November 8, 2013

AASLD 2013: Hepatitis Debrief by Mark Sulkowski MD

Provided by NATAP

Reported by Jules Levin

from Jules: In this very well done AASLD Hepatitis Debrief presented at the very end of the conference by Dr Mark Sulkowski he takes us through the key presentations & messages presented at this AASLD. The conference was breathtaking because of the new data from studies of new oral HCV treatments (DAAs, direct acting antivirals). This update covers new data reviews for Simeprevir & Faldaprevir in combination with Peg/Rbv, Sofosbuvir in combination with Peg/Rbv, and coinfection data including Sofosbuvir+Rbv for 24 weeks in GT 1 coinfected. As well key GT3 data are reported from the VALENCE Study with Sofosbuvir+Peg/Rbv. The SYNERGY Study from the NIH in African-Americans provided data supporting that DAA oral therapies will be equally effective for African-Americans (see the report, link below). The COSMOS Study, cohorts 1 & 2 report results of the IFN-free regimen of Simeprevir+Sofosbuvir in null responders & advanced disease with 96-100% SVR rates. Previously reported Daclatasvir+Sofosbuvir IFN-free results showed 100% SVR in HCV treatment-naives & for those previously treated & who failed telaprevir & boceprevir. Several select epidemiological studies are covered here including confirming the risk for HCC even after SVR highlighting the compelling key to avoid undue delay of HCV therapy, and the Global Burden of HCC. The FDA is expected to announce by the end of November & the beginning of December that Simeprevir+Peg/Rbv will be approved, that Sofosbuvir+Peg/Rbv & Sofosbuvir+RBv will be approved. In 2014 both Abbvie & Gilead will be submitting applications to the FDA for approvals for their IFN-free oral regimens to treat HCV for 12 weeks. In development, earlier developmental stages are BMS, Merck, & Boehringer Ingelheim with similarly promising IFN-free all oral IFN-free regimens, with all these 3 companies's regimens presented at this conference, phase 2 data, and mentioned below.

Here is a link to the NATAP conference coverage which had already reported these data during the conference in real-time:
64rd Annual Meeting of the American Association for the Study of Liver Diseases Washington, DC Nov 1-5 2013

Presented at AASLD 2013 Nov 1-4 Wash DC by

Mark Sulkowski, MD
Professor of Medicine
Division of Infectious Diseases and Gastroenterology/Hepatology
Johns Hopkins University School of Medicine
Baltimore, MD.





Continue here to view remaining slides ……


Studies Support Baby Boomer Hepatitis C Screening

Medscape Medical News > Conference News

Miriam E. Tucker

November 08, 2013

WASHINGTON, DC — Screening baby boomers in the care of the US Department of Veterans Affairs (VA) for hepatitis C virus, as well as those seen in emergency departments, yields particularly high infection rates, 2 new studies have found.

The prevalence of confirmed hepatitis C infection in these settings — 9.9% in the VA and 8.7% in the emergency department — is about triple the overall 3.3% prevalence seen in those born from 1945 to 1965 — the so-called baby boomer cohort.

Both the US Preventive Services Task Force and the Centers for Disease Control and Prevention (CDC) have recommended 1-time hepatitis C screening for everyone.

Results from the 2 studies were presented here at The Liver Meeting 2013.

Our assumption was that we would pick up 3% of patients with hepatitis C. These 2 presentations indicate that in VA and emergency department settings, our assumptions need to be adjusted, said session comoderator Donald Jensen, MD, director of the Center for Liver Diseases at the University of Chicago Medical Center.

"In these enriched populations, we're going to pick up many, many more patients. We have to be able to identify these individuals and link them to care," he told Medscape Medical News.

Many Vets Remain Undiagnosed

The VA data were presented by Lisa Backus, MD, from the VA Office of Public Health/Population Health and the Veterans Health Administration in Palo Alto, California.

