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 http://medicine.missouri.edu/.

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

Summary
Background
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.

Aim
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.

Methods
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.

Results
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.

Conclusions
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

Summary
Introduction
Materials and methods
Results
Discussion
Authorship
Acknowledgements

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

ORIGINAL RESEARCH ARTICLE

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

Abstract
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.

Methods

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.

Results

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.

Conclusions

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

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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.

Reference
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) -– http://dx.doi.org/10.1016/j.rdc.2016.09.011
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

KEY POINTS

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

STOCKHOLM--(BUSINESS WIRE)--Regulatory News:

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 www.clinicaltrials.gov 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 http://news.cision.com

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

Source

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.)

Liver Cancer After Treatment For Hepatitis C

Page updated: July 2017

Liver Cancer After Treatment For Hepatitis C
Research demonstrates that while SVR markedly reduced liver-related complications and liver cancer, some long-term risk for liver cancer remained in those who were cured of Hepatitis C. But after direct-acting antiviral therapy does the risk of developing liver cancer increase?

This page offers an index of links to current data investigating the possible risk of developing liver cancer (hepatocellular carcinoma, or HCC) during and after direct-acting antiviral therapy in patients with hepatitis C.

July 2017
July 26, 2017
Medscape
With Hepatitis C Virus on the Run, Meet the New Challenge: Hepatocellular Carcinoma
Significant advances in the clinical practice of hepatology were addressed during this year's Digestive Disease Week. This review focuses on the concerns related to the apparent increase in the incidence of hepatocellular carcinoma (HCC).

July 16
Hepatitis C virus eradication with direct antiviral agents and liver cancer recurrence: Is the best the enemy of the good? Antiviral therapy has long been perceived as an adjuvant treatment modality worth to be offered to patients with chronic hepatitis C virus (HCV) infection after successful removal of a hepatocellular carcinoma (HCC), an approach dating more than two decades since interferon was first employed to treat non-A, non-B hepatitis.

July 10
DAAs do not affect HCC risk, SVR reduces risk
July 10, 2017
Recently published data showed a link between sustained virologic response and a reduced risk for hepatocellular carcinoma among patients treated with direct-acting…

July 3
Sustained response to direct-acting HCV antivirals tied to lower HCC risk
July 3, 2017
by Marilynn Larkin
NEW YORK (Reuters Health) - A sustained virologic response to direct-acting antiviral treatment of hepatitis C (HCV) is associated with a “considerable” reduction in the risk of hepatocellular carcinoma (HCC), researchers say.
Dr. Fasiha Kanwal of Baylor College of Medicine in Houston, Texas and colleagues analyzed data on 22,500 HCV patients (mean age 62) from 129 Veterans Health Administration hospitals who filled more than one prescription of sofosbuvir, simeprevir, ledipasvir, a combination of paritaprevir/ritonavir or ombitasvir and dasabuvir, and daclatasvir in 2015.

June 2017
June 26, 2017
Challenges in Treatment of Hepatitis C among Patients with Hepatocellular Carcinoma

June 3, 2017
Medscape Coverage from the International Liver Congress (ILC) 2017
Navigating the Hep C Treatment and Cancer Risk Minefield

May 2017
May 26
Hepatocellular carcinoma and direct- acting antivirals: A never ending story?
Vincenza Calvaruso* andAntonio Craxì Version of Record online: 24 MAY 2017 DOI: 10.1111/liv.13421
Liver International
Volume 37, Issue 6, pages 812–814, June 2017

Key Points
• The benefit of SVR is higher in patients without clinically significant portal hypertension
• HCC occurrence in patients with compensated cirrhosis is comparable to historical controls of patients who achieved SVR after interferon-based therapy.
• Patients who achieve SVR with DAAs had a lower risk of developing liver cancer than those patients whose HCV infection was not cured.
• Data available on patients with previous HCC do not show an increased risk of HCC recurrence and report a comparable rate of reappearance of cancer among DAA-treated and untreated patients.

