October 21, 2013

Video: Faldaprevir plus peginterferon/ribavirin improved response in HCV patients

Provided by Healio

October 21, 2013

SAN DIEGO — Christophe Moreno, MD,PhD, reports that treatment-naive patients with chronic hepatitis C genotype 1 infection showed significantly increased sustained virological response 12 weeks after planned end of treatment when treated with faldaprevir plus pegylated interferon alfa-2a and ribavirin compared with peginterferon and ribavirin alone.

Moreno, director of the gastroenterology department at Erasme Hospital, Brussels, discusses the final results of STARTVerso1, a randomized, double blind, placebo-controlled, phase 3 trial at the American College of Gastroenterology Annual Scientific Meeting.

Disclosure: Moreno is a board member with Janssen, Gilead, MSD and Bristol-Myers Squibb, received grants from Janssen, Roche and Novartis and is a member of the speakers bureau with MSD, Janssen and Bristol-Myers Sqibb.


Risks of Waiting to Treat HCV in HIV/HCV-Coinfected Patients

October 21, 2013

Rajesh T. Gandhi, MD reviewing Macías J et al. Clin Infect Dis 2013 Oct 4.

In a retrospective study, patients with advanced fibrosis, particularly those with cirrhosis, had a significant risk for hepatic decompensation within a relatively short period.

As the pace of drug development for hepatitis C virus (HCV) infection accelerates, physicians and their patients are faced with the question of whether to treat with current regimens or wait until better agents become available. To assess the risk of waiting, investigators in Spain examined the likelihood of liver decompensation among HIV/HCV-coinfected patients with advanced fibrosis.

In a retrospective analysis involving 892 HIV/HCV-coinfected patients, liver biopsy or liver stiffness measurement (LSM) by hepatic transient elastography was used to diagnose advanced fibrosis (stage 3 or 4 on biopsy; pre-cirrhosis or cirrhosis on LSM). Liver decompensation was defined as development of spontaneous bacterial peritonitis, portal hypertensive gastrointestinal bleeding, ascites, hepatorenal syndrome, encephalopathy, nonobstructive jaundice, or hepatocellular carcinoma.

Among the 317 individuals with advanced fibrosis diagnosed by biopsy, 12.6% had liver decompensation during a median follow-up of 5.4 years; among the 575 with advanced fibrosis diagnosed by LSM, 9.2% developed liver decompensation during a median follow-up of 2.1 years. In both groups, more-advanced fibrosis (stage 4 or cirrhosis, vs. stage 3 or pre-cirrhosis) was associated with greater risk for hepatic decompensation; in those diagnosed by LSM, a platelet count ≤100,000 was independently associated with higher risk. Overall, 97% to 98% of patients with pre-cirrhosis or stage-3 fibrosis remained free of hepatic decompensation at 3 years of follow-up, compared with only 83% to 87% of those with cirrhosis or stage-4 fibrosis.


This study suggests that HIV/hepatitis C virus–coinfected patients with advanced fibrosis — particularly those with stage-4 fibrosis or cirrhosis — should receive expeditious HCV treatment. In those with advanced fibrosis who do not yet have cirrhosis, especially if the platelet count is declining, close monitoring for worsening liver disease is essential, perhaps with hepatic transient elastography (a test that received FDA approval earlier this year but is not yet widely available in the U.S.). Fortunately, new and more-effective drugs will soon be here: Sofosbuvir, an HCV polymerase inhibitor, and simeprevir, an HCV protease inhibitor, are scheduled for FDA review this year, and all-oral interferon-sparing regimens are in advanced phases of testing.


Macías J et al. Risk of liver decompensation among HIV/hepatitis C virus–coinfected individuals with advanced fibrosis: Implications for the timing of therapy. Clin Infect Dis 2013 Oct 4; [e-pub ahead of print]. (http://dx.doi.org/10.1093/cid/cit537)


What opportunity for Gilead’s hepatitis C therapy sofosbuvir before interferon-sparing regiments reach the market?

Physician Views: What opportunity for Gilead’s hepatitis C therapy sofosbuvir before interferon-sparing regiments reach the market?

(Ref: FirstWord)

October 21st, 2013

One of the key features of the hepatitis C treatment landscape over the past year to 18 months has been a trend for physicians to warehouse patients in anticipation for the launch of all oral therapies that do not require treatment with interferon or ribavirin, thus significantly reducing side-effect burden.

A Physician Views poll run by FirstWord in December 2012 (among 74 US-based gastroenterologists) indicated that on average around 30 percent of diagnosed hepatitis C patients were being warehoused.

Understandably, this trend is likely to increase as the approval of oral, interferon-free treatments moves closer (anticipated in 2015). Indeed, a more recent survey of the US hepatitis C landscape carried out by analysts at Wells Fargo in May suggested that on average 36 percent of diagnosed patients remain untreated.

Momentum towards an oral, interferon-free treatment landscape should receive a notable boost this week when an FDA advisory committee discusses Gilead’s sofosbuvir and Johnson & Johnson’s simeprevir. Analysts expect positive recommendation to be followed by approval in late 2013/early 2014.

As a potential first-in-class NS5B polymerase inhibitor, sofosbuvir is broadly expected to act as a key backbone therapy for oral, interferon-free treatment regimens that emerge from 2015 onwards (including Gilead’s proposed once-daily, one-pill combination of sofosbuvir and ledipasvir). But what of its commercial opportunity in the meantime, assuming the drug is launched in early 2014.

Sofosbuvir – when used in combination with ribavirin – will offer the first all-oral treatment (and one which does not require interferon) to patients with genotype 2 and 3 hepatitis C, who account for approximately 25 percent of US patients. Thus among this patient subset, a viable new treatment option could become available within months.

In genotype 1 patients – which account for the vast majority of the US hepatitis C population – the outlook is more complicated. Treatment with sofosbuvir will still require co-administration with ribavirin and interferon, however, the duration of therapy will be significantly reduced versus current standard of care with a protease inhibitor, ribavirin and interferon (12 weeks versus 48 weeks) which could encourage uptake among both warehouse and newly diagnosed patients.

Significantly, although the commercial opportunity for simeprevir is expected to be fairly limited in 2014 – until Johnson & Johnson launches its own oral, interferon combinations – data from the COSMOS study have demonstrated that when used in combination with sofosbuvir this treatment regimen demonstrates compelling efficacy in genotype 1 null responder patients.

Set against these data, this week’s Physician Views poll will ask US and EU5-based gastroenterologists and infectious disease specialists how they expect to use sofosbuvir based on its likely initial label, and prior to the entry of oral interferon-free regimens that can be used across a broad spectrum of patient genotypes. Results should help to gauge how much of the warehousing effect will be left intact when subsequent oral, interferon-free drugs are launched in 2015. Specifically this week’s poll will ask...

What percentage of warehoused genotype 2/3 patients they plan to treat with sofosbuvir + ribavirin assuming Gilead’s drug is approved late 2013/early 2014 prior to the approval of subsequent oral therapies?

What percentage of newly-diagnosed genotype 2/3 patients they plan to treat with sofosbuvir + ribavirin assuming Gilead’s drug is approved late 2013/early 2014 prior to the approval of subsequent oral therapies?

What percentage of warehoused genotype 1 patients they plan to treat with sofosbuvir + pegylated interferon + ribavirin prior to the approval of subsequent oral, interferon-sparing therapies?

What percentage of newly diagnosed genotype 1 patients they plan to treat with simeprevir + pegylated interferon + ribavirin prior to the approval of subsequent oral, interferon-sparing therapies?

Based on available data from the COSMOS study, what percentage of null responder genotype 1 patients they anticipate treating with an off-label combination of sofosbuvir + simeprevir (with or without ribavirin) prior to the approval of subsequent therapies?

You will be able to read the results and analysis on Wednesday.

Results and related analysis will be published for FirstWord Pharma PLUS subscribers to read, with the opportunity for non-FirstWord Pharma PLUS subscribers to purchase these findings. To be notified when poll results and analysis become available, please click here.

As always, FirstWord would very much like to receive your feedback and suggestions.

Note: FirstWord Polls are powered by MedePolls, a fast-turnaround service to conduct instant polls of up to five questions with guaranteed samples that include physicians from dozens of specialities and over 100 markets. To conduct this poll with a different audience, or an entirely different poll, contact us at info@firstwordpharma.com.

To read more Physician Views articles, click here.


Gilead (Sofosbuvir) and Johnson & Johnson(Simeprevir) Face the FDA

Provided by The Motley Fool

Gilead and Johnson & Johnson Face the FDA

By Brian Orelli | More Articles
October 21, 2013 

Gilead Sciences (NASDAQ: GILD ) and Johnson & Johnson (NYSE: JNJ ) will face Food and Drug Administration advisory committees this week when the panels review their respective hepatitis C drugs. Advisory committee meetings can be the start of a downfall for a drug's chances for approval, but Gilead and Johnson & Johnson don't appear to have much to worry about.

A means to an end
Gilead's sofosbuvir and Johnson & Johnson's simeprevir are just building blocks of eventual all-oral treatments for hepatitis C. For genotype 1 patients, the most common strain of hepatitis C in the U.S., the drugs will need to be used in combination with one of the injected drugs already on the market: Merck's (NYSE: MRK ) Pegintron or Roche's Pegasys.

In addition to genotype 1, Gilead is also asking the FDA to approve sofosbuvir for the other five genotypes. Patients infected with genotypes 2 and 3 virus will get to skip Pegintron/Pegasys and take sofosbuvir with a generic drug called ribavirin. Like genotype 1 patients, those infected with genotype 4, 5, and 6 will still have to take PegIntron or Pegasys with sofosbuvir and ribavirin.

The ultimate goal for Gilead, Johnson & Johnson, and all the other hepatitis C drugmakers is to skip Merck's Pegintron and Roche's Pegasys because -- in addition to needing to be injected -- they often produce annoying flu-like symptoms over the months that patients have to take the drugs.

For now, the drugs will replace the first generation oral hepatitis C drugs -- Merck's Victrelis and Vertex Pharmaceuticals' Incivek -- but aren't likely to reach their full potential until other drugs in development are approved to create an all-oral cocktail.

Tuesday and Wednesday are key
Johnson & Johnson's advisory committee meeting is actually on Thursday and Gilead's is on Friday, but investors will get a first look at what the FDA thinks of the drugs two days before those meetings when the agency publicly releases its briefing documents for the panel members.

I doubt there are going to be any issues with efficacy. The drugs appear to be substantially better than Victrelis and Incivek with clean clinical endpoints. Patients are either rid of the virus or they're not. It's hard to see how the companies could get tripped up.

It's the places where the data are a little more obtrusive to the public that investors have to worry about. Sometimes, for instance, the FDA brings up results from preclinical animal studies, asking the panel of outside experts whether they think the findings are worrisome.

Not that I have any reason to think that'll happen to Gilead or Johnson & Johnson this week.

Neither does anyone else
And that's kind of the problem with the stocks. For both drugs, an approval is widely expected because there haven't been any red flags to think otherwise. There doesn't seem to be much upside to me.

In fact, I wouldn't be surprised to see Gilead go down after the documents are released. There's bound to be something negative in the briefing documents -- the FDA's job is to find every potential issue, no matter how small -- and considering that Gilead is up more than 80% this year, an overreaction wouldn't be surprising.

If you're an owner of Johnson & Johnson, simeprevir is just a small part of the pharma giant's long-term growth plan, so I doubt Johnson & Johnson's stock will react unless something really bad is revealed in the briefing documents.

Fool contributor Brian Orelli has no position in any stocks mentioned. The Motley Fool recommends Gilead Sciences and Johnson & Johnson. The Motley Fool owns shares of Johnson & Johnson. Try any of our Foolish newsletter services free for 30 days. We Fools may not all hold the same opinions, but we all believe that considering a diverse range of insights makes us better investors. The Motley Fool has a disclosure policy.


Association Between the Hepatitis B and C Viruses and Metabolic Diseases in Patients Stratified by Age

Liver International

Wen-Cheng Li, Yi-Yen Lee, I-Chuan Chen, Cheng Sun, Feng-Hsiang Chiu, Chung-Hsun Chuang

Liver International. 2013;33(8):1194-1202.

Abstract and Introduction


Background Hepatitis B/C viruses cause liver disease and metabolic disturbances.

Aims The purpose of this study was to evaluate the association between hepatitis B/C infection and metabolic syndrome (MS).

Methods In total, 26 305 subjects were included in this multicentre, cross-sectional study. Systolic and diastolic blood pressures, body mass index and waist circumference were measured. Total cholesterol, high- and low-density lipoprotein cholesterol, triglyceride, fasting blood glucose and uric acid were determined, and hepatitis B serum antigen (HBsAg) and anti-HCV antibodies were assayed using commercial kits.

Results MS was diagnosed in 2712 (23.0%) females, including 131 and 166 positive for HBsAg and anti-HCV respectively. In the men, 4594 (31.6%) were diagnosed with MS, including 326 positive for HBsAg and 131 positive for anti-HCV. No significant difference in the prevalence of MS was identified in any group, except men and women >45 years who were anti-HCV positive. Various metabolic alterations in both men and women >45 years were noted, including waist circumference, body mass index, fasting blood glucose and systolic and diastolic blood pressure. Notably, high- and low-density lipoproteins were significantly lower in positive subjects compared to those weakly positive and/or negative for anti-HCV.

Conclusions There were obvious metabolic derangements in patients coinflicted with MS and hepatitis C infections, particularly those >45 years of age. There is a pressing need to identify strategies to improve/resolve metabolic derangements to maximize sustained virological response rates in patients infected with HCV (and potentially HBV).


Approximately 170 million (3% of the world's population) people are infected with the hepatitis C virus (HCV), and an overwhelming 2 billion people are currently infected with the hepatitis B virus (HBV) worldwide.[1–3] HBV and HCV are particularly prevalent in Asia and Taiwan. Over time, the hepatitis C and B viruses cause liver disease that often progresses from chronic hepatitis to fibrosis, cirrhosis and in some cases, hepatocellular carcinoma.[1, 2] In addition to being hepatotropic, the HCV is also known to cause metabolic disturbances, referred to as HCV-associated dysmetabolic syndrome (HCADS) characterized by steatosis, hypocholesterolaemia and insulin resistance (IR)/diabetes.[1]

The 'classic' metabolic syndrome (MS), which includes glucose abnormalities, central obesity, dyslipidaemia and hypertension, is increasingly common in Eastern countries, largely because of an obesity epidemic caused by the Westernization of many countries.[4] It is now widely accepted that patients with chronic HCV have a higher incidence of IR and type 2 diabetes mellitus than in patients with other liver diseases.[1] Further, several studies have suggested an association between chronic HCV and MS, reporting a prevalence of MS ranging from 4.1% to 44%.[5–7] It is also reported that insulin resistance, type 2 diabetes mellitus and HCADS negatively impact sustained virological responses (SVRs) to pegylated interferon- with ribavirin, and that MS is an independent predictor of a suboptimal SVR.[1] To date, the prevalence of full-blown MS (regardless of whether it is the classic form or the viral form, as described by Bugianesi et al.) among patients infected with HCV remains unknown.[8] Unlike HCV, the link between HBV and MS is not as well studied, despite the fact that infection with HBV is more common than HCV.

The purpose of this large, multi-centre, cross-sectional study was to evaluate the association between infection with either HBV or HCV and metabolic diseases, including MS and diabetes mellitus. The prevalence of both HBV and HCV infections, as well as type 2 diabetes, IR, obesity and MS, continue to increase at an alarming rate. There is therefore a pressing need to identify strategies for improving/resolving metabolic derangements to maximize SVR rates in patients infected with HCV (and potentially HBV). The findings of this study are anticipated to impact the prevention and long-term management of a multitude of HCV-positive individuals in the near future.

Continue reading full article here …..

NUS scientists identify molecular switch that suppresses development of liver cancer

21 October 2013 National University of Singapore

    A team of scientists from the National University of Singapore (NUS) has found that activating a family of small protein, known as Rho, could suppress liver malignancies. This is the first time that a research group has provided evidence to show that the signaling crosstalk between different protein switches has an influence on the development of cancer tissues. The findings pave the way for the development and application of therapeutics targeted at liver cancer.

    The team, led by Associate Professor Low Boon Chuan from the Department of Biological Sciences at the NUS Faculty of Science and the Mechanobiology Institute at NUS, first published the research in the journal Oncogene.

    Importance of signalling crosstalk between proteins

    The proteins Ras and Rho are among the key molecular switches that control cell dynamics, cell growth and tissue development through their distinct signalling pathways. Although much has been studied about their individual functions, the underlying molecular mechanism of signalling crosstalk between these two proteins in an in vivo context remains largely unknown, especially in the area of liver development and formation of liver tumours.

    In order to identify the consequences of their signalling crosstalk, the research team generated different scenarios with different liver-specific proteins and genes that have the potential to cause cancer, using the zebrafish as an in vivo model.

    Due to its ability to reverse and forward genetics and low incidence of spontaneous tumours, the zebrafish is fast becoming a popular model for studying human cancers.

    Through the use of quantitative bioimaging and molecular markers, the team found that when the zebrafish is induced to produce an active state of Kras (a form of Ras), which is an oncogene, liver enlargement is observed, and liver cancer that resembles the human liver cancer was formed. Subsequently, in adult zebrafish, the hepatocellular carcinoma, a major form of liver cancer, was developed. However, when the same cells were made to turn on Rho, these abnormalities were abated.

    The team also found that when an inactive form of Rho was introduced when Kras is kept active, the Kras-mediated liver overgrowth and tumour formation were elevated.

    These findings provided evidence about the significance of the previously understudied signalling crosstalk between the proteins Kras and Rho in regulating liver overgrowth, transformation of liver tissue and cancer mortality. As Rho is a known inducer of mechanical force, the team’s findings also implicate the possible role of mechanical and physical forces in regulating cancer development and other functions in the liver.  

    The Next Step

    The group is now investigating the exact chain of biochemical reactions that specify such unique signalling crosstalk. They are also investigating the aspects of cell metabolism and other major growth related pathways that are being affected to address the inherent inconsistency associated with cell-based studies. They hope to establish zebrafish as an alternative drug screening platform that is relatively cheap and convenient to identify novel targets for therapeutic intervention. 


    Family caregivers live longer than their peers

    By C. E. Huggins

    NEW YORK | Fri Oct 18, 2013 5:04pm EDT

    NEW YORK (Reuters Health) - Caring for a disabled family member can be overwhelmingly hard. But caregivers may live longer than those who don't bear such responsibilities, new research suggests.

    In a nationwide study, adults who provided care for a chronically ill or disabled family member had a lower death rate than a similar group of non-caregivers.

    The finding is something of a surprise.

    In the past, researchers have found just the opposite - an increased risk of death as well as poorer mental and physical health among caregivers. Such detrimental health effects have been found among people caring for a disabled spouse or a person with dementia, for example.

    "(We want to) emphasize the positive message that caregiving is a healthy thing that we should be doing in our families," lead study author Dr. David L. Roth, director of the Johns Hopkins University Center on Aging and Health, told Reuters Health.

    Dolores Gallagher-Thompson, who directs the Geriatric Education Center at Stanford University School of Medicine in California told Reuters Health the current study's findings are "surprising… because prior studies did find an association between caregiver stress and mortality."

    Gallagher-Thompson pointed out that the caregivers included in Roth's study were not heavily stressed, however. They didn't all have their ill family member living with them full time. Some caregivers may have just visited their charges, the report indicates.

    The study also did not distinguish between caregivers of people with dementia and those with other conditions.

    "Previous studies that have reported high stress and increased mortality have focused on dementia," said Gallagher-Thompson.

    Roth noted that poorer health among caregivers is "undoubtedly true" in some cases, particularly among those caring for people with dementia. However, "caregiving stress has been over exaggerated," he said.

    Of the 3,503 caregivers included in the study, over 80% said they were experiencing either no mental or emotional strain or only a moderate level of such strain.

    Only 578 - or less than one in five - felt their caregiving caused them "high strain."

    Roughly two thirds of the caregivers were female. About a third were adult children, and about one in five were spouses. Slightly more than half provided care for less than 14 hours a week.

    Regardless of the nature of their responsibilities, caregivers appeared to reap benefits from their own selflessness. Death rates were 18% lower among caregivers than among their non-caregiving counterparts, Roth and his team report in the American Journal of Epidemiology.

    During the 2003-2012 study period, about 7.5 percent of caregivers died, compared to about 9 percent of the same number of noncaregivers.

    "In a way you can say this is good news," said Gallagher-Thompson, who was not involved in the study. "If you‘re caring for someone with long-term (illness or disability in some cases), it may actually provide you with some health benefits."

    Reasons for the lower rate of death among caregivers may have to do with their own self-selection, Roth said. Considering the low number of spouse caregivers included in the study, the non-spouse caregivers who chose to provide care to their family members "may be healthier, better adjusted people who have their own house in order," he said.

    Gallagher-Thompson thinks maybe altruism, spirituality, and resilience among caregivers also played a role. "Some caregivers are able to roll with the punches," she said.

    The study's sample was drawn from the national Reasons for Geographic and racial Differences in Stroke (REGARDS) Study of African American and white adults aged 45 years and older. Study participants were largely recruited from the southern region of the United States. Caregivers from this sample were statistically matched with noncaregivers according to a number of factors, including age, race, gender, educational and income level, self-rated health, and mental status.

    Still, the narrow focus on only African American and white adults limits the generalizability of this study's findings, said Gallagher-Thompson. We have "no idea whether these findings may apply to other races, cultures, or ethnicities."

    SOURCE: bit.ly/H6ejhF American Journal of Epidemiology, online October 3, 2013.


    Summary of pharmacokinetic drug-drug interactions for simeprevir (TMC435), a hepatitis C virus Ns3/4A protease inhibitor

    Provided by NATAP

    14th European AIDS Conference
    Oct 16-19 2013
    Brussels, Belgium

    Reported by Jules Levin
    14th European AIDS Conference (EACS)
    16-19 October 2013 · Brussels, Belgium

    Sivi Ouwerkerk-Mahadevan,1 Alexandru simion,2 Monika Peeters,2 Maria Beumont-Mauviel2
    1Janssen Research and Development, Beerse, Belgium; 2Janssen Infectious Diseases, Beerse, Belgium

    Address correspondence to:
    Sivi Ouwerkerk-Mahadevan,
    Janssen Research & Development,
    Turnhoutseweg 30, Beerse,
    2340 Belgium.
    e mail: SOUWERKE@its.jnj.com
    Tel: 0032 (0)14605730


    Continue here to view posters …..

    STARTVerso 4 Phase iii trial of faldaprevir once-daily plus peg interferon α-2a and ribavirin (PR) in patients with HiV and HCV genotype-1 co-infection

    Provided by NATAP

    Reported by Jules Levin
    14th European AiDS Conference, October 16-19, 2013, Brussels, Belgium

    JK Rockstroh1, M Nelson2, V Soriano3, K Arastéh4, J Guardiola5, S Bhagani6, J Mallolas7, C Tural8, M Puoti9, P ingiliz10, M Battegay11, MK Jain12, M Nunez13, K Marks14, J Kort15, JO Stern15, R Vinisko15, M Manero16, D Dieterich17

    1University of Bonn, Bonn, Germany; 2Chelsea and Westminster Hospital, London, UK; 3Hospital Carlos iii, Madrid, Spain; 4EPiMED, Vivantes Auguste-Viktoria Hospital, Berlin, Germany; 5Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 6Royal Free Hospital, London, UK; 7Hospital Clínic, Barcelona, Spain; 8Hospital Universitari Germans Trias i Pujol, Barcelona, Spain; 9AO Ospedale Niguarda Ca Granda, Milan, italy; 10Medizinisches infektiologiezentrum Berlin (MiB), Berlin, Germany; 11Division of infectious Diseases and Hospital Epidemiology, Basel, Switzerland; 12UT Southwestern Medical Center, Dallas, TX, USA; 13Wake Forest University, Winston-Salem, NC, USA; 14Weill Cornell Medical College, NY, USA; 15Boehringer ingelheim Pharmaceuticals inc. Ridgefield, USA; 16Boehringer ingelheim Espana S.A., Barcelona, Spain; 17Mount Sinai School of Medicine, NY, USA


    Continue here to view posters …..

    Use of Hepatitis B surface antigen–positive grafts in liver transplantation: A matched analysis of the US national database

    Liver Transplantation

    Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

    Original Article

    Zhiwei Li, Zhenhua Hu, Jie Xiang, Jie Zhou, Sheng Yan, Jian Wu, Lin Zhou, Shusen Zheng*

    DOI: 10.1002/lt.23774

    ©2013. American Association for the Study of Liver Diseases

    Keywords: Liver transplant; HbsAg; HBIG; Registry; Marginal donor


    The scarcity of available donor organs is the key challenge in orthotopic liver transplantation. A viable way to expand the donor pool is the use of liver grafts from hepatitis B virus surface antigen–positive donors. The present study used the US Scientific Registry of Transplant Recipients database (1987–2010), and 78 patients undergoing OLTs with HBsAg-positive grafts were each matched for urgent status, gender of donor and recipient, age of donor and recipient, transplant date, Model for End-Stage Liver Disease score, and warm ischemia time with four patients receiving HBsAg-negative grafts. Overall graft and patient survival was similar in recipients with HBsAg-positive grafts and matched controls (five-year survival: 66% versus 64%, P = 0.954 and 71% versus 71%, P = 0.870, respectively). Cox proportional regression analysis adjusting for other variables showed no impact of donor HBsAg status on graft or patient survival. The use of hepatitis B immunoglobulin was independently associated with better post-transplant graft and patient survival in recipients with HBsAg-positive grafts (HR = 0.23, 95% CI = 0.06–0.81 and HR = 0.16, 95% CI = 0.04–0.75, respectively). In conclusion, the use of HBsAg-positive liver grafts did not reduce post-transplant graft or patient survival. Moreover, matching these donors to recipients treated with HBIG may improve safety. Liver Transpl , 2013. © 2013 AASLD.


    Coffee Reduces Risk for Hepatocellular Carcinoma: An Updated Meta-analysis

    Clinical Gastroenterology and Hepatology
    Volume 11, Issue 11 , Pages 1413-1421.e1, November 2013

    Francesca Bravi,  Cristina Bosetti,  Alessandra Tavani, Silvano Gallus, Carlo La Vecchia,

    published online 08 May 2013.


    Background & Aims

    Coffee consumption has been suggested to reduce the risk for hepatocellular carcinoma (HCC). We performed a meta-analysis of epidemiological studies to provide updated information on how coffee drinking affects HCC risk.


    We performed a PubMed/MEDLINE search of the original articles published in English from 1966 through September 2012, on case-control or cohort studies that associated coffee consumption with liver cancer or HCC. We calculated the summary relative risk (RR) for any, low, and high consumption of coffee vs no consumption. The cut-off point for low vs high consumption was set to 3 cups per day in 9 studies and 1 cup per day in 5 studies.


    The summary RR for any coffee consumption vs no consumption was 0.60 from 16 studies, comprising a total of 3153 HCC cases (95% confidence interval [CI], 0.50–0.71); the RRs were 0.56 from 8 case-control studies (95% CI, 0.42–0.75) and 0.64 from 8 cohort studies (95% CI, 0.52–0.78). Compared with no coffee consumption, the summary RR was 0.72 (95% CI, 0.61–0.84) for low consumption and 0.44 (95% CI, 0.39–0.50) for high consumption. The summary RR was 0.80 (95% CI, 0.77–0.84) for an increment of 1 cup of coffee per day. The inverse relationship between coffee and HCC risk was consistent regardless of the subjects’ sex, alcohol drinking, or history of hepatitis or liver disease.


    From this meta-analysis, the risk of HCC is reduced by 40% for any coffee consumption vs no consumption. The inverse association might partly or largely exist because patients with liver and digestive diseases reduce their coffee intake. However, coffee has been shown to affect liver enzymes and development of cirrhosis, and therefore could protect against liver carcinogenesis.

    Keywords: Chemoprevention, Epidemiology, Caffeine, Neoplasm

    Abbreviations used in this paper: BMI, body mass index, CI, confidence interval, d, day, HbsAg, hepatitis B surface antigen, HBV, hepatitis B virus, HCC, hepatocellular carcinoma, HCV, hepatitis C virus, OR, odds ratio, RR, relative risk, w, week

    Conflicts of interest The authors disclose no conflicts.

    Funding Supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) (grant no. 10068).

    PII: S1542-3565(13)00609-5


    © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.


    Survey on knowledge of liver cancer and viral hepatitis


    On 17 October Janssen announced the results of a new survey to mark Liver Cancer Awareness Month (October). The survey showed a lack of awareness among the general public about viral hepatitis and its link to liver cancer – approximately nine out of ten (91%) people surveyed do not know anything or only very little about viral hepatitis and only around one in six (15%) name hepatitis as the main cause of liver cancer. 

    The survey, commissioned by Janssen, with the support of the World Hepatitis Alliance (WHA), the European Liver Patients Association (ELPA) and the International Liver Cancer Association (ILCA), was conducted in Russia, Spain, Turkey and the United Kingdom (UK) involving more than 5,000 members of the general public to provide a snapshot of public awareness across the WHO European Region.

    The survey highlights the lack of awareness of viral hepatitis and demonstrated that improved public awareness about the virus is necessary so that people can assess whether they have been at risk of infection, and come forward for testing. This survey clearly reinforces the need for national governments across Europe to develop comprehensive strategies to address this.

    Read the full press release here and download visual infographics detailing the key findings of the survey and information on viral hepatitis via the links below.

    Infographic Awareness of Hepatitis C and Liver Cancer
    Infographic Viral Hepatitis – A global pandemic

    Janssen Liver Cancer Awareness Month Survey Results


    Inovio Pharmaceuticals to Initiate Clinical Trial for its Hepatitis C Therapeutic Vaccine (INO-8000) Later this Year

    Phase I/IIa Trial Follows Preclinical Study Demonstrating for First Time that a Multi-Antigen HCV Vaccine Can Generate Potent T-Cell Response in Liver

    Jan 9, 2013

    BLUE BELL, Pa., Jan. 9, 2013 /PRNewswire/ -- Inovio Pharmaceuticals, Inc. (NYSE MKT: INO) and its development partner VGX International, Inc. (KSE: 011000) will move Inovio's hepatitis C (HCV) DNA vaccine into a phase I/IIa clinical trial by the end of 2013. This advancement is based on outstanding results of a preclinical study which demonstrated for the first time that a multi-antigen SynCon® HCV vaccine can generate robust T-cell responses not only in the blood but, more importantly, in the liver, an organ known to supress T-cell activity. VGX International is funding all preclinical and clinical development.

    In preparation for entering clinical trials with its HCV vaccine (INO-8000), Inovio has completed manufacturing of its multi-antigen HCV vaccine and is performing IND (Investigational New Drug application)-enabling toxicity testing in animals. INO-8000 is a SynCon HCV therapeutic vaccine targeting NS3/4A, NS4B, and NS5A proteins of HCV. INO-8000 was designed with Inovio's SynCon process to broadly cover HCV genotypes 1a and 1b, the types that have been most difficult to treat with drug therapies.   

    It is estimated that more than 5 million people in the United States are infected with hepatitis C, and perhaps as many as 200 million around the world. This makes HCV one of the greatest public health threats of this century.

    HCV vaccine research to date has mostly focused on one area of the virus (the NS3/4A proteins) to induce T-cell responses; however, there has been little research aimed at elucidating whether vaccines targeting proteins other than NS3/4A can induce potent T-cell responses within the liver. In this study, Inovio and its collaborators developed SynCon antigen constructs that targeted three other areas of the HCV virus (NS4B, NS5A and NS5B) and then demonstrated that each vaccine construct expressed its respective protein and that all three constructs induced potent HCV-specific T-cells in mice.

    Prior research has also identified that a successful HCV vaccine must be able to induce not only strong HCV-specific T-cell responses that target several components of the virus but that these cells must migrate to the liver and remain activated. In this study, Inovio researchers observed in the liver not only NS4B-, NS5A- and NS5B-specific CD4+ and CD8+ (or killer T-cell) responses, but also a large pool of vaccine-specific T-cells. This pool of vaccine-specific T-cells was shown to be fully functional in an environment in which T-cell activity is usually suppressed. In fact, using a transient HCV infection model in mice, therapeutic immunization with INO-8000 was able to clear HCV antigens from the liver, demonstrating the therapeutic potential of this vaccine.        

    The pioneering preclinical research appears in the peer-reviewed journal Plos One in an article entitled: "Induction of Intrahepatic HCV NS4B, NS5A and NS5B Specific Cellular Immune Responses following Peripheral Immunization."

    In addition to moving forward with INO-8000, Inovio has a long-standing partnership with ChronTech Pharma, which is developing its NS3/4A-based HCV DNA vaccine using Inovio's proprietary delivery technology. Interim results of ChronTech's open-label, randomized phase II trial are expected later in the first quarter of this year.      

    Dr. J. Joseph Kim, Inovio's President and CEO, said, "Inovio is a leader in developing therapeutic vaccines for HCV and HBV. The major hurdle to developing therapeutic vaccines for these ailments has been the inability to generate a functional T-cell response in the liver. The fact that our preclinical model demonstrated functional T-cells in the liver in this published study suggests that INO-8000 has the capacity to clear that hurdle. There have been important recent drug therapy advances for HCV; however, a safe and effective therapeutic vaccine could play a vital role in enhancing the potency of HCV treatments, especially for genotype 1, while achieving the desired goal of eliminating the use of interferon/ribavirin and their undesirable side effects."

    About Hepatitis C and Inovio's SynCon® Vaccines

    Hepatitis C is an infectious disease affecting primarily the liver, caused by the hepatitis C virus (HCV). The infection is often asymptomatic, but chronic infection can lead to liver failure or liver cancer. Approximately 80% of people who become infected with hepatitis C virus develop chronic infection.

    The major obstacle to HCV vaccine development has been the extensive genetic variation between different strains and genotypes, and even the significant antigenic variation among virus within individual patients. In addition, the absence of a clearly defined protective immune response after natural infection has historically complicated the prospects of developing a vaccine against HCV infection. 

    However, unlike traditional vaccines constrained by the paradigm of matching a preventive or therapeutic vaccine to a single pathogen strain or strains, Inovio's SynCon vaccines are based on genetic code for a specific antigen from multiple strains of the target pathogen. Thus, while the SynCon antigens may not be perfectly (100%) matched to the pathogenic strains, they are designed to protect against multiple existing strains as well as changing strains of a virus. Extensive preclinical data has validated their ability to protect against many strains of a disease; initial human data for our influenza vaccine has also provided evidence of this capability.

    About Inovio Pharmaceuticals, Inc.

    Inovio is revolutionizing vaccines to prevent and treat today's cancers and challenging infectious diseases. Its SynCon vaccines are designed to provide universal cross-strain protection against known as well as newly emergent unmatched strains of pathogens such as influenza. These synthetic vaccines, in combination with Inovio's proprietary electroporation delivery, have been shown in humans to generate best-in-class immune responses with a favorable safety profile. Inovio's clinical programs include phase II studies for cervical dysplasia, leukemia and hepatitis C virus and phase I studies for influenza and HIV. Partners and collaborators include the University of Pennsylvania, Merck, ChronTech, National Cancer Institute, U.S. Military HIV Research Program, NIH, HIV Vaccines Trial Network, University of Southampton, US Dept. of Homeland Security, University of Manitoba and PATH Malaria Vaccine Initiative. More information is available at www.inovio.com.

    This press release contains certain forward-looking statements relating to our business, including our plans to develop electroporation-based drug and gene delivery technologies and DNA vaccines and our capital resources. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials and product development programs (including, but not limited to, the fact that pre-clinical and clinical results referenced in this release may not be indicative of results achievable in other trials or for other indications, that the studies or trials may not be successful or achieve the results desired, that pre-clinical studies and clinical trials may not commence or be completed in the time periods anticipated, that results from one study may not necessarily be reflected or supported by the results of other similar studies and that results from an animal study may not be indicative of results achievable in human studies), the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA vaccines, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by the company or its collaborators, including alternatives that may be more efficacious or cost-effective than any therapy or treatment that the company and its collaborators hope to develop, evaluation of potential opportunities, issues involving product liability, issues involving patents and whether they or licenses to them will provide the company with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether the company can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of the company's technology by potential corporate or other partners or collaborators, our ability to secure new partnerships and collaborations, capital market conditions, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2011, our Form 10-Q for the quarter ended September 30, 2012, and other regulatory filings from time to time. There can be no assurance that any product in Inovio's pipeline will be successfully developed or manufactured, that final results of clinical studies will be supportive of regulatory approvals required to market licensed products, or that any of the forward-looking information provided herein will be proven accurate.

    Investors: Bernie Hertel, Inovio Pharmaceuticals, 858-410-3101, bhertel@inovio.com
    Media: Jeff Richardson, Inovio Pharmaceuticals, 267-440-4211, jrichardson@inovio.com

    (Logo: http://photos.prnewswire.com/prnh/20120131/LA44118LOGO)

    SOURCE Inovio Pharmaceuticals, Inc.


    HepatiC™, HCV Patient Registry and Database to Aid in the Management of HCV-Infected Patients Receiving Direct Acting Antiviral Therapy

    Reuters is not responsible for the content in this press release.

    Mon Oct 21, 2013 6:00am EDT

    HepatiC™, HCV Patient Registry and Database to Aid in the Management of HCV-Infected Patients Receiving Direct Acting Antiviral Therapy

    Advanced Biological Laboratories (ABL) S.A. is pleased to announce the signing of a contract with the Spanish Association for the Study of the Liver (Asociación para el Estudio del Hídago, AEEH, www.aeeh.es) for the development and licensing of the new HepatiC™ software and database system.

    ABL undertakes the development, maintenance and upgrades and provides national access to the HepatiC™ program to the Spanish Community of Hepatologists to aid in the optimal personalized management of their HCV patients, especially those being treated with Direct Acting Antiviral (DAA) therapy.

    "The HepatiC™ initiative in Spain will facilitate the creation of a national HCV patient Registry and Database", stated Pr Esteban, Head of the Internal Medicine and Hepatology Department, Hospital Vall d'Hebron in Barcelona. "This tool is key to the support of our epidemiological studies, the monitoring of patient outcomes and the reporting to regional, national and international institutions".

    The design and scientific content of HepatiC™ was directed by Spanish key opinion leaders and experts. The ABL experienced team ensures the development, the implementation and maintenance of the HepatiC™ system.

    ABL is also in charge of the HepatiC™ commercialization outside Spain and undertakes to provide HepatiC™ to the largest community of physicians treating HCV-infected patients. "We are honoured to be working with the AEEH and the Spanish experts on liver diseases and to share our respective knowledge with them" said Dr Sayada, ABL CEO. "HepatiC™ shall reinforce ABL business in viral hepatitis, infectious diseases and oncology in the near future, in several continents".

    The HepatiC™ initiative official launch took place on the 18th of October at the Hotel NH Constanza (Barcelona).

    About ABL

    Advanced Biological Laboratories (ABL), S.A., is a biotech company founded in 2000 as a spin-off from the European academic research center, CRP-Santé Luxembourg and in 2004, acquired the control of TherapyEdge, Inc, a biotech company spin-off from Triangle Pharmaceuticals, Inc. and in 2013 acquired the Viral Hepatitis B & C related assets from EVIVAR MEDICAL, a biotech company spin-off from Melbourne Health in Australia. ABL has a comprehensive suite of healthcare management tools, including TherapyEdge®, ViroScore®, SeqHepB, DeepChek®, VisibleChek® and HepatiC™, which are used for data and patient management, monitoring and personalized reporting applications. In 2012, ABL's products received respectively CE-marking and IVD certifications. ABL's products offer infectious disease clinicians and virology laboratories optimal and efficient IT solutions, for sequencing, clinical genotyping and drug resistance analysis, including powerful fully integrated databases and analysis systems combining standard and high-throughput Next Generation Sequencing data. The clinical and biological outcomes aid in the generation of clinically meaningful genotyping reports for personalized healthcare.

    Dr Chalom Sayada
    Tel : +352 2638 8921


    More investment in specialist nurses could help eradicate hepatitis C

    Provided by Nursing Times

    21 October, 2013

    Hepatitis C could be eradicated in a generation if the government prioritised the condition and invested more in services including specialist nurses, a charity has claimed.

    The Hepatitis C Trust claims deaths and hospital admissions for hepatitis C-related end stage liver disease and liver cancer have nearly quadrupled in the last 15 years with many of these likely to be avoidable.

    The report said there was evidence that specialist nursing services in the community were a better alternative to numerous hospital appointments and admissions for hepatitis C patients.

    Charles Gore, chief executive of The Hepatitis C Trust, said many patients faced a “postcode lottery of care” due to the lack of a national liver strategy.

    He added: “Instead of letting this virus continue to take the lives of the poorest fastest, we could effectively eradicate it in England within a generation. However, to do this we must diagnose and offer care to everyone, regardless of their geographical location or background.”

    Jayne Dodd, a hepatitis specialist nurse, works as part of a nurse led network providing specialist care in hospitals, the community and in prisons.

    She said: “It’s vitally important to have specialist hepatitis C in-reach or an equivalent service in the primary care setting.

    “The majority of nurses in primary care are required to meet more general clinical needs yet hepatitis C is a such complicated disease area that specialist knowledge is essential to provide the best duty of care.”


    Cuomo should sign bill to offer screening for hepatitis C


    on October 21, 2013 - 12:01 AM

    By Alyssa Aguilera

    New York can be a national leader in protecting the health of baby boomers if Gov. Andrew M. Cuomo signs legislation that would require health care providers to screen for the potentially fatal hepatitis C virus.

    The bipartisan bill, which is backed by a coalition of groups that include the AARP and NAACP, is modeled on new guidelines from the Centers for Disease Control and Prevention that recommend doctors offer a one-time test to everyone born between 1945 and 1965.

    Although baby boomers have the highest rate of hepatitis C infection of any age group, it’s not something doctors screen for. Since people can live with hepatitis C for decades without any noticeable symptoms, most people living with the virus have no idea.

    More than 200,000 New Yorkers are believed to have hepatitis C, a leading cause of liver disease that kills more people nationwide than HIV/AIDS. Many were infected through blood transfusions before regular screening of the blood supply was introduced in 1992; others through any history of injection drug use, even just one time.

    The good news is that most people with hepatitis C can be cured, and even more effective medicines will be on the market in the next couple of years. But people can’t access care and treatment unless they first get diagnosed, and too many people now find out they have hepatitis C after there’s been significant damage to their liver and overall health.

    Last year, Erie County Commissioner of Health Dr. Gale Burstein called the spread of viral hepatitis a “silent epidemic” and cited the need for expanded testing to connect those infected with potentially life-saving care. Based on VOCAL’s analysis of state health department data, we estimate that nearly two-thirds of Erie County residents living with hepatitis C don’t know their status. The picture may be even worse in other areas of Western New York.

    So who would oppose empowering people with hepatitis C to learn their status and take steps to get treatment, prevent transmission and save millions of dollars in avoidable health care costs?

    Some hospitals and doctors initially objected to the bill because the U.S. Preventive Services Task Force hadn’t issued a strong recommendation in favor of hepatitis C screening for baby boomers. That’s no longer the case. Just days before the State Senate passed New York’s screening bill, the task force upgraded its recommendation and joined the CDC in calling on health care providers to test patients for hepatitis C.

    There are a lot of chronic health conditions affecting New Yorkers that we still struggle to find reliable tests and effective medication for. Hepatitis C isn’t one of them.

    Alyssa Aguilera is political director for VOCAL New York, a grass-roots organization dedicated to creating healthy and just communities.


    Also See:

    Prevention and Risk Factors of Hepatitis B Recurrence after Living Donor Liver Transplantation

    J Gastroenterol Hepatol. 2013 Oct 3. doi: 10.1111/jgh.12403. [Epub ahead of print]

    Na GH, Kim DG, Han JH, Kim EY, Lee SH, Hong TH, You YK, Choi JY.

    Department of Surgery, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.


    BACKGROUND AND AIM: Without effective prophylaxis, liver transplantation (LT) for hepatitis B virus (HBV)-related liver disease is frequently complicated by severe and rapidly progressive HBV recurrence. We analyzed the combination of low-dose hepatitis B immunoglobulin (HBIG) and the new nucleos(t)ide analogue, entecavir, as prophylaxis for HBV recurrence after living donor liver transplantation (LDLT).

    METHODS: A total of 315 patients with positive hepatitis B surface antigen (HBsAg) underwent LDLT at our transplant center between July 2003 and December 2011. Our protocol for post-transplantation HBV prophylaxis was a combination of low-dose HBIG and nucleos(t)ide analogues.

    RESULTS: During a median follow-up period of 49 months post-transplant, 10 patients (3.2%) had HBV recurrence, which was significantly related to HCC at transplantation (p = 0.041) and post-LT antiviral agent (p < 0.001) in multivariate analysis. The level of HBV DNA and hepatitis B e antigen (HBeAg) state at transplantation were not significant factors for HBV recurrence (p = 0.342 and p = 0.802 respectively). In 170 patients with HCC at LDLT, HCC recurrence was significantly related to HBV recurrence (p < 0.001). Among 10 patients with HBV recurrence, three are alive and two had lost HBsAg. The remaining seven patients died of HCC recurrence.

    CONCLUSIONS: The combination of low-dose HBIG and nucleos(t)ide analogues is safe and effective for HBV prophylaxis after LDLT. As a post-LT antiviral treatment, entecavir is more effective than lamivudine. HCC at transplantation was significantly associated with HBV recurrence. HBV-related HCC patients who undergo LDLT require close virological monitoring.

    This article is protected by copyright. All rights reserved.

    KEYWORDS: Entecavir, Hepatitis B immunoglobulin, Hepatitis B virus, Hepatocelluar carcinoma, Liver transplantation, Nucleos(t)ide analogue

    PMID: 24117684 [PubMed - as supplied by publisher]