Wednesday, November 30, 2016

Acetaminophen, supplements and other medications may trigger drug-induced liver injury

Acetaminophen, supplements and other medications may trigger drug-induced liver injury

Figure 1:
Risk factors for development of drug-induced liver injury (DILI).
Original art: graphic art created by Roger Yoder Iconic Images, provided by PresenterMedia.

Download Full Text Article @ AACN Advanced Critical Care

More than 1,000 medications, with acetaminophen being the most common, have been associated with drug-induced liver injury (DILI).

Diagnosis can be challenging due to the multitude of contributing factors, and timely recognition and clinical response may mean the difference between recovery and acute liver failure or even death.

DILI affects an estimated fewer than 10 people in every 10,000 exposed persons. The condition is dose-dependent or an adverse reaction to a medication, dietary supplement or other substance.

An article in the current issue of AACN Advanced Critical Care, "Drug-Induced Liver Injury," discusses the clinical impact of DILI and reviews the medications that most frequently cause it.

The article is co-authored by Leslie Hamilton, PharmD, BCPS, BCCCP, associate professor of clinical pharmacy in the College of Pharmacy at University of Tennessee Health Science Center, Knoxville; Angela Collins-Yoder, RN, PhD, CCNS, ACNS-BC, clinical professor, University of Alabama Capstone College of Nursing, Tuscaloosa, and critical care nurse specialist, Sacred Heart Pensacola Hospital, Pensacola, Florida; and Rachel E. Collins, BA, Auburn University Harrison School of Pharmacy, Auburn, Alabama.

"The liver helps remove toxins, which makes it especially vulnerable to injury from either short-term intake above recommended levels or long-term usage that allows toxins to build up," Collins-Yoder said. "Recognizing the clinical signs and symptoms is crucial to prompt treatment and effective patient care." Depending on the contributing factors and the level of damage to the liver, patients with mild and moderate signs and symptoms may recover normal liver function after the triggering substance is identified and use is discontinued. Other patients may experience more severe damage, progressing to acute liver failure.

About 46 percent of persons with acute liver failure in the United States have liver damage associated with acetaminophen, making it the most common cause of DILI. Since acetaminophen is often an ingredient in over-the-counter and prescription pain medications, patients may take higher doses than needed.

A more infrequent type of DILI is triggered by an adverse reaction to prescription medications, herbal dietary supplements or other substances, including:

• Nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, naproxen and others

• Antibiotics and antiviral agencies, such as amoxicillin-clavulanate, sulfamethoxazole-trimethoprim and nitrofurantoin

• Antileptic agents, such as volproic acid and carbamazepine

• Statins

• Novel anticoagulants

• Proton pump inhibitors

• Methotrexate

• Azathioprine

• Sulfasalazine

• Herbal and dietary supplements

The article follows a presentation by the authors at the National Teaching Institute and Critical Care Exposition, the annual conference of the American Association of Critical-Care Nurses (AACN), which publishes the journal.

Story Source:
Materials provided by American Association of Critical-Care Nurses (AACN). Note: Content may be edited for style and length.

Journal Reference:
L. A. Hamilton, A. Collins-Yoder, R. E. Collins. Drug-Induced Liver Injury. AACN Advanced Critical Care, 2016; 27 (4): 430 DOI: 10.4037/aacnacc2016953

Nanotechnology a 'green' approach to treating liver cancer

Nanotechnology a 'green' approach to treating liver cancer

Minimally invasive procedure targets, destroys precancerous cells in mice
University of Missouri-Columbia

According to the American Cancer Society, more than 700,000 new cases of liver cancer are diagnosed worldwide each year. Currently, the only cure for the disease is to surgically remove the cancerous part of the liver or transplant the entire organ. However, an international study led by University of Missouri School of Medicine researchers has proven that a new minimally invasive approach targets and destroys precancerous tumor cells in the livers of mice and in vitro human cells.

"The limitations when treating most forms of cancer involve collateral damage to healthy cells near tumor sites," said Kattesh Katti, Ph.D., Curators' Professor of Radiology and Physics at the MU School of Medicine and lead author of the study. "For more than a decade we have studied the use of nanotechnology to test whether targeted treatments would reduce or eliminate damage to nearby healthy cells. Of particular interest has been the use of green nanotechnology approaches pioneered here at MU that use natural chemical compounds from plants."

The study was conducted in the United States and Egypt, and it involved the use of gold nanoparticles encapsulated by a protective stabilizer called gum Arabic. The nanoparticles were introduced to the livers of mice intravenously and were heated with a laser through a process known as photothermal therapy.

"Gum Arabic is a natural gum made of the hardened sap from acacia trees," said Katti, who also serves as director of the MU Institute of Green Nanotechnology and is the Margaret Proctor Mulligan Distinguished Professor of Medical Research at the MU School of Medicine. "It is FDA-approved for human consumption and is primarily used in the food industry as an additive. It also promotes adhesion of gold nanoparticles engineered to attract to precancerous and malignant cells - which are much more susceptible to lower levels of heat than healthy cells. Once the nanoparticles travel and adhere to cancerous cells, they are heated to a temperature that destroys them but leaves healthy tissue unaffected."

Katti's team studied a total of 224 mice. Half were identified as having precancerous cells in their livers. The other half had normal liver tissue. Outside of the control group, the mice received either an intravenous injection of gum Arabic alone or gum Arabic-encapsulated gold nanoparticles with or without laser therapy.

"The administration of gum Arabic, gold nanoparticles and photothermal therapy caused no change to healthy tissue, which confirmed the safe use of these treatments," Katti said. "However, the use of gum Arabic-encapsulated nanoparticles combined with photothermal therapy resulted in the targeted eradication of the precancerous cells and their genetic code in both our mice model and the human in vitro cell model we developed for this study."

Katti said the next step for further developing the technique into a cancer treatment for humans will be a clinical trial.

"The components for this new therapy are inexpensive, do not have any issues associated with a shelf-life and are easy to produce," Katti said. "Most importantly, it does not involve the use of harsh chemotherapy drugs or radiation. It is a 'green' approach that also may lead to successful treatment of other forms of cancer."

The study, "Photothermal Therapy Mediated by Gum Arabic-conjugated Gold Nanoparticles Suppresses Liver Preneoplastic Lesions in Mice," recently was published in the Journal of Photochemistry and Photobiology B: Biology. Co-authors from the research group include Menka Khoobchandani, Ph.D.; Sagar Gupta, Ph.D.; Kavita Katti, Ph.D.; and Ravi Shukla, Ph.D. Support for the study was provided by the MU School of Medicine, the MU Interdisciplinary Intercampus Research Program and the National Research Centre in Cairo, Egypt.

About the MU School of Medicine
The MU School of Medicine has improved health, education and research in Missouri and beyond for more than 165 years. MU physicians treat patients from every county in the state, and more Missouri physicians received their medical degrees from MU than from any other university. For more information, visit

IMAGE: Kattesh Katti, Ph.D., Curators' Professor of Radiology and Physics at the MU School of Medicine and lead author of the study.
Credit: Justin Kelley, MU Health

VIDEO: Don’t be surprised by weight gain in men after HCV cure

VIDEO: Don’t be surprised by weight gain in men after HCV cure
Publish date: November 15, 2016
By: Kari Oakes Frontline Medical News

– In the new era of direct-acting antiviral (DAA) therapy, physicians will be seeing more and more patients who have achieved a cure of their hepatitis C virus (HCV). Once freed from the burden of a chronic illness, patients feel better and may eat better. Unexpected weight gain and potential associated health effects may be the next set of challenges patients and their physicians will face.

A single-center retrospective study of patients who had achieved sustained virologic response (SVR) after treatment for HCV found a small but significant weight gain in men, but not women. Additionally, according to noninvasive assessments, liver fat increased significantly in men, but not women, after SVR was achieved

View the article and video, here.

Simeprevir in combination with sofosbuvir in treatment-naïve and -experienced patients with hepatitis C virus genotype 4 infection: a Phase III, open-label, single-arm study (PLUTO)

Simeprevir in combination with sofosbuvir in treatment-naïve and -experienced patients with hepatitis C virus genotype 4 infection: a Phase III, open-label, single-arm study (PLUTO)

Authors M. Buti, J. L. Calleja, S. Lens, M. Diago, E. Ortega, J. Crespo, R. Planas, M. Romero-Gómez, F. G. Rodríguez, J. M. Pascasio, B. Fevery, D. Kurland, C. Corbett, R. Kalmeijer, W. Jessner

First published: 29 November 2016
Full publication history DOI: 10.1111/apt.13883

Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis and subsequent hepatocellular carcinoma. HCV genotype 4 is found widely in the Middle East, Egypt and Africa, and has also spread into Europe. There are limited data available regarding the use of direct-acting antiviral agents in HCV genotype 4-infected patients with cirrhosis.