Full Text

Link Provided By
Henry E. Chang via Twitter

May 26
Summary Of  Available Data:
New Hep C Treatment Not Linked to Liver Cancer
Contrary to some earlier research, most recent studies see no association between response to DAAs and HCC

Do HCV DAAs Increase HCC Recurrence Risk or Not?
Does the administration of direct-acting antiviral (DAA) therapy increase a patient’s risk of hepatocellular carcinoma (HCC) recurrence?

Direct-acting-antivirals (DAA) can cure patients of the life-threating hepatitis C virus (HCV) infection, with cure rates exceeding 95%. However, questions have been raised about the long-term consequences of curing patients with DAAs, including a potential link between DAA treatment and the development of hepatocellular carcinoma (HCC).

Improved survival of patients with hepatocellular carcinoma and compensated HCV-related cirrhosis who attained SVR
Few studies examined the outcome of patients with HCV-related cirrhosis who developed hepatocellular carcinoma (HCC). The relative weight as determinant of death for cancer versus endstage-liver-disease (ESLD) and the benefit of HCV eradication remain undefined. This multicenter, retrospective analysis evaluates overall survival (OS), rate of decompensation and tumor recurrence in compensated HCC patients treated with IFN according to HCV status since HCC diagnosis.

Of Interest
HCC in presence of HCV decreases cure rate in DAA treatment
Patients with hepatocellular carcinoma and hepatitis C were less likely to achieve sustained virologic response while receiving direct-acting antiviral therapy compared with patients without HCC, according to results of a retrospective study.

International Liver Congress
April 21,2017
Direct-acting antivirals for hepatitis C not linked to higher liver cancer risk in most studies
People with hepatitis C who take treatment with direct-acting antivirals (DAAs) do not appear to have a higher risk of developing liver cancer compared to those treated with interferon, and the seemingly higher rates seen in some studies are attributable to risk factors such as older age and more advanced liver disease, according to a set of studies presented on Thursday at the International Liver Congress in Amsterdam. The congress is the annual meeting of the European Association for the Study of the Liver (EASL).

April 20, 2017
#ILC 2017: Is direct-acting antiviral therapy for Hepatitis C associated with an increased risk of liver cancer? The debate continues
Eight studies being presented at The International Liver Congress™ 2017 demonstrate contrasting evidence on the potential link between direct-acting antiviral treatment for Hepatitis C and liver cancer

Commentary on this study
Hepatitis C Patients At No Elevated Risk of Developing HCC Following DAA Compared To Interferon
Patients were at no elevated risk of developing hepatocellular carcinoma (HCC) after achieving sustained virologic response (SVR) following treatment with direct-acting antiviral therapy (DAA) for hepatitis C compared to interferon therapy, according to results of a meta-analysis reported at the 2017 International Liver Congress (ILC).

Timing of DAA therapy and HCC response may impact recurrence rate
April 20, 2017
AMSTERDAM — Unexpectedly high hepatocellular carcinoma recurrence rates were reported among patients who achieved sustained virologic response after receiving direct-acting antiviral therapy, according to data presented at the International Liver Congress.
“This update further supports our findings about an unexpected high recurrence rate associated in time with DAA, but also exposes a more aggressive pattern of recurrence and faster tumor evolution,” Maria Reig, MD, of the Barcelona Clinic Liver Cancer Group, Liver Unit, Hospital Clinic Barcelona, at the University of Barcelona, said in her presentation.

Liver International
April 20, 2017
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Direct-acting antiviral therapy decreases hepatocellular carcinoma recurrence rate in cirrhotic patients with chronic hepatitis C
Arrival of direct-acting antiviral (DAA) agents against hepatitis C virus (HCV) with high-sustained virological response (SVR) rates and very few side effects has drastically changed the management of HCV infection. The impact of DAA exposure on hepatocellular carcinoma (HCC) recurrence after a first remission in patients with advanced fibrosis remains to be clarified

Editorial - Healio
April 20, 2017
HCC After DAAs Requires More Study, but no Cause for Withheld Treatment
HCV Next, April 2017
As we continue to see the success of direct-acting antiviral therapy in treating hepatitis C virus, we must be aware of any potential complications from the underlying liver disease after successful treatment, especially hepatocellular carcinoma.