Her team identified 5,500,392 veterans in the VA Corporate Data Warehouse who had at least 1 outpatient visit in 2012.

Most of the patients were male (93%), 65% were white, 15% were black, and 6% were Hispanic. Nearly half (46.2%) were born from 1945 to 1965, 37.4% were born before 1945, and 16.4% were born after 1965.

At some point from 1999 to 2012, 54.7% had undergone antibody testing for hepatitis C.

Veterans in the baby boomer cohort were more likely to have undergone screening than those in the younger and older cohorts (64.2% vs 58.0% vs 41.5%).

Nevertheless, 35.8% of the baby boomer cohort had not undergone hepatitis C screening, Dr. Backus reported.

Of the 215,354 veterans who tested positive for hepatitis C antibodies, 95.1% had confirmatory testing with viral load or genotype tests.

Rates of confirmatory testing were highest in the baby boomer cohort, but were still high in the younger and older cohorts (95.8% vs 94.1% vs 88.6%).

"The high rate of confirmatory testing increases confidence in the observed infection prevalence," she noted.

The prevalence of hepatitis C infection was considerably higher in the veteran population than in the general population in the United States (6.1% vs 1.2%). It was also higher in the veteran baby boomer cohort than in the baby boomer population in the United States (9.9% vs 2.5%).

The prevalence of hepatitis C infection was much higher in veterans first screened in 1999 than in those first screened in 2012 (33.2% vs 5.7%).

The researchers extrapolated the most recent hepatitis C infection prevalence to the 905,571 veterans in the baby boomer cohort who had not been screened, and estimated that screening would identify 51,000 veterans, Dr. Backus explained.

After the presentation, an audience member asked if there might have been selection bias because those screened before the 2012 recommendation from the CDC that all baby boomers be screened would have been more likely to have had symptoms.

Dr. Backus noted that this would be less likely in the VA population because many VA centers began screening their populations in 2005, after a study suggested that Vietnam-era military service was a risk factor (Hepatology. 2005;41:88-96).

"In a way, we were already doing some birth-cohort screening, functionally based on year of service," she noted.

Six-week data from an emergency department hepatitis C screening program were presented by James Galbraith, MD, associate professor of emergency medicine at the University of Alabama at Birmingham.

Emergency Department a Screening Venue

Previous studies have suggested that nonwhites, Medicaid recipients, and the uninsured are all disproportionately affected by hepatitis C, and that those who lack insurance coverage and a usual source of medical care are less likely to know their hepatitis C status. "This suggests that screening efforts that work through the healthcare system might not be successful in reaching individuals infected with hepatitis C," Dr. Galbraith said.

These facts led the emergency department at his institution to initiate a routine opt-out hepatitis C baby boomer screening program, similar to the all-ages screening program that had been established for HIV at the institution.

During the study period — from September 3 to October 17 — 2363 unique visits to the emergency department were made by baby boomers. Nurses administered questionnaires to 1721 of these patients that asked whether they had ever been tested for hepatitis C, and if they had, if they knew their status.

Overall, 1287 patients (74.8%) were unaware of their status, and 984 underwent testing for hepatitis C antibodies. Of those, 118 patients (12.0%) had antibodies for hepatitis C — 71 had positive confirmatory viral RNA results, 27 had negative viral results, and 20 have not yet had the confirmatory test.

Males were more likely than females to have positive antibody screening tests (16.5% vs 7.7%; P < .001) and positive confirmatory RNA results (80.0% vs 57.6%), but there were no differences by race.

Table. Insurance Status of Patients With Positive Results*

Insurance Percent
None 16.7
Public or Medicaid 17.2
Medicare 10.5
Private 4.4

*P < .001 for all.

There were no significant differences in confirmed hepatitis C viremia when comparing insurance type or race, Dr. Galbraith noted.

On the basis of the 6-week data, 1-year projection suggests that 7872 emergency department patients would be screened, and 864 would be antibody-positive, Dr. Galbraith reported.