The Phase III, open-label, single-arm PLUTO study evaluated the efficacy and safety of 12 weeks of simeprevir (HCV NS3/4A protease inhibitor) plus sofosbuvir (HCV nucleotide-analogue NS5B polymerase inhibitor) in treatment-naïve and (peg)interferon ± ribavirin-experienced HCV genotype 4-infected patients, with or without compensated cirrhosis.

Adult patients with chronic HCV genotype 4 infection received simeprevir 150 mg once-daily and sofosbuvir 400 mg once-daily for 12 weeks. The primary efficacy endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12). Safety was also assessed.

Forty patients received treatment; the majority were male (73%) and treatment-experienced (68%). Overall, 7/40 (18%) patients had compensated cirrhosis. All patients achieved SVR12 [100% (Clopper-Pearson 95% confidence interval: 91–100%)]. Adverse events, all Grade 1 or 2, were reported in 20/40 (50%) patients. No serious adverse events were reported and no patients discontinued study treatment. Grade 3 treatment-emergent laboratory abnormalities were noted in 2/40 (5%) patients.

Treatment with simeprevir plus sofosbuvir for 12 weeks resulted in SVR12 rates of 100% in treatment-naïve and -experienced patients with HCV genotype 4 infection with or without compensated cirrhosis, and was well tolerated. [NCT02250807]

Discussion Only
View full text article online, here.

Treatment for 12 weeks with simeprevir in combination with sofosbuvir resulted in an SVR rate of 100% (40/40 patients) in HCV genotype 4-infected treatment-naïve and -experienced patients with and without compensated cirrhosis in the PLUTO study.

Although patient numbers were small for subgroups, all patients achieved SVR12 regardless of fibrosis stage [7/40 (18%) of patients had compensated cirrhosis], IL28B genotype or prior treatment history. It has been previously reported that IL28B genotype is strongly associated with SVR in patients with HCV genotype 4 infection receiving treatment with PR;[14] however, the results of this study demonstrate that simeprevir in combination with sofosbuvir was effective regardless of IL28B genotype. As expected, the NS3 Q80K polymorphism was not observed in this HCV genotype 4-infected population.

The results of this study provide support for the clinical effectiveness of simeprevir in combination with sofosbuvir for the treatment of HCV genotype 4 infection in treatment-naïve and -experienced patients with and without compensated cirrhosis. The 100% SVR12 rate in this study is complemented by the Phase IIa OSIRIS study, which investigated 12 weeks of simeprevir plus sofosbuvir in HCV genotype 4-infected patients in Egypt, and reported an SVR12 rate of 100% (43/43 patients) regardless of prior treatment history or fibrosis stage [23/43 (53%) patients had cirrhosis].[15] In contrast, the PLUTO study investigated simeprevir plus sofosbuvir in a predominantly Caucasian HCV genotype 4-infected population.

The results of this study are comparable with those of the Phase III OPTIMIST-1 study in HCV genotype 1-infected patients without cirrhosis treated with simeprevir plus sofosbuvir for 12 weeks [97% (150/155) achieved SVR12],[12] and improve upon those of the Phase III OPTIMIST-2 study in patients with cirrhosis treated with simeprevir plus sofosbuvir for 12 weeks [83% (86/103) achieved SVR12].[13] Of note, a limited number of patients with cirrhosis were included in the PLUTO study.

Real-world evidence has also highlighted 12 weeks of this treatment combination as a simple, effective and well-tolerated IFN-free regimen. Treatment-naïve and -experienced patients in a study in Egypt that included patients with cirrhosis, reported an SVR4 rate of 96% (207/215 patients).[16] In a study in Qatar, 100% (17/17) of HCV genotype 4-infected patients with cirrhosis achieved SVR12.[17] Similar results have also been reported in a study in Belgium, with 100% (23/23) of HCV genotype 4-infected patients with cirrhosis, treated with or without ribavirin, achieving HCV RNA below the lower limit of quantification at Week 12 of treatment.[18]

Similar results were observed in an open-label study that assessed the combination of sofosbuvir and ledipasvir for 12 weeks in HCV genotype 4-infected patients, reporting an SVR12 rate of 93% (41/44 patients).[19] In contrast, a lower SVR12 rate of 78% (14/18 patients) was reported in HCV genotype 4-infected patients treated with sofosbuvir and ledipasvir plus ribavirin for 12 weeks.[20] Furthermore, the treatment combination of 12 weeks of ritonavir-boosted paritaprevir and ombitasvir (without dasabuvir), with and without ribavirin, resulted in SVR12 rates of 100% (42/42) and 91% (40/44), respectively, for HCV genotype 4-infected treatment-naїve patients without cirrhosis in the Phase IIb PEARL study.[21] Ritonavir-boosted paritaprevir and ombitasvir with ribavirin for 12 weeks has also shown favourable results in HCV genotype 4-infected patients with compensated cirrhosis in the AGATE-1 study, in which SVR12 rates of 97% (57/59 patients) were reported.[22] Another DAA treatment combination, grazoprevir in combination with elbasvir without ribavirin, was studied in the Phase 3 C-EDGE study, in which treatment-naïve and -experienced patients with HCV genotype 4 infection achieved SVR12 rates of 100% (18/18 patients) and 78% (7/9 patients), respectively, with 12 weeks of treatment.[23-25]

The safety and tolerability of DAAs has previously been described in detail. Whilst DAAs have drastically reduced side effects when compared with IFN-containing regimens, subgroup-specific contraindications and safety-related limitations are being studied further.[26] Notably, in this study, the 2-DAA regimen of simeprevir plus sofosbuvir was safe and well-tolerated, with all AEs Grade 1 or 2. Of the treatment-emergent laboratory abnormalities, no Grade 3 or 4 increases in AST, ALT or bilirubin were noted. The safety profile seen in this study is in-line with the OPTIMIST-1 and -2 studies.[12, 13]

Strengths of the PLUTO study included the short 12-week IFN-free treatment regimen without ribavirin. The benefits of ribavirin-free regimens have been further highlighted in a recent article comparing patient-reported outcomes data from multicentre, multinational, Phase 3 studies of sofosbuvir with and without IFN and ribavirin. In a multivariate analysis, the use of ribavirin was independently associated with −9.0% worsening of the patient-reported outcome scores, and ribavirin-free regimens were associated with better patient experience and work productivity during treatment.[27]

Limitations of the PLUTO study included the limited sample size overall and in the subgroups, including patients with cirrhosis, and therefore the results of this study must be interpreted with caution. Due to the small number of patients with cirrhosis, the proportions of patients with albumin <40 g/L and platelets <90 × 109/L were limited and the use of this regimen in patients with advanced liver disease was not investigated. In addition, the patient population was predominantly Caucasian and therefore the results need to be confirmed in the HCV genotype 4-infected populations in many countries. The open-label nature of the study and the lack of a comparator arm could formally be viewed as potential limitations; however, the US Food and Drug Administration draft guidance, and guidance from the European Medicines Agency, include historical-controlled trials as one of the accepted Phase 3 study designs.[28-30]

In conclusion, the combination of simeprevir and sofosbuvir for 12 weeks resulted in a 100% SVR12 rate and was well-tolerated (with no Grade 3/4 AEs or treatment discontinuations reported) by treatment-naïve and treatment-experienced patients with chronic HCV genotype 4 infection, regardless of fibrosis stage or prior treatment history. These data are encouraging with respect to the potential use of this regimen in this patient population

Materials and methods

New Zealanders with Hepatitis C are turning to generic, legally-imported treatments

NZers turn to generic Hepatitis C meds

New Zealanders with Hepatitis C are turning to generic, legally-imported treatments that cure the virus and give sufferers a new lease on life.

Ms Heal has genotype 3 Hepatitis C, and was told last year she could fund her own treatment for about $115,000.

She found she could buy the medication she needed through an Australian doctor for a fraction of the price - just a little over $2000 per treatment.