March 15, 2017
Full Text - Download PDF
Hepatitis C-related hepatocellular carcinoma in the era of new generation antivirals
Abstract
Hepatitis C virus infection is a major cause of hepatocellular carcinoma worldwide. Interferon has been the major antiviral treatment, yielding viral clearance in approximately half of patients. New direct-acting antivirals substantially improved the cure rate to above 90%. However, access to therapies remains limited due to the high costs and under-diagnosis of infection in specific subpopulations, e.g., baby boomers, inmates, and injection drug users, and therefore, hepatocellular carcinoma incidence is predicted to increase in the next decades even in high-resource countries. Moreover, cancer risk persists even after 10 years of viral cure, and thus a clinical strategy for its monitoring is urgently needed. Several risk-predictive host factors, e.g., advanced liver fibrosis, older age, accompanying metabolic diseases such as diabetes, persisting hepatic inflammation, and elevated alpha-fetoprotein, as well as viral factors, e.g., core protein variants and genotype 3, have been reported. Indeed, a molecular signature in the liver has been associated with cancer risk even after viral cure. Direct-acting antivirals may affect cancer development and recurrence, which needs to be determined in further investigation.
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Feb 27, 2017
People with HIV and hepatitis C virus (HCV) co-infection who are successfully treated for hepatitis C using interferon-free direct-acting antiviral (DAA) therapy do not appear to have an increased likelihood of developing hepatocellular carcinoma (HCC), according to a study presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2017) this month in Seattle.

Accepted Manuscript
Gastroenterology Accepted Date: 23 January 2017
Genome-wide Association Study Identifies TLL1 Variant Associated With Development of Hepatocellular Carcinoma After Eradication of Hepatitis C Virus Infection

Media Coverage of this Article
Feb 22, 2017
Genetic variant linked to risk of liver cancer after hep C eradication
NEW YORK (Reuters Health) – A single nucleotide polymorphism (SNP) in the tolloid-like 1 (TLL1) gene is associated with the development of hepatocellular carcinoma (HCC) after eradication of hepatitis C virus (HCV) infection, researchers from Japan report.
“When we constructed different models for predicting HCC in patients with mild as opposed to advanced hepatic fibrosis by combining this TLL1 variant with other distinct risk factors, these proposed models including TLL1 variant could be useful for predicting the occurrence of HCC after achieving sustained virological response (SVR) in the clinical practice,” Dr. Yasuhito Tanaka from Nagoya City University Graduate School of Medical Sciences told Reuters Health by email.
Continue reading...

Feb 8, 2017
High Rates of Hepatocellular Carcinoma After Hepatitis C Treatment
NEW YORK (Reuters Health) - Patients treated with direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV)-related cirrhosis appear to have high rates of hepatocellular carcinoma (HCC).

"If these findings are confirmed from other centers, studies are suggested to examine mechanisms of these findings," Dr. Ashwani Singal from University of Alabama at Birmingham told Reuters Health by email.

Some studies have shown unexpectedly high HCC recurrence rates after DAA therapy, whereas others have shown no such association.

Dr. Singal and colleagues examined the occurrence of de novo HCC in their retrospective study of 66 patients with HCV-related cirrhosis who received DAA between 2015 and 2016.

Typically, patients with HCV cirrhosis have an HCC incidence of 3%-5% per year, the researchers say.

But six of these patients (9.1%) developed HCC during or within six months after treatment, and two additional patients (3%) developed indeterminate liver lesions, according to their letter online February 1st in Gastroenterology.

They note that another study showed a reduced risk of HCC occurrence among DAA-treated patients who achieved sustained viral responses (SVR) versus those not achieving SVR, so they suggest prospective multicenter studies to confirm these findings.

"Be aware of this potential issue and consider more intensive HCC surveillance of HCV cirrhotics during and after HCV therapy," Dr. Singal concluded.

