Friday, December 2, 2016

Sofosbuvir, daclatasvir combo best treatment for HCV cryoglobulinemia vasculitis

Conference Coverage
Sofosbuvir, daclatasvir combo best treatment for HCV cryoglobulinemia vasculitis
By: Deepak Chitnis
Frontline Medical News

– A combined regimen of sofosbuvir and daclatasvir is the best option to treat patients with hepatitis C virus infections experiencing cryoglobulinemia vasculitis, according to the findings of a new study presented at the annual meeting of the American College of Rheumatology.

“The HCV cryoglobulinemia vasculitis is a very important vasculitis because it represents 5% of chronically infected HCV patients in the world,” explained David Saadoun, MD, of Sorbonne Universities, Paris. “It’s sometimes a life-threatening vasculitis because patients may develop inflammation [so] there’s a need for very active and well-tolerated treatment.”​

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HCV Experts Discuss Impact of Trump Administration​ AND Got Hep B and Worried About the Trump Effect on Your Obamacare?

Article Published Online @ Healio
HCV experts discuss impact of Trump administration​
Results of a Reuters/Ipsos poll taken during Nov. 9-14, 2016 indicated that more than 20% of Americans wanted President-elect Donald J. Trump to focus on health care in his first 100 days in office. However, when HCV Next reached out to a cross-section of experts for commentary on exactly what Trump could realistically expect to accomplish in health care, and how he would accomplish it, there were more questions than answers. Of note, some experts declined to comment.
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Article Published Online @ Hepatitis C Foundation
Got Hep B and Worried About the Trump Effect on Your Obamacare? Experts Say No Changes Expected Before 2018
By Christine Kukka
It is time to sign up, re-enroll or change your health insurance plan in the Affordable Care Act’s Health Insurance Marketplace, also known as Obamacare. Millions of Americans – many of them with pre-existing medical conditions such as hepatitis B — get their much-needed health insurance through this plan.

But President-elect Donald Trump has promised to repeal the Affordable Care Act (ACA), which funds the program, and now Republicans will have control of the House and Senate. What should we, who require health insurance to cover our doctor visits, lab tests and costly antiviral treatment to keep our livers healthy, do? Should we sign up for 2017?
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Wales approves new hepatitis C drug while England deliberates

BMJ 2016; 355 doi:
(Published 01 December 2016)
Cite this as: BMJ 2016;355:i6499

Wales approves new hepatitis C drug while England deliberates
Piotr Ozieranski1, Lawrence King2

A new drug for hepatitis C has been approved for use in Wales ahead of its appraisal by the National Institute for Health and Care Excellence (NICE) for use in England and is being made available to patients in line with the Welsh strategy to prevent the transmission of the virus.

The All Wales Medicines Strategy Group recommended Epclusa (sofosbuvir with velpatasvir) for use in the NHS in Wales after concluding that the treatment would be cost effective for most patients.1 The treatment will be funded under the Welsh patient access scheme. The price proposed by its manufacturer, Gilead, is confidential but likely to involve a discount from the UK list price of about £40 000 (€47 000; $50 000) …

Download Article, here....

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Thursday, December 1, 2016

NIH Statement on World AIDS Day 2016

NIH Statement on World AIDS Day 2016

Anthony S. Fauci, M.D., Director, National Institute of Allergy and Infectious Diseases
Carl W. Dieffenbach, Ph.D., Director, Division of AIDS, NIAID

This year, the world marked the 35th anniversary of the first published reports of what would come to be known as HIV/AIDS. This disease has wrought enormous suffering and devastation and caused more than 35 million deaths. Yet today, thanks to remarkable achievements in biomedical science and public health, we have the tools to build a better future for individuals living with HIV and for those at risk of infection. We are hopeful that new approaches currently under exploration could expedite the end of the HIV/AIDS pandemic.

