http://www3.interscience.wiley.com/journal/122679630/abstract?CRETRY=1&SRETRY=0

Cancer
See Also:
Cancer Cytopathology
CA: A Cancer Journal for Clinicians
Early View (Articles online in advance of print)
Published Online: 6 Nov 2009
Copyright © 2009 American Cancer Society

Original Article
Hepatitis B virus reactivation and role of antiviral prophylaxis in lymphoma
patients with past hepatitis B virus infection who are receiving
chemoimmunotherapy

Yu Xuan Koo 1, Daniel S. W. Tan, MBBS, MRCP 2, Iain B. Tan, MBBS, MRCP 2, Miriam
Tao, MBBS, MRCP 2, Wan Cheng Chow, MBBS, MRCP 3, Soon Thye Lim, MBBS, MRCP 2 *

1Yong Loo Lin School of Medicine, National University of Singapore, Singapore
2Department of Medical Oncology, National Cancer Center Singapore, Singapore
3Department of Gastroenterology and Hepatology, Singapore General Hospital,
Singapore

email: Soon Thye Lim (dmolst@...)
*Correspondence to Soon Thye Lim, Department of Medical Oncology, National
Cancer Centre Singapore, 11 Hospital Drive, Singapore S(169610)
Fax: (011) 65 6225 6283

Abstract

BACKGROUND:
Individuals who had past hepatitis B virus (HBV) infection appeared to clear
their serum hepatitis B surface antigen (HBsAg) while producing antibody to the
hepatitis B core antigen (HBcAb), which is detectable in their serum. Currently,
it is uncertain whether patients with past HBV infection require routine
antiviral prophylaxis during chemotherapy, although some cancer agencies
recommend its routine use. The objective of the current study was to determine
the prevalence of past HBV infection in patients with lymphoma and its relevance
in terms of HBV-related complications.

METHODS:
The authors reviewed 430 patients with lymphoma from May 2006 to May 2008.

RESULTS:
Among the 430 patients, 233 had both the HBsAg and HBcAb tests performed,
whereas 197 had only the HBsAg test performed. Among those with both tests
performed, 34.3% (80 of 233) were HBcAb positive only. Of these 80 patients, 58
had a concomitant HBV DNA level test, which was positive in 3 (5.2%). Of the 67
patients with past and 26 with chronic HBV infection who received chemotherapy,
HBV reactivation occurred in 1.5% and 42.3% of patients, respectively (P<.0001).
Prophylactic lamivudine was administered in 7 (10.4%) patients with past HBV
infection and in 18 (69.2%) with chronic HBV infection.

CONCLUSIONS:
The low rate of HBV reactivation reported in our study coupled with the high
prevalence of past HBV infection in an endemic area suggests that routine usage
of antiviral prophylaxis may not be required for all patients with past HBV
infection. Close surveillance remains a reasonable and viable option for the
majority of patients. Cancer 2009. © 2009 American Cancer Society.
--------------------------------------------------------------------------------
Received: 8 January 2009; Revised: 7 May 2009; Accepted: 11 May 2009
Digital Object Identifier (DOI)
10.1002/cncr.24742

http://jama.ama-assn.org/cgi/content/short/302/18/1949?rss=1

Silent Epidemic of Viral Hepatitis May Lead to Boom in Serious Liver Disease
Bridget M. Kuehn

JAMA. 2009;302(18):1949-1954.

  Since this article does not have an abstract, we have provided the first 150
words of the full text and any section headings.



Washington, DC
More than 500 million persons worldwide are infected with hepatitis B or C
virus, estimates the World Health Organization, and more than 5 million US
residents have such infections, according to the US Centers for Disease Control
and Prevention (CDC). Yet these infections often go undetected and untreated
because patients and physicians may be unaware of who is at risk or may fail to
pursue testing.

As more individuals immigrate to the United States from regions where hepatitis
B virus infection is prevalent, US physicians may see higher rates of
complications from such infection.

Although prevention efforts have helped dramatically reduce the incidence of
hepatitis B and C viral infections in the general US population, demographic
shifts are leading to growing numbers of chronically infected patients who may
develop severe complications such as cirrhosis and hepatic cell carcinoma.

CME/CE-CERTIFIED MANAGEMENT SERIES
Understanding and Implementing the AASLD’s 2009 Practice Guidelines* on the
Diagnosis, Management, and Treatment of Hepatitis C: An Update







Revised treatment guidelines from the American Association for the Study of
Liver Diseases (AASLD) address the significant advances that have taken place in
the field of hepatitis C. In this CME/CE-certified program, CCO's expert faculty
members discuss how to incorporate these guidelines into daily practice.
Click here to review this program or select an activity below.
Interactive Virtual Presentations




In an engaging, interactive format, you are invited to respond to various
treatment questions for HCV-infected patients. A graphic will compare your
answers with those of your colleagues, as expert faculty comment on the options.



Click here to review the 3 Interactive Virtual Presentations and download
accompanying slidesets by Ira M. Jacobson, MD; John G. McHutchison, MD, FRACP;
and David L. Thomas, MD, MPH.
Interactive Case Challenges
CCO expert faculty members present 6 unique and challenging patient cases in
which you make treatment decisions that determine how the cases unfold.
Click here to begin an Interactive Case Challenge.
Downloadable Worksheet





HCV Management Algorithm
This downloadable worksheet is a quick reference guide derived from the AASLD’s
HCV Practice Guidelines Update.

To download this worksheet, click here.

This Clinical Management Series program is located online at:
http://clinicaloptions.com/Hepatitis/Management%20Series/2009%20AASLD%20HCV%20Gu\
idelines.aspx













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http://www.hivandhepatitis.com/2009icr/aasld/docs/111309_a.html

HIV and Hepatitis.com Coverage of the
60th Annual Meeting of the American Association
for the Study of Liver Diseases (AASLD 2009)
October 30 - November 3, 2009, Boston, MA

Oral HCV Polymerase Inhibitor RG7128 plus Protease Inhibitor RG7227 (ITMN-191)
Suppresses HCV Viral Load without Interferon or Ribavirin

   SUMMARY: Combination hepatitis C treatment using the nucleoside analog
hepatitis C virus (HCV) polymerase inhibitor RG7128 (formerly R7128) plus the
HCV NS3/4A protease inhibitor RG7227 (formerly R7227, also known as ITMN-191)
produced potent antiviral activity in a 2 week study, researchers reported this
month at the 60th Annual Meeting of the American Association for the Study of
Liver Diseases (AASLD 2009) in Boston. If confirmed in larger studies, these
findings from the INFORM-1 trial -- the first to test an all-oral combination
anti-HCV regimen -- suggest that effective treatment may be possible without
interferon or ribavirin.


By Liz Highleyman
Combination therapy consisting of pegylated interferon plus ribavirin is the
current standard of care for chronic hepatitis C, but there is a need for
treatments that are more effective, easier to administer (oral rather than
injected), and have fewer side effects.
The INFORM-1 trial -- conducted by Roche in collaborations with InterMune and
Pharmasset -- tested a combination regimen consisting of 2 directly targeted
oral anti-HCV agents without interferon or ribavirin. As with antiretroviral
therapy for HIV, combining agents targeting multiple steps of the viral
lifecycle may offer greater potency and reduce the emergence of drug resistance.
In this Phase 1 double-blind, ascending-dose trial, 64 adults with genotype 1
chronic hepatitis C were randomly assigned (8 per cohort) to receive various
combinations of RG7128 and RG7227 (or placebo) for up to 14 days. Some
participants were treatment-naive and others were treatment experienced,
including some who had a null response to previous interferon-based therapy (HCV
RNA decrease <1 log10 in 4 weeks or <2 log10 in 12 weeks).
The first 2 study cohorts received low-dose monotherapy with either 500 mg
RG7128 twice-daily or 100 mg RG7227 3-times-daily on days 1-3. Both cohorts then
received a combination of both drugs on days 4-7. Next, additional cohorts
received escalating doses of RG7128 (500 or 1000 mg twice-daily) plus RG7227
(600 or 900 mg twice-daily, or 100 or 200 mg 3-times-dialy) for 14 days.
None of the participants took pegylated interferon or ribavirin during
RG7128/RG7227 dosing, but did received standard of care therapy using pegylated
interferon alfa-2a (Pegasys) plus ribavirin after the initial 2-week dosing
period.
The results presented at the AASLD meeting focused on the final 3 cohorts,
consisting of patients who received the higher-dose twice-daily regimens. Data
from the initial lower-dose cohorts were previously reported at the European
Association for the Study of the Liver (EASL) meeting this past April.