The medications produced in India and made available through the FixHepC Buyers Club, set up by Tasmanian GP Dr James Freeman, have drastically improved Ms Heal's - and other New Zealanders' - quality of life.

Continue Reading...

Tuesday, November 29, 2016

What’s Important to the Patient? Informational Needs of Patients Making Decisions About Hepatitis C Treatment


First Online: 23 November 2016
DOI: 10.1007/s40271-016-0207-7

What’s Important to the Patient? Informational Needs of Patients Making Decisions About Hepatitis C Treatment

Donna M. Evon1 • Carol E. Golin2 • Teodora Stoica1 • Rachel E. Jones1 • Sarah J. Willis3 • Joseph Galanko1 • Michael W. Fried1

Full Text

Background and Objectives

Multiple treatment options with direct-acting antivirals are now available for hepatitis C virus (HCV). Study aims were to understand (1) the informational topics patients want to have to make informed treatment decisions; (2) the importance patients place on each topic; and (3) the topics patients prioritize as most important.


We used a mixed-methods study of two samples recruited from an academic liver center. Participants were not currently on treatment. Sample I (n = 45) free listed all informational topics deemed important to decision making. Raw responses were coded into several broad and subcategories. Sample II (n = 38) rated the importance of the subcategories from Sample I and ranked their highest priorities on two surveys, one containing topics for which sufficient research existed to inform patients (‘static’), and the other containing topics that would require additional research.


The topics listed by Sample I fell into six broad categories with 17 total subcategories. The most oft-cited informational topics were harms of treatment (100%), treatment benefits (62%), and treatment regimen details (84%). Sample II rated 16 of 17 subcategories as “pretty important’ or “extremely important”. Sample II prioritized (1) viral cure, (2) long-term survival, and (3) side effects on the survey of topics requiring additional research, and (1) liver disease, (2) lifestyle changes, and (3) medication details on the second survey of the most important static topics patients needed.


Patients weighed several informational topics to make an informed decision about HCV treatment. These findings lay the groundwork for future patient-centered outcomes research in HCV and patient-provider communication to enhance patients’ informed decision making regarding direct-acting antiviral treatment options.

Key Points for Decision Makers
Patients contemplating hepatitis C virus treatment want a great deal of information to make informed treatment decisions.

The most commonly cited informational topics included treatment harms such as side effects, treatment benefits such as viral cure, details of the treatment regimen, details about the virus, liver disease, and the risks of not receiving treatment.

The most important topics that require additional investigation were information about viral cure, long-term survival, and treatment side effects. The most important topics for which we have sufficient information that can be shared with patients include liver disease, lifestyle changes needed for treatment, and details about the medications and treatment protocol.

Continue To Full Text Article - Download PDF

Full Text Articles @ Henry E. Chang
I highly suggest you follow Henry E. Chang on Twitter if you are interested in reading full text articles about the treatment and management of hepatitis C.

Three anti-HCV regimens “highly effective” in achieving SVR

Three anti-HCV regimens “highly effective” in achieving SVR

A comparison of three different anti-HCV regimens concluded that all of them appeared highly effective in achieving sustained virologic response (SVR).

A study at the University of Southern California compared the SVR rates achieved 12 weeks post-treatment in 11,464 patients treated with three such agents by the Veterans Health Administration.

Without controlling for other risk factors, a SVR at least 12 weeks post treatment was achieved in 92% of ledipasvir/ sofosbuvir, 86% of ombitasvir/paritaprevir/ritonavir/dasabuvir, and 83% of simeprevir/sofosbuvir patients.

After adjusting for patient characteristics, simeprevir/sofosbuvir (93.3%) and ledipasvir/sofosbuvir (96.2%) patients were statistically more likely than ombitasvir/paritaprevir/ritonavir/dasabuvir (91.8%) patients to demonstrate a SVR.

HIV, HBV, diabetes, obesity, previous treatment history and augmentation therapy using ribavirin did not impact the SVR rates. Sustained SVR rates were lower for patients under age 65, with cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, indications of fibrosis or a non-genotype 1 infection. Women and Caucasian patients were more likely to achieve a SVR.

Comparative treatment effectiveness of direct acting antiviral regimens for hepatitis C: data from the Veterans Administration. Fox DS, McGinnis JJ, Tonnu-Mihara I et al. J Gastroenterol Hepatol. 2016 Nov 21 [Epub ahead of print]

DAA treatment restricted for Canadian hepatitis C patients

DAA treatment restricted for Canadian hepatitis C patients
By Mark L. Fuerst

Patients infected by hepatitis C virus (HCV) in Canada have limited access to direct-acting antiviral (DAA) agents, according to a new study.

“There are many new DAAs, marketed by different pharmaceutical companies. We studied reimbursement practices for simeprevir, sofosbuvir, ledipasvir-sofosbuvir and paritaprevir-ritonavir-ombitasvir plus dasabuvir.

We found that 85% to 92% of the provinces and territories in Canada restrict access to these medications to persons with moderate fibrosis,” lead author Alison Marshall from the Kirby Institute at the University of New South Wales—Australia, told Medical Economics.

Marshall and colleagues reviewed the reimbursement criteria for those DAAs in Canada’s 10 provinces and three territories. Although Canada's 10 provinces and three territories are collectively governed by the Canada Health Act, every jurisdiction administers its own health plan.

Monday, November 28, 2016

Hepatitis C Virus Infection and Rheumatic Diseases - The Impact of Direct-Acting Antiviral Agents

Rheum Dis Clin N Am - (2016) -–
February 2017 Volume 43, Issue 1, Pages 123–132

Hepatitis C Virus Infection and Rheumatic Diseases
The Impact of Direct-Acting Antiviral Agents

Patrice Cacoub MD, Cloé Commarmond MD, David Sadoun MD, PhD, Anne Claire Desbois MD


Hepatitis C virus infection is associated with many extrahepatic manifestations, including rheumatic disorders such as arthralgia, myalgia, cryoglobulinemia vasculitis, and sicca syndrome.

The treatment of hepatitis C virus infection has long been based on interferon alfa, which was contraindicated in many autoimmune/inflammatory disorders.

The emergence of new oral interferon-free combinations now offers an opportunity for patients infected with hepatitis C virus with extrahepatic manifestations, including autoimmune/inflammatory disorders, to be cured with a short treatment duration and a low risk of side effects

Full Text

Janssen has initiated phase IIb study of simeprevir, odalasvir and AL-335

Medivir announces that Janssen has initiated an open-label phase IIb study of the 3DAA combination of simeprevir, odalasvir and AL-335 (JNJ-4178)

November 28, 2016 02:51 AM Eastern Standard Time


Medivir AB (STO:MVIRB) today announces that a phase IIb open-label study of the combination of simeprevir, odalasvir and AL-335, also known as JNJ-4178, has been initiated by Janssen Research & Development, LLC., part of the Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen), in treatment-naive and treatment-experienced subjects with chronic hepatitis C virus infection without cirrhosis. This global, multi-center study includes clinical trial sites in North America, Europe and Asia and forms part of Janssen’s global development program for JNJ-4178.

The objectives of the phase IIb study are to investigate the efficacy, safety and pharmacokinetics of JNJ-4178/ AL-335 (800mg QD), odalasvir (25mg QD), and simeprevir (75mg QD) in treatment-naive and treatment-experienced non-cirrhotic subjects with chronic hepatitis C virus genotype 1, 2, 4, 5, and 6 infection.

Patients in the study will receive the triple combination for either six or eight weeks, and the primary efficacy endpoint will be the percentage of patients with a sustained virological response 12 weeks after the end of treatment (SVR12).

An ongoing phase IIa study is assessing the same triple combination in patients with or without compensated cirrhosis.

Further information on the trial planning and conduct can be found on with identifier NCT02765490.

Medivir is required under the Securities Markets Act to make the information in this press release public.

The information was submitted for publication at 8.30 CET on 28 November 2016.

About Medivir

Medivir is a research based pharmaceutical company with a research focus on oncology and infectious diseases. We have a leading competence within protease inhibitor design and nucleotide/nucleoside science and we are dedicated to develop innovative pharmaceuticals that meet great unmet medical need. Our commercial organization provides a portfolio of specialty care pharmaceuticals on the Nordic market. Medivir is listed on the Nasdaq Stockholm Mid Cap List.

This information was brought to you by Cision

Mylan to produce and market a generic version of Bristol-Myers Squibb's DAKLINZA™ (daclatasvir) for low and middle income countries

Mylan Signs Sub-license Agreement with the Medicines Patent Pool to Increase Access to Hepatitis C Treatment in Developing Countries

HERTFORDSHIRE, England and BENGALURU, India, Nov. 28, 2016 /PRNewswire/ -- Mylan N.V. (NASDAQ, TASE: MYL) today announced that the company has signed an agreement with the Medicines Patent Pool (MPP) to expand access to chronic hepatitis C medicines in developing countries. The agreement licenses Mylan to produce and market a generic version of Bristol-Myers Squibb's DAKLINZA™ (daclatasvir) Tablets, 30 mg and 60 mg, for distribution in 112 low and middle income countries.

Daclatasvir Tablets, 30 mg and 60 mg, are indicated for use with sofosbuvir, with or without ribavirin, for the treatment of patients with chronic hepatitis C virus (HCV) genotype 1 or genotype 3 infection in the U.S. and genotype 1, 3 and 4 in Europe. The license allows Mylan to develop fixed-dose combinations that offer the potential to treat all of the six major genotypes of HCV. Earlier this year, the World Health Organization added several new hepatitis C treatments, including daclatasvir, to its essential medicines list, highlighting the urgent need to promote equitable access to innovative medicines1.

Commenting on today's announcement, Mylan President Rajiv Malik said, "We're committed at Mylan to reducing the burden of hepatitis C on communities around the world by providing access to high quality medicines that treat the disease. We are pleased to work together with the MPP and Bristol-Myers Squibb to help make daclatasvir available to low and middle income countries at affordable prices."

Globally, 130 to 150 million people have chronic hepatitis C infection2 and the vast majority live in low and middle income countries3


Thursday, November 24, 2016

Wednesday, November 23, 2016

Settlement reached on state Medicaid denial of pricy hep C drugs

Settlement reached on state Medicaid denial of pricy hep C drugs

The Health Care Authority on Monday reached a settlement agreement in a class action lawsuit that sought broader coverage of costly hepatitis C drugs for Medicaid patients in Washington state.

The settlement has yet to be approved by a judge but lawyers are hopeful it will be soon.

In the past several years, multiple pharmaceutical companies nationwide have developed direct-acting antiviral drugs that cure hepatitis C in more than 90 percent of patients. But the drugs are extremely expensive - for example, Harvoni, introduced in 2014, has a list price of $1,100 a day, or $94,500 for a 12-week course. (After automatic drug rebates and other discounts, Medicaid pays about half that price for each patient.)

Tuesday, November 22, 2016

Emerging Hepatitis C Treatment Strategies For Difficult‐to‐Cure Patients

Emerging Hepatitis C Treatment Strategies For Difficult‐to‐Cure Patients

Faculty: Mark S. Sulkowski, MD, Tram T. Tran, MD, Paul Kwo, MD and Fred Poordad, MD
Release Date: November 12, 2016

Sadly not everyone who treats hepatitis C is cured, over at Practice Point those difficult to cure patients are discussed in a new learning activity. Although this video/lecture is aimed at clinicians, the use of clinical vignettes or patient-related cases and scenarios provides a somewhat patient friendly program.

Welcome and Introductions - Mark S. Sulkowski, MD
HCV in Cirrhotics - Tram T. Tran, MD
Renal Considerations in HCV - Paul Kwo, MD
HCV Resistance Testing - Fred Poordad, MD
Closing Remarks - Mark S. Sulkowski

Sit back and watch a panel of renowned HCV experts discuss the following topics;
  1. Review recent updates and changes to AASLD-IDSA recommendations for testing, managing, and treating hepatitis C
  2. Discuss the efficacy of various DAA regimens in patients who have failed prior DAA therapies
  3. Describe the efficacy and safety of different DAA regimens in the new difficult-to-cure patients
Register here. After a free quick registration, begin here.

View additional HCV learning activities and research articles;

Hep C Treatment Prognosis Continues to Amaze

American College of Gastroenterology (ACG) 2016 Annual Scientific Meeting

Hep C Treatment Prognosis Continues to Amaze
Damian McNamara
November 22, 2016

LAS VEGAS — Rapid advances in the treatment of hepatitis C have clinicians seeing outcomes they never thought possible, and experts are optimistic that more complex and challenging patients will respond to therapy.

However, treatment choice can be tricky. And caveats are emerging, including reports that direct-acting antivirals used for the treatment of hepatitis C might increase the risk for hepatitis B reactivation and liver cancer in some patients.

But the big picture is one of clinical success. "We know that 95% to 100% of patients treated for hepatitis C can be cured. It's pretty amazing," said Tram Tran, MD, from the Cedars–Sinai Medical Center and the University of California at Los Angeles.

Continue reading @ Medscape

Of Interest
Nov 21, 2016
NATAP ​- Reported by Jules Levin
New HCV Drugs at AASLD
Key presentations of new HCV DAA regimens

(Epclusa) Sofosbuvir plus velpatasvir “best options” for HCV G3

Epclusa for Hep C: What Pharmacists Should Know
JANUARY 04, 2017
Hepatitis C is an infection of the liver caused by the hepatitis C virus (HCV). It is one of the leading causes of chronic liver disease in the United States with the CDC estimating that between 2.7 and 3.9 million people in the United States are infected with chronic HCV.1 Over the past several years, a number of direct acting antivirals have been approved to treat the infection.

In June 2016, the FDA approved Epclusa, a fixed-dose combination product containing sofosbuvir, an HCV NS5B polymerase inhibitor, and velpatasvir, an HCV NS5A inhibitor, for treatment of chronic hepatitis C genotypes 1, 2, 3, 4, 5, or 6. With its approval, Epclusa became the first antiviral indicated for all 6 major forms of HCV.

This article highlights several key therapeutics areas with Epclusa that every pharmacist should know

Sofosbuvir plus velpatasvir “best options” for HCV G3

An analysis of published studies on direct acting antivirals (DAAs) found that regimens containing sofosbuvir and velpatasvir were the best option for patients with HCV genotype three (G3).

The analysis indicated that ribavirin significantly increased rates of SVR and should be considered if tolerated.

Researchers at Radboud University Medical Centre in the Netherlands performed a Bayesian network meta-analysis using a random effects model to indirectly compare DAA regimens in HCV G3 patients with and without cirrhosis. They found 27 appropriate studies involving 3,415 patients.

Among patients without cirrhosis, the greatest rates of SVR were estimated for those receiving sofosbuvir + velpatasvir with ribavirin (99%) and without ribavirin (97%), for sofosbuvir + daclatasvir + ribavirin (96%), and for sofosbuvir + peginterferon + ribavirin (95%), all for 12 weeks.

Among patients with cirrhosis, the highest rates of SVR were estimated for those receiving sofosbuvir + velpatasvir for 24 weeks (96%), for sofosbuvir + daclatasvir + ribavirin for 24 weeks (94%), and for sofosbuvir + velpatasvir + ribavirin for 12 weeks (94%).

Ribavirin increases efficacy in patients with and without cirrhosis (odds ratios 2.6 and 4.5).

Identification of the best direct-acting antiviral regimen for patients with hepatitis C virus genotype 3 infection: a systematic review and network meta-analysis. Berden FA, Aaldering BR, Groenewoud H et al. Clin Gastroenterol Hepatol. 2016 Nov 10 [Epub ahead of print]

Nov 21, 2016
Sofosbuvir/velpatasvir improved patient-reported outcomes, knocked out HCV genotypes 1-6
– When given with ribavirin, a fixed-dose combination of sofosbuvir/velpatasvir (Epclusa) achieved a sustained viral response at 12 weeks (SVR-12) in 94% of decompensated cirrhotic patients with hepatitis C virus (HCV) genotypes 1-6 infection, according to Zobair M. Younossi, MD.

Patients with and without cirrhosis also reported meaningful improvements across a variety of outcome measures after successfully completing treatment with Epclusa or sofosbuvir (Harvoni), said Dr. Younossi of Inova Fairfax Hospital in Falls Church, Va. “Although on-treatment patient-reported outcomes improved more with ribavirin-free regimens, post-SVR improvements were similar,” regardless of whether patients had received ribavirin, he reported at the annual meeting of the American Association for the Study of Liver Diseases.
Continue reading..

