I thought I was going to escape this call without having been asked one single question. So thank you very much. As you know, we have now succeeded with our ledipasvir/sofosbuvir fixed dose combination to actually incredibly shorten treatment duration to 8 weeks and 12 weeks and Sovaldi treatment experience with response rates that go up to 95% or higher.

But we’re not stopping there. This is, of course, for genotype 1. We have another fixed dose combination in development, 5816 combined with sofosbuvir. You will see some of those early data at EASL, and we’re still waiting for the treatment experienced cirrhotic genotype 3 cohort to make a decision or to feel really comfortable going into Phase III.

And then finally, as you know, we have efforts underway to shorten the treatment duration even further, to six weeks, by adding a third drug. So you know, all of those things are ongoing, and I think we will be competitive with our, you know, you can’t really do much more than having one single pill, once daily. Very safe, very well tolerated tablet, given for eight weeks and achieving response rates of 95%.”

Source Seeking Alpha

Read full transcript here …….

Alcohol-linked deaths a problem for the Americas

Elizabeth DeVita-Raebrun
Reuters
3:05 p.m. CST, February 4, 2014

NEW YORK (Reuters Health) - Liver disease and brain disorders due to alcohol abuse are important causes of premature death in the Americas, a new study concludes.

The toll of too much drinking is especially high among men and among middle-aged people, according to the report, whose authors say it's the first to tabulate deaths resulting solely from alcohol.

"This provides direct evidence of the impact of alcohol on the health of countries in the region," said one of the study's authors, Dr. Vilma Pinheiro Gawryszewski, an advisor on health information and analysis for the Pan American Health Organization(PAHO).

In the 16 North, Central, and South American countries studied, alcohol was the sole cause of 79,456 deaths a year, the researchers say. That represented 1.4 percent of deaths from all causes, and alcohol-related liver disease alone accounted for 0.6 percent of all-cause mortality.

The study was based on data collected between 2007 and 2009 for countries in the PAHO mortality database.

The researchers excluded deaths from vehicle accidents and other fatal situations where alcohol might have been involved but there could also have been other causes.

Looking just at deaths due directly to alcohol, they found 63 percent were from liver disease and 32 percent were from neurological and psychiatric conditions grouped under "degeneration of the brain and nervous system."

Other listed causes of death included alcohol poisoning, alcohol-linked heart and gastric problems and fetal alcohol syndrome.

The death toll is the "tip of the iceberg," meaning that there are probably many more alcohol-related deaths that the researchers were not able to identify, said another of the study's authors, Dr. Maristela Monteiro, regional advisor on alcohol and substance abuse at PAHO.

Monteiro said that raising the price of alcohol and increasing taxes would help to prevent some of these deaths. Many countries have found these steps effective in controlling tobacco use, but such measures have not been used to control alcohol consumption, she said.

Even the U.S., which was included in the study, has not done as much as it could, said David Jernigan, director of the Center on Alcohol Marketing and Youth at Johns Hopkins Bloomberg School of Public Health.

"The single most efficient thing you can do is to raise taxes," Jernigan told Reuters Health. "Many states haven't raised it in decades. That means the price doesn't go up with inflation, and alcohol gets cheaper every year."

And while the U.S. and other countries have limited tobacco advertising, alcohol advertising "is virtually everywhere," he said.

Mortality due to alcohol was highest in El Salvador, Guatemala and Nicaragua, with death rates of 27.4, 22.3 and 21.3 per 100,000 people, respectively. These were also the countries with the highest consumption of hard liquor, the authors noted.

Colombia, Argentina and Canada had the lowest death rates attributable to alcohol at 1.8, 4.0 and 5.7 per 100,000, respectively. The alcohol death rate in the United States was "intermediate," at 6.7 per 100,000, Monteiro said.

Men accounted for 84 percent of the deaths overall, but that proportion was not the same in all countries. The risk of a man dying from alcohol in El Salvador was nearly 30 times higher than that of a woman, but only about three times higher in Canada and the U.S.

People in the mid-to-late 50s and 60s age range were at the highest risk. This later in life risk, Jernigan said, points to the long-term impact of heavy drinking.

"Mostly in this country, we talk about alcohol and the risk for the young," in whom drunk driving, violence, and accidents are important causes of death, Jernigan said. "This really shows the impact over the life course."