Results
  All patients receiving twice-daily RG7128/RG7227 regimens experienced a
continual decline in HCV RNA during the study period, with viral decline showing
a biphasic pattern.
  The highest response rate at day 13 -- 88% with viral load below the lower
limit of quantification (LLOQ, <43 IU/mL) and 63% below the lower limit of
detection (LLOD, <15 IU/mL) -- was seen in treatment-naive patients receiving
1000 mg RG7128 plus 900 mg RG7227 twice-daily.
  In previous null responders receiving the same doses, the corresponding
response rates were 50% below LLOQ and 25% below LLOD.
  In the 1000/900 mg dose cohorts, HCV RNA fell by a median -5.1 log10 IU/mL for
treatment-naive participants and -4.9 log10 for prior null responders.
  Participants who received the lower 600 mg dose of RG7227 plus 1000 mg RG7128
had lower response rates, 50% below LLOQ and 13% below LLOD.
  However, there were also no significant differences between twice-daily and
3-times-daily dosing.
  Patients with HCV genotype 1a and 1b also responded similarly.
  1 patient who received a lower dose (500/200 mg) of RG7128/RG7227 experienced
viral rebound, but had no identified resistance mutations and went on to achieve
undetectable viral load on standard-of-care therapy.
  The RG7128/RG7227 combination was generally well-tolerated.
  No treatment-related serious adverse events, dose modifications, or drug
discontinuations were reported.
  The most commonly reported adverse events were headache, nausea, and diarrhea,
which occurred with a frequency similar to that seen in the lower-dose cohorts.
  No emergent resistance to RG7128 or RG7227 was observed during the study
period.

Based on these findings, the researchers concluded that the combination of
RG7128 and RG7227 for up to 14 days "provided significant antiviral potency in
treatment-naive and experienced patients, sustained viral reductions, and
appears safe and well-tolerated as a twice-daily oral regimen."
"The results from this study of the RG7227/RG7128 combination raise hopes that
we can deliver an interferon-free regimen for our patients in the future," said
lead investigator Edward Gane, MD, in a press release issued by InterMune.
"Current HCV therapy includes up to 12 months of weekly interferon injections
which can be associated with significant side effects. In addition, not all
patients can take interferon due to intolerance or contraindications. We look
forward to the results of additional studies with these potent compounds."
The collaborating companies announced that Roche will initiate a Phase 2 trial
program in the first quarter of 2010. INFORM-2 will assess rapid virological
response (undetectable HCV RNA after 4 weeks of therapy) in prior non-responder
genotype 1 patients receiving twice-daily RG7128/RG7227 alone and in combination
with pegylated interferon alfa-2a, ribavirin, or both. Longer-term studies
evaluating sustained virological response (undetectable HCV RNA 24 weeks after
completing therapy) are anticipated for the first half of 2010.
Roche, Palo Alto, CA; Intermune, Brisbane, CA; Pharmasset, Princeton, NJ;
Auckland Clinical Studies, Auckland, New Zealand; The Alfred, Melbourne,
Victoria, Australia; Christchurch Clinical Studies, Christchurch, New Zealand;
Austin Hospital, Heidelberg, Victoria, Australia; Royal Adelaide Hospital,
Adelaide, SA, Australia.
11/10/09


Reference
EJ Gane, SK Roberts, CA Stedman, and others. Combination Therapy with a
Nucleoside Polymerase (R7128) and Protease (R7227/ITMN-191) Inhibitor in HCV:
Safety, Pharmacokinetics, and Virologic Results from INFORM-1. 60th Annual
Meeting of the American Association for the Study of Liver Diseases (AASLD
2009). Boston. October 30-November 1, 2009. Abstract 193. (Slides available
online).

S Le Pogam, M Chhabra, S Ali, and others. Combination Therapy with Nucleoside
Polymerase R7128 and Protease R7227/ITMN-191 Inhibitors in Genotype 1 HCV
Infected Patients: Interim Resistance Analysis of INFORM-1 Cohorts A-D. 60th
Annual Meeting of the American Association for the Study of Liver Diseases
(AASLD 2009). Boston. October 30-November 1, 2009. Abstract 1585.

PN Morcos, R Kulkarni, D Ipe, and others. Pharmacokinetics/Pharmacodynamics
(PK/PD) of Combination R7227 and R7128 Therapy from INFORM-1 Demonstrates
Similar Early HCV Viral Dynamics when R7227 is Combined with either
PEG-IFN/Ribavirin (SOC) or R7128. 60th Annual Meeting of the American
Association for the Study of Liver Diseases (AASLD 2009). Boston. October
30-November 1, 2009. Abstract 1594.

Other Sources
InterMune. INFORM-1 Results: Robust Antiviral Suppression Achieved with
Combination of Nucleoside Analog Polymerase Inhibitor RG7128 and Protease
Inhibitor RG7227. Press release. November 3, 2009.
AASLD. INFORM Study: HCV Protease R7227+HCV Nucleoside R7128; Twice Daily Oral
Medication Shows Promise in Treating Patients with Hepatitis C. Press release.
November 2, 2009.

http://www.hivandhepatitis.com/2009icr/aasld/docs/111309_b.html


HIV and Hepatitis.com Coverage of the
60th Annual Meeting of the American Association
for the Study of Liver Diseases (AASLD 2009)
October 30 - November 3, 2009, Boston, MA


Entecavir (Baraclude) and Tenofovir (Viread) Rescue Therapy for Chronic
Hepatitis B Patients with Advanced Fibrosis and Prior Treatment Failure


SUMMARY: A "rescue therapy" regimen combining entecavir (Baraclude) and
tenofovir (Viread) is safe and effective for chronic hepatitis B patients with
advanced liver disease who have experienced past treatment failure or developed
extensive drug resistance, according to a study presented this month in Boston
at the 60th Annual Meeting of the American Association for the Study of Liver
Diseases (AASLD 2009).

By Liz Highleyman


In this open-label cohort study, investigators from 8 referral centers in Europe
assessed the efficacy and safety of tenofovir plus entecavir in
treatment-experienced hepatitis B patients with advanced liver disease.


Past treatment with single nucleoside/nucleotide analog drugs as sequential
monotherapy has left many patients with hepatitis B virus (HBV) that harbors
multiple resistance mutations, the researchers noted as background. Drug
resistance renders older therapies less effective or ineffective, putting
patients with advanced liver fibrosis or cirrhosis at risk of further damage due
to hepatic "flares," or episodes of worsening disease.


Of the 39 study participants, more than half were hepatitis B "e" antigen
(HBeAg) positive. They had multidrug resistant HBV or a history of only partial
response to previous treatment. The median age was 48 years, and patients had
used an average of 3 (range 1-6) past treatment regimens. At baseline, the
median ALT level was 1.2 x upper limit of normal (ULN) and the median HBV DNA
level was 1.7 x 10(4) IU/mL.



Results

The median treatment duration after initiating combination therapy was 10.5
months (range 1-42 months).

During this period, no significant clinical side effects were observed.

The median HBV DNA level dropped significantly after starting the combination
regimen, by 3.5 log (range 0-8 log; P < 0.0001).

Nearly 80% (31 of 39 patients) achieved undetectable HBV DNA (< 80 IU/mL).

HBV DNA decline was accompanied by a significant ALT decrease (median 0.68 x
ULN; P = 0.001).

All patients with detectable HBV DNA were treated for less than 6 months.

3 patients experienced HBeAg loss (after 18, 21, and 24 months).

1 person showed hepatitis B surface antibody (HBs) seroconversion.

Patients with liver cirrhosis at baseline did not develop clinical
decompensation.

However, 2 patients with cirrhosis who had undetectable HBV DNA nevertheless
developed hepatocellular carcinoma.

There was no significant decrease in adherence among patients taking the 2
medications.


Based on these findings, the investigators concluded, "Rescue therapy with
entecavir and tenofovir in HBV monoinfected patients harboring complex viral
resistance patterns or showing only partial antiviral responses to preceding
therapies was highly efficient, safe, and well tolerated in patients with
advanced liver disease."


However, they added, "More data are certainly needed to judge about the
long-term safety, efficacy and prevention of emergence of new viral mutations in
this difficult to treat patient population."