Dr. Jensen said he wondered whether all the patients understood the questionnaire. "In my practice, I see patients who think hepatitis C is what you get after you've had hepatitis B. I don't think you can just ask people if they've had hepatitis C. A lot of people don't know what that is," he told Medscape Medical News.

Of course, finding a way to link patients tested in the emergency department with care is an issue, given that many are underinsured or uninsured and lack access to primary care services.

Dr. Galbraith said he was "very surprised" by the degree of hepatitis C reactivity, and that his emergency department has been "overwhelmed" by the volume of patients newly diagnosed with chronic hepatitis C. Before the program started, his team suspected that the prevalence would be less than half of what it was. "This degree of reactivity has had a tremendous impact on our timeliness to provide linkage to care and costs, including linkage to care and confirmatory testing," he said.

“We're now seeing a second blip in the 20s, mainly among injection drug users.”

Although his emergency department has established a process for helping newly diagnosed patients to obtain a primary care physician and a hepatitis C specialist, Dr. Galbraith explained that "the greatest barrier is not the availability of specialists, but rather the financial barriers related to a lack of health insurance or the ability for many of these individuals to pay."

There have been delays for Medicaid-dependent patients obtaining a primary care appointment and the subsequent Medicaid-required referral to the hepatitis treatment specialist. "We have overcome these barriers for many already, but there is a growing list of patients in need, and the resource requirement is large," Dr. Galbraith told Medscape Medical News.

"A nationwide focus on linkage to care for these disproportionately affected populations is needed," he added. "Mirroring successes in our emergency department linkage to care for newly diagnosed HIV-infected individuals will be a start. We are hopeful that we will provide every person identified in our screening with the opportunity to see a liver specialist."

Making matters potentially worse is the recent emergence of hepatitis C infection in young adults, Dr. Jensen told Medscape Medical News.

We're now seeing a second blip in the 20s, mainly among injection drug users," he said. "We can't do everything, so we need to focus and not spread ourselves too thin. For now, just screening the baby boomer cohort will identify 800,000 new cases."

Dr. Galbraith has disclosed no relevant financial relationships. Dr. Jensen reports financial relationships with Abbott Laboratories, Astex Pharmaceuticals, Biotica Technology, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Gilead Science, Inhibitex, Johnson & Johnson, Merck, Pharmasset, Roche, Tibotec, and Vertex Pharmaceuticals.

The Liver Meeting 2013: American Association for the Study of Liver Diseases (AASLD). Abstracts 21 and LB-6. Presented November 3 and 4, 2013.


VIDEO: Triple therapy with sofosbuvir yields high SVR rates among cirrhotic patients with HCV

Provided by Healio

November 7, 2013

WASHINGTON — Eric J. Lawitz, MD, of the Texas Liver Institute at the University of Texas, San Antonio, discusses the results of the LONESTAR-2 trial, presented during the Late-Breaking Abstract session at the Liver Meeting 2013.

The study evaluated the efficacy of 400 mg daily sofosbuvir with pegylated interferon and ribavirin for 12 weeks in a cohort of patients with hepatitis C genotype 2 and 3 who had failed previous therapy with peginterferon and ribavirin, including patients with and without cirrhosis.

The cohort had a sustained virologic response rate of 89%, with high response rates observed among patients with and without cirrhosis. Two virologic failures occurred, both among patients with HCV genotype 3, including one cirrhotic patient and one without cirrhosis.

Nearly all patients experienced adverse events, but the incidence of events did not increase compared with therapy containing peginterferon and ribavirin alone.

Disclosure: Lawitz reports numerous financial disclosures.

For more information:

Lawitz EJ. LB-4. Late-Breaking Abstract Session. Presented at: The Liver Meeting 2013; Nov. 1-5, Washington.


Liver Meeting speaker: HCC exceptions contributing to MELD inflation, transplant inequity

Provided by Healio

November 3, 2013

WASHINGTON – Changes should be considered to the Model for End-stage Liver Disease scoring system to improve equity on the transplant waiting list,Patrick G. Northup, MD, of the division of gastroenterology and hepatology in the department of medicine at the University of Virginia, said at The Liver Meeting.

“Regulatory authorities and the transplant community should decide whether transplant should be preferential to HCC [hepatocellular carcinoma], or whether it should treat all diseases equally,” he said. “The current system is self-fulfilling ... HCC exceptions have better wait-list survival and better short-term outcome.”

Researchers analyzed all adult, initial transplant candidates listed for liver transplantation from 2005 to 2012, other than status one candidates, to determine whether HCC exceptions are related to the increase in MELD scores on the U.S. liver transplant waiting list.

The study found those candidates with HCC exceptions experienced significantly fewer mean days on the waiting list in comparison to those without exceptions, largely due to the lower lab-based MELD score. Those with HCC waited a mean of 257 days, compared with 420 days for non-HCC patients (P<.0001)

Similar results were seen in HCC vs. non-HCC transplantation rates (65.4% to 44.2%, P<.0001) and waiting-list death rate (13.5% to 22.3%).

Furthermore, the number of exceptions granted for HCC patients was found to be directly and independently associated with the average MELD score of all candidates at the time of removal (P<.00001), Northup said.

Overall, MELD scores are increasing about 2% per year, he said, noting a strong association between those increasing scores and the upgrades transplant candidates with HCC exceptions are given.

“We should ask ourselves: ‘Does the current system truly give access to the sickest first?’ ” Northup said, before concluding that “we should use extreme caution when considering adding new exceptions to the MELD system … as upgrades to the current MELD system have unintended consequences.”

Disclosure: Northup receives grant and research support from Hemosonics, Bristol Myers Squibb.

For more information:

Northup P #1: MELD Inflation: The Current Hepatocellular Carcinoma Exception Policy is Primarily Responsible for Steadily Increasing MELD Scores at the Time of Liver Transplant in All Regions of the U.S. Presented at: The Liver Meeting 2013; Nov. 1-5, Washington.


Video: New HCV treatments show promise; reinfection tied to drug use

Provided by Healio

Stefan Mauss, MD, PhD, co-founder of the Center for HIV and Hepatogastroenterology in Düsseldorf, Germany, reviews current treatment strategies for hepatitis C virus in patients with HIV coinfection, including triple therapy for HCV genotype 4. Mauss also discusses problems arising in Europe associated with risky behaviors — particularly crystal methamphetamine use — and the subpopulations that are at greatest risk for reinfection.


Prometic Presents Positive Results For PBI-4050 In Liver Fibrosis


LAVAL, QUEBEC -- (Marketwired) -- 11/04/13 -- ProMetic Life Sciences Inc. (TSX:PLI)(OTCQX:PFSCF), ("ProMetic" or the "Corporation") presented new preclinical data at the 2013 annual meeting of the American Association for the Study of Liver Diseases (AASLD) held in Washington on November 2-4 supporting the claims that PBI-4050 anti-fibrotic activity could also be used to address various liver conditions such as nonalcoholic steatohepatitis ("NASH"), a condition affecting 2% to 5% of Americans.

PBI-4050's favorable effect in reducing the progression of fibrosis in liver was demonstrated in two different "gold-standard" animal models. The first is a diabetic mouse model in which the animals develop liver steatosis. Similar to what is observed in humans, the untreated animals accumulate fat in the liver causing inflammation and leading to permanent damage and scarring, and reducing the ability for the liver to function properly. Diabetic mice treated with PBI-4050 had a significant reduction of liver lesions and steatosis measured by histology as well as a significant reduction in key biomarkers such as including TGFbeta-1, Collagen 1, MMP2 and TIMP-1.

In a second model, the liver fibrosis is induced by chronic administration of carbon tetrachloride (CCL4), a chemical which at high chronic dose, causes irreversible damage to the liver and the kidney. Again animals treated with PBI-4050 displayed a significant reduction of liver lesions as evidenced by histology and relevant biomarkers.

"These results clearly indicates that PBI-4050 anti-fibrotic activity is at the core of the fibrosis regulation pathway affecting multiple organs and tissues", stated Dr. Lyne Gagnon, Head of Biology & Immunology at ProMetic.

Dr. John Moran, a member of ProMetic's Board of Directors stated "Since patients with diabetes are more likely to develop complications affecting the kidneys and liver, the positive effects observed with PBI-4050 in multiple challenging animal models bodes well for its potential use in this patient population."

The presentation at the AASLD annual conference is available on the ProMetic website:

More on NASH

Nonalcoholic steatohepatitis or NASH is a common, often "silent" liver disease. It resembles alcoholic liver disease, but occurs in people who drink little or no alcohol. The major feature in NASH is fat in the liver, along with inflammation and damage. Most people with NASH feel well and are not aware that they have a liver problem. Nevertheless, NASH can be severe and can lead to cirrhosis, in which the liver is permanently damaged and scarred and no longer able to work properly. NASH affects 2 to 5 percent of Americans

About ProMetic Life Sciences Inc.

ProMetic Life Sciences Inc. ( is a long established biopharmaceutical company with globally recognized expertise in bioseparations, plasma-derived therapeutics and small-molecule drug development. ProMetic offers its state of the art technologies for large-scale purification of biologics, drug development, proteomics and the elimination of pathogens to a growing base of industry leaders and uses its own affinity technology that provides for highly efficient extraction and purification of therapeutic proteins from human plasma in order to develop best-in-class therapeutics and orphan drugs. ProMetic is also active in developing its own novel small-molecule therapeutic products targeting unmet medical needs in the field of fibrosis, cancer and autoimmune diseases/inflammation. Headquartered in Laval (Canada), ProMetic has R&D facilities in the UK, the U.S. and Canada, manufacturing facilities in the UK and business development activities in the U.S., Europe and Asia.

Forward-Looking Statements

This press release contains forward-looking statements about ProMetic's objectives, strategies and businesses and the Offering that involve risks and uncertainties. These statements are "forward-looking" because they are based on our current expectations about the markets we operate in and on various estimates and assumptions. Actual events or results may differ materially from those anticipated in these forward-looking statements if known or unknown risks affect our business, or if our estimates or assumptions turn out to be inaccurate. Such risks and assumptions include, but are not limited to, ProMetic's ability to develop, manufacture, and successfully commercialize value-added pharmaceutical products, the availability of funds and resources to pursue R&D projects, the successful and timely completion of clinical studies, the ability of ProMetic to take advantage of business opportunities in the pharmaceutical industry, uncertainties related to the regulatory process and general changes in economic conditions. You will find a more detailed assessment of the risks that could cause actual events or results to materially differ from our current expectations on page 26 of ProMetic's Annual Information Form for the year ended December 31, 2012, under the heading "Risk and Uncertainties related to ProMetic's business" and in the Final Prospectus under the heading "Risk Factors". As a result, we cannot guarantee that any forward-looking statement will materialize. We assume no obligation to update any forward-looking statement even if new information becomes available, as a result of future events or for any other reason, unless required by applicable securities laws and regulations. All amounts are in Canadian dollars unless indicated otherwise.

Company inquiries:
Pierre Laurin
President and CEO
ProMetic Life Sciences Inc.

Frederic Dumais
Director, Communications and
Investor Relations
ProMetic Life Sciences


CNIO scientists decipher how the immune system induces liver damage during hepatitis


Contact: Nuria Noriega

Centro Nacional de Investigaciones Oncologicas (CNIO)

The immune system causes liver damage when the organ becomes inflamed by the JunB gene, a member of the AP-1 complex


This is an inflamed liver containing immune cells expressing AP-1 protein (brown).

Viral infections are the primary cause of liver inflammation or hepatitis, affecting hundreds of millions of people all over the world, and they represent a public health problem worldwide. The acute condition can cause irreversible damage to the liver, and if not cured can become chronic, leading to serious diseases such as cirrhosis or cancer.

A study published today in the online edition of The Journal of Clinical Investigation, and carried out by Erwin Wagner's team, Director of the BBVA Foundation-CNIO Cancer Cell Biology Programme and holder of an ERC Advanced Grant, shows how the immune system 'attacks' liver cells during hepatitis by using the AP-1 gene JunB.

Latifa Bakiri, one of the study's authors and a researcher in Wagner's laboratory details: "The activation of the JunB/AP-1 gene in a subset of immune cells, called NK cells, increases the production of interferon-gamma that attacks liver cells while the organ is suffering from hepatitis".

With this discovery, the study's authors propose a new mechanism by which AP-1 acts as a double-edged sword in the liver: it's a first line of defence against viruses that cause the disease, but also encourages liver damage depending on the diet or genetics of the patient.

"The balance of these signals is fundamental to the understanding of the pathogenesis of inflammatory liver disease and to design new therapeutic approaches to reverse this disease", says Wagner.

NK-type immune cells are also part of the micro-environment surrounding tumours. Researchers point out in the discussion of the article that a better knowledge of these cells may be vital for designing immune-therapies that specifically target tumour cells.


The study has been supported by the BBVA Foundation, the European Research Council, Boehringer Ingelheim and the Ministry of Economy and Competitiveness.

Reference article:

JUNB/AP-1 controls IFN-γ during inflammatory liver disease. Martin K. Thomsen, Latifa Bakiri, Sebastian C. Hasenfuss, Rainer Hamacher, Lola Martinez, Erwin F. Wagner. The Journal of Clinical Investigation (2013). DOI: 10.1172/JCI70405


In nonalcoholic steatohepatitis, men more likely to have severe fibrosis

NOV 6, 2013  | Reuters Health News

NEW YORK (Reuters Health) – Men with nonalcoholic steatohepatitis (NASH) are more likely to have severe fibrosis than are premenopausal women with the disease, according to a new study.

“Our findings suggest a protective effect from estrogen against development of severe fibrosis,” Dr. Ayako Suzuki from Central Arkansas Veterans Healthcare System in Little Rock, Arkansas, said in a statement. “Further study of the impact of estrogen on fibrosis progression in NASH patients in needed.”

Dr. Suzuki and colleagues used data from the Duke University Health System NAFLD (non-alcoholic fatty liver disease) Clinical Database to assess whether gender and menopause are associated with the severity of liver fibrosis. Their study, online October 1 in Hepatology, included 541 adult patients with a histological diagnosis of NASH.

Just over a third of the patients were men, 28% were premenopausal women, and 37% were postmenopausal women. After adjusting for site, grade of portal inflammation, hepatocyte ballooning, black race, body mass index, diabetes and hypertension, the risk of having severe liver fibrosis (stage 3 or 4) was 60% higher in men than in premenopausal women (p=0.03) and 40% higher in postmenopausal women (p=0.17).

Age of 50 years or older, the average age of menopause in the U.S., was also associated with a significantly increased risk of having more advanced fibrosis among women, but not among men.

In an exploratory analysis, estrogen replacement (in 23 of the 199 postmenopausal women) was associated with a 50% reduction in the risk of severe fibrosis, although this fell short of statistical significance.

“Considering the findings from previous animal experiments, the observed association between premenopausal women and a decreased risk of hepatic fibrosis may be explained by protective effects of estrogens in fibrogenesis,” the researchers conclude.

“Further studies are warranted to investigate the impact of estrogen on fibrosis progression in patients with NASH and potential preventive and/or therapeutic effects of estrogen among postmenopausal women with NASH.”