Dr. Gaetano Serviddio from University of Foggia, Italy, who has reported on the outcomes of DAA therapy, told Reuters Health by email, "DAAs have completely changed the prognosis of chronic hepatitis C patients who have a unique possibility to be cured definitively. To discover that such drugs have some tumor risks is particularly terrible. In any case, the number of events is small, and the data are not enough to support the hypothesis that the risk is directly related to the drugs."

"DAAs are safe and powerful drugs; millions of lives will be saved with such drugs," he said. "Studies should be supported to completely define patients at risk of HCC recurrence."
SOURCE: http://bit.ly/2lmDbXa
Gastroenterol 2017.

January 2017
In Press, Corrected Proof
Digestive and Liver Disease
Available online 21 January 2017
HCV clearance by direct antiviral therapy and occurrence/recurrence of hepatocellular carcinoma: A “true-or-false game”
Three years ago, the new direct antiviral therapies (DAAs) were approved for HCV treatment and the scenario completely changed. The share of patients in whom eradication is obtained raised to over 90% [7], the limits in the stage of the disease that can be treated disappeared, but solid data on the long-term outcome of cirrhotics treated with these new drugs are lacking.

A totally unexpected, intriguing and somehow hard-to-believe report of an increased incidence of HCC with rapid recurrence after HCV eradication with DAAs was first presented at the 2016 EASL meeting and then published in the Journal of Hepatology.....
Continue to full text article...

2016
AASLD 2016 and International Liver Congress 2016
Two studies presented at The Liver Meeting® 2016, and research presented in April at the International Liver Congress 2016.

Patients With HCV Who Treated With Interferon-based Therapy  
We begin with a study presented at AASLD 2016; The impact of sustained virological response to HCV infection on long term risk of hepatocellular carcinoma: the BC Hepatitis Testers Cohort, that suggested patients achieving SVR were still at risk for hepatocellular carcinoma, more specifically older patients and those with cirrhosis, commentary on the study is available over at Healio; SVR post–interferon-based therapy reduces, not eliminates risk for HCC, below is a summary of the study followed by slides @ NATAP 

Liver cancer risk reduced in patients cured of HCV
A large study found that the risk of hepatocellular carcinoma was reduced by 80% in people cured of HCV compared to those who were not cured.

This was a study of the entire population of people treated for HCV in British Columbia province, Canada, between 1990 and 2013. The study identified 8147 people treated with interferon-based regimens, 57% of whom were cured. Treated individuals were followed for a median of 5.6 years.

The liver cancer incidence was highest among those with cirrhosis who did not achieve a SVR (21 cases per 1000 patient-years of follow-up). In comparison, the liver cancer incidence was 6.4 per 1000 patient-years in those with cirrhosis who achieved SVR, 7.2 in those without cirrhosis who did not achieve SVR12 and 1.1 per 1000 patient-years in those without cirrhosis who achieved SVR12.

In a multivariable analysis liver cancer was associated with cirrhosis, age over 50 years, genotype three infection versus genotype one, alcohol consumption and being male in those who were not cured. In those who were cured of hepatitis C, only cirrhosis, age over 50 and being male were associated with an increased risk of liver cancer.

The researchers concluded that although curing HCV greatly reduces the risk of developing liver cancer, it does not eliminate the risk entirely. Older people and those with cirrhosis are at higher risk than others, underlining the importance of early diagnosis and treatment.

Reference
The impact of sustained virological response to HCV infection on long term risk of hepatocellular carcinoma: the BC Hepatitis Testers Cohort. Janjua NZ et al. The 67th Meeting of the American Association for the Study of Liver Diseases, Boston 2016. Abstract 175
Summary Source - https://www.basl.org.uk/

Review Slides

Patients With HCV Who Treated With Oral DAAs
In a prospective study presented at the 2016 AASLD; Incidence and pattern of "de novo" hepatocellular carcinoma in HCV patients treated with oral DAAs, reported that treatment with direct-acting antiviral therapy did not increase the risk of developing hepatocellular carcinoma in patients with HCV, but patients with advanced liver disease should continue to be monitored for liver cancer after treatment, here is the AASLD press release, followed by slides @ NATAP.

AASLD Press Release;
AASLD 2016 - Is There an Increased Risk of Cancer After Taking Direct-Acting Antiviral Medication?
BOSTON, Nov. 11, 2016
A new study presented this week at The Liver Meeting® — held by the American Association for the Study of Liver Diseases — found patients with hepatitis C who take direct-acting antiviral medication are at no higher risk for developing liver cancer than those who do not take the medication. However, they might be at an increased for more aggressive, infiltrative patterns of cancer, should they develop it.

"Data on clinical outcomes in cirrhotic patients with hepatitis C treated with direct-acting antiviral agents (DAAs) are still scanty and somehow controversial, and this is particularly true for development of a liver cancer, one of the most frequent and deadly complications of the disease," says Alfredo Alberti; professor of gastroenterology at University of Padova in Padova, Italy, and lead investigator in the study.

Recent studies have suggested the possibility of increased risk of developing liver cancer (hepatocellular carcinoma, or HCC) during and after DAA treatment in patients with hepatitis C (HCV). Dr. Alberti's team recently looked at the incidence of new cases of liver cancer among 3,075 HCV patients with advanced liver disease who were treated with DAAs. Almost 70 percent of the patients studied were men, and nearly 86 percent had cirrhosis (scarring of the liver). HCV genotypes one through four were all represented in the study, and patients with a past history of liver cancer were excluded.

All participants were treated with oral DAA therapy and monitored monthly. At the time of Dr. Alberti's team's analysis, patients had an average follow up of nearly 305 days from the time they started DAA therapy. During this period, the researchers found 41 patients had developed liver cancer, and the overall incidence (per 100 patient years) was 1.64.

Dr. Alberti's team further noted an incidence rate of 0.23 in patients without cirrhosis and of 1.93 in those with cirrhosis (1.93 for men and 1.94 for women). Incidence rates varied among HCV genotypes as well, with HCV-1 at the low end (1.70) and HCV-3 at the high end (2.44). Finally, cirrhotic patients with a Child-Pugh score of 'A' had an incidence rate of 1.64 and those with more advanced disease and a score of 'B' had a rate of 2.92.

"These rate incidences were not significantly different from those observed in historical control cohorts of similar patients from the same geographic area, not receiving antiviral therapy, indicating that the risk of developing HCC is not increased by oral DAAs, being closely dependent on stage of disease as in untreated cases," says Dr. Alberti.

Liver cancer was diagnosed four weeks after starting DAA therapy in three patients, at week eight in three patients, week 12 in six patients, between week 12 and 24 in thirteen patients, and after treatment ended in sixteen patients. Fifty percent of patients who developed liver cancer developed a single nodular cancer with a typical vascular pattern, while 50 percent had a more aggressive pattern. Finally, 28 out of the 41 patients who developed cancer were successfully cured of HCV (reaching a sustained virological response at 12 weeks), while the remaining 13 relapsed.

In different analyses of the data, Dr. Alberti's team found elevated liver enzymes and low platelet count to be associated with liver cancer risk, while gender, age, HCV genotype and DAA regimen were not. The best baseline predictor of liver cancer risk was APRI scores (which calculate scarring in the liver). The researchers find the risk of developing liver cancer increased linearly by 10 percent at each one-point increase in APRI value.

"The results of this study, while confirming that DAAs treatment doesn't increase the overall risk of HCC, indicate that there is no pharmacological prevention of HCC even with successful antiviral therapy, at least during the first six to 12 months after initiation of treatment when microscopic and therefore initially invisible HCC foci might even be boosted in their growth as consequence of the profound immunological and molecular changes in the liver microenvironment following abrupt cessation of HCV replication," explains Dr. Alberti. "Therefore, it is mandatory that patients treated with DAAs with advanced liver disease should continue to be monitored for HCC."

This release contains updated data. Dr. Alberti will present these findings at AASLD's press conference in Room 313 at John B. Hynes Veterans Memorial Convention Center in Boston on Saturday, November 12 at 4pm. The study entitled "Incidence and pattern of "de novo" hepatocellular carcinoma in HCV patients treated with oral DAAs" will be presented by Antonietta Romano, MD in Ballroom A on Sunday, November 13 at 10am. The corresponding abstract (number 19) can be found in the journal, Hepatology – Special Issue: The 67th Annual Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting 2016.

View the slides @ NATAP Reported by Jules Levin

Another look at both studies;  Incidence and pattern of `de novo` hepatocellular carcinoma in HCV patients treated with oral DAAs and The impact of sustained virological response to HCV infection on long term risk of hepatocellular carcinoma: the BC Hepatitis Testers Cohort.

Keith Alcorn
People who are cured of hepatitis C after a course of direct-acting antiviral treatment do not have a higher risk of developing liver cancer (hepatocellular carcinoma), and probably have a reduced risk, studies from Italy and Canada presented at The Liver Meeting this week in Boston have shown. However, Italian researchers also found that those people who did develop liver cancer during or shortly after antiviral treatment were more likely to develop an aggressive form of liver cancer, perhaps because of changes in immune surveillance in the liver as a result of treatment.

Patients With HCV And History Of Liver Cancer Who Treated With New Antivirals
As a reference point two studies presented in April at the International Liver Congress 2016 found; patients with a history of hepatocellular carcinoma have the highest risk of developing a tumor after direct-acting antiviral therapy, but new diagnoses were also reported. ​​Read the report; Liver Cancer Found in Hepatitis C Patients on New Antivirals provided below, or over at Medscape.

Liver Cancer Found in Hepatitis C Patients on New Antivirals
Kate Johnson
April 15, 2016
BARCELONA, Spain — In a surprising number of patients with hepatitis C and cirrhosis, hepatocellular carcinoma develops within weeks of starting treatment with direct-acting antivirals, new research suggests.

"I do not think that direct-acting antivirals are directly responsible," said lead investigator Stefano Brillanti, MD, from the University of Bologna, Italy.

"The hypothesis is that immune surveillance may be reduced too rapidly," he told Medscape Medical News. "You have an immediate drop in viremia, but also attenuation of inflammation. I think inflammation is a bad thing in terms of hepatitis progression, but it may be a good thing in terms of controlling cancer."

The study by Dr Brillanti's team, presented here at the International Liver Congress 2016, suggests that patients with hepatitis C should be closely monitored after treatment with direct-acting antivirals. Two days earlier, a study conducted by a team from the University of Barcelona in Spain suggested the same thing (J Hepatol. Published online April 12, 2016).

Both studies indicate that patients with a history of hepatocellular carcinoma have the highest risk of developing a tumor after direct-acting antiviral therapy, but new diagnoses were also reported.

The EMA has extended the scope of its review of the six direct-acting antivirals approved for use in the European Union for the treatment of chronic hepatitis  C infection to include the risk for early liver cancer recurrence, the agency reported.

Tumor Risk
"Patients with previous hepatocellular carcinoma are, of course, at risk of recurrence anyway," Dr Brillanti said. "A 30% rate over 3 years from initial surgery or ablation is normal. What was surprising to us was that we were observing 4 cm lesions after 12 weeks."

The retrospective cohort study involved 344 consecutive patients with hepatitis C and cirrhosis who were treated with one or two direct-acting antivirals and followed for 24 weeks after therapy. Median age was 63 years.
In this cohort, 237 patients were infected with hepatitis C genotype 1, 191 had received previous antiviral treatment, and 59 had been successfully treated for hepatocellular carcinoma.

Contrast-enhanced ultrasonography and CT scans or MRIs were performed at baseline to exclude active hepatocellular carcinoma, and then again 12 and 24 weeks after treatment.
During the follow-up period, 26 of the 344 patients (7.6%) were diagnosed with hepatocellular carcinoma. This included 17 of the 59 patients previously treated for hepatocellular carcinoma, and nine of the 285 patients (3.2%) with no history of carcinoma.

There was no association between recurrence and hepatitis C genotype, direct-acting antiviral regimen, or treatment response for patients who did not develop hepatocellular carcinoma or for those who did. The sustained viral response rate at 12 weeks was 89% in the two groups.
For patients with a history of hepatocellular carcinoma, those who developed a recurrence were significantly younger than those who did not (56 vs 73 years), were more frequently treatment-experienced (88.2% vs 61.9%), and had more advanced liver fibrosis at baseline.

More patients who developed hepatocellular carcinoma during the follow-up period, regardless of history, had advanced cirrhosis than those who did not, indicated by a Child-Pugh class B score (26.9% vs 10.1%; P =.02). They also had more liver stiffness, indicated by a measure above 21.3 Kpa (61.5% vs 31.8%; P = .005), and fewer platelets at baseline (102.3 vs 124.4 × 1000/mm³; P = .02).

Second Study
In the Spanish study, all 58 hepatitis C patients had a history of hepatocellular carcinoma (with complete radiologic response), and all but three were cirrhotic at the start of direct-acting antiviral therapy. After a median follow-up of 5.7 months, the rate of tumor recurrence was 27.6%, with a median time to recurrence of 3.5 months. The sustained viral response rate at 12 weeks was 97.5%.

In their publication, the Spanish authors note that these findings "raise a concern about the benefits" of direct-acting antiviral therapy in the subgroup of hepatitis C patients with a history of hepatocellular carcinoma. Although the therapies "offer a major hope for current and future patients, we may face a drawback that may change these predictions in specific groups of patients," they point out.

Dr Brillanti said he is less concerned. "Clones of the hepatocellular carcinoma were present before the therapy," he pointed out, suggesting that direct-acting antivirals simply accelerated their inevitable progression. Either way, he said, an increased risk for hepatocellular carcinoma should not deter clinicians or patients from pursuing treatment with direct-acting antivirals when it is needed.

"This is a different cancer than elsewhere in oncology — it is a cancer within an advanced chronic disease — so the prognosis, the life expectancy, is related not only to the liver cancer but also to the liver disease and liver function," he explained. "If you don't treat these patients and ameliorate their liver function, and if hepatocellular carcinoma occurs, you have no chance of curing them. But if you ameliorate liver function and they develop hepatocellular carcinoma, you can cure it better because their improved liver function will allow an ablation."

This finding is "quite striking and unexpected, but we have to be cautious," said Laurent Castera, MD, PhD, from Hôpital Beaujon in Clichy, France, who is vice-secretary of the European Association for the Study of the Liver, and was not involved with the research.

"It is potentially worrying, but these are retrospective studies, with possible referral bias, and no long-term follow-up," he told Medscape Medical News.

Dr Brillanti reports receiving research grants from Gilead Sciences and being on the advisory board for Janssen and Gilead Sciences. Dr Castera reports serving on the speaker's bureau for Echosens.
International Liver Congress (ILC) 2016: Abstract LBP506. Presented April 14, 2016.
Source - Medscape

Feb 2017
Of Interest - In The News
Risk of liver cancer low in patients with cirrhosis, study finds
01 Feb 2017
The results of a study by researchers at The University of Nottingham suggest that the risk of liver cancer in patients with cirrhosis may be much lower than previously thought.

Liver cancer – or hepatocellular carcinoma (HCC) – is one of the most serious complications of cirrhosis, or scarring of the liver, caused by long-term liver damage.

However, an analysis of health records, published in the academic journal Alimentary Pharmacology and Therapeutics, found that the 10-year incidence of HCC in UK patients with cirrhosis is actually only four per cent, or lower.

Joe West, Professor of Epidemiology in the University’s School of Medicine, led the study and believes that the results could better inform doctors on how best to focus resources for the benefit of patients with liver damage.

He said: “This very low incidence of HCC occurrence in people with cirrhosis caused by alcohol or of unknown origin suggests that surveillance for HCC among these groups is likely to benefit patients little.