Asklepiosklinik St. Georg, Liver Center Hamburg IFI Institute, University of
Hamburg, Germany; University Hospital Hamburg Eppendorf, Hamburg, Germany; Hotel
Dieu Hospital Lyon, Lyon, France; University Hospital Hamburg Eppendorf,
Hamburg, Germany; University Medical Center, Rotterdam, Netherlands; Charite
University Medical Center, Berlin, Germany; Fondazione IRCCS Maggiore Hospital,
University of Milan, Italy; Service d Hepato-Gastroenterologie, Universite
Pierre et Marie Curie, Paris, France; Hospital Vall de Hebron, Barcelona, Spain;
Goethe University Hospital, Frankfurt, Germany.


11/13/09


Reference
J Petersen, M Lutgehetmann, F Zoulim, and others. Entecavir and Tenofovir
combination therapy in chronic Hepatitis B: Rescue therapy in patients with
advanced fibrosis and multiple previous treatment failures. Results from an
international multicenter cohort study. 60th Annual Meeting of the American
Association for the Study of Liver Diseases (AASLD 2009). Boston. October
30-November 1, 2009. Abstract 405.

http://www.ncbi.nlm.nih.gov/pubmed/19885876

Hepatology. 2009 Aug 31. [Epub ahead of print]

Severe sepsis in cirrhosis.

Gustot T, Durand F, Lebrec D, Vincent JL, Moreau R.

Institut National de la Santé et de la Recherche Médicale (INSERM), U773, Centre
de Recherche Bichat-Beaujon CRB3, Paris 75018, France.


Sepsis is physiologically viewed as a proinflammatory and procoagulant response
to invading pathogens. There are three recognized stages in the inflammatory
response with progressively increased risk of end-organ failure and death:
sepsis, severe sepsis, and septic shock. Patients with cirrhosis are prone to
develop sepsis, sepsis-induced organ failure, and death. There is evidence that
in cirrhosis, sepsis is accompanied by a markedly imbalanced cytokine response
("cytokine storm"), which converts responses that are normally beneficial for
fighting infections into excessive, damaging inflammation. Molecular mechanisms
for this excessive proinflammatory response are poorly understood. In patients
with cirrhosis and severe sepsis, high production of proinflammatory cytokines
seems to play a role in the worsening of liver function and the development of
organ/system failures such as shock, renal failure, acute lung injury or acute
respiratory distress syndrome, coagulopathy, or hepatic encephalopathy. In
addition, these patients may have sepsis-induced hyperglycemia, defective
arginine-vasopressin secretion, adrenal insufficiency, or compartmental
syndrome. In patients with cirrhosis and spontaneous bacterial peritonitis
(SBP), early use of antibiotics and intravenous albumin administration decreases
the risk for developing renal failure and improves survival. There are no
randomized studies that have been specifically performed in patients with
cirrhosis and severe sepsis to evaluate treatments that have been shown to
improve outcome in patients without cirrhosis who have severe sepsis or septic
shock. These treatments include recombinant human activated C protein and
protective-ventilation strategy for respiratory failure. Other treatments should
be evaluated in the cirrhotic population with severe sepsis including the early
use of antibiotics in "non-SBP" infections, vasopressor therapy, hydrocortisone,
renal-replacement therapy and liver support systems, and selective
decontamination of the digestive tract or oropharynx. (HEPATOLOGY 2009.).

PMID: 19885876 [PubMed - as supplied by publisher]

http://aje.oxfordjournals.org/cgi/content/abstract/kwp375

American Journal of Epidemiology Advance Access published online on November 12,
2009
American Journal of Epidemiology, doi:10.1093/aje/kwp375

American Journal of Epidemiology © The Author 2009. Published by Oxford
University Press on behalf of the Johns Hopkins Bloomberg School of Public
Health. All rights reserved. For permissions, please e-mail:
journals.permissions@....
--------------------------------------------------------------------------------
Original Contribution

Molecular Sequence Data of Hepatitis B Virus and Genetic Diversity After
Vaccination

W. Marijn van Ballegooijen*, Robin van Houdt, Sylvia M. Bruisten, Hein J. Boot,
Roel A. Coutinho and Jacco Wallinga
* Correspondence to Dr. W. Marijn van Ballegooijen, RIVM, National Institute for
Public Health and the Environment, PO Box 1, 3720 BA Bilthoven, the Netherlands
(e-mail: marijn.van.ballegooijen@...).

Received for publication December 8, 2008. Accepted for publication August 21,
2009.


The effect of vaccination programs on transmission of infectious disease is
usually assessed by monitoring programs that rely on notifications of
symptomatic illness. For monitoring of infectious diseases with a high
proportion of asymptomatic cases or a low reporting rate, molecular sequence
data combined with modern coalescent-based techniques offer a complementary tool
to assess transmission. Here, the authors investigate the added value of using
viral sequence data to monitor a vaccination program that was started in 1998
and was targeted against hepatitis B virus in men who have sex with men in
Amsterdam, the Netherlands. The incidence in this target group, as estimated
from the notifications of acute infections with hepatitis B virus, was low;
therefore, there was insufficient power to show a significant change in
incidence. In contrast, the genetic diversity, as estimated from the viral
sequence collected from the target group, revealed a marked decrease after
vaccination was introduced. Taken together, the findings suggest that
introduction of vaccination coincided with a change in the target group toward
behavior with a higher risk of infection. The authors argue that molecular
sequence data provide a powerful additional monitoring instrument, next to
conventional case registration, for assessing the impact of vaccination.


--------------------------------------------------------------------------------
Editor's note: An invited commentary on this article appears on page 000, and
the authors’ response is published on page 000.

From:
  Therapeutics Daily (news@...)

Sent:
Wed 11/11/09 8:07 AM

















Valeant Pharmaceuticals Highlights Taribavirin Phase IIb End of Study Data
Presentation
From PR Newswire US - Nov 03, 2009
Valeant Pharmaceuticals today announced that results from the week-72 analysis
for its Phase IIb  dose-finding clinical trial for taribavirin, a prodrug of
ribavirin which is in development for  the treatment of chronic hepatitis C in
conjunction with a pegylated interferon, were presented  at the American
Association for the Study of Liver Disease 60th Annual Meeting in Boston.
  Read Full Article      Article Summary



Idenix Pharmaceuticals Initiates Phase II Trial of IDX184 in Combination With
Pegylated Interferon and Ribavirin for HCV
From PR Newswire US - Nov 03, 2009
CAMBRIDGE, Mass., Nov. 3 /PRNewswire-FirstCall/ -- Idenix Pharmaceuticals, Inc.,
a biopharmaceutical company engaged in the discovery and development of drugs
for the treatment of human viral diseases, announced today that it has initiated
a Phase II clinical trial evaluating IDX184, a liver-targeted nucleotide prodrug
candidate for the treatment of HCV, in combination with pegylated interferon and
ribavirin, in treatment-naive hepatitis C genotype 1-infected patients.
Antiviral activity, safety and tolerability of the triple combination will be
assessed at 14 days.
  Read Full Article      Article Summary




TapImmune Signs License Agreement With Crucell N.V.
From GlobeNewswire - Nov 04, 2009
TapImmune Inc., a biotechnology company specializing in the development of
immunotherapeutic vaccines for cancer and infectious diseases, has signed a
license agreement with Crucell N.V.  Under the license TapImmune may use the
proprietary PER.C6 cells in its development programs.
  Read Full Article      Article Summary




Scynexis' SCY-635 Demonstrates Positive Antiviral Activity in Combination with
Approved and Investigational Anti-HCV Agents
From Business Wire NewsExpress - Nov 03, 2009
RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)--Nov 3, 2009 - Drug discovery
company Scynexis,  Inc. today presented positive data from an in vitro study
evaluating the antiviral activity of  SCY-635 in combination with approved and
investigational non-nucleoside polymerase inhibitors, nucleoside polymerase
inhibitors, protease inhibitors, ribavirin and interferon alpha 2b.
  Read Full Article      Article Summary




Idera Pharmaceuticals Presents Preclinical Data on IMO-2125,at Liver Meeting
2009
From Business Wire NewsExpress - Nov 03, 2009
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Nov 3, 2009 - Idera Pharmaceuticals, Inc.
today presents  preclinical data on the mechanism by which IMO-2125 was shown to
induce immune activation through  Toll-like Receptor 9 (TLR9). Two presentations
are being made today at the 60th Annual Meeting of  the American Association for
the Study of Liver Diseases being held in Boston, MA.
  Read Full Article      Article Summary


[Non-text portions of this message have been removed]

http://www3.interscience.wiley.com/journal/122670911/abstract?CRETRY=1&SRETRY=0

Journal of Viral Hepatitis
Volume 16 Issue 12, Pages 833 - 843
Published Online: 2 Nov 2009
© 2009 Blackwell Publishing Ltd


Management of chronic hepatitis C patients who have relapsed or not responded to
pegylated interferon alfa plus ribavirin

D. T. Dieterich 1 , M. Rizzetto 2 and M. P. Manns 3

1 Mount Sinai School of Medicine, New York, NY, USA ;   2 Division of
Gastro-Hepatology, Ospedale S. Giovanni Battista (Molinette), Torino, Italy ;
and   3 Department of Gastroenterology, Hepatology, and Endocrinology, Medical
School Hannover, Hannover, Germany
Correspondence to Professor Douglas T. Dieterich, Professor of Medicine Division
of Liver Disease, Director of CME, Mount Sinai School of Medicine, 1425 Madison
Ave, LC 01 MC Level, New York, NY 10029. E-mail:
Douglas.Dieterich@...

