February 12, 2014

Hepatology

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

Original Article

J. Vergniol1, J. Boursier2,4, C. Coutzac1,  S. Bertrais4, J. Foucher1, C. Angel2, F. Chermak1, I. Fouchard Hubert2,4, W. Merrouche1, F. Oberti2,4, V. de Lédinghen1,3, P. Calès2,4

DOI: 10.1002/hep.27069

Copyright © 2014 American Association for the Study of Liver Diseases

Publication History
Accepted manuscript online: 12 FEB 2014 05:58AM EST
Manuscript Accepted: 6 FEB 2014
Manuscript Revised: 25 JAN 2014
Manuscript Received: 29 SEP 2013

Keywords: hepatitis C;  survival;  prognosis;  fibrosis;  cirrhosis;  liver stiffness;  FibroScan;  blood fibrosis test

Abstract

Introduction: No data are available about the prediction of long-term survival using repeated non-invasive tests of liver fibrosis in chronic hepatitis C (CHC). We aimed to assess the prognostic value of 3-year liver stiffness measurement (LSM), APRI, and FIB-4 evolution in CHC.

Patients and methods: CHC patients with two LSM (1000-1500 days interval) were prospectively included. Blood fibrosis tests APRI and FIB-4 were calculated the day of baseline (bLSM) and follow-up (fLSM) LSM. Evolution of fibrosis tests was expressed as delta: (follow-up-baseline results)/duration. Date and cause of death were recorded during follow-up that started the day of fLSM.

Results: 1025 patients were included. Median follow-up after fLSM was 38.0 months (IQR: 27.7-46.1) during which 35 patients died (14 liver-related death) and 7 had liver transplantation. Prognostic accuracy (Harrell C-index) of multivariate models including baseline and delta results was not significantly different between LSM and FIB-4 (p≥0.24) whereas FIB-4 provided more accurate prognostic models than APRI (p=0.03). By multivariate analysis including LSM variables, overall survival was independently predicted by bLSM, delta (dLSM), and SVR. Prognosis was excellent in patients having bLSM <7 kPa, SVR, or no increase (<1 kPa/year) in 7-14 kPa bLSM. Prognosis was significantly impaired in patients with increase (≥1 kPa/year) in 7-14 kPa bLSM, or decrease (≤0 kPa/year) in ≥14 kPa bLSM (p=0.949 between these two groups). Patients with increase (>0 kPa/year) in ≥14 kPa bLSM had the worst prognosis. Baseline and delta FIB-4 also identified patient subgroups with significant different prognosis.

Conclusion: Three-year evolution of non-invasive tests of liver fibrosis has a strong prognostic value in CHC patients. These tests should be repeated to monitor patients and predict their outcome. (Hepatology 2014;)

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The global AIDS response can help in fighting hepatitis C

By Paul Farmer, Wednesday, February 12, 8:08 PM

Paul Farmer is a professor at Harvard University and an infectious disease physician with the Brigham and Women’s Hospital in Boston. He co-founded Partners in Health.

A decade after the global AIDS response began in earnest, it’s worth asking whether the lessons learned will be sustained over time and used to avoid past mistakes when tackling new challenges.

One such challenge is chronic hepatitis C infection, which afflicts an estimated 170 million people worldwide. Since its discovery 25 years ago, hepatitis C has become the leading indication for liver transplant in the United States and a common cause of liver failure around the world. For some, however, it is about to become eminently curable.

When I trained as an infectious disease physician in the mid-1990s, I traveled frequently between Boston’s teaching hospitals and rural Haiti. AIDS had become a leading cause of death in both places but was rapidly declining in Boston while soaring in Haiti, as it was across Africa.

This divergence was thrown into relief at a 1996 AIDS conference where researchers presented data showing that combination antiretroviral therapy could transform HIV infection from a death sentence into a manageable chronic disease. The conference’s theme that year was “One World, One Hope.” A coalition of activists, noting the $15,000 annual cost of the lifesaving drugs and the lack of an international plan for ensuring access among those living in poverty, held up their own signs reading “One World, No Hope.”

By 2000, more than 6 million people were dying in poor countries each year from HIV, tuberculosis and malaria — diseases for which effective therapeutics were available to those who could afford them. Here was a failure not of science but of delivery.

Thankfully, and in no small part because of the relentless efforts of AIDS activists, an abiding cynicism about the limits of an international response to these pandemics gave way to an unprecedented “delivery decade.” This was inaugurated in the early 2000s with the U.S. President’s Emergency Plan for AIDS Relief and the Global Fund to Fight AIDS, Tuberculosis and Malaria.

As I recounted in the New England Journal of Medicine in December, linking this funding to effective delivery mechanisms had profound effects in some of the world’s poorest and most disrupted places. By the end of 2012, almost 10 million patients in low- and middle-income countries were on antiretroviral therapy. In Haiti and Rwanda, AIDS-related mortality rates fell more sharply than in the United States after its introduction of antiretroviral therapy in the mid-1990s.

Despite such progress, much remains to be done. Nearly half of all people living with HIV who need treatment still don’t receive it. But the coupling of an equity plan with a commitment to building effective delivery systems surely ranks among the most important achievements in the history of medicine and public health.

Today, the world faces a “1996 moment” in the fight against hepatitis C.

As in 1996, highly effective new therapies are coming online. Regimens containing the new polymerase inhibitor sofosbuvir, in particular, have the potential to cure more than 90 percent of patients with common strains of the virus after just 12 to 24 weeks of once-daily pills. But is there a plan that can link funding to delivery for those living in poverty?

Sofosbuvir’s initial price has been set at $80,000 to $90,000 per 12-week course — about $1,000 per pill. Like those infected with HIV, 90 percent of hepatitis C patients live in low- and middle-income countries ; most would not earn $80,000 over the course of two lifetimes.

In the face of such numbers, it is tempting to give in to pessimism. “Poor countries could never afford these prices; the demand simply isn’t there,” some say. But when the share of those infected with hepatitis C reaches 1 in 40 people alive today, claims of weak demand are not credible. Such language is often code for ability to pay, not actual burden of disease. In many years practicing medicine, I have yet to meet a patient — rich or poor — with a treatable disease who doesn’t want to get better.

Drug prices are not immutable, and price is not the same as cost. Pharmacologists with Liverpool University recently analyzed manufacturing processes for new hepatitis C regimens and concluded that they could be sold at profit in poor countries for less than $500 per course. A recent pledge by Gilead, the developer of sofosbuvir, to work with generic pharmaceutical firms in India is a promising start, but it is just a start.

Precipitous drops in price are not unprecedented; in the delivery decade, innovative partnerships through financing mechanisms such as UNITAID led to declines of as much as 99 percent in the effective price of antiretroviral therapy for the world’s poorest.

Smart investments in accurate diagnosis and in effective therapy for hepatitis C could save millions of lives in the coming years, radically cut transmission and pave the way toward eradication of the virus. Or, we could choose to ignore the lessons of the AIDS response and stand by as outcomes improve solely among the fortunate few who enjoy ready access to the fruits of modern medicine. Divergence of outcomes occurs within nations and across them; they grow whenever innovation is not coupled with implementation among the most vulnerable.

But we live in one world. As infectious pathogens such as HIV and hepatitis remind us, our hopes are tied together more closely than we might imagine.

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Presented at CDDW

Tags: Hepatitis, ribavirin, sofosbuvir

By Thomas S. May

TORONTO -- February 11, 2014 -- A 24-week course of ribavirin plus sofosbuvir resulted in sustained virologic response rates 12 weeks after treatment (SVR12) in over 90% of treatment-naïve patients with hepatitis C virus (HCV) genotype 3.

The findings were presented here on February 10 at Canadian Digestive Diseases Week 2014 (CDDW) by Josée Brisebois, MD, Gilead Sciences Canada, Mississauga, Ontario.

Analysis of the data from the phase 3 VALENCE trial also indicated that the dual regimen of sofosbuvir and ribavirin yielded high SVR rates in treatment-experienced patients with HCV genotype 3 without cirrhosis and in patients with genotype 2 after 12 weeks of treatment.

In the VALENCE study, treatment-naïve or treatment-experienced patients with HCV genotype 2 or 3 were randomised 4:1 to receive sofosbuvir (400 mg/day) plus ribavirin (1,000 or 1,200 mg/day) or placebo for a period of 12 weeks. The trial was subsequently amended to extend treatment duration to 24 weeks for patients with HCV genotype 3, due to emerging data suggesting that these patients would benefit from longer treatment.