Despite the grim statistics, Jernigan says studies like this one are a positive sign.

"On one hand, you could say, 'this is a huge problem, and not enough is being done.' On the other," he said, "you could say, 'we're getting better at documenting it and showing that, until we take meaningful action, it's not going to go away.'"

In poorer countries, other factors contributing to the deaths could include infectious diseases that hasten the course of liver disease, as well as poor nutrition and limited access to health services.

"In the U.S., people wouldn't wait until they were too sick for help to seek out services, because treatment is available," said Monteiro. That is not always the case, she said, in other countries.

Source: http://bit.ly/1enwJIT Addiction, online January 14, 2014.

Source

The Risk of Long-term Morbidity and Mortality in Patients With Chronic Hepatitis C

JAMA Internal Medicine

February 2014, Vol 174, No. 2

Original Investigation | February 2014

Results From an Analysis of Data From a Department of Veterans Affairs Clinical Registry

Jeffrey McCombs, PhD1; Tara Matsuda, BA1,2; Ivy Tonnu-Mihara, PharmD2; Sammy Saab, MD3; Patricia Hines, BA4; Gilbert L’Italien, PhD4; Timothy Juday, PhD4; Yong Yuan, PhD4

[+] Author Affiliations

JAMA Intern Med. 2014;174(2):204-212. doi:10.1001/jamainternmed.2013.12505.

Abstract

Importance The impact of viral load suppression, genotype, race, and other factors on the risk of late-stage liver-related events in patients with hepatitis C (HCV) has been assessed previously using data from small observational cohorts or clinical trials. Data from large real-world practice samples are needed to improve risk factor estimates for late-stage liver events and death in HCV.

Objective To describe the natural history of HCV in real-world clinical practice.

Design, Setting, and Participants Observational cohort study. Patients with a detectable viral load (>25 IU/mL) and a recorded baseline genotype were selected from the Veterans Affairs (VA) HCV clinical registry (CCR), which compiles electronic medical records data from 1999 to present.

Exposures Risk factors included genotype, race, age, sex, and time to achieving an observed undetected viral load.

Main Outcomes and Measures The primary outcomes were time to death and time to a composite of liver-related clinical events. Secondary outcomes included the components of the composite clinical outcome. Outcomes were measured using a time-to-event format and were analyzed using Cox proportional hazards models.

Results A total of 28 769 of 360 857 unique HCV CCR patients met all study criteria. Only 24.3% of patients received treatment, and 16.4% of treated patients (4.0% of all patients) achieved an undetectable viral load. The unadjusted death rates were 6.8 (95% CI, 6.0-7.7) per 1000 person-years for patients who achieved viral load suppression vs 21.8 (95% CI, 21.5-22.2) deaths per 1000 person-years in patients who did not achieve this goal. Cox model results found that achieving viral suppression reduced risk of the composite clinical end point by 27% (hazard ratio [HR], 0.73 [95% CI, 0.66-0.82]) and the risk of death by 45% (HR, 0.55 [95% CI, 0.47-0.64]). Genotype 2 patients were at significantly lower risk, and genotype 3 patients were at higher risk for all study outcomes relative to genotype 1. Black patients were at lower risk for all liver events than white patients.

Conclusion and Relevance Achieving an undetectable viral load was associated with decreased hepatic morbidity and mortality. It remains to be determined whether newer treatment regimens can offer higher response rates with fewer adverse effects in real-world settings.

Source

CIHR Canadian HIV Trials Network Coinfection and Concurrent Diseases Core: Canadian guidelines for management and treatment of HIV/hepatitis C coinfection in adults

Can J Infect Dis Med Microbiol. 2013 Winter;24(4):217-38.

Hull M1, Klein M2, Shafran S3, Tseng A4, Giguère P5, Côté P6, Poliquin M6, Cooper C7.

Abstract

BACKGROUND: Hepatitis C virus (HCV) coinfection occurs in 20% to 30% of Canadians living with HIV, and is responsible for a heavy burden of morbidity and mortality. HIV-HCV management is more complex due to the accelerated progression of liver disease, the timing and nature of antiretroviral and HCV therapy, mental health and addictions management, socioeconomic obstacles and drug-drug interactions between new HCV direct-acting antiviral therapies and antiretroviral regimens.