Copyright © 2009 Blackwell Publishing Ltd

ABSTRACT
Summary. Development of therapeutic strategies for patients with chronic
hepatitis C who experience virological breakthrough, relapse or nonresponse lag
behind those for treatment-naïve patients. The probability of a previously
treated patient responding to re-treatment depends on the nature of the previous
regimen, the magnitude of the response to previous treatment and the patient's
characteristics. Relapsers have higher sustained virological response rates than
nonresponders when re-treated with pegylated interferon plus ribavirin.
Re-treatment of nonresponders to pegylated interferon plus ribavirin with the
standard 48-week regimen resulted in an approximate 6% sustained response rate
in the EPIC-3 program. In the REPEAT trial, the sustained response rate was
significantly higher in nonresponders to pegylated interferon alfa-2b (12 kD)
plus ribavirin randomized to 72 weeks of peginterferon alfa-2a (40 kD) plus
ribavirin, compared with a 48-week regimen (16%vs 8%, P = 0.0006). Based on
available data, extended treatment is the best option for these individuals.
Undetectable viral RNA at week 12 is an important criterion for re-treatment in
the REPEAT and EPIC studies. Maintenance therapy with pegylated interferon is
generally ineffective in nonresponders and cannot be recommended. Directly
acting antivirals may increase response rates and the burden of adverse events
when combined with the standard of care, but will not be available for some
years. In conclusion, after careful evaluation of an individual's benefit–risk
ratio, a 72-week regimen is the preferred strategy for optimizing sustained
response rates in patients who have not responded to the standard of care,
provided that viral RNA is undetectable at week 12 of re-treatment.

--------------------------------------------------------------------------------
Received June 2009; accepted for publication July 2009
DIGITAL OBJECT IDENTIFIER (DOI)
10.1111/j.1365-2893.2009.01218

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> University Medical Center is accredited by the Accreditation Council for
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> Medical Education to provide continuing medical education for physicians. Rush
> University Medical Center designates this educational activity for a maximum
of
> 1 AMA PRA Category 1 Credit™. Physicians should only claim credit
> commensurate with the extent of their participation in this activity.
>
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> on Accreditation. This activity is for 1 contact hour.
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http://www.infectioncontroltoday.com/hotnews/difficult-to-treat-cases-of-hepatit\
is-c.html

Patients With More Difficult to Treat Forms of Hepatitis C are Half as Likely to
Treat the Disease
11/09/2009

A new study by Mount Sinai researchers has for the first time found that
patients with more difficult to treat forms of hepatitis C are half as likely to
initiate treatment for the disease, when compared to patients with hepatitis C
that is easier to treat. Marital status also affected whether patients chose
treatment, as did whether or not they had other diseases. The study is published
in the Nov. 1 issue of Journal of Health Care for the Poor and Underserved.
“Overall, only about 30 percent of hepatitis C patients choose to initiate
treatment for the disease,” said Thomas McGinn, MD, senior study author and
chief of general internal medicine at Mount Sinai School of Medicine. “It’s a
huge problem that needs to be addressed. This study confirms that genotype is a
major barrier to treatment. We hope these findings will lead to changes in how
physicians approach patient care in a way that increases the rate of treatment
initiation.”
Researchers analyzed all patients referred to Mount Sinai’s Primary Care
Treatment and Screening Program for Hepatitis C between January 2003 and May
2007. The analysis included all hepatitis C clinic patients who were eligible
for treatment and to whom treatment was offered.
Of the 168 treatment-eligible patients, 41 began treatment and 127 chose not to.
Patients with genotypes 1 and 4 of the disease, which are less responsive to
treatment, were less likely to initiate treatment, as were unmarried patients
and patients with multiple diseases, or medical comorbidities. Age, gender,
language, race, and other risk factors were not found to be significant in the
study. Researchers found that:

-- Only 21 percent of individuals with genotypes 1 and 4 initiated treatment,
compared to 42 percent of patients with genotypes 2 or 3.
-- 46 percent of patients who chose treatment were married, as opposed to just
19 percent of the patients who declined treatment.
-- Patients who chose treatment had an average of 2.9 medical comorbidities,
while patients who did not treat their hepatitis C had an average of 5.2 medical
comorbidities.
“More research is needed to determine why these factors affect treatment
initiation,” said McGinn. “Because of existing studies on other diseases, we
were not surprised that marital status and comorbidities were contributing
factors to low treatment rates. However, this is the first study to associate
hepatitis C genotype with lower rates of treatment initiation.
“Duration of treatment may be a factor,” said McGinn. “Genotypes 1 and 4 of the
disease require longer treatment courses, about 9 to 12 months, versus an
average of 6 months for genotypes 2 and 3. It’s possible the longer duration
discourages patients from choosing treatment. Furthermore, patients with
genotypes 1 and 4 often need a liver biopsy, which many patients incorrectly
think are extremely painful. As a result of this study, Mount Sinai has started
a program called ‘Biopsy Buddies,’ in which a patient who has already undergone
a liver biopsy consults with a patient who needs one. We’re hopeful that by
building more support systems for patients we will increase the likelihood that
they will choose to receive treatment.”