The current analysis included a total of 419 patients: 73 with HCV genotype 2, 261 with genotype 3 -- including 11 treated for 12 weeks before the protocol change -- and 85 patients with genotype 2 or genotype 3 who received placebo. Approximately 60% of the participants had been treated previously for HCV but were either null-responders or prior relapsers.

Results showed that a high percentage of patients responded to treatment in both arms. SVR12 was achieved by 68 of 73 (93%) of those with HCV genotype 2 after 12 weeks of treatment, while 212 of 250 (85%) of those with genotype 3 disease achieved SVR12 following 24 weeks of treatment.

Patients with HCV genotype 2 had high response rates regardless of previous treatment status and cirrhosis status with 12 weeks of sofosbuvir/ribavirin. SVR12 rates were 97% for treatment-naïve patients without cirrhosis, 100% for treatment-naïve patients with cirrhosis, 91% for treatment-experienced patients without cirrhosis, and 88% for treatment-experienced patients with cirrhosis.

Treatment with sofosbuvir plus ribavirin was generally safe and well tolerated, with headache and fatigue being the most frequently occurring adverse events. The investigators also noted that no additional adverse events were associated with the extension of treatment from 12 weeks to 24 weeks.

Funding for this study was provided by Gilead Sciences Inc.

Canadian Digestive Diseases Week 2014 is presented by the Canadian Association of Gastroenterology (CAG) and the Canadian Association for the Study of the Liver (CASL).

[Presentation title: Sofosbuvir Plus Ribavirin for 12 or 24 Weeks for Patients With HCV Genotype 2 or 3: The Valence Trial. Abstract A340]

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Vasc Health Risk Manag. 2014 Jan 21;10:55-62. doi: 10.2147/VHRM.S53557. eCollection 2014.

Roed T1, Kristoffersen US2, Knudsen A3, Wiinberg N4, Lebech AM1, Almdal T5, Thomsen RW6, Kjær A2, Weis N7.

Abstract

OBJECTIVE: Chronic hepatitis C is a global health problem and has been associated with coronary artery disease. Our aim was to examine the prevalence of coronary artery disease risk markers including endothelial biomarkers in patients with chronic hepatitis C and matched comparisons without manifest cardiovascular disease or diabetes in a cross-sectional design.

METHODS: Sixty patients with chronic hepatitis C (mean age 51 years) were recruited from the Department of Infectious Diseases at Copenhagen University Hospital, and compared with 60 age-matched non-hepatitis C virus-infected individuals from a general population survey. We examined traditional coronary artery disease risk factors, metabolic syndrome, carotid intima media thickness, and a range of endothelial biomarkers.

RESULTS: Patients with chronic hepatitis C had more hypertension (40% versus 25%, prevalence ratio [PR] 1.6; 95% confidence interval [CI] 0.9-2.7) and smoked more (53% versus 38%, PR 1.4; 95% CI 0.9-2.1). The two groups had similar body mass index (mean 25.0 versus 25.7 kg/m(2)), whereas those with chronic hepatitis C had less dyslipidemia (including significantly lower low-density lipoprotein and cholesterol/high-density lipoprotein ratio), higher glycosylated hemoglobin level (mean 6.2 versus 5.7, difference of means 0.5; 95% CI 0.3-0.8), and a higher prevalence of metabolic syndrome (28% versus 18%, PR 1.6; 95% CI 0.8-3.0). Increased carotid intima media thickness above the standard 75th percentile was seen more frequently in chronic hepatitis C (9% versus 3%, PR 1.7; 95% CI 0.4-6.7), though difference of means was only 0.04 mm (95% CI 0.00-0.10). Patients with chronic hepatitis C had increased hsCRP (high-sensitivity C-reactive protein), sICAM-1 (soluble intercellular adhesion molecule-1), sVCAM-1 (soluble vascular cell adhesion molecule-1), and soluble E-selectin, but lower levels of tPAI-1 (tissue-type plasminogen activator inhibitor-1), MMP9 (matrix metallopeptidase 9), and MPO (myeloperoxidase) than their comparisons.

CONCLUSION: Our findings indicate that patients with chronic hepatitis C have increased prevalence of several coronary artery disease risk markers. These results may be important when evaluating the appropriateness of screening for coronary artery disease and its risk factors in chronic hepatitis C.