The greatest scientific accomplishment in HIV research has been the development of effective treatments that suppress the virus and prolong the lives of those living with HIV. Over time, scientists have refined and optimized antiretroviral therapy, delivering safer, more effective drugs that are easier to take. Today, a person living with HIV on antiretroviral therapy can expect to live a nearly normal lifespan.

Antiretroviral therapy has been transformational for both individuals and communities. Large studies conducted in diverse settings, from U.S. cities to African villages, have demonstrated the power of treatment to preserve the health of those living with HIV. Additionally, studies have proven that when an individual living with HIV is on antiretroviral therapy and the virus is durably suppressed, the risk that he or she will sexually transmit the virus is negligible. Research also has repeatedly demonstrated that HIV incidence diminishes when HIV testing is aggressively implemented, individuals with HIV infection are linked to treatment, and support is provided to keep them in care. The power of treatment as prevention cannot be underestimated in helping to achieve global targets to dramatically reduce new infections and improve the health of those already living with HIV.

The National Institutes of Health (NIH) is supporting the development of new, innovative methods to prevent the spread of HIV, building on proven HIV prevention tools such as antiretroviral treatment; condoms; voluntary medical male circumcision; and pre-exposure prophylaxis (PrEP), a daily pill that uninfected people can take to prevent infection. Earlier this week, NIH announced the start of HVTN 702, a large HIV vaccine efficacy trial in South Africa that builds on the modest success of the RV144 vaccine trial conducted in Thailand. The HVTN 702 vaccine candidate is designed to prevent infection by the HIV strain most commonly found in southern Africa. About 3,700 people become infected with HIV every day in sub-Saharan Africa.

In April, NIH launched the Antibody-Mediated Prevention Trial (AMP) to test whether a broadly neutralizing antibody delivered intravenously to uninfected individuals is safe, tolerable and effective at preventing HIV infection. Many scientists believe that if an HIV vaccine could elicit broadly neutralizing antibodies in people, it would protect them from infection. By giving participants this antibody directly, researchers expect to gain critical insights to inform HIV prevention and vaccine science.

NIH is testing HIV prevention options that address the unique needs of women, such as a vaginal ring infused with the antiretroviral drug dapivirine, which reduced the risk of HIV infection by only a modest 27 percent in a large clinical trial reported this year. Additional analyses suggest that this product may be much more effective when used regularly. A study launched in July aims to clarify further the relationship between adherence to the ring and efficacy, as well as to understand better the complexities women face when adhering to a vaginal ring.

Science has made remarkable strides in preventing the transmission of HIV from mother to infant during pregnancy, birth and breastfeeding. This summer, researchers reported the results of the PROMISE study, which demonstrated that for mothers living with HIV whose immune systems are in good health, taking a three-drug antiretroviral regimen during breastfeeding essentially eliminates HIV transmission to their infants.

While preventing new infections is essential, it remains critical that the 36.7 million people living with HIV globally benefit from cutting-edge science. Today’s treatments are lifesaving, yet people living with HIV still suffer from higher rates of chronic disease than their uninfected counterparts. Clinical trials are exploring interventions to help prevent these diseases. One example is the REPRIEVE study, a large, international trial exploring the use of a statin drug to prevent heart disease in women and men living with HIV.

Researchers also are working toward the goal of inducing sustained viral remission or absence of viral rebound following discontinuation of antiretroviral therapy. They are testing a number of approaches to successfully withdraw antiretroviral therapy in individuals whose virus is well controlled. In October, a provocative and potentially important advance was achieved in an animal study: An antibody directed against a cell surface marker involved in the homing of lymphocytes to the gut given together with antiretroviral therapy for 5 weeks in monkeys infected with a monkey version of HIV led to a sustained suppression of viral rebound for up to 2 years following discontinuation of all therapy. A study is now underway to explore this strategy in people living with HIV.

These global efforts bring hope on this World AIDS Day that an end to the HIV/AIDS pandemic is achievable. We applaud the trial participants, researchers, health care professionals, advocates and others who are working to make this future a reality.

NIAID conducts and supports research — at NIH, throughout the United States, and worldwide — to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit

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