Dr. Suzuki did not respond to a request for comments.


Hepatology 2013.


HCV Regimen: No Interferon, No Ribavirin, No Problem

Meeting Coverage

Published: Nov 8, 2013 | Updated: Nov 8, 2013

Coverage of Hepatitis C Virus is supported in part by an independent educational grant from AbbVie Pharmaceuticals.

This report is part of a 12-month Clinical Context series.

By Ed Susman , Contributing Writer, MedPage Today

Reviewed by F. Perry Wilson, MD, MSCE; Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Action Points

  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
  • Note that in this uncontrolled trial of patients with HCV, the combination of daclatasvir plus asunaprevir was very effective in inducing virologic response rates.
  • Be aware that the trial only enrolled patients who had failed or were ineligible for interferon therapy.

WASHINGTON -- Patients who failed to respond to standard treatment for hepatitis C virus (HCV) infection achieved greater than 80% sustained virologic response at 24 weeks with an all-oral regimen that eschewed both interferon and ribavirin, researchers reported here.

Among 135 patients who were either ineligible for interferon therapy or who were intolerant of the treatment, 87.4% achieved a sustained virologic response -- basically a treatment cure, reported Kazuaki Chayama, MD, PhD, professor of medicine and director of Hiroshima University Hospital.

In his plenary session report at the annual meeting of the American Association for the Study of Liver Diseases, Chayama also reported that 80.5% of 87 previous non-responders or partial responders achieved a sustained virologic response at 24 weeks.

He said that the response at 12 weeks was virtually the same as at 24 weeks: 88.1% of those ineligible or intolerant of interferon-based therapy reached the milestone compared with 80.5% of the non-responders or partial responders achieving a sustained virologic response at 12 weeks.

"Overall, 84.7% of these patients with limited therapeutic options and those patients typically associated with poor responses to other therapies were able to achieve a sustained virologic response," he said.

The 135 patients in the study received daclatasvir 60 mg once daily plus asunaprevir 100 mg twice daily. The researchers also enrolled 87 non-responders to previous therapy who received the same treatment regimen.

"Current treatment for chronic hepatitis C virus infection consists of pegylated interferon/ribavirin combined with a direct-acting antiviral," he explained. "In Japan, many patients are excluded from therapy due to the combined effect of an aging Japanese population with chronic hepatitis C virus and the poor tolerability profile with peginterferon/ribavirin-based therapy in this population."

He noted that although telaprevir/peginterferon/ribavirin therapy was approved for both treatment-naïve and treatment-experienced patients, the efficacy in nonresponder patients with hepatitis C virus genotype-1 was insufficient -- about one-third of patients responded.

The two investigative agents attack the virus in different ways. Daclatasvir is a potent NS5A replication complex inhibitor with pan-genotypic antiviral activity. Asunaprevir is a potent NS3 protease inhibitor with antiviral activity against genotypes 1, 4, 5, and 6. Chayama said the phase III study he described follows successful phase II studies showing a strong impact on patients with genotype 1b.

The median age of the 222 participants in the trial was 62.5, about 35% were men, and about 10% were diagnosed with cirrhosis. Baseline factors, including male gender, advanced age, high baseline hepatitis C virus RNA, and cirrhosis, did not appear to have an impact on response rates, Chayama said.

Overall 12.6% of the patients in the study discontinued therapy -- 6.8% due to lack of efficacy and 5% due to adverse events. Chayama said 5.6% of patients experienced serious adverse events. There were no deaths in the study.

Although the study was conducted among a Japanese population, Michael Fried, MD, professor of medicine and director of the University of North Carolina Liver Center in Chapel Hill, told MedPage Today, "These results can be extrapolated to an American or European hepatitis C virus population that had genotype 1 infection."

"It will work in this population but it will be tested in this population as well. These drugs will have to be more broadly studied. As you have seen if we get the right combination of drugs we can get successful results," Fried said.

The Japanese population mainly had genotype 1b infections, he said. Yet the success rate in achieving sustained virologic response was greater than 80%. "When I first started treating hepatitis C virus infection in the 1990s we were getting sustained virologic response rate in the 7% area, and to be getting response in the 80% to 90% levels we are seeing today is phenomenal."

He acknowledged that historically genotype 1 hepatitis C infection has been considered a more difficult disease to treat than genotypes 2 or 3, but in studies presented at The Liver Meeting 2013, "What has emerged is that genotype 3 is the new genotype 1. With these new drugs I think there has been a surprise that we get suboptimal results with genotype 3."

Primary source: American Association for the Study of Liver Diseases
Source reference: Chayama M, et al "All-oral combination of daclatasvir plus asunaprevir in interferon ineligible naive/intolerant and nonresponder Japanese patients chronically infected with HCV genotype 1b: Results from a phase 3 trial" AASLD 2013.


Also See: BMS Submits First All-Oral, Interferon-Free and Ribavirin-Free Treatment Regimen for Regulatory Review in Japan for Patients with Chronic Hepatitis C Infection

Hepatitis C Pretreatment Cuts Transplant Infections

Meeting Coverage

Published: Nov 7, 2013 | Updated: Nov 7, 2013

By Michael Smith, North American Correspondent, MedPage Today


WASHINGTON -- Successful hepatitis C (HCV) treatment before a liver transplant markedly reduced the risk of re-infection, a researcher said here.

Without treatment, HCV re-infection of the transplanted liver is "universal," according to Michael Curry, MD, of Beth Israel Deaconess Medical Center in Boston.

But 64% of patients successfully treated with the investigational agent sofosbuvir along with the standard medication ribavirin remained virus-free 12 weeks after the transplant, Curry reported at the annual meeting of the American Association for the Study of Liver Diseases.

The only predictor for success, he said, was a period of at least 30 days in a row before transplant when HCV could not be detected in the patient.

Curry was also an author on a bookend study, presented earlier at this meeting, that showed that the same agents delivered after transplant can also improve outcomes.

Taken together, the studies hold out hope for HCV patients who need a new liver, commentedMichael Fried, MD, of the University of North Carolina Chapel Hill, who was not part of the study.

Recurrent HCV infection after transplant leads quickly to renewed illness, graft loss, and often death, Fried told MedPage Today. "If you go in viremic, you come out viremic," he said.

Moreover, the post-transplant course of the disease is much faster than it was in the first place, he noted. So "finding strategies to try to prevent re-infection is, of course, very attractive," he said, and transplant specialists are watching these trials with great interest.

Curry reported data on 44 patients who have been transplanted following the drug treatment, of whom 41 had virus below the lower limit of quantification at the time of surgery.

One patient of the 41 has been lost to follow-up and another has not reached the 12-week follow-up after surgery, Curry reported, but of the remaining 39, 25 have undetectable virus.

In a multivariate analysis, the only factor that predicted success, Curry said, was the continuous length of time in the run-up to transplant in which the virus could not be detected.

For each such day, the odds ratio for avoiding re-infection rose 4%, he said -- an odds ratio of 1.042 (95% CI 1.012-1.083, P=0.0007.)

Indeed, of the 25 patients who remain virus-free 12 weeks after transplant, all but five had more than 30 days "target not detected," Curry said.

In contrast, only one patient whose HCV recurred had more than 30 days without the virus being detected.

The study, Fried said, seems to show clearly that: "If you can get people virus-negative for at least 30 days prior to their transplant, they have an extremely low risk of having recurrence."

But he cautioned that the numbers in the study are small and it's "hard to make set judgments on 30 or 40 patients."

But if sofosbuvir is approved, he said, it's very likely that transplant centers will be eager try it out, which will quickly yield better real-world data on outcomes and any possible problems.


Also See: