HCV: Interferon-Free Regimen Works in Hard-to-Treat Patients

Medscape Medical News

Nancy A. Melville

Aug 27, 2013

Patients with chronic hepatitis C (HCV) in a traditionally difficult-to-treat population respond well to an interferon-free oral treatment regimen of sofosbuvir and ribavirin, according to research published in the August 28 issue of JAMA.

"Because treatment of HCV is evolving from an interferon-based combination therapy to an all-oral, interferon-free directly acting antiviral agent regimen, these results are encouraging and provide important information regarding the expected treatment responses in a population representative of the US epidemic," Anuoluwapo Osinusi, MD, MPH, from the National Institutes of Health, Bethesda, Maryland, write.

The 2-part, open-label phase 2 study involved 60 treatment-naive patients with HCV genotype 1. Among the participants, 83% were black, 66% were men, 23% had advanced liver disease, 48% had a body mass index of 30 kg/m² or higher, 70% had HCV genotype 1a, and 62% had baseline HCV RNA levels of 800,000 or higher.

In the first part of the study, 10 patients with early to moderate liver fibrosis were treated with 400 mg/day sofosbuvir and ribavirin dosage based on weight for 24 weeks. The 50 participants in the second part of the study had all stages of liver fibrosis and were randomly assigned 1:1 to receive 400 mg sofosbuvir with either weight-based ribavirin or low-dose 600 mg/day ribavirin for 24 weeks.

Nine participants (90%) in the first part of the study achieved a sustained virologic response (SVR), defined as an undetectable HCV viral load for 24 weeks after the completion of treatment. In the second part of the study, 68% (95% confidence interval, 46% - 85%) of the patients in the weight-based dosage group achieved SVR for 24 weeks compared with 48% (95% confidence interval, 28% - 69%) of the patients in the low-dose group (P = .20).

Seven (28%) participants in the weight-based group and 10 (40%) participants in the low-dose group relapsed after completing treatment. Baseline factors most associated with relapse included male sex, advanced liver disease, and high baseline HCV RNA levels.

The most common adverse events included headache, anemia, fatigue, and nausea. Although most adverse events were described as mild to moderate, 7 patients developed grade 3 adverse events including anemia, neutropenia, nausea, hypophosphatemia, and cholelithiasis or pancreatitis. There were no deaths or discontinuation of treatment resulting from adverse events, and the combination regiment was considered safe and well-tolerated.

"This study demonstrates the efficacy of an interferon-free regimen in a traditionally difficult-to-treat population while exploring the reasons for treatment relapse," the authors write.

"As new direct-acting antiviral agent regimens are being evaluated, it is important that these studies involve populations most affected by the disease."

Interferon has, among its disadvantages, weekly injections and fatigue from influenza-like symptoms, and it is furthermore contraindicated in patients with HCV who have advanced liver disease, making the findings on the new all-oral regimen even more encouraging, said Michael Saag, MD, clinical director for the Center for AIDS Research and the Division of Infectious Diseases at the University of Alabama at Birmingham.

"Anything that allows these people to have success without the injection is an important step forward," he told Medscape Medical News.

Although the overall rate of 68% achieving sustained virologic response was lower than that observed in populations with more favorable treatment predictors, it is still higher than is typically seen in the black male population, Dr. Saag noted.

"The SVR rate in this population is usually in the 40% to 50% range, due to some [genotype differences], so 68% is relatively good," added Dr. Saag, who is also a spokesperson for the Infectious Disease Society of America's hepatitis task force. "I think we're on the verge of a very exciting revolution in HCV care, and this is the first of what I believe will be several landmark articles that will change how we approach the treatment of this disorder over the next 5 years."

The study was funded by the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and the German Research Foundation. One coauthor has reported serving as research consultant for Roche Pharma and Novartis. One coauthor has reported serving on the Gilead and Merck Advisory Boards and as a speaker for Gilead. One coauthor has reported serving as a speaker for Merck and performing research funded by Vertex pharmaceuticals. One coauthor has reported being a member of the Regional Advisory Boards for Abbott and Gilead. Three coauthors are employees of Gilead Pharmaceuticals. Dr. Saag disclosed that he has consulted for Gilead Pharmaceuticals in the past but was not involved in the current study.

JAMA. 2013;310:804-811.

Source

Also See:

Sofosbuvir and Ribavirin for Hepatitis C Genotype 1 in Patients With Unfavorable Treatment Characteristics: A Randomized Clinical Trial (Journal of the American Medical Association-Abstract)

Investigational oral regimen for hepatitis C shows promise in NIH trial (NIH Press Release)

Vertex’s VX-135 partial hold signals heightened FDA scrutiny toward HCV drugs

August 27, 2013 3:35 pm

By Christine Livoti in New York

This article is provided to FT.com readers by BioPharm Insight—a news service focused on providing insight into the most price sensitive issues in the global pharmaceutical market. www.biopharminsight.com

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

Vertex Pharmaceuticals’ (NASDAQ:VRTX) hepatitis C virus (HCV) drug VX-135 and the recent partial clinical hold placed on it signal heightened FDA scrutiny toward HCV drugs, experts said.

Still, most experts expressed optimism the partial hold will be removed and that the 200mg dose will advance.

On 25 July, the company announced the FDA had issued a partial clinical hold on Vertex’s ongoing Phase II US study of VX-135, a nucleotide (nuc) pyrimidine analogue. The agency’s decision prevents evaluation of the 200mg dose, following observation of reversible elevated liver enzymes in patients receiving 400mg VX-135 in combination with ribavirin in a Phase II study in Europe. Evaluation of a 100mg dose in combination with ribavirin in the 12-week Phase II US study is continuing as planned, according to the press release.

Vertex recently completed dosing of 100mg and 200mg VX-135 in combination with ribavirin in the 12-week Phase II European study, and both doses were well tolerated with no discontinuations. No serious adverse events (SAEs) have been reported and no liver or cardiac safety issues have been identified, according to the release. An adverse event is any undesirable experience associated with a medical product. The event is considered serious when the outcome is death, hospitalization, disability or permanent damage and/or congenital anomaly, among other important medical events, according to the FDA. Following completion of enrollment in the 100mg and 200mg arms of the European study, the study was amended to evaluate a 400mg dose in combination with ribavirin in 10 patients. Elevated liver enzymes were observed in three patients in this dose group, including one SAE, and the study’s 400mg arm was discontinued. After discontinuation, liver enzyme levels returned to baseline in all three patients, according to the same release.

Continue reading full article here …..

Santaris Pharma A/S Completes Enrollment in Phase 2 Clinical Trial of Miravirsen

Santaris Pharma A/S Completes Enrollment in Phase 2 Clinical Trial of Miravirsen In Null Responders to Pegylated Interferon and Ribavirin for the Treatment of the Hepatitis C Virus

-- Enrollment also begins in study investigating miravirsen in combination with telaprevir and ribavirin in null responders to pegylated interferon and ribavirin --

Hørsholm, Denmark/San Diego, California, August 27, 2013 — Santaris Pharma A/S, a clinical-stage biopharmaceutical company focused on the discovery and development of RNA-targeted therapies, today announced the completion of enrollment of its Phase 2 miravirsen 12-week monotherapy study of miravirsen, a host-targeted, pan-HCV genotype antiviral agent, in subjects who were "null responders" to pegylated interferon alpha and ribavirin (peg-IFNα/RBV). The company also announced the enrollment of the first patient into another Phase 2 study of miravirsen in combination with telaprevir and ribavirin, also in null responders to peg-IFNα/RBV.

"The current standard of treatment for HCV is a combination of a direct acting-antiviral agent protease inhibitor with pegylated-interferon plus ribavirin. However, there remains a pressing need for therapeutic regimens that can attain high sustained virologic responses without peg-IFNα/RBV, which is poorly tolerated, and without drug-drug interactions. Miravirsen’s unique mode-of-action has shown potential in providing antiviral activity in patients who have failed previous treatment regimens for the hepatitis C virus," said Maribel Rodriguez-Torres, M.D., president of Fundacion de Investigacion and the study’s Principal Investigator. "We are excited to have completed enrollment and look forward to following the enrolled patients and reporting the data from this study. So far, the emerging viral load data suggest that miravirsen might be a unique treatment option, in combination with other antivirals, for the treatment of this type of difficult to treat patients."

The Phase 2, open-label study assesses the safety, antiviral activity and pharmacokinetics of miravirsen monotherapy over a total of 12 weeks of treatment. Patients enrolled in the study were chronically infected with HCV genotype 1 and had previously failed treatment with peg-IFNα/RBV therapy. Miravirsen was given as a total of five doses over five weeks, followed by a further four doses once every other week over seven weeks.

Developed using Santaris Pharma A/S proprietary Locked Nucleic Acid (LNA) Drug Platform, miravirsen is an inhibitor of miR-122, a liver specific microRNA that the hepatitis C virus requires for replication. Miravirsen is designed to recognize and sequester miR-122, making it unavailable to the hepatitis C virus. As a result, the replication of the virus is effectively inhibited and the levels of HCV RNA are profoundly reduced.

Santaris Pharma A/S has also enrolled its first patient into another Phase 2 clinical trial that will assess the safety, tolerability and antiviral activity of miravirsen given for 12 weeks in combination with telaprevir (TVR) and ribavirin (RBV) in patients with HCV infection who are non-responders to peg-IFNα/RBV.

"We are pleased to report on the progress in the miravirsen clinical program," said Michael R. Hodges, MD, Vice President and Chief Medical Officer at Santaris Pharma A/S. "We hope that data from these two 12-week studies in the hard to treat patients will confirm the earlier promising efficacy and safety data from the four-week monotherapy study in treatment naïve patients that was recently published in the New England Journal of Medicine. We continue to believe that miravirsen given in combination with direct acting-antiviral agent(s) has the potential to cure chronic HCV infection in hard-to-treat patients."

The first series of non-clinical and clinical studies demonstrated the following key attributes for miravirsen:

• Miravirsen has a novel mechanism of action, inhibits a well conserved hepatic host target thus has an high barrier to resistance with predicted activity against all HCV genotypes, is not metabolized by cytochrome P450 enzymes therefore drug interactions are unlikely
• In in vitro studies, miravirsen was active against all six HCV genotypes, additive activity to direct acting antiviral agents (DAAs), active against DAA resistant virus and a showed a high barrier to resistance
• In clinical trials with four weeks of monotherapy, miravirsen was well tolerated, showed dose dependent antiviral activity that can be maintained weeks after the end of therapy
• In two separate drug-drug interaction clinical trials, miravirsen showed no interactions with peg-IFNα/RBV or with telaprevir

About Hepatitis C

Hepatitis C infection is a viral disease caused by the hepatitis C virus that leads to inflammation of the liver. The World Health Organization estimates that approximately 3 percent of the world’s population have been infected with HCV and that some 170 million have chronic hepatitis C and are at risk of developing liver cirrhosis and/or liver canceri. Approximately 3-4 million Americans are chronically infected with an estimated 40,000 new infections per yearii. In Europe, there are about 4 million carriersi. The current standard of care treatment for genotype 1 is a protease inhibitor given with pegylated-interferon α and ribavirin. This triple combination is effective in about 70-80% of those treatedii. Even though in Europe and the United States genotype 1 is the most prevalent, there are 50-70 million people worldwide that are infected with a non-genotype 1 virus. In these patients, the combination of pegylated-interferon α and ribavirin remains the currently approved standard of care treatmentiii. Patients that are not effectively treated have an increased risk for the progression of liver disease. By 2029, total annual medical costs in the United States for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion^iv.

About microRNAs

MicroRNAs have emerged as an important class of small RNAs encoded in the genome. They act to control the expression of sets of genes and entire pathways and are thus thought of as master regulators of gene expression. Recent studies have demonstrated that microRNAs are associated with many disease processes. Because they are single molecular entities that dictate the expression of fundamental regulatory pathways, microRNAs represent potential drug targets for controlling many biologic and disease processes.

About Locked Nucleic Acid (LNA) Drug Platform

The LNA Drug Platform and Drug Discovery Engine developed by Santaris Pharma A/S combines the company’s proprietary LNA chemistry with its highly specialized and targeted drug development capabilities to rapidly deliver LNA-based drug candidates against RNA targets, both mRNA and microRNA, for a range of diseases including cardiometabolic disorders, infectious and inflammatory diseases, cancer and rare genetic disorders. LNA is also sometimes referred to as BNA (Bicyclic or Bridged Nucleic Acid). LNA-based drugs are a promising new class of therapeutics that enable scientists to develop drugs that work through previously inaccessible clinical pathways. The LNA Drug Platform overcomes the limitations of earlier antisense and siRNA technologies to deliver potent single-stranded LNA-based drug candidates across a multitude of disease states. The unique combination of small size and very high affinity allows this new class of drugs candidates to potently and specifically inhibit RNA targets in many different tissues without the need for complex delivery vehicles. The most important features of LNA-based drugs include excellent specificity providing optimal targeting; increased affinity to targets providing improved potency; and favorable pharmacokinetic and tissue-penetrating properties that allow systemic delivery of these drugs without complex and potentially troublesome delivery vehicles.

About Santaris Pharma A/S

Santaris Pharma A/S is a privately held, clinical-stage biopharmaceutical company focused on the discovery and development of RNA-targeted therapies. The Locked Nucleic Acid (LNA) Drug Platform and Drug Discovery Engine developed by Santaris Pharma A/S combine the company’s proprietary LNA chemistry with its highly specialized and targeted drug development capabilities to rapidly deliver potent single-stranded LNA-based drug candidates across a multitude of disease states. The company’s research and development activities focus on infectious diseases and cardiometabolic disorders, while partnerships with major pharmaceutical companies address a range of therapeutic areas including cancer, cardiovascular disease, infectious and inflammatory diseases, and rare genetic disorders. The company has strategic partnerships with RaNA Therapeutics, Bristol-Myers Squibb, miRagen Therapeutics, Shire, Pfizer, GlaxoSmithKline, and Enzon Pharmaceuticals. As part of its broad patent estate, the company holds exclusive worldwide rights to manufacture and sell products that comprise LNA as active ingredient for studies performed with a view to obtaining marketing approval. Santaris Pharma A/S, founded in 2003, is headquartered in Denmark with operations in the United States. Please visit www.santaris.com for more information.

Santaris Pharma A/S® is a registered trademark of Santaris Pharma A/S. Santaris^TM, Santaris Pharma^TM, Cureon^TM and LNA-antimiR™ are trademarks of Santaris Pharma A/S.

Media Contacts: Liz Narrillos Roux, Edelman (liz.narrillosroux@edelman.com) - Office: (323)202-1074

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Sofosbuvir and Ribavirin for Hepatitis C Genotype 1 in Patients With Unfavorable Treatment Characteristics: A Randomized Clinical Trial

Journal of the American Medical Association

Preliminary Communication | August 28, 2013

Anuoluwapo Osinusi, MD, MPH^1,2; Eric G. Meissner, MD, PhD¹; Yu-Jin Lee¹; Dimitra Bon, MS³; Laura Heytens, RN⁴; Amy Nelson, RN¹; Michael Sneller, MD¹; Anita Kohli, MD¹; Lisa Barrett, MD, PhD¹; Michael Proschan, PhD⁵; Eva Herrmann, PhD³; Bhavana Shivakumar, MS¹; Wenjuan Gu, PhD⁶; Richard Kwan, PAC⁴; Geb Teferi, MD⁷; Rohit Talwani, MD⁸; Rachel Silk, RN²; Colleen Kotb, RN²; Susan Wroblewski, RN¹; Dawn Fishbein, MD⁹; Robin Dewar, PhD⁶; Helene Highbarger, MS⁶; Xiao Zhang, MS¹; David Kleiner, MD¹⁰; Brad J. Wood, MD¹¹; Jose Chavez, MD⁷; William T. Symonds, PharmD¹²; Mani Subramanian, MD, PhD¹²; John McHutchison, MD¹²; Michael A. Polis, MD, MPH¹; Anthony S. Fauci, MD¹; Henry Masur, MD⁴; Shyamasundaran Kottilil, MD, PhD¹

[+-] Author Affiliations

¹Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
²Clinical Research Directorate/Clinical Monitoring Research Program, Science Applications International Corp (SAIC)–Frederick Inc, Frederick National Laboratory for Cancer Research, Frederick, Maryland
³Institute of Biostatistics and Mathematical Modeling, Johann Wolfgang Goethe University, Frankfurt, Germany
⁴Critical Care Medicine Department, National Institutes of Health Clinical Center, National Institutes of Health, Bethesda, Maryland
⁵Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
⁶SAIC-Frederick Inc, Frederick National Laboratory for Cancer Research, Frederick, Maryland
⁷Unity Health Care Inc, Washington, DC
⁸Department of Infectious Diseases, University of Maryland, Baltimore
⁹Department of Infectious Diseases, MedStar Washington Hospital Center, Washington, DC
¹⁰Department of Pathology, National Cancer Institute, Bethesda, Maryland
¹¹Center for Interventional Oncology, Radiology and Imaging Sciences, NIH Clinical Center and National Cancer Institute, Bethesda, Maryland
¹²Gilead Sciences, Foster City, California

JAMA. 2013;310(8):804-811. doi:10.1001/jama.2013.109309.

Abstract

Objective  To determine the efficacy and safety of sofosbuvir with weight-based or low-dose ribavirin among a population with unfavorable treatment characteristics.

Design, Setting, and Patients  Single-center, randomized, 2-part, open-label phase 2 study involving 60 treatment-naive patients with hepatitis C virus (HCV) genotype 1 enrolled at the National Institutes of Health (October 2011-April 2012).

Interventions  In the study’s first part, 10 participants with early to moderate liver fibrosis were treated with 400 mg/d of sofosbuvir and weight-based ribavirin for 24 weeks. In the second part, 50 participants with all stages of liver fibrosis were randomized 1:1 to receive 400 mg of sofosbuvir with either weight-based or low-dose 600 mg/d of ribavirin for 24 weeks.

Main Outcomes and Measures  The primary study end point was the proportion of participants with undetectable HCV viral load 24 weeks after treatment completion (sustained virologic response of 24 weeks [SVR₂₄]).

Results  In the first part of the study, 9 participants (90%; 95% CI, 55%-100%) achieved SVR_24. In the second part, 7 participants (28%) in the weight-based group and 10 (40%) in the low-dose group relapsed after treatment completion leading to SVR₂₄ rates of 68% (95% CI, 46%-85%) in the weight-based group and 48% (95% CI, 28%-69%; P = .20) in the low-dose group. Twenty individuals participated in a pharmacokinetic-viral kinetic substudy, which demonstrated a slower loss rate of infectious virus in relapsers than in participants who achieved SVR (clearance, 3.57/d vs 5.60/d; P = .009). The most frequent adverse events were headache, anemia, fatigue, and nausea. There were 7 grade 3 events including anemia, neutropenia, nausea, hypophosphatemia, and cholelithiasis or pancreatitis. No one discontinued treatment due to adverse events.

Conclusion and Relevance  In a population of patients with a high prevalence of unfavorable traditional predictors of treatment response, a 24-week regimen of sofosbuvir and weight-based or low-dose ribavirin resulted in SVR₂₄ rates of 68% and 48%, respectively.

Trial Registration  clinicaltrials.gov Identifier: NCT01441180

Source

Also See: Investigational oral regimen for hepatitis C shows promise in NIH trial

Investigational oral regimen for hepatitis C shows promise in NIH trial

Embargoed for Release: Tuesday, August 27, 2013, 4 p.m. EDT

Side effects minimized with combination therapy in hard-to-treat patients

In a study of an all-oral drug regimen, a majority of volunteers with liver damage due to hepatitis C virus (HCV) infection were cured following a six-month course of therapy that combined an experimental drug, sofosbuvir, with the licensed antiviral drug ribavirin. The results showed that the regimen was highly effective in clearing the virus and well tolerated in a group of patients who historically have had unfavorable prognoses.

Scientists from the National Institute of Allergy and Infectious Diseases (NIAID) and the NIH Clinical Center, parts of the National Institutes of Health, led the Phase II trial. The findings appear in the Aug. 28 issue of the Journal of the American Medical Association (JAMA).

More than 3 million Americans have chronic HCV infection, a condition that is a major cause of cirrhosis (liver tissue scarring) and liver cancer, and a leading reason for liver transplantation. Deaths from HCV-related liver disease number about 15,000 every year. Standard treatment for HCV can last up to a year and usually involves weekly injections of pegylated interferon-alpha given with the oral drug ribavirin and an HCV protease inhibitor. Side effects from this treatment can be severe, notably from interferon-alpha, and can include depression, flu-like symptoms and anemia.

“There is a pressing need for hepatitis C virus treatments that are less burdensome to the patient, have fewer side effects and take less time to complete. Building on previous work, this trial provides compelling evidence that interferon-free regimens can be safe and effective,” said NIAID Director and study co-author Anthony S. Fauci, M.D.

The current study involved 60 volunteers with genotype-1 HCV, which tends to be less responsive to interferon-based treatment. Fifty of the 60 participants were African-American.

“While African-Americans make up about 13 percent of the U.S. population, they represent more than 22 percent of people with chronic HCV infection and, compared to whites, have lower cure rates with traditional HCV therapy,” said NIAID researcher Shyam Kottilil, M.D., Ph.D., the principal investigator of the trial. “Several recently completed trials testing interferon-free regimens have yielded promising results, but most volunteers in those studies were white.”

The new study also differs from many previous trials because it enrolled people with severe liver damage as well as those with mild or moderately scarred livers.

The study was divided into two parts. The first part enrolled 10 people with mild or moderate liver fibrosis. Volunteers received oral ribavirin at a dosage based on their weight along with the experimental drug sofosbuvir, also in pill form, taken daily for six months. Gilead Sciences, Inc., of Foster City, Calif., manufactures sofosbuvir and supplied it to the study physicians.

Nine volunteers completed the course of therapy. Virus was undetectable in all nine volunteers 12 weeks after the end of therapy and continued undetectable when they were tested again 24 weeks after finishing therapy. HCV does not integrate itself into human DNA. If the virus cannot be detected for a period of 12 weeks after stopping therapy, the patient is considered cured, Dr. Kottilil said.

The second part of the trial enrolled 50 volunteers, 13 of whom had liver damage rated as serious. Twenty-five received ribavirin based on their weight, and 25 received a low dose (600 milligrams per day). All received sofosbuvir.

“Because ribavirin can cause serious side effects, including anemia, we wanted to compare response rates in patients taking low-dose ribavirin with results from patients on a weight-based dosage,” said Dr. Kottilil.

At four, 12 and 24 weeks after the end of treatment, volunteers were tested for the presence of HCV. HCV levels were undetectable in 24 of the volunteers in the weight-based arm when treatment ended. Of those, 17 continued to have undetectable virus levels 24 weeks later and were considered cured of infection. In the low-dose arm, three volunteers dropped out of the study. Of the remaining 22, all responded to the treatment, but only 12 were considered cured at 24 weeks after the end of treatment.

“We saw an overall cure rate of about 70 percent using regimens that did not include interferon,” said Dr. Kottilil. “This is an encouraging result, especially considering the proportion of volunteers who had characteristics — such as being male, having HCV genotype-1 infection, being African-American and having advanced liver damage — that are recognized as predictors of poor response to treatment.”

Additional trials are underway to further determine if regimens without interferon or ribavirin can help people with chronic HCV infection, particularly those who have both HIV and HCV infections said Dr. Kottilil. These trials include two studies in which volunteers with or without HIV infection take a combination of HCV drugs (but no interferon or ribavirin) for periods of three months or less. Information about these trials is available at clinicaltrials.gov using the identifiers NCT01805882 and NCT01878799.

Further information about the HCV trial described in the current issue of JAMA is available at clinicaltrials.gov using the trial identifier NCT01441180.

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 at http://www.niaid.nih.gov.

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 www.nih.gov.

NIH...Turning Discovery Into Health^®

Reference

A Osinusi et al. Sofosbuvir and ribavirin for hepatitis C genotype 1 in patients with unfavorable treatment characteristics: A randomized clinical trial. JAMA DOI: 10.1001/JAMA.2013.109309 (2013).

Source

Also See: Investigational oral regimen for hepatitis C shows promise in NIH trial

Magnetic resonance laparoscopy: A new non-invasive technique for the assessment of chronic viral liver disease

Hepatol Res. 2013 Aug;43(8):836-45. doi: 10.1111/hepr.12025. Epub 2013 Feb 28.

Ogura S, Saitoh S, Kawamura Y, Sezaki H, Hosaka T, Akuta N, Kobayashi M, Suzuki F, Suzuki Y, Arase Y, Ikeda K, Kumada H.

Department of Hepatology, Toranomon Hospital, Tokyo, Japan.

Abstract

AIM: Laparoscopy-guided liver biopsy is the most accurate method for assessing liver fibrosis but have several limitations. We designed a non-invasive method, called magnetic resonance laparoscopy (MRL), based on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging, to assess liver fibrosis in patients with chronic hepatitis B and C virus.

METHODS: We prospectively analyzed 49 patients with normal liver and 353 patients with chronic viral hepatitis, laparoscopic liver biopsy was performed on 109 patients and 244 patients were diagnosed as having liver cirrhosis clinically. The MRL findings of the liver surface were classified into three categories: (i) smooth (essentially smooth surface of the entire liver or with limited areas of depression); (ii) partially irregular (several interconnected depressions on the surface mainly in the left lobe of the liver); and (iii) diffusely irregular (nodules present on the liver surface). Patients with diffusely irregular liver surface was diagnosed as liver cirrhosis.

RESULTS: The liver surface changed with the progression of liver fibrosis from smooth, partially irregular to diffusely irregular, irrespective of viral type. The sensitivity, specificity, positive and negative predictive values for the diagnosis of cirrhosis according to the surface findings on MRL were 96%, 100%, 95% and 95%, respectively. The cirrhotic liver showed: (i) disappearance of impression of the right ribs; (ii) enlargement of the lateral segment; and (iii) atrophy of the right lobe according to Child-Pugh classification.

CONCLUSION: Our data indicated that MRL is a potentially useful non-invasive examination for evaluation of liver fibrosis associated with viral hepatitis.

© 2012 The Japan Society of Hepatology.

KEYWORDS: chronic hepatitis, gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid, laparoscopy, multiple resonance imaging, multiple resonance laparoscopy

PMID: 23445460 [PubMed]

Source

Healthline Partners with Timothy Ray Brown Foundation to Launch "You've Got This"

Public Service Initiative Aims to Give Hope to Those Recently Diagnosed with HIV

San Francisco, CA (PRWEB) August 27, 2013

You've Got This

“Many people who are faced with a recent diagnosis of HIV feel completely alone. This initiative is meant to provide them with some hope and a feeling of community”

There are over two million people recently diagnosed with HIV worldwide. These are two million people who have felt frightened, anxious unsupported and completely unsure about what the future holds for them. Healthline has launched a new public service initiative with the goal of giving hope and advice to those who have been recently diagnosed with HIV. “You’ve Got This” encourages people to upload a video of themselves letting those with HIV know they are not alone and that they’ve “got this.” The videos will be posted on Healthline.com and shared with the Healthline HIV Awareness Facebook community.

In addition to providing hope, participants should know that Healthline will donate $10 for every video created to the Timothy Ray Brown Foundation (TRBF) of the World AIDS Institute. TRBF is the first and only organization in the 31-year history of AIDS created with the sole mission of finding a cure, its central tenant is HIV cure awareness, education and to secure cure funding and support cutting-edge therapies.

“Many people who are faced with a recent diagnosis of HIV feel completely alone,” said Director of Marketing, Tracy Rosecrans at Healthline. This initiative is meant to provide them with some hope and a feeling of community. They have a place to go to get some sound advice from those who are dealing with the disease themselves. The goal is to let them know that they can still live a full and healthy life and that they’ve got this.”

“We are proud to be a partner in You’ve Got This,” said Timothy Ray Brown co-founder of the Timothy Ray Brown Foundation of the World AIDS Institute. “The initiative is very much in line with our mission of giving those diagnosed with HIV hope for the future.”

Submit a “You’ve Got This” video and view videos from Jack Mackenroth, Olympian Ji Wallace, Paul Lekakis, Kevin Maloney from Rise Up To HIV, and activist Josh Robbins at http://www.healthline.com/health/hiv-aids/youve-got-this.

How to Make a ‘You’ve Got This’ Video:

• In order to upload your video, the person must have or create a valid YouTube account.
• Offer useful advice on living with HIV and let them know how you are managing it. Uplift them and give them hope.
• Use the title “You’ve Got This” and include your name and location (ex: “You’ve Got This: Tracy from Michigan”).
• Tag your video. Use tags to describe your video so that other people can find it (ex: “California HIV couple” or “HIV non-profit”).
• Make sure the sound on your video is clear.
• Make sure light is on your face and not behind you (i.e. don't sit in front of a bright window).
• Include a caption script. If you can, submit a transcript of your video as a caption file on YouTube. This will help to make sure that your video is accessible to deaf and hard-of-hearing individuals, as well as those who use Google translate.

About Healthline

Healthline’s mission is to improve health through information. They focus on offering readers and visitors objective, trustworthy, and accurate health information, guided by the principles of responsible journalism and publishing. Their editorial philosophy is to use relevant and accurate content to promote a healthy lifestyle and facilitate disease prevention, as well as to offer clinically significant, medically reviewed information for those who are seeking answers to their health questions. All original content is produced by highly skilled writers or experienced health professionals who are adept at researching a variety of topics and delivering concise, accurate, and engaging information in an easy-to-understand format. When applicable, articles are reviewed by a health professional—a doctor, nurse, dietician, nutritionist, etc.—to ensure the information is accurate. All articles are then reviewed and edited by a member of the Healthline Editorial Team before publication. The information presented on Healthline.com is not in any way meant to replace the doctor-patient relationship or the professional healthcare experience. Learn more at http://www.healthline.com.

About the Timothy Ray Brown Foundation of the World AIDS Institute

Timothy Ray Brown, the first to be cured of HIV, announced the establishment of The Timothy Ray Brown Foundation of the World AIDS Institute on July 24, 2012 during the 19th International AIDS (removed Society) Conference. As the first and only organization in the 31-year history of AIDS created with the sole mission of finding a cure, its central tenant is to secure funding and support cutting-edge therapies. Timothy Ray Brown is also Co-Founder of the World AIDS Institute with offices in Washington, DC and Las Vegas. Learn more at: http://www.worldaidsinstitute.org

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