Of Interest
Nov 17, 2016
AbbVie Pangenotypic Combination Cures Hard-to-Treat People with HCV Genotype 3

October 2016
Short-duration Treatment With Elbasvir/Grazoprevir and Sofosbuvir - HCV GT1 or GT3 with or without cirrhosis

Vol 4, Supplement 1 (October 2016): Annals of Translational Medicine

Pan-genotypic treatment regimens for hepatitis C virus: Advantages and disadvantages in high- and low-income regions

Journal of Viral Hepatitis
Pan-genotypic treatment regimens for hepatitis C virus: Advantages and disadvantages in high- and low-income regions

During the last 5 years, the availability of direct-acting antiviral (DAA) agents has revolutionized the treatment of hepatitis C virus (HCV). Compared with interferon/ribavirin—the previous standard of care—DAA combination regimens offer improved sustained virological response (SVR) rates, shorter treatment durations of 8-24 weeks, convenient once-daily single-tablet formulations and more favourable tolerability profiles. HCV treatment is complex, and the choice of therapy must consider a complex range of factors, including baseline viral load, fibrosis stage, the HCV genotype and subgenotype, and the presence of resistance-associated substitutions at baseline. Globally, HCV genotype 1 predominates, and there are extensive data and various treatment options available for this genotype. Genotypes 2–6 are prevalent and may even predominate in different geographical regions, reflecting diverse factors including human migration patterns and unsafe use of injection drugs and blood products. Such factors are themselves influenced by socio-economic factors, and poor regions often have the greatest unmet need for effective HCV therapies. The latest pan-genotypic DAA combination regimens provide the potential to eradicate HCV around the globe, regardless of genotype, hence minimizing the need for virological testing services, which often are unavailable in poorer regions. Economics inevitably remain a barrier to access, and extensive cooperation will be required between clinical organisations and pharmaceutical manufacturers to agree appropriate pricing policies, especially in poorer economic regions. This review considers key data and treatment guidelines for DAA therapies, including pan-genotypic combination regimens, in the context of regional differences in HCV genotype and socio-economic factors.

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Saturday, November 19, 2016

VIDEO: Cost to treat HCV could be as low as $80 in the US

BOSTON — In this exclusive video at The Liver Meeting, Andrew M. Hill, PhD, discusses data from a new study that show the price of a direct-acting antiviral generic regimen could be as low as $80 in the U.S. to cure hepatitis C virus infection in one patient.

“The potential to lower prices and treat far more people is enormous,” Hill said.
Hill and colleagues extracted data from an online database of Indian export ledgers for per-kilogram prices and volumes of direct-acting antiviral API’s exported from India between January and June 2016.

“We found these drugs are being exported from India as raw materials for very low prices,” Hill said.

Direct-acting antiretrovirals in genotype 1 HCV patients with mental health conditions safe, well tolerated

Direct-acting antiretrovirals in genotype 1 HCV patients with mental health conditions safe, well tolerated
Publish date: November 18, 2016
By: Whitney McKnight Frontline Medical News

Direct-acting antiretroviral therapies are safe and well tolerated in hepatitis C virus patients with comorbid psychiatric conditions, a study showed.

The finding that sustained virologic response (SVR) rates at 1 year were similar in genotype 1 HCV patients with and without psychiatric comorbidities could help end the stigma against treating this patient subgroup, stemming from when treatment with interferon risked psychiatric decompensation. That’s according to nurse practitioner Anne Moore, winner of this year’s Poster of Distinction Award at the American Association for the Study of Liver Diseases

Continue reading..

Friday, November 18, 2016

UK - ALCOHOL will cause around 135,000 cancer deaths over the next 20 years

Alcohol will cause around 135,000 cancer deaths over the next 20 years and will cost the NHS an estimated £2 billion in treatments, according to estimates from a new report* by Sheffield University, commissioned by Cancer Research UK**.

“These new figures reveal the devastating impact alcohol will have over the coming years." - Alison Cox, Cancer Research UK

The new figures, published today (Friday), reveal that by 2035 the UK could see around 7,100 cancer deaths every year that are associated with alcohol. Of the cancer types included in the report, oesophageal cancer is set to see the largest increase, followed by bowel cancer, mouth and throat cancer, breast cancer and liver cancer***.

The report also forecasts that there will be over 1.2 million hospital admissions for cancer over the 20 year period, which will cost the NHS £100 million, on average, every year.

The results were based on analyses that assume alcohol drinking trends will follow those seen over the last 40 years, and takes recent falls in alcohol consumption, including among young people, into account****.

Evidence suggests that the more alcohol you drink, the higher the risk of cancer. UK government guidelines, published earlier this year, advise that both men and women drink no more than 14 units of alcohol a week.

The latest figures follow a Cancer Research UK study published earlier in the year that showed 9 in 10 people are unaware of the link between alcohol and cancer *****.

The report also examined the impact of introducing a minimum unit price for alcohol in England. It found that over 20 years a 50p minimum price per units of alcohol could reduce deaths linked to alcohol by around 7,200, including around 670 cancer deaths. It would also reduce healthcare costs by £1.3 billion. This follows a recent court decision in Scotland which found that a minimum unit price would not break European law.

Alison Cox, the director of prevention at Cancer Research UK, said: “These new figures reveal the devastating impact alcohol will have over the coming years. That’s why it’s hugely important the public are aware of the link between alcohol and cancer, and what they can do to improve their risk.

“If we are to change the nation’s drinking habits and try to mitigate the impact alcohol will have then national health campaigns are needed to provide clear information about the health risks of drinking alcohol.”

Professor Sir Ian Gilmore, chair of the Alcohol Health Alliance (link is external), said: “These latest figures show the serious consequences for individuals, the NHS and society if the UK government continues to ignore the consequences of the nation’s drinking. In particular they reinforce the need for a minimum unit price (MUP) for alcohol. It is clear from the report that MUP will save lives, including those lost to cancer, and ease the burden on our health service. Importantly, MUP will do this while leaving moderate drinkers and prices in pubs and bars unaffected.

"In addition, we need mandatory health information on the labels of all alcoholic products, informing the public of the link between alcohol and cancer, and the new low-risk drinking guidelines.

"The public have the right to know about how their drinking impacts their health, so that they are empowered to make informed choices.”

* Angus C, Holmes J, Pryce R, Meier P & Brennan A (2016) Alcohol and cancer trends: Intervention Studies University of Sheffield and Cancer Research UK.

Notes to Editor
** Alcohol trends were estimated across the whole population for England in 2015-2035. Using a scenario that incorporates both the recent shifts in consumption alongside longer-term trends, the average consumption is estimated to be 14.6 units/week and the abstention rate 20.7%.
ScenarioIn 20 years with no change (baseline)
Health outcomes: mortality
All deaths from alcohol-related conditions12,778
All deaths from alcohol-related cancers7,097
of which:Oesophageal cancer3,674
Other mouth and throat cancer887
Colorectal cancer1,369
Liver cancer333
Breast cancer835

**** Smoking drinking and drug use among young people in England in 2014: Health and Social Care Information Centre, 2015. (link is external)

*****Based on figures from a Cancer Research UK commissioned report ‘An investigation of public knowledge of the link between alcohol and cancer’, 2016.

Upcoming hepatitis C clinical trial - Glecaprevir/Pibrentasvir in Adults With Chronic Hepatitis C Virus (HCV) Genotype 5 or 6 Infection Identifier:
Drug: Glecaprevir/Pibrentasvir
Phase 3

A Phase 3b, open-label, multicenter study to evaluate the efficacy and safety of glecaprevir (ABT-493)/pibrentasvir (ABT-530) for an 8- or 12-week treatment duration in participants with chronic Hepatitis C Virus (HCV) genotype (GT) 5 or 6 infection, with or without compensated cirrhosis, who are either HCV treatment-naïve or treatment experienced with interferon (IFN) or pegylated interferon (pegIFN) with or without ribavirin (RBV) (defined as P/R treatment-experienced) or sofosbuvir (SOF) plus RBV with or without pegIFN (defined as SOF plus RBV treatment-experienced).

Estimated Enrollment: 80
Study Start Date: December 2016

    AASLD 2016 Review - Watch Advances in Chronic Hepatitis C: Management and Treatment

    After each conference this blog links to a series of education-related information on important findings related to ongoing challenges of managing and treating viral hepatitis. Listed below are three programs offering a review of key studies presented at the American Association for the Study of Liver Diseases 67th Annual Meeting 2016.

    Internet symposium at ViralEd - Advances in Chronic Hepatitis C: Management and Treatment
    The CME Internet Symposium: AASLD 2016 Expert Review will feature four HCV experts reviewing and discussing key presentations on chronic hepatitis C presented at AASLD 2016. The review and discussion will focus on HCV therapeutic options and developments, including: current treatment and management strategies, algorithms and recommendations; therapies in development; epidemiology; and diagnosis and clinical management of specific patient populations, including HCV/HIV co-infected and cirrhotic patients.

    Clinical Care Options - Clinical Impact of New Hepatology Data From Boston 2016*
    November 11-15, 2016 | Boston, Massachusetts
    Examine Capsule Summaries, download slides, and review analysis by expert faculty on key studies from Boston 2016.
    Free Registration Required, click here to register

    Conference Coverage AASLD: Practice Point 5 Minute Video Clips
    At Practice Point a series of 5 minute video clips highlighting hot hepatitis topics presented at the Liver Meeting 2016 is offered. 
    This activity is jointly provided by the University of Nebraska Medical Center,
    University of Florida College of Pharmacy
    and Practice Point Communications

    Thursday, November 17, 2016

    Adding Voxilaprevir to Sofosbuvir/Velpatasvir Effective for HCV Genotype 3: Presented at AASLD

    Adding Voxilaprevir to Sofosbuvir/Velpatasvir Effective for HCV Genotype 3: Presented at AASLD
    By Frances Morin

    BOSTON -- November 17, 2016 -- Adding voxilaprevir to the combination tablet containing sofosbuvir and velpatasvir (Epclusa) for 8 weeks shows similar efficacy to sofosbuvir/velpatasvir alone for 12 weeks in the treatment of patients with hepatitis C virus (HCV) genotype 3 and cirrhosis.

    “The results show that sofosbuvir/velpatasvir and voxilaprevir for 8 weeks and sofosbuvir/velpatasvir for 12 weeks each provide simple, safe, and effective treatment regimens for patients with HCV genotype 3 and cirrhosis,” said Graham R. Foster, MD, Royal London Hospital, London, United Kingdom, at The Liver Meeting, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).

    In efforts to treat HCV with direct acting antivirals, genotype 3 infection has become notably difficult to cure, particularly in patients with cirrhosis.

    For the phase 3 POLARIS-3 trial, the researchers investigated the addition of voxilaprevir 100 mg/day to sofosbuvir/velpatasvir 400 mg/100 mg/day for 8 weeks compared with sofosbuvir/velpatasvir 400 mg/100 mg/day alone for 12 weeks in 219 patients with genotype 3 HCV infection and cirrhosis.

    The results showed that 96% of patients in each group achieved a sustained virologic response for at least 12 weeks after treatment (SVR12).

    In the voxilaprevir group, there were 2 relapses, 1 patient withdrew consent, and there was 1 death. In the sofosbuvir/velpatasvir group, there was 1 on-treatment failure, 1 relapse, 1 discontinuation due to an adverse event (AE), and 1 lost to follow-up.

    In looking at patients according to prior treatment, 96% of treatment-naïve patients in the voxilaprevir group (72/75) achieved SVR12 compared with 99% of the sofosbuvir/velpatasvir group (76/77). Among those who received prior treatment, 97% and 91% achieved SVR 12, respectively.

    The most common AEs (>10% of patients) were fatigue and headache. Rates of nausea and diarrhoea were higher in the voxilaprevir group (21% and 15%, respectively), compared with the sofosbuvir/velpatasvir group (9% and 5%).

    According to the researchers, baseline NS5A resistance-associated substitutions, including Y93H, did not impact treatment outcomes for either group.

    Funding for this study was provided by Gilead Sciences.

    [Presentation title: A Randomized Phase 3 Trial of Sofosbuvir/Velpatasvir/ Voxilaprevir for 8 Weeks and Sofosbuvir/Velpatasvir for 12 Weeks for Patients With Genotype 3 HCV Infection and Cirrhosis: The POLARIS-3 Study]

    To read more Conference Dispatch articles, click here.

    Hepatitis C virus tricks liver cells to sabotage immune defenses

    Hepatitis C virus tricks liver cells to sabotage immune defenses 
    November 17,2016
    Virus induces liver cells to make molecules that inhibit production of a key immune signaling receptor

    University of Washington Health Sciences/UW Medicine

    The virus that causes hepatitis C protects itself by blocking signals that call up immune defenses in liver cells, according to University of Washington researchers and colleagues reporting Nov. 14 in Nature Medicine.

    "The finding helps explain why many patients fail certain drug treatments, and should help develop more effective alternate treatment protocols," said Ram Savan, the study's corresponding author and an assistant professor of immunology in the UW School of Medicine.

    Hepatitis C virus is the most common cause of chronic hepatitis and the leading cause of liver cancer in the United States. It is primarily spread through contact with infected blood. Each year, more than 30,000 Americans become infected. As many as 85 percent develop life-long chronic infections. Of these patients, about one in 10 will eventually develop cirrhosis and liver cancer.

    In the latest study, lead author Abigail Jarret, now a graduate student at Yale University, and her group showed that hepatitis C virus sabotages the antiviral defenses of liver cells by blunting the effect of key immune proteins called interferons.

    When cells become infected, they release interferons. These in turn spur hundreds of genes that generate virus-fighting proteins within the cell. Interferons can even provoke cells to self-destruct to prevent the virus from propagating.

    One of these interferons, called interferon-alpha, has been used for many years to treat chronic hepatitis C virus infections, either alone or in concert with an antiviral called ribavirin. These treatments helped many patients get rid of the virus, but the treatment fails to cure more than 60 percent of patients.

    Newer, more effective drugs with fewer side effects have now largely replaced interferon-based therapies. However, it was not clear why interferon treatment failed so often. From this study, researchers hypothesized that the virus' ability to evade interferons was related to the cells themselves.

    In a previous study, Savan's research team discovered that when hepatitis C virus invades a liver cell, the virus induces the cell to activate two genes -- MYH7 and MYH7B. These genes are usually active only in smooth skeletal muscle and heart cells. Once activated, these genes produce two microRNAs, molecules that can interfere with the production of other proteins.

    Savan and his fellow researchers showed that these microRNAs interfered with the cell's production of two interferons. By activating the MYH7 and MYH7B genes, the invading hepatitis C viruses limit liver cells' ability to generate these interferons. The cells are then less able to resist and remove the virus.

    The investigators also showed that these virally-induced microRNAs inhibit production of a receptor crucial to the cell's interferon-driven antiviral response.

    Thus, these hepatitis C virus-induced microRNAs can blunt liver cell interferon-driven antiviral defenses in two ways, Jarret explained.

    First, the virus inhibits the cell's ability to produce its own type III interferons.

    Second, it prevents the cells from making the receptors needed in order for type I interferons to be effective.

    "This may in part explain why interferon treatments, which harness a type I interferon, fail in so many patients," Jarret said.

    This project was funded partly by the National Institutes of Health.

    The Nature Medicine article is "Hepatitis-C-virus-induced microRNAs dampen interferon-mediated antiviral signalling."

    A Growing Group Of Doctors Are Big-Money Prescribers In Medicare

    A Growing Group Of Doctors Are Big-Money Prescribers In Medicare

    The number of doctors who each prescribe millions of dollars of medications annually in Medicare's drug program has soared, driven by expensive hepatitis C treatments and rising drug prices overall, federal data obtained by ProPublica show.

    The number of providers who topped the $5 million mark for prescriptions increased more than tenfold, from 41 in 2011 to 514 in 2015. The number of prescribers — mostly physicians but also nurse practitioners — exceeding $10 million in drug costs jumped from two to 70 over the same time period, according to the data.

    Most of the doctors atop the spending list prescribed Harvoni or Sovaldi, relatively new drugs that cure hepatitis C. Other providers on the list prescribed pricey drugs to treat cancer, multiple sclerosis and rheumatoid arthritis.

    Wednesday, November 16, 2016

    Coffee Consumption and Herbal Tea Tied to Lower Liver Stiffness

    Herbal Tea, Coffee Consumption Tied to Lower Liver Stiffness

    Tea and coffee consumption is ubiquitous around the world. Both contain polyphenols, caffeine, as well as other chemical components. Polyphenols and caffeine are suspected to improve liver health; for example, previous research has suggested that coffee might prevent liver cirrhosis. However, whether or not this is true for fibrosis in the general population is not known.

    AASLD Coverage
    Nov 11, 2016
    Herbal Tea, Coffee Consumption Tied to Lower Liver Stiffness
    Herbal tea and coffee might protect the liver among healthy adults, according to findings presented at The Liver Meeting® 2016.

    “High coffee consumption appears protective of liver stiffness even in individuals with no known liver disease,” reported lead study coauthor Louise J. Alferink, of the Gastroenterology and Hepatology of the Erasmus Medical Center, Rotterdam, Netherlands. 
    Continue reading...

    Additional updates @ MPR

    People who drink coffee are less likely to develop nonalcoholic fatty liver disease (NAFLD), a new literature review suggests. And people with NAFLD who drink coffee regularly are less likely to develop liver fibrosis.

    AASLD Coverage
    Nov 12,2016
    Drinking Coffee Found to Significantly Decrease NAFLD Risk
    Coffee drinkers significantly decrease their risk of nonalcoholic fatty liver disease (NAFLD), and regular drinking also decreases risk of liver fibrosis, according to results of a systematic review and meta-analysis presented at The Liver Meeting® 2016.

    “Whether consumption of coffee could be considered as a preventative measure against NAFLD needs further investigations,” reported Karn Wijarnpreecha, MD, of the department of internal medicine at Bassett Medical Center and Columbia University College of Physicians and Surgeons, Cooperstown, NY, and colleagues.
    Continue reading...

    Additional updates @ MPR

    Hepatitis C Treatment Uptake among Patients Who Have Received Opioid Substitution Treatment: A Population-Based Study

    Hepatitis C Treatment Uptake among Patients Who Have Received Opioid Substitution Treatment: A Population-Based Study
    Håvard Midgard , Jørgen G. Bramness, Svetlana Skurtveit, John W. Haukeland, Olav Dalgard Published: November 15, 2016

    Full Text

    Background and Aims
    There is limited data on hepatitis C (HCV) treatment uptake among people who inject drugs including individuals receiving opioid substitution treatment (OST). We aimed to calculate cumulative HCV treatment uptake, estimate annual treatment rates, and identify factors associated with HCV treatment among individuals who have received OST in Norway.

    This observational study was based on linked data from The Norwegian Prescription Database and The Norwegian Surveillance System for Communicable Diseases between 2004 and 2013. Both registries have national coverage. From a total of 9919 individuals who had been dispensed OST (methadone, buprenorphine or buprenorphine-naloxone), we included 3755 individuals who had been notified with HCV infection. In this population, dispensions of HCV treatment (pegylated interferon and ribavirin), benzodiazepines, selective serotonin reuptake inhibitors and antipsychotics were studied.

    Among 3755 OST patients notified with HCV infection, 539 (14%) had received HCV treatment during the study period. Annual HCV treatment rates during OST ranged between 1.3% (95% confidence interval [CI] 0.7–2.2) in 2005 and 2.6% (95% CI 1.9–3.5) in 2008 with no significant changes over time. HCV treatment uptake was not associated with age or gender, but associated with duration of active OST (adjusted odds ratio [aOR] 1.11 per year; 95% CI 1.07–1.15), high (> 80%) OST continuity (aOR 1.62; 95% CI 1.17–2.25), and heavy benzodiazepine use (aOR 0.65; 95% CI 0.49–0.87).

    Cumulative HCV treatment uptake among OST patients notified with HCV infection in Norway between 2004 and 2013 was 14%. Annual treatment rates during OST remained unchanged below 3% per year. High continuity of OST over time and absence of heavy benzodiazepine use predicted HCV treatment uptake. Increased awareness for HCV among OST patients is needed as tolerable and efficient directly acting antiviral treatment is being introduced.

    Discussion Only
    View full text article

    This population-based observational study evaluated HCV treatment uptake in Norway between 2004 and 2013 among individuals who had received OST and were notified with HCV infection. Cumulative HCV treatment uptake was 14% and annual treatment rates during OST ranged between 1.3% and 2.6% with no significant changes over time. HCV treatment was associated with duration of active OST, high OST continuity and absence of heavy benzodiazepine use, but was not associated with age or gender. This study provides unique baseline data on HCV treatment uptake among OST patients over a ten-year period prior to the availability of DAA treatment.

    The results from this study are consistent with findings from a Norwegian cohort of PWID who previously had been admitted for residential drug dependency treatment, in which 19% of individuals with chronic HCV infection had received HCV treatment during a 16 years observation period [45]. The majority of treated individuals in the present study had received HCV treatment during OST. Still, annual treatment uptake during OST was only marginally higher than treatment rates reported in community-based cohorts of PWID not engaged in OST [1215]. Although the Norwegian OST program was expanding during the study period, this did not translate into increasing HCV treatment uptake. This could be explained by a reluctance to offer OST patients IFN-based treatment, but might also suggest a low awareness of HCV infection in OST programs in general. Prescription of OST to more vulnerable individuals during the final part of the study period could also have played a role. Stable low treatment rates in this population might therefore reflect ongoing drug use as a barrier to HCV care on both patient- and provider-levels [19]. However, there has been a trend in Norway to increasingly provide HCV treatment for active PWID [43].

    Cumulative HCV treatment uptake was similar in all age groups and there was no association between age and HCV treatment. Among diseased HCV RNA positive individuals in a large Norwegian cohort of PWID, advanced liver fibrosis or cirrhosis on autopsy was seen in 35% of those who died 25 years or more after exposure to the virus [46]. In the same cohort, liver disease was the cause of death in 30% of deceased individuals above 50 years of age [4]. Given the high burden of HCV-related liver disease reported from this and other ageing cohorts of PWID with untreated HCV infection [47], it is a concern that treatment uptake was only 15% among individuals above 50 years at the end of the observation.

    Certain characteristics of OST were associated with HCV treatment. The odds of receiving HCV treatment increased by 11% for every year spent in active OST. OST continuity by itself was also important; in fact, individuals in active OST more than 80% of the time had 64% increased odds of receiving HCV treatment compared to those with low OST continuity. These are novel findings that raise the hypothesis that retention in OST could promote health-seeking behaviour and facilitate HCV treatment.

    This study also found associations between specific drug dispensions and HCV treatment. Heavy, but not moderate benzodiazepine use was associated with decreased odds of receiving HCV treatment, a finding that might reflect a psychosocial vulnerability that characterizes a group of OST patients. Benzodiazepine use is common among Norwegian OST patients and is shown to be associated with negative outcomes including poor social functioning and reduced retention in OST programs [48]. Psychiatric disease is a well-known barrier for IFN-based HCV treatment [18], but no association between dispensions of antipsychotics and HCV treatment was found in this study. SSRI use, however, was more common in patients treated for HCV, but this difference could be attributed to SSRI use initiated during or after HCV treatment. This finding might imply that the increased SSRI use was a consequence of psychiatric side effects of IFN-based treatment [49].

    The main strength of this study is its population-based approach, providing a large sample of individuals with opiate dependency who had received OST during a ten-year period. A liberal inclusion of individuals with only sporadic or short-term exposure to OST has ensured a study population more representative of Norwegian PWID. This study is the first to document HCV treatment uptake in this essential target group for HCV treatment, providing important baseline data prior to the availability of DAA treatment.

    An inherent limitation of this study is the lack of clinical data available from the registries. This may have impeded detection of factors associated with HCV treatment, although novel pharmaco-epidemiological associations have been identified. Another limitation is that OST administered to institutionalized patients was not registered in NorPD prior to 2008. HCV treatment, however, has almost exclusively been initiated in the outpatient setting and has therefore been captured by the registry throughout the study period. Consequently, annual HCV treatment rates during OST may have been underestimated prior to 2008, since some individuals probably have been misclassified as being treated prior to OST. This might explain the lower trend in treatment rates observed in this period. This bias may also have undervalued OST duration and OST continuity in some individuals, but cumulative HCV treatment uptake has not been affected.

    The quality of the MSIS data brings important limitations to this study. Firstly, the registry does not adequately discriminate chronic HCV infections from acute HCV infections with spontaneous clearance. Thus, by including all notified individuals regardless of the method of detection, treatment uptake may have been underestimated. Secondly, the low notification rate is a recognized problem that probably reflects vulnerable notification routines and lacking notifications of chronic infection prior to 2008, as well as low testing activity in OST programs. Also, this study may have missed some individuals notified prior to the study period. Nevertheless, this study has shown that only 38% of OST patients were notified with HCV infection and that only 57% of patients treated for HCV were notified. Although notifications rates among treated individuals improved, it is still a concern that one in four individuals treated for HCV remained un-notified towards the end of the study period.

    Restricting the study population to individuals notified with HCV infection has limited the sample size and excluded more than 40% of all patients actually treated for HCV. Although most characteristics were similar between notified and un-notified individuals, un-notified patients were on average three years older than notified individuals. This suggests that the linkage to MSIS may have introduced an age-related selection bias, excluding a group of older HCV infected individuals. Treatment uptake in older age groups may therefore have been underestimated. However, this bias has probably not altered the main finding of the study. Cumulative HCV treatment uptake among all OST patients was 9.5%, and assuming 60% HCV RNA prevalence in the ageing OST population [26, 37], this finding would correspond to 16% treatment uptake among all individuals with presumed chronic HCV infection.

    The current availability of tolerable, short-duration and highly efficient DAA regimens has led to significant therapeutic optimism with possibilities for broadened treatment uptake and subsequent HCV elimination among PWID [23, 5052]. Although derived from IFN-based treatment, the findings from this study are highly relevant, providing baseline data on HCV treatment uptake prior to the introduction of DAAs. Collectively, the findings from this study underscore the need for increased awareness for HCV infection in a growing population of PWID including OST patients now being eligible for HCV treatment. The results should inform health political decisions and support improved HCV testing activity and linkage to HCV care among individuals receiving OST. Although treatment uptake is expected to increase, challenges concerning drug pricing and delivery of care will probably remain. Future studies should therefore monitor treatment rates in this population.

    In conclusion, this study has shown that HCV treatment uptake among patients who have received OST in Norway was low and stable during the final ten years of the IFN-based treatment era. Although long-term stability in OST might facilitate HCV treatment, the findings from this study highlight the need for improved awareness for HCV infection in this increasingly important target group for HCV treatment.

    Tuesday, November 15, 2016

    AbbVie's Glecaprevir/Pibrentasvir (G/P) Shows High SVR Rates in Chronic Hepatitis C Patients with Severe Chronic Kidney Disease

    AbbVie's Investigational, Pan-Genotypic Regimen of Glecaprevir/Pibrentasvir (G/P) Shows High SVR Rates in Chronic Hepatitis C Patients with Severe Chronic Kidney Disease

    - 98 percent of patients across all major HCV genotypes (GT1-6) with severe chronic kidney disease (CKD), including patients on dialysis, achieved SVR12 with 12 weeks of G/P in the primary intent-to-treat analysis, regardless of previous treatment status or presence of compensated cirrhosis
    - 100 percent of patients achieved SVR12 in a modified intent-to-treat analysis
    - G/P is an investigational, pan-genotypic, once-daily, ribavirin-free, fixed-dose combination for the treatment of chronic HCV
    - Development of new regimens to treat HCV patients with CKD remains a critical unmet medical need across genotypes1

    NORTH CHICAGO, IL, USA I November 15, 2016 I AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced 98 percent (n=102/104) of chronic hepatitis C virus (HCV) infected patients with severe chronic kidney disease (CKD) achieved sustained virologic response following 12 weeks of treatment (SVR12) with its investigational, pan-genotypic regimen of glecaprevir (ABT-493)/pibrentasvir (ABT-530) (G/P) in the primary intent-to-treat (ITT) analysis. In a modified intent-to-treat (mITT) analysis, SVR12 was achieved in 100 percent (n=102/102) of severe CKD patients; mITT excludes patients who did not achieve SVR for reasons other than virologic failure. These new data from the Phase 3 EXPEDITION-4 study, evaluating patients with chronic HCV infection across all major genotypes (GT1-6) and severe CKD, will be presented as a late-breaker today at The Liver Meeting®, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston.

    The EXPEDITION-4 results are the latest to be released from registrational studies in AbbVie's G/P clinical development program, designed to investigate a faster path to virologic cure* for all major HCV genotypes (GT1-6) and with the goal of addressing areas of continued unmet need.

    "HCV patients with severe chronic kidney disease present a complex challenge for physicians to treat, particularly as kidney disease progresses, and if the patient has genotype 2 or 3 or has compensated cirrhosis," said Ed Gane, M.D., professor of medicine at the University of Auckland in Auckland, New Zealand. "The results seen in EXPEDITION-4 are a positive development in AbbVie's investigation of the G/P regimen for patients with chronic kidney disease, who currently have limited HCV treatment options."

    HCV is common among people with severe CKD, reaching prevalence of up to 80 percent in some regions of the world.2 In the U.S., it is estimated that over 500,000 people have both chronic HCV and CKD.3 Some chronic HCV infected patients with severe CKD, particularly those with GT2 and GT3 HCV infection, currently don't have access to direct-acting antivirals (DAAs). The development of new, safe and effective regimens to treat HCV in these patients remains a critical unmet medical need.1

    "With our investigational, pan-genotypic regimen, our goal is to provide a safe and effective cure to patients across genotypes, including patients with severe chronic kidney disease, regardless of previous treatment status or presence of compensated cirrhosis," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "Our clinical development program reflects our ongoing commitment to addressing treatment areas of continued unmet need."

    The EXPEDITION-4 study enrolled 104 patients with severe chronic kidney disease, including 85 patients (82 percent) who were receiving dialysis at enrollment and 20 patients (19 percent) who had compensated cirrhosis. The study also included those who were not cured with previous sofosbuvir (SOF) with ribavirin (RBV) or interferon (IFN) with RBV; with or without SOF (44 patients, 42 percent).

    The majority of treatment related adverse events (AEs) were mild or moderate. The most commonly reported AEs included pruritus, fatigue and nausea. Of the 24 percent of patients who experienced serious AEs, none were considered related to G/P. Four AEs (4 percent) led to the discontinuation of G/P and one patient died after achieving SVR4 due to a serious AE (intracerebral hemorrhage) considered not-related to G/P.

    *Patients who achieve a sustained virologic response at 12 weeks post treatment (SVR12) are considered cured of hepatitis C.

    About the EXPEDITION-4 Study

    EXPEDITION-4 is a single-arm, open-label, Phase 3 study evaluating the safety and efficacy of 12 weeks of G/P in patients with GT1-6 chronic HCV infection and chronic kidney disease, including those on dialysis. The primary efficacy endpoint is SVR12.

    Patients had severe or end stage kidney disease (stage 4 and 5 CKD), with an eGFR < 30 mL/min/1.73 m2 required at screening. Prior treatment in the study is defined as treatment with IFN/pegIFN ± RBV, or SOF + RBV ± pegIFN therapy.

    Additional information on the clinical trials for G/P is available at

    About AbbVie's HCV Clinical Development Program

    AbbVie's glecaprevir/pibrentasvir (G/P) clinical development program was designed to investigate a faster path to virologic cure* for all major HCV genotypes (GT1-6) and with the goal of addressing treatment areas of continued unmet need.

    G/P is an investigational, pan-genotypic regimen that is being evaluated as a potential cure in 8 weeks for HCV patients without cirrhosis and who are new to treatment, who make up the majority of HCV patients. AbbVie is also studying G/P in patients with specific treatment challenges, such as genotype 3, patients who were not cured with previous DAA treatment and those with CKD, including patients on dialysis.

    G/P is an investigational, once-daily regimen that combines two distinct antiviral agents in a fixed-dose combination of glecaprevir (300mg), an NS3/4A protease inhibitor, and pibrentasvir (120mg), an NS5A inhibitor. G/P is dosed once-daily as three oral tablets.

    Glecaprevir (GLE) was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors.

    About AbbVie
    AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases. Together with its wholly-owned subsidiary, Pharmacyclics, AbbVie employs more than 28,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit Follow @abbvie on Twitter or view careers on our Facebook or LinkedIn page.

    Forward-Looking Statements

    Some statements in this news release may be forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry.

    Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2015 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

    1 American Association for the Study of Liver Diseases. Recommendations for Testing, Managing, and Treating Hepatitis C, February 24, 2016, Accessed March 15, 2016.
    2 Fabrizi F, Poordad FF, Martin P. Hepatitis C infection in the patient with end stage renal disease. Hepatology. 2002;36(1):3-10.
    3 IMS Health, July 2016. Parsippany, NJ; Medivo, July 2016. New York, NY (Estimate based on IMS Health Dx Medical Claims 12/2013-4/2016; IMS Health Life Link Patient Level Data 12/2013-4/2016; Medivo Lab Data 12/2013-4/2016).