KEYWORDS: atherosclerosis, biomarkers, endothelial dysfunction, intima media thickness, metabolic syndrome, risk factors

PMID: 24482574 [PubMed - in process] PMCID: PMC3905100

Source

Am J Gastroenterol. 2014 Feb 11. doi: 10.1038/ajg.2014.11. [Epub ahead of print]

Altekruse SF1, Henley SJ2, Cucinelli JE3, McGlynn KA4.

Abstract

OBJECTIVES:The objectives were to describe Surveillance, Epidemiology and End Results (SEER) hepatocellular carcinoma (HCC) incidence trends and the US liver cancer mortality trends by geography, age, race/ethnicity, and gender.METHODS:HCC incidence data from SEER 18 registries and liver cancer mortality data from the National Center for Health Statistics were analyzed. Rates and joinpoint trends were calculated by demographic subgroup. State-level liver cancer mortality rates and trends were mapped.RESULTS:HCC incidence rates in SEER registries did not significantly increase during 2007-2010; however, the US liver cancer mortality rates did increase. HCC incidence and liver cancer mortality rates increased among black, Hispanic, and white men aged 50+ years and decreased among 35-49-year-old men in all racial/ethnic groups including Asians/Pacific Islanders. Significantly increasing incidence and mortality rates among women were restricted to blacks, Hispanics, and whites aged 50+ years. Asian/Pacific Islander liver cancer mortality rates decreased during 2000-2010 with decreasing rates among women aged 50-64 years and men aged 35-49 years and stable rates in other groups. During 2006-2010, among individuals 50-64 years of age, blacks and Hispanics had higher incidence and mortality rates than Asians/Pacific Islanders. Liver cancer mortality rates were highest in Louisiana, Mississippi, Texas, and Washington, DC.CONCLUSIONS:Decreasing HCC incidence and liver cancer mortality rates among Asians/Pacific Islanders, men aged 35-49 years, and the nonsignificant increase in overall HCC incidence rates suggest that the peak of the epidemic may be near or have passed. Findings of geographic variation in mortality rates can inform control efforts.Am J Gastroenterol advance online publication, 11 February 2014; doi:10.1038/ajg.2014.11.

PMID: 24513805 [PubMed - as supplied by publisher]

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Wednesday, Feb 12th drug pricing protests target Gilead over price of Sovaldi, its new Hepatitis C drug: $84,000 for a twelve week supply—or $1,000 per pill!

  • New York City Protest—12pm to 1pm, Leerink Swann Global Healthcare Conference, Waldorf Astoria Hotel, 301 Park Ave, NY, NY 10022
  • San Francisco Protest March—12pm to 1pm, March from SF City Hall to the Federal Building

February 12, 2014 08:00 AM Eastern Standard Time

NEW YORK--(BUSINESS WIRE)--Advocates from AIDS Healthcare Foundation (AHF), the nation’s largest HIV/AIDS nonprofit medical provider, is spearheading two protests in New York City and San Francisco on Wednesday February 12th at 12 noon in each city targeting Gilead Sciences over the price of Sovaldi (sofosbuvir), its new Hepatitis C drug. The drug, which was approved by the Food and Drug Administration (FDA) in early December, was immediately priced by Gilead at $84,000 Wholesale Acquisition Cost (WAC) for a twelve-week supply of the drug—or $1,000 per pill.

       
     
WHAT:
NEW YORK DRUG PRICING PROTEST/Gilead Sciences’ $1K Hepatitis pill
 
WHEN:
WEDNESDAY, Feb. 12, 2014
     
12:00 – 1:00pm EASTERN Time
 
WHERE:
Leerink Swann Global Healthcare Conf., Waldorf Astoria Hotel, 301 Park Ave, NYC 10022
 
WHO:
Jessica Reinhart, Senior Grassroots Community Manager, AHF
Michael Camacho, MPH, NYC Regional Director, AHF
And 15-20 drug pricing advocates & protesters with “Gilead-Outrage!” banners, signs and face masks
 
NY CONTACT:
     
Jessica Reinhart, Senior Grassroots Community Manager, AHF +1 (323) 203-6146.
 
WHAT:
SAN FRANCISCO DRUG PRICING PROTEST MARCH/Gilead Sciences’ $1K pill
 
WHEN:
WEDNESDAY, Feb. 12, 2014
12:00 – 1:00pm PACIFIC Time
 
WHERE:
Marching FROM:
San Francisco CITY HALL, 1 Dr. Carlton B. Goodlett Place, S.F., CA 94102
Marching TO:
San Francisco FEDERAL BUILDING, 90 7th Street (corner Mission & 7th) S. F., CA 94103
 
WHO:
Jesse Brooks, Regional Advocacy Consultant
Dale R. Gluth, Bay Area Regional Director, AHF
And 15-20 drug pricing advocates & protesters with “Gilead-Outrage!” banners, signs and face masks
 
SF CONTACT:
     
Jesse Brooks, Regional Advocacy Consultant (510) 575-8245.
 

“Gilead’s $84,000 drug Sovaldi is only one portion of a two drug, twelve-week combination treatment for Hepatitis C, which affects and estimated 3.2 million people in the United States. The two-drug combo pushes treatment to well over $100,000 per patient—a price point that is simply not sustainable,” said Jessica Reinhart, Senior Grassroots Community Manager, for AHF, in anticipation of the New York protest held during the Leerink Swann Global Healthcare Conference at the Waldorf Astoria Wednesday February 12th. “Gilead’s history of predatory pricing on its lifesaving medications—first on its HIV drugs, and now, for this new hepatitis medication—sets the stage for protests like ours as well as for direct action from government officials and drug purchasers for government programs seeking to compel Gilead to cut its outrageous pricing. We also want to let the financial industry know that we are not going to simply stand by and watch this price gouging.”

“In addition to protesting the pricing of Sovaldi, our protests will serve as a reminder of Gilead’s previous bad deeds in its pricing and policies,” said Dale R. Gluth, Bay Area Regional Director for AHF in anticipation of the San Francisco protest march from City Hall to the Federal Building set for Wednesday February 12th. “In late 2012, within days of FDA-approval of Gilead’s four-in-one AIDS treatment combination Stribild, the company immediately priced that treatment at $28,500 per patient, per year, Wholesale Acquisition Cost (WAC)—a whopping 37% more than the price of Gilead’s best-selling three-in-one AIDS treatment, Atripla. For the record, $28,500 is more than most U.S. AIDS patients earn in any given year!”

“For Gilead, we have outrage, pure and simple,” said Michael Weinstein, President of AIDS Healthcare Foundation. “There can be no better example of the unbridled greed of the pharmaceutical industry than Gilead’s latest move: pricing its new hepatitis drug at $28,000 per 28-tablet bottle or $1,000 per pill! Gilead’s predatory pricing of Sovaldi is a direct threat to public heath, and it sets the stage for legislators and advocates to demand that officials who purchase drugs for government programs like Medicaid, Medicare and the AIDS Drug Assistance Programs act decisively to rein in pricing and protect patient access to lifesaving medications.”

Gilead did not even pay to research and develop Sovaldi. In 2011—for $11 billion in cash—it purchased Pharmasset, the company that had already developed the drug. Advocates now believe the pricing of Sovaldi is being driven by Gilead’s desire to recoup its financial investment in Pharmasset, and assumes it can accomplish this by charging Medicaid and other taxpayer-funded programs whatever it wants.

AIDS Healthcare Foundation (AHF), the largest global AIDS organization, currently provides medical care and/or services to more than 282,000 individuals in 32 countries worldwide in the US, Africa, Latin America/Caribbean, the Asia/Pacific Region and Eastern Europe. To learn more about AHF, please visit our website: www.aidshealth.org, find us on Facebook: www.facebook.com/aidshealth and follow us on Twitter: @aidshealthcare

Contacts

NEW YORK
AIDS Healthcare Foundation
Jessica Reinhart
Sr. Grassroots Community Mgr.
Cell: +1-323-203-6146
Jessica.reinhart@aidshealth.org
or
SAN FRANCISCO
AIDS Healthcare Foundation
Jesse Brooks
Regional Advocacy Consultant
Cell +1-510-575-8245
Jesse.brooks@aidshealth.org
pr
LOS ANGELES
AIDS Healthcare Foundation
Ged Kenslea
Senior Director, Communications
+1-323-308-1833 [work] +1-323-791-5526 [cell]
gedk@aidshealth.org

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