OBJECTIVE: To develop national standards for the management of HCV-HIV coinfected adults in the Canadian context.

METHODS: A panel with specific clinical expertise in HIV-HCV co-infection was convened by The CIHR HIV Trials Network to review current literature, existing guidelines and protocols. Following broad solicitation for input, consensus recommendations were approved by the working group, and were characterized using a Class (benefit verses harm) and Level (strength of certainty) quality-of-evidence scale.

RESULTS: All HIV-HCV coinfected individuals should be assessed for HCV therapy. Individuals unable to initiate HCV therapy should initiate antiretroviral therapy to slow liver disease progression. Standard of care for genotype 1 is pegylated interferon and weight-based ribavirin dosing plus an HCV protease inhibitor; traditional dual therapy for 24 weeks (for genotype 2/3 with virological clearance at week 4); or 48 weeks (for genotypes 2-6). Therapy deferral for individuals with mild liver disease may be considered. HIV should not be considered a barrier to liver transplantation in coinfected patients.

DISCUSSION: Recommendations may not supersede individual clinical judgement.

KEYWORDS: Antivirals, Direct-acting antivirals, HCV, HIV, Pharmacokinetics

PMID: 24489565 [PubMed]

Source

How heroin kills you

By Jen Christensen, CNN
updated 11:05 AM EST, Tue February 4, 2014

(CNN) -- The autopsy results aren't in yet, but police believe heroin played a role in the death of Academy Award winning actor Philip Seymour Hoffman -- if not the primary role.

Using heroin can kill you, but it may not be in the way you think. If Hoffman did die from using heroin, his death was atypical in some aspects. Here's how heroin kills.

The numbers

Drug overdose deaths in the United States have risen steadily since 1970. Painkillers actually kill more Americans than heroin and cocaine combined, according to the Centers for Disease Control, but heroin is still one of the No. 1 killers of illegal drug users. Only one in 10 heroin overdoses ends in death.

Overdose deaths from heroin have increased recently, and heroin use is also on the rise. In 2011, 4.2 million Americans over the age of 11 had tried heroin at least once, according to the National Institute on Drug Abuse.

An estimated 23% of them will become addicts. And it's addicts who die more frequently than new users, studies show.

How heroin works

Heroin is most often mixed with water and injected. Injecting it minimizes the lag time between when the drug is taken and effects are felt -- with injection, the effects are almost immediate.

It can also be smoked, snorted or eaten, but smoking or eating destroys some of the drug and mutes its effects.

When someone takes heroin there is an immediate rush. Then the body feels an extreme form of relaxation and a decreased sense of pain.

What's happening inside the body is the heroin is turning into morphine. Morphine has a chemical structure similar to endorphins -- the chemicals your brain makes when you feel stressed out or are in pain. Endorphins inhibit your neurons from firing, so they halt pain and create a good feeling.

Morphine, acting like your endorphins, binds to molecules in your brain called opioid receptors. When those receptors are blocked, that creates a high.

Why you die

Most people die from heroin overdoses when their bodies forget to breathe.

"Heroin makes someone calm and a little bit sleepy, but if you take too much then you can fall asleep, and when you are asleep your respiratory drive shuts down," said Dr. Karen Drexler, director of the addiction psychiatry residency training program and an associate professor in Emory University's psychiatry and behavioral sciences department.

"Usually when you are sleeping, your body naturally remembers to breathe. In the case of a heroin overdose, you fall asleep and essentially your body forgets."

A heroin overdose can also cause your blood pressure to dip significantly and cause your heart to fail.

Studies show intravenous heroin users are 300 times more likely to die from infectious endocarditis, an infection of the surface of the heart.

Heroin use can also cause an arrhythmia -- a problem with the rate or rhythm of the heartbeat. During an arrhythmia, the heart may not be able to pump enough blood to the body, and lack of blood flow affects your brain, heart and other organs.

Heroin use can also cause pulmonary edema. That's when the heart can't pump blood to the body well. The blood can back up into your veins, taking that blood through your lungs and to the left side of the heart.

As pressure in the blood vessels increases and fluid goes into the alveoli, the air spaces in the lungs, this reduces the normal flow of oxygen through your lungs, making it hard to breathe. This too can give you a heart attack or lead to kidney failure.

Heroin can also come with other toxic contaminants that can harm a user -- although deaths from such instances, while not unheard of, are thought to be rare.

Studies suggest instantaneous death -- like what may have happened in Hoffman's case -- is unusual. The actor was found dead on his bathroom floor with a needle sticking out of his left arm, authorities have said.

Such deaths, where a needle and syringe are still in place, would be considered instant by scientists. One study showed this accounts for only 14% of heroin-related deaths.

Heroin deaths increase when...

There are some common social characteristics in heroin deaths that would make Hoffman more of a typical case. Most fatalities involve men, particularly those who have struggled with other drugs or alcohol (he admitted to this in the past) and other drugs or alcohol are often present.

While many are single (Hoffman had a partner), most users die in their homes and/or in the company of another person.

An addict does have a much higher chance of dying if he or she leaves treatment. The risk of death is higher for newly clean heroin addicts. A number of fatalities appear to happen after periods of reduced use, one 2000 study showed.

In fact, long-term users who die from overdoses are likely to have heroin levels no higher than those who survive.

That may be in part because those who are newly clean don't know how much of the drug to give themselves any more, Drexler said. They won't need the same amount to get high as when they were using more regularly.

There are also some studies that show tolerance to the respiratory depressive effects of opiates increases at a slower rate than tolerance to the euphoric and analgesic effects. As your tolerance to the drug develops, you typically need more of it to produce the high you are used to getting. This may be why long-term users are potentially at greater risk of overdose than novices.

Statistics suggest that newer heroin users aren't the ones most likely to die. One study showed only 17% of the deaths studied were in new heroin users.

However, Drexler said newer users can overdose because they don't know how much drug to take, compared to experienced users. "I think it is misleading to say you would not die if you only use it once or twice," she said.

A person's chances of dying from heroin use increase dramatically after 20 years of use. Studies show that after 30 years of use, 16% of heroin users have died, compared with 6.5% of cocaine users and 1.5% of meth users.

Source

AbbVie hep. C combo wows in hard-to-treat

Provided by MM&M

KEVIN MCCAFFREY

FEBRUARY 03, 2014

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AbbVie unveiled Phase-III trial results for its multi-drug hep. C regimen Friday, and the all-oral regimen looks impressive. Up to 99% of genotype-1b, treatment-naive patients taking the cocktail achieved SVR12 (sustained virologic response, or cure, at 12 weeks). And up to 96% of cirrhotic patients, or those with liver scarring and poor liver function, reached SVR after a three-month course of the regimen, which consists of ABT-450/r + -267 + -333.

Some specialists might find value in using a regimen like AbbVie's for their cirrhotic patients, but the question is how they compare against those offered up last December by Gilead for its HCV fixed-dose oral therapy. Gilead's two-drug all-oral regimen, which pairs recently approved antiviral Sovaldi with the experimental drug ledipasvir and ribavirin (RBV), saw 97% SVR12 in the treatment-naïve, while 94% of those in the same population got to SVR12 taking a RBV-free regimen.

Gilead has yet to break down how effective its regimen is in cirrhotic patients, but ISI Group analyst Mark Schoenebaum, in an investor note Friday, estimated the lower boundary to be around 95% SVR12 rate with and without ribavirin, based on other trial data.

While AbbVie's regimen showed strong efficacy, and demonstrated it in what has been the largest Phase-III program of an all-oral, interferon-free therapy for HCV GT1 patients to date, Schoenebaum—in another investor note from Friday—shared concerns that it may fall short when compared to Gilead's fixed-dose combo and that AbbVie's results were “right in-line with Street expectations.”

“Gilead's regimen continues to have potential commercial advantages on multiple points,” he wrote. Of those competitive advantages, Schoenebaum cited the Gilead regimen's lower pill burden (one pill daily vs. AbbVie's expected four to six), a potential for shorter duration (8 weeks vs. 12 weeks) and a possibly larger population to cater to that includes GT1-naïve patients, as well as a lack of ribavirin, which can lead to anemia.

Gilead's combo also stands to hit pharmacy shelves before the competition. The Foster City, CA, drugmaker said it will file within the first quarter of this year. AbbVie confirmed, along with Friday's data, that it won't file its regimen with regulators until the early part of the second quarter of this year.

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Also See: Abbvie completes largest phase III program of an all-oral, interferon-free therapy for the treatment of hepatitis C genotype 1

Video: Efficacy of an Interferon- and Ribavirin-Free Regimen of Daclatasvir, Asunaprevir, and BMS-791325 in Treatment-Naive Patients With HCV Genotype 1 Infection

Published on Jan 15, 2014

Dr. Gregory T. Everson discusses his manuscript "Efficacy of an Interferon- and Ribavirin-Free Regimen of Daclatasvir, Asunaprevir, and BMS-791325 in Treatment-Naive Patients With HCV Genotype 1 Infection." To view abstract http://bit.ly/1astcIL.

Also See: Efficacy of an Interferon- and Ribavirin-Free Regimen of Daclatasvir, Asunaprevir, and BMS-791325 in Treatment-Naive Patients With HCV Genotype 1 Infection – Full Text

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BPA Exposure in Womb Linked with Liver Tumors

Provided by Nature World News

By Staff Reporter Feb 03, 2014 06:13 AM EST

mice

mice exposed to BPA have high risk of liver tumors. (not pictured) (Photo : REUTERS/Asmaa Waguih)

University of Michigan School of Public Health researchers found liver tumors in mice whose mothers were exposed to the chemical BPA.

Bisphenol A or BPA is a chemical used in plastics and epoxy resins. The chemical is found in many products including water bottles, cups and impact resistant material. Compact discs Epoxy resin is used to coat metal products such as food cans, bottles and cup.

Previous research has shown that BPA can affect fertility in animals. A related study on mice had linked the chemical with prostate cancer in the rodents.

The study shows a direct link between BPA and cancer. The mice in the study were exposed to the chemical during gestation and nursing.

For the study, researchers fed female mice with food containing BPA. These mice were then allowed to mate and were given one of three chemical doses (50 µg, or 50 mg of BPA per kg diet) during gestation and nursing.

The scientists then followed one male and female mouse from each litter and tracked their growth for ten months.

They found that mice whose mothers were exposed to 50 mg of BPA per kg diet had seven times higher risk of developing liver tumor than other non-exposed mice.

"We found that 27 percent of the mice exposed to one of three different doses of BPA through their mother's diet developed liver tumors and some precancerous lesions. The higher the dosage, the more likely they were to present with tumors," said Caren Weinhouse, U-M doctoral student in the School of Public Health's Department of Environmental Health Sciences and first author of the paper, according to a news release.

Also, researchers found that BPA didn't discriminate between male and female. "In general, females are at lower risk of spontaneous development of liver cancer," she said in a news release. "That distinction was erased in this study, with both males and females showing tumors."

The study is published in the journal Environmental Health Perspectives.

Source

Liver disease and diabetes: Association, pathophysiology, and management

Diabetes Res Clin Pract. 2014 Jan 14. pii: S0168-8227(14)00005-9. doi: 10.1016/j.diabres.2014.01.003. [Epub ahead of print]

Ahmadieh H1, Azar ST2.

Abstract

Diabetes is associated with a spectrum of liver diseases including nonalcoholic liver disease, steatohepatitis, and liver cirrhosis with their increased complications and mortality. Hepatitis C virus (HCV) and its associated liver cirrhosis has been associated with diabetes through insulin resistance. Cryptogenic diabetes occurs as a consequence of liver cirrhosis with the pathophysiology being complex, but mostly attributed to the increased insulin resistance in muscle, liver, and adipose tissue. As for the management of diabetes in patients with liver disease, lifestyle modification plays an important role. Oral diabetic medications are contraindicated in patients with advanced liver diseases with associated cirrhosis, ascites, or encephalopathy. As for stable liver disease, metformin and thiazolenediones have shown mixed results, with some showing them to be effective in improving liver transaminases in addition to histological improvement in steatosis and inflammation. α-glucosidase inhibitors may be helpful in decreasing hepatic encephalopathy. Upregulation of Dipeptidyl peptidase-4 (DPP-4) has been suggested as a possible pathogenetic mechanism for HCV-related insulin resistance, and treatment with DPP-4 inhibitors could improve insulin sensitivity in diabetic patients with liver disease. Patients with impaired liver function with associated insulin resistance may need increased insulin requirements. On the other hand patients with altered liver metabolism might need decreased insulin requirements.

Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

KEYWORDS: Diabetes mellitus, liver disease, liver transaminases, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis

PMID: 24485856 [PubMed - as supplied by publisher]

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