“As surveillance incurs substantial cost, it is therefore unlikely to represent value for money for the NHS. There may well be other ways of spending this money that would benefit patients far more.”

Cirrhosis is caused by long-term damage to the liver, which leads to a build-up of scar tissue which replaces healthy tissue and eventually can result in liver failure.

The researchers identified more than 3,000 patients with cirrhosis of the liver using the UK’s General Practice Research Database between 1987 and 2006 and then cross-referenced this information with diagnoses of HCC on linked national cancer registries.

The study found that only 1.2 per cent of patients with alcoholic cirrhosis and 1.1 per cent of patients with cirrhosis of unknown cause will develop HCC within a decade. The highest 10-year incidence of HCC was among those with cirrhosis due to chronic viral hepatitis (four per cent).
http://www.nottingham.ac.uk/news/pressreleases/2017/january/risk-of-liver-cancer-low-in-patients-with-cirrhosis-study-finds.aspx

March 2017
Antiviral medication successful for treating HCV in hepatocellular carcinoma

Hepatocellular Carcinoma Decreases the Chance of Successful Hepatitis C Virus Therapy with Direct-Acting Antivirals
The new medications for hepatitis C have excellent cure rates. However, our study shows that in patients with both liver cancer and hepatitis C, they do not achieve these cure rates. Patients with liver cancer are almost 6 times more likely to fail hepatitis C treatment than patients without liver cancer

AGA Institute Clinical Practice Update: Care of Patients Who Have Achieved a Sustained Virologic Response (SVR) Following Antiviral Therapy for Chronic Hepatitis C Infection
Ira M. Jacobson M.D., Joseph K. Lim, M.D., and Michael W. Fried, M.D.
ACCEPTED MANUSCRIPT
DOI: http://dx.doi.org/10.1053/j.gastro.2017.03.018

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Abstract
Chronic hepatitis C virus (HCV) infection is well-recognized as a common blood borne infection with global public health impact, affecting 3 to 5 million persons in the U.S. and over 170 million persons worldwide. Chronic HCV infection is associated with significant morbidity and mortality due to complications of liver cirrhosis and hepatocellular carcinoma (HCC). Current therapies with all-oral directly acting antiviral agents (DAAs) are associated with high rates of sustained virologic response (SVR), generally exceeding 90%. SVR is associated with a reduced risk of liver cirrhosis, hepatic decompensation, need for liver transplantation, and both liver-related and all-cause mortality. However, a subset of patients who achieve SVR will remain at long-term risk for progression to cirrhosis, liver failure, HCC, and liver-related mortality. Limited evidence is available to guide clinicians on which post-SVR patients should be monitored versus discharged, how to monitor and with which tests, how frequently should monitoring occur, and for how long. In this clinical practice update, available evidence and expert opinion are used to generate best practice recommendations on the care of patients with chronic HCV who have achieved SVR.

Index
Assessment of HCV RNA after SVR12 has been attained
With the initiation of trials of DAA regimens, initially in combination with interferon and later
without it, the attainment of SVR 12 weeks after completion of treatment replaced SVR24 as
the primary endpoint, defined as undetectable HCV RNA on a highly sensitive PCR assay (lower
limit of detection <12 IU/mL).  This transition was based upon the rarity of relapse after follow
up week 12, and it helped move the field ahead by shortening the intervals between successive
trials in development programs (22). It has become apparent that late relapse beyond this time
point is no more common, and perhaps less so, than it was after interferon-based therapy

Ongoing surveillance for hepatocellular carcinoma after SVR
Is HCC risk after SVR exclusive to patients with advanced fibrosis and cirrhosis?
Can HCC surveillance ever be discontinued?
How should screening for, and management of, varices be affected by SVR?
Should patients be routinely monitored for regression of advanced fibrosis or
cirrhosis?
Recurrent HCC After SVR
Reinfection
Lifestyle Measures
Conclusions
Continue reading...

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.

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; https://hepatitiscnewdrugs.blogspot.com/search/label/HCV-Education

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

Related
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).

Reference
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.
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Of Interest
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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