> U.S. Department of Health and Human Services
> NATIONAL INSTITUTES OF HEALTH NIH News
> National Center for Research Resources (NCRR) <http://www.ncrr.nih.gov/>
> Embargoed for Release: Tuesday, November 10, 2009, 11:00 a.m. EST
>
> CONTACT: Cindy McConnell, 301-435-0888, <e-mail:info@...>
>
> NIH ANNOUNCES FIRST NATIONAL RESEARCH STUDY RECRUITMENT REGISTRY
> Nationwide Registry to "Match" Volunteers with Researchers
>
> Individuals who want to participate in research studies now can connect online
with researchers nationwide through the first disease-neutral, volunteer
recruitment registry.
>
> <ResearchMatch.org> is a not-for-profit secure Web site, designed to provide
people who are interested in participating in research the opportunity to be
matched with studies that may be the right fit for them.
>
> ResearchMatch offers an easy-to-use, free and safe way for volunteers to
connect with thousands of researchers who are conducting research on a wide
range of diseases.
>
> The site is a collaborative effort of the national network of medical research
institutions affiliated with the Clinical and Translational Science Awards
(CTSAs). The CTSA program, which is led by the , a part of the National
Institutes of Health, is focused on enhancing local and national efforts to
enhance the translation of laboratory discoveries into treatments for patients.
>
> "Participant recruitment continues to be a significant barrier to the
completion of research studies nationwide - recent NIH data indicates that just
4 percent of the U.S. population has participated in clinical trials," said NCRR
Director Barbara Alving, M.D. "ResearchMatch is a tool that can improve the
connection and communication between potential participants and researchers
providing opportunities for the public to contribute to advancing new
treatments."
>
> The convenient and user-friendly registry employs a familiar research matching
model that is complementary to Clinicaltrials.gov. One key difference is that
ResearchMatch places the burden of connecting the right volunteers with the
right study on the researchers, whereas Clinicaltrials.gov asks volunteers to
identify the trials that could work for them.
>
> "ResearchMatch offers a convenient solution to the complex, competitive and
often costly participant recruitment system," said Gordon Bernard, M.D.,
principal investigator of the Vanderbilt CTSA, which hosts the national
registry. "NIH data indicates that 85 percent of trials don't finish on time due
to low patient participation, and 30 percent of trial sites fail to enroll even
a single patient. We aim to help combat these challenges with ResearchMatch."
>
> HOW RESEARCHMATCH WORKS
>
> ResearchMatch will match any interested individual residing in the United
States with researchers who are approved to recruit potential research
volunteers through the system. After an individual has self-registered to become
a volunteer, ResearchMatch's security features ensure that personal information
is protected until volunteers authorize the release of their contact information
to a specific study that may be of interest to them. Volunteers are notified
electronically when they are a possible match and then make the decision
regarding the release of their contact information. It also will promote choice
as there are no obligations on the volunteer to participate in studies.
>
> For the first year of the project, only researchers affiliated with
participating CTSA institutions are eligible to use ResearchMatch. However,
plans are in place to make ResearchMatch available beyond the CTSA consortium by
2011. Currently 52 individual institutions associated with 40 CTSA sites are
part of the ResearchMatch network. A list of these institutions may be viewed
here
(http://ncrr.nih.gov/clinical_research_resources/clinical_and_translational_scie\
nce_awards/researchmatch).
>
> To learn more about ResearchMatch and to register as a volunteer, visit:
<www.researchmatch.org>.
>
> ABOUT THE CTSA CONSORTIUM
>
> The CTSA consortium is a national network of 46 medical research institutions
working together to improve the way biomedical research is conducted across the
country. The consortium, funded through Clinical and Translational Science
Awards (CTSAs), shares a common vision to reduce the time it takes for
laboratory discoveries to become treatments for patients and to engage
communities in clinical research efforts. It also is fulfilling the critical
need to train a new generation of clinical researchers. The CTSA program is led
by the National Center for Research Resources, part of National Institutes of
Health.
>
> Launched in 2006, this network now includes awardees in 26 states. When the
program is fully implemented, it will support approximately 60 CTSAs across the
nation.
>
> For more information about the CTSA program, visit <www.ncrr.nih.gov/ctsa>.
The CTSA consortium Web site, which provides information on the consortium,
current members and new grantees, can be accessed at <www.CTSAweb.org>.
>
> The National Center for Research Resources, part of NIH, provides laboratory
scientists and clinical researchers with the resources and training they need to
understand, detect, treat and prevent a wide range of diseases. NCRR supports
all aspects of translational and clinical research, connecting researchers,
patients and communities across the nation. For more information, visit
<www.ncrr.nih.gov>.
>
> The National Institutes of Health (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. It is the primary federal agency for
conducting and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both common and rare
diseases. For more information about NIH and its programs, visit <www.nih.gov>.
>
> ##
>
> This NIH News Release is available online at:
> <http://www.nih.gov/news/health/nov2009/ncrr-10.htm>.
>
> To subscribe (or unsubscribe) from this list, go to
> <http://list.nih.gov/cgi-bin/wa?SUBED1=nihpress&A=1>.



[Non-text portions of this message have been removed]

IAC Express
Immunization news from the Immunization Action Coalition

More than 35,000 subscribers read IAC Express.
Subscribe to IAC Express and our other free publications at
  http://www.immunize.org/subscribe

A web page version of this issue is available at
  http://www.immunize.org/express/issue833.asp

The September 2009 issue of Needle Tips, including Ask the
Experts, is now online. Visit http://www.immunize.org/nt

***Combined Federal Campaign (CFC)***
Federal employees, including military, may contribute to IAC
by using code #10612 on their pledge cards.
===========================================================

Issue Number 833
November 9, 2009

CONTENTS OF THIS ISSUE

1. CDC updates its H1N1 web section with information on
vaccine supply, dosage, administration, and storage--and
much more
2. Leading physician groups urge pregnant women to get both
seasonal and 2009 H1N1 influenza vaccines
3. MMWR publishes article on fatal case of human rabies in
Missouri in 2008
4. Healthy pregnant women mount a robust immune response
after receiving one dose of 2009 H1N1 influenza vaccine
5. HHS orders intravenous antiviral influenza medication to
help patients hospitalized with 2009 H1N1 influenza
6. Health Alert Network (HAN) Info Service Message advises
clinicians about antiviral treatments for 2009 H1N1
7. AAP offers information on coding for influenza vaccine
and its administration
8. IAC's Video of the Week--"Sneezing 101"--shows how a
simple hygiene step can keep you and others healthy
9. "CDC Features" educate the public about issues related to
2009 H1N1 influenza
10. Keep vaccinating against seasonal influenza!
11. Immunization Techniques video (DVD or VHS) offers a great
way to give staff high-quality vaccination training
12. CDC's two new flyers educate healthcare providers and
parents about the Vaccines for Children program
13. October issue of CDC's Immunization Works electronic
newsletter recently released
14. Correction: IAC Express amends statistic on annual number
of meningitis cases reported among U.S. infants
15. Notice: November 17 teleconference on infant
meningococcal diseases has been postponed
16. Laminated seasonal influenza vaccine pocket guides--
FREE!--from the National Influenza Vaccine Summit
17. VISs for 2009 H1N1 influenza vaccines available in 12
additional languages
18. VIS translation: VIS for PPSV vaccine now available in
Turkish
19. Pediatrics publishes "Recommendations for Screening,
Monitoring, and Referral of Pediatric Chronic
Hepatitis B"
20. MMWR publishes article on 2009 human vaccinia infection
after contact with raccoon rabies vaccine bait in
Pennsylvania
21. Physician toolkit for adolescent immunization ready for
downloading
22. Summary report of ACIP's special July meeting on H1N1
influenza is now online
23. National Conference on Immunization and Health Coalitions
set for May 26-28 in Chicago; abstracts due February 1

[Non-text portions of this message have been removed]

http://informahealthcare.com/doi/abs/10.1517/14656560903321521

Summary
Expert Opinion on Pharmacotherapy
Posted online on 06 Nov 2009.

Pharmacotherapy of chronic hepatitis C virus infection – the IDEAL trial: ‘2b or
not 2b (= 2a), that is the question?’

Hidenori Toyoda�† MD PhD FACP & Takashi Kumada� MD PhD

Ogaki Municipal Hospital, Department of Gastroenterology, 4-86 Minaminokawa,
Ogaki, Gifu 503-8502, Japan +81 584 81 3341; +81 584 75 5715;
tkumada@...
†Author for correspondence


Background: There has been no direct comparison of the antiviral efficacy and
the adverse effects of peginterferon (PEG-IFN) alfa-2a and PEG-IFN alfa-2b when
used in combination therapy with ribavirin for chronic hepatitis C virus (HCV)
infection. Objective: A head-to-head comparison of the antiviral efficacy and
the adverse effects of PEG-IFN alfa-2a and PEG-IFN alfa-2b was made based on the
results from the IDEAL trial, a large, multicenter, prospective, randomized,
controlled study performed in the United States to provide guidance for the
selection of the right PEG-IFN in clinical settings. Methods: The results of the
IDEAL trial were analyzed. Results/conclusion: The antiviral efficacy, as well
as the adverse effects, of PEG-IFN alfa-2a and PEG-IFN alfa-2b are similar in US
patients with HCV genotype 1 when used in a standard dosing regimen in
combination with ribavirin.

http://www.hivandhepatitis.com/2009icr/aasld/docs/111009_b.html
HIV and Hepatitis.com Coverage of the
60th Annual Meeting of the American Association
for the Study of Liver Diseases (AASLD 2009)
October 30 - November 3, 2009, Boston, MA













Boosted Narlaprevir plus Pegylated Interferon and Ribavirin Leads to Rapid Viral
Suppression in Genotype 1 Hepatitis C Patients
















SUMMARY: In the NEXT-1 study, presented at the 60th Annual Meeting of the
American Association for the Study of Liver Diseases (AASLD) last week in
Boston, the experimental HCV NS3 protease inhibitor narlaprevir (formerly SCH
900518), boosted with ritonavir, demonstrated potent antiviral activity in
combination with pegylated interferon and ribavirin among treatment-naive
patients with genotype 1 chronic hepatitis C. Across the doses tested, 53% to
87% of narlaprevir recipients achieved undetectable HCV RNA by week 4.
Nalraprevir/ritonavir demonstrated no unique or treatment-limiting adverse
effects.









The NEXT-1 study was conducted to identify the optimal treatment regimen of
ritonavir-boosted narlaprevir/pegylated interferon/ribavirin combination
therapy, and to compare outcomes against those using pegylated
interferon/ribavirin alone. The inclusion of pegylated interferon and ribavirin
is expected to reduce the emergence of resistance that can occur when
directly-targeted antiviral agents are used as monotherapy.
The study included 111 previously untreated chronic hepatitis C patients treated
in the U.S. About 60% were men, most (72% to 95% in the various treatment arms)
were white, 13% were black, and the average age was about 45 years. About
three-quarters (78%) had high baseline viral load (> 600,000 IU/mL) and 61% had
genotype 1a.

Using a response-guided treatment strategy, participants received 12 weeks of
narlaprevir at doses of 200 or 400 mg once-daily or 100 mg twice-daily, boosted
with 100 mg ritonavir per dose, plus 1.5 mcg/kg/week pegylated interferon
alfa-2b (PegIntron) plus 600-1400 mg/day weight-adjusted ribavirin. Some
participants received pegylated interferon/ribavirin for a 4-week lead-in period
before starting narlaprevir. Based on response at week 4 of narlaprevir, study
protocol called for 12 or 36 additional weeks of pegylated interferon/ribavirin.
Narlaprevir regimens were compared with standard therapy using pegylated
interferon/ribavirin.

The primary study endpoint was rapid virological response (RVR), or undetectable
HCV-RNA at week 4, as well as response at week 12.


Results





Through week 4, participants in the triple therapy lead-in arms had higher
response rates that those who did not have a lead-in period.


By week 12, however, there was no difference in the rates of patients who
achieved undetectable HCV RNA in the lead-in and no lead-in arms.


All null responders in the lead-in arms (<1 log10 drop in HCV RNA after 4 weeks
of pegylated interferon/ribavirin) responded well to the addition of
narlaprevir, achieving undetectable viral load at week 4.







9 of these patients still had undetectable HCV RNA at week 12.


2 participants in the 200 mg once-daily narlaprevir arm experienced virological
breakthrough by week 8.


Narlaprevir combination therapy was well-tolerated overall.


Adverse events included gastrointestinal symptoms, lethargy, elevated liver
enzymes, and loss of appetite, and psychiatric symptoms.


Adverse events generally occurred with similar frequency, except anemia and
dizziness were more common in the narlaprevir arms.







P/R

P/R
NVR200QD

P/R
NVR400QD

LI P/R
NVR200QD

LI P/R
NVR400QD

P/R
NVR100BID

LI Wk 4

NA

NA

NA

6%

5%

NA

P/R/N Wk 1

ND

15%

0%

60%

50%

6%

P/R/N Wk 2

0%

35%

16%

80%

60%

29%

P/R/N Wk 4

0%

75%

58%

87%

85%

53%

P/R/N Wk 12

17%

85%

84%

87%

85%

65%
* Patients with at least 1 dose of narlaprevir, excluding P/R control arm
P/R = pegylated interferon/ribavirin; N = narlaprevir/ritonavir; NVR200QD =
narlaprevir 200 mg once-daily; NVR400QD = narlaprevir 400 mg once-daily;
NVR100BID = narlaprevir 100 mg twice-daily; LI = pegylated interferon/ribavirin
lead-in; NA = not applicable; ND = not determined.

Based on these findings, the study investigators concluded that narlaprevir "has
potent antiviral activity" against HCV, and the addition of once-daily
narlaprevir "greatly improved viral clearance at week 4" compared with a
standard-of-care pegylated interferon/ribavirin regimen in genotype 1 hepatitis
C patients.

"These interim results, while preliminary, are very encouraging, and showed that
narlaprevir has potent antiviral activity in hepatitis C," lead investigator
John Vierling, MD, from Baylor College of Medicine said in a press release
issued by Schering-Plough. "In this study, once-daily narlaprevir greatly
improved viral clearance at week 4 of treatment in genotype 1 hepatitis C
infection compared to the control group. We look forward to further results from
this ongoing study."

11/10/09

Reference
JM Vierling, F Poordad, E Lawitz, and others. Once daily narlaprevir (SCH
900518) in combination with PegIntron (peginterferon alfa-2b)/ribavirin for
treatment-naive subjects with genotype-1 CHC: interim results from NEXT-1, a
phase 2a study. 60th Annual Meeting of the American Association for the Study of
Liver Diseases (AASLD 2009). Boston. October 30-November 1, 2009. Abstract LB4.

Other source
Schering-Plough Corporation. Schering-Plough Reports Potent Antiviral Activity
With Narlaprevir (SCH 900518), an Investigational, Once-Daily Protease Inhibitor
for Hepatitis C. Press release. November 2, 2009.





[Non-text portions of this message have been removed]

http://www.hivandhepatitis.com/2009icr/aasld/docs/111009_d.html

HIV and Hepatitis.com Coverage of the
60th Annual Meeting of the American Association
for the Study of Liver Diseases (AASLD 2009)
October 30 - November 3, 2009, Boston, MA

High HBV Viral Load and Being HBeAg Positive Are Associated with Decreased Life
Expectancy for People with Hepatitis B

   SUMMARY: Despite the availability of an effective vaccine, hepatitis B virus
(HBV) infection remains a significant cause of morbidity and mortality in the
U.S. Individuals with chronic hepatitis B have a shorter life expectancy than
uninfected people, according to a mathematical model presented last week at the
60th Annual Meeting of the American Association for the Study of Liver Diseases
(AASLD) in Boston. High HBV viral load and being hepatitis B "e" antigen (HBeAg)
positive were associated with shorter survival.


By Liz Highleyman

Hepatitis B Virus
Researchers at the University of Cincinnati constructed a Markov state
transition model to simulate the natural history of hepatitis B progression over
the lifetime of a hypothetical cohort, and to estimate quality adjusted life
expectancies in various groups of people with current or past HBV infection.
The target population was defined as U.S. adults age 35 or older, classified as
being not HBV infected, immune to HBV (e.g., due to vaccination), or chronically
infected (defined as hepatitis B surface antigen [HBsAg] positive). The chronic
infection group was further stratified according to HBeAg status, HBV DNA viral
load, and liver function tests (e.g., ALT liver enzyme levels).
The investigators used published studies in the medical literature to determine
ranges of seroconversion, liver fibrosis progression, development of
hepatocellular carcinoma, and end-stage liver disease. Life expectancies for
each cohort were determined by running the Markov simulation until only 1 out of
10,000 members remained alive.
Results
  Individuals without active HBV infection or with HBV immunity had higher life
expectancies (both 44.6 years) than those with chronic HBV infection (37.7
years).
  Among HBeAg positive people with normal liver function tests, considered to be
immune tolerant, overall life expectancy was 30.7 years, but this varied
according to HBV DNA level:
    High viral load: 27.5 years;
  Low viral load: 34.5 years.

  Among HBeAg negative people with normal liver function tests, considered to be
chronic asymptomatic, life expectancy was 36.8 years:
    High viral load: 33.3 years;
  Low viral load: 34.9 years.

"Life expectancy differences were observed across chronic subgroups, with HBeAg
positive having shorter projected lifespans," the researchers determined. "High
viral load is the most important factor associated with decreased life
expectancy. Sensitivity analyses demonstrate that spontaneous seroconversion
rates significantly affect outcomes."
"The model demonstrates that all chronic HBV subgroups have decreased survival,
but there is considerable variability in overall life expectancy which is highly
sensitive to HBV viral load," they concluded.
Division of Digestive Disease, University of Cincinnati, Internal Medicine,
Cincinnati, OH; Division of General Internal Medicine and Center for Clinical
Effectiveness, University of Cincinnati, Internal Medicine, Cincinnati, OH.
11/10/09

Reference
TE Kaiser, KE Sherman, and MH Eckman. Simulation Modeling of the Natural History
of Hepatitis B Progression in a United States Adult Population - Determining
Life Expectancies. 60th Annual Meeting of the American Association for the Study
of Liver Diseases (AASLD 2009). Boston. October 30-November 1, 2009. Abstract
420.

http://www.hivandhepatitis.com/2009icr/aasld/docs/111009_a.html

  HIV and Hepatitis.com Coverage of the
60th Annual Meeting of the American Association
for the Study of Liver Diseases (AASLD 2009)
October 30 - November 3, 2009, Boston, MA

HCV Protease Inhibitor Telaprevir Demonstrates Good Efficacy in Both
Treatment-experienced and Treatment-naive Patients

   SUMMARY: Vertex's experimental hepatitis C virus (HCV) protease inhibitor
telaprevir (formerly known as VX-950) -- which, along with Schering-Plough's
boceprevir is the most advanced of the directly targeted oral anti-HCV drugs in
development -- continues to demonstrate good efficacy with acceptable
tolerability, according to data presented last week at the 60th Annual Meeting
of the American Association for the Study of Liver Diseases (AASLD 2009) in
Boston. Final results from the PROVE3 trial showed that patients with prior
treatment failure can be successfully treated with a telaprevir-based regimen,
while Study C208 indicated that twice-telaprevir works as well as 3-times-daily
dosing.


By Liz Highleyman
PROVE Studies
John McHutchison and colleagues presented final data from the Phase 2 PROVE3
trial; the researchers previously presented interim 36-week data at last year's
AASLD meeting.
The study included 453 genotype 1 chronic hepatitis C patients who were
non-responders, partial responders, or relapsers following a prior course of
interferon plus ribavirin. Two-thirds were men, about 90% were white, 9% were
black, and the median age was about 50 years. Most (92%) had baseline HCV RNA>
800,000 IU/mL. About 40% had bridging fibrosis or compensated cirrhosis. About
60% were prior non-responders (never achieved undetectable HCV RNA) and about
30% were relapsers (undetectable HCV RNA during treatment, but viral load
recurred after completing therapy).
Participants were randomly allocated to 4 arms, receiving 750 mg 3-times-daily
telaprevir plus 180 mcg/week pegylated interferon alfa-2a (Pegasys), with or
without 1000-1200 mg/day weight-adjusted ribavirin. One group received all 3
drugs for 12 weeks followed by Pegasys plus ribavirin without telaprevir for 12
additional weeks (T12/PR24). A second group received all 3 drugs for 24 weeks,
followed by Pegasys plus ribavirin for 24 additional weeks (T24/PR48). A third
group took telaprevir plus Pegasys without ribavirin for 24 weeks (T24/P24).
Finally, a control arm received standard therapy using Pegasys plus ribavirin
for 48 weeks (PR48).
HCV RNA was measured at week 4 (rapid virological response, or RVR), week 12
(early virological response, or EVR), end of treatment (EOT), and 24 weeks after
completion of therapy (sustained virological response, or SVR); telaprevir
recipients who achieved SVR were tested again 48 weeks after completing
treatment. The study protocol included a stopping rule that required patients to
discontinue treatment if they did not achieve a response by week 4 or 12, or if
they experienced viral breakthrough.

Results
  About half the participants completed their assigned treatment.
  Proportions discontinuing treatment due to meeting the defined stopping rule
were 15% in the T12/PR24 arm, 23% in the T24/PR48 arm, and 37% in the T12/P24
arm, compared with 59% in the standard therapy arm.
  Proportions discontinuing therapy due to adverse events were 10%, 25%, 9%, and
4%, respectively.
  Overall SVR rates were 51% in the T12/PR24 arm, 53% in the T24/PR48 arm, 24% in
the T12/P24 arm, and 14% in the standard therapy arm, but varied according to
type of prior failure:
  Prior non-responders: 39%, 38%, 11%, and 9%, respectively.
  Prior relapsers: 69%, 76%, 42%, and 20%, respectively.
  Prior viral breakthough while on treatment: 57%, 63%, 36%, and 40%,
respectively.

  Rates of viral breakthrough during treatment were 13% in the T12/PR24 arm, 12%
in the T24/PR48 arm, 32% in the T12/P24 arm, and 3% in the standard therapy arm
  Overall relapse rates during the 24-week post-treatment follow-up period were
30%, 13%, 53%, and 53%, respectively.
  Among patients who completed their assigned regimen, relapse rates were 28%,
4%, 53%, and 52%, respectively.
  No late relapses were observed during the longer 48-week post-treatment
follow-up period for telaprevir recipients.
  Adverse events occurring with greater frequency in the telaprevir compared with
standard therapy arms included fatigue, nausea, diarrhea, headache, skin rash,
pruritus (itching), anemia, insomnia, fever, chills, and hair loss.
  Rash leading to treatment discontinuation occurred in 4%, 6%, 5%, and 0% of
patients in the T12/PR24, T24/PR48, T24/P24, and standard therapy arms,
respectively.
  Anemia leading to discontinuation occurred in 0%, 2%, 1%, and 1%, respectively.
Based on these findings, the researchers stated, "SVR rates in all treatment
groups receiving [telaprevir plus pegylated interferon plus ribavirin] regimens
were significantly higher than with [pegylated interferon plus ribavirin]. Other
than 1 patient lost to follow-up, all patients who completed [a telaprevir]
regimen and achieved SVR maintained virologic response 48 weeks after the end of
treatment."
Participants who did not include ribavirin in their regimen were about half as
likely to achieve SVR as those who used all 3 drugs, demonstrating the
importance of ribavirin in preventing relapse. Overall, prior relapsers and
those who previously experienced viral breakthrough during treatment had better
sustained response rates than prior non-responders. For prior non-responders,
SVR rates were similar in the 24-week and 48-week treatment arms, although prior
relapsers and breakthroughs tended to respond better with longer treatment.
"Patients who failed prior [pegylated interferon plus ribavirin] therapy can
successfully be treated with a telaprevir-based regimen and maintain SVR 1 year
after the end of treatment," the investigators concluded.
In addition, Gregory Everson and colleagues presented a poster describing
findings from a sub-analysis of "difficult-to-cure" patients in the Phase 2b
PROVE1 and PROVE2 trials. These trials included treatment-naive genotype 1
chronic hepatitis C patients. Final PROVE1 results were reported at the 2008
EASL meeting and final PROVE2 findings presented last year at AASLD.
The present analysis pooled data from PROVE1 and PROVE2 participants who
received the T12/PR24 regimen or standard therapy. Overall SVR rates were 65%
and 44%, respectively, in these arms. In a logistic regression analysis, lower
baseline HCV RNA (< 800,000 IU/mL), younger age (< 45 years), and white race
were predictors of SVR. The investigators concluded that, "Telaprevir-based
triple therapy improved SVR rates in patients predicted to have low virologic
response to the current standard treatment."
Study C208
Study C208 was an open-label, Phase 2 trial conducted by Tibotec in Europe. This
trial included 161 previously untreated genotype 1 chronic hepatitis C patients.
About half were men, about 90% were white, the mean age was about 45 years, and
about 20% had fibrosis.
Participants were randomly allocated to 4 treatment arms, received telaprevir at
doses of either 750 mg 3-times-daily (every 8 hours) or 1125 mg twice-daily
(every 12 hours). Each dose was combined with either Pegasys or pegylated
interferon alfa-2b (PegIntron) plus ribavirin. Patients took telaprevir for 12
weeks, followed by pegylated interferon/ribavirin for at least an additional 12
weeks.
In a response-guided design, patients who achieved RVR at week 4 and maintained
undetectable viral load (< 25 IU/mL) through week 20 could stop all treatment at
24 weeks; they were then followed for 6 months post-treatment to evaluate SVR.
The study protocol required that patients who did not meet these criteria
receive pegylated interferon plus ribavirin for a total of 48 weeks.

Results
  18% of patients across all treatment arms were required to continue treatment
through week 48.
  In an intent-to-treat analysis, similar proportions of patients in the
3-times-daily and twice daily arms -- as well as those receiving Pegasys vs
PegIntron -- achieved SVR, not a statistically significant difference:
  85% taking 3-times-daily telaprevir plus Pegasys;
  81% taking 3-times-daily telaprevir plus PegIntron;
  83% taking twice-daily telaprevir plus Pegasys;
  82% taking twice-daily telaprevir plus PegIntron.

  Looking only at patients who achieved RVR, the SVR rates were 91%, 93%, 91%,
and 92%, respectively.
  Among patients who completed their assigned regimen, 3% experienced viral
relapse during post-treatment follow-up.
  6% of patients experienced viral breakthrough during telaprevir treatment.
  Safety and tolerability were similar with 3-times-daily and twice-daily
regimens.
  The most common adverse events were pruritis, nausea, rash, anemia, flu-like
illness, fatigue, and headache, occurring with similar frequency in the both
arms.
  5% of participants permanently discontinued therapy due to serious adverse
events, mostly rash (3%) and anemia (2%).
Based on these findings, the researchers concluded that "treatment with
telaprevir [every 8 hours] or [every 12 hours] in combination with [pegylated
interferon/ribavirin] yielded high and comparable rates of virological response
at week 12, independent of baseline viral load or viral subtype.
"With high SVR rates and similar safety outcomes between the twice-daily and
3-times-daily treatment groups, the results from this exploratory study support
the future evaluation of telaprevir-based regimens dosed twice daily," Dr
Marcellin said in a press release issued by Vertex. "These results also
highlight the potential future role for response-guided therapy with the goal of
improving treatment outcomes and potentially shortening the duration of therapy
for the majority of patients."
11/10/09

References
JG McHutchison, MP Manns, A Muir, and others. PROVE 3 Final Results and 1-Year
Durability of SVR with Telaprevir-Based Regimen in Hepatitis C Genotype
1-Infected Patients with Prior Non-response, Viral Breakthrough or Relapse to
Peginterferon-Alfa-2a/b and Ribavirin Therapy. 60th Annual Meeting of the
American Association for the Study of Liver Diseases (AASLD 2009). Boston.
October 30-November 1, 2009. Abstract 66.

GT Everson, GM Dusheiko, P Ferenci, and others. Telaprevir, Peginterferon
Alfa-2a and Ribavirin Improved Rates of Sustained Virologic Response (SVR) in
"Difficult-to-Cure" Patients With Chronic Hepatitis C (CHC): a Pooled Analysis
From the PROVE 1 and PROVE 2 Trials. 60th Annual Meeting of the American
Association for the Study of Liver Diseases (AASLD 2009). Boston. October
30-November 1, 2009. Abstract 1565.

P Marcellin, X Forns, T Goeser, and others. Virological Analysis of Patients
Receiving Telaprevir Administered q8h or q12h with Peginterferon-Alfa-2a or
-Alfa-2b and Ribavirin in Treatment-Naïve Patients with Genotype 1 Hepatitis C:
Study C208. 60th Annual Meeting of the
American Association for the Study of Liver Diseases (AASLD 2009). Boston.
October 30-November 1, 2009. Abstract 194.

Other sources
Vertex Pharmaceuticals. More than 80% of Hepatitis C Patients Treated in Study
C208 Achieved an SVR with Telaprevir-Based Regimens. Press release. October 31,
2009.

http://www.hivandhepatitis.com/2009icr/aasld/docs/111009_e.html

  HIV and Hepatitis.com Coverage of the
60th Annual Meeting of the American Association
for the Study of Liver Diseases (AASLD 2009)
October 30 - November 3, 2009, Boston, MA

Rapid Liver Fibrosis Progression and Successful Treatment of Acute Infection
Suggest Benefits of Routine HCV Screening for HIV Positive Men

   SUMMARY: Researchers from Mt. Sinai School of Medicine presented data last
week at the 60th Annual Meeting of the American Association for the Study of
Liver Diseases (AASLD) in Boston that further characterize a cohort of HIV
positive men with apparently sexually transmitted acute hepatitis C virus (HCV)
infection. This group continues to experience more rapid than expected liver
fibrosis progression. Hepatitis C treatment has been highly successful if
started during the acute phase, but less so thereafter. The researchers
recommended routine ALT and HCV antibody testing to allow for prompt treatment
and to prevent liver disease progression.


By Liz Highleyman
Starting around 2002, clinicians in large cities in the U.K. and Europe began
reporting outbreaks of acute HCV infection among HIV positive gay and bisexual
men, which were associated with sexual risk factors and reflected social and
sexual networks. Such outbreaks have since been reported in Australia and the
U.S.
Dr. Daniel Fierer and colleagues have been following a cohort of HIV/HCV
coinfected men seen at Mt. Sinai in New York City. They first reported on rapid
fibrosis progression in this group at the Conference on Retroviruses and
Opportunistic Infections (CROI) in 2007, following up with data from the growing
cohort at CROI 2008 and CROI 2009, and in the September 1, 2008 Journal of
Infectious Diseases.
This year at AASLD, Dr. Fierer presented data from 51 HIV positive men who have
sex with men (MSM) who experienced 53 episodes of acute hepatitis C (some were
infected twice). Acute HCV infection was defined as newly identified HCV
antibody seroconversion, marked elevation in liver function tests (ALT> 5 times
the upper limit of normal), or large fluctuations in HCV RNA level (>1 log in 4
weeks).
ACUTE HEPATITIS C

The median age of the coinfected cohort was 40 years. About half (27 men) were
white, 17 were Hispanic, 6 were black, and 1 was Asian. Most (49 men) had HCV
genotype 1. The median duration of HIV infection was 7 years (range 0 to 20
year) and the median CD4 cell count was 471 cells/mm3; 14 men -- 27% of the
cohort -- had never received antiretroviral therapy for HIV.
Out of this group, 21 patients and 21 age-matched HIV positive but HCV
uninfected men were included in a case-control analysis to identify sexual and
drug use risk factors for acute HCV infection. In addition, 30 of the coinfected
men underwent liver biopsy histology evaluation (median 4.4 months after their
first ALT elevation) and 34 were treated with pegylated interferon plus
ribavirin.
Results
  Spontaneous HCV clearance occurred in only 5 cases (9%), with 3 still under
evaluation.
  In the case-control study of 21 matched pairs, the factors significantly
associated with increaed risk of HCV infection were:
  Unprotected receptive anal intercourse with ejaculation (P = 0.04);
  Unprotected receptive anal intercourse without ejaculation (P = 0.03);
  Unprotected receptive oral sex with ejaculation (P = 0.03);
  Use of sex toys (P = 0.03);
  Sex while "high" (P = 0.01);
  Marijuana use (P = 0.04).

  Protected receptive anal intercourse, protected receptive oral sex, and fisting
-- risk factors reported in some other HIV positive MSM coinfection cohorts --
were not significantly associated with acute HCV infection (all P> 0.05).
  The traditional risk factors of injection drug use and sharing injection
equipment also were not significantly linked to HCV infection (again, all P>
0.05).
  Among the treated patients:
  1 was lost to follow-up;
  15 were still receiving therapy;
  16 were assessed for sustained virological response (SVR) 24 weeks after
completing treatment;
  1 achieved an end-of-treatment response and was pending further follow-up to
assess SVR.

  Of the 16 patients who completed therapy and were evaluated for SVR:
  12 (75%) achieved a sustained response.
  1 never suppressed HCV RNA;
  2 responded but experienced viral breakthrough during treatment;
  1 achieved virological response but relapsed after completing treatment.

  3 of the 4 patients who did not achieve SVR started treatment after the acute
phase (i.e., more than 6 months after their first ALT elevation).
  Among the 30 participants who underwent liver biopsies:
  21 (70%) had stage 2 (moderate) fibrosis using the Scheuer scale (0 to 4);
  2 (7%) had stage 3 (advanced) fibrosis;
  5 (17%) had stage 1 (mild) fibrosis;
  2 (7%) had stage 0 (absent) fibrosis.

  77% participants had fibrosis stage> 2 at this phase of infection, while just
24% had stage < 2.
  Fibrosis stage increased with time-to-biopsy; of the 7 biopsies performed more
than 1 year after the first ALT elevation, all showed stage> 2 fibrosis.
These findings indicate poorer outcomes among individuals who are already HIV
positive at the time of acute HCV infection. The spontaneous clearance rate of
9% is considerable lower than the approximately 25% reported in most studies of
HIV negative people. Furthermore, the extent of liver damage during acute or
early infection was dramatically greater than that observed in most studies of
HIV negative patients. One such study, for example, found that all 87 patients
assessed during acute infection had stage 0 fibrosis, with none having stage 1
or higher.
Participants in the Mt. Sinai study had none of the usual risk factors
associated with pre-existing liver fibrosis, including a history of ALT
elevation or heavy alcohol use. Hepatitis B triple infection was rare. Most had
a healthy body weight and normal blood sugar levels. One-quarter had never taken
antiretroviral drugs and some reported never using any recreational drugs.
Based on these findings, the researchers concluded that acute HCV infection of
HIV positive MSM in New York City is sexually transmitted and results in "rapid
and significant" liver fibrosis progression. They added that acute HCV infection
was associated with unprotected receptive sex.
"This epidemic represents a new clinical syndrome for HCV infection that turns
much of our knowledge on its ear," Dr. Fierer said in a press release issued by
AASLD. This is "a new risk group becoming infected through a previously rare
route of transmission resulting in unprecedented progression of liver fibrosis."
"Treatment is highly successful when initiated in the acute phase, but may be
less successful if initiated soon after," the investigators noted. "Thus, it is
crucial to detect HCV infection in the acute phase to allow successful treatment
and prevent further progression of the already significant liver fibrosis."
"We therefore recommend ALT testing every 3 months and HCV antibody testing
every 6-12 months for all HIV-infected MSM," they advised. "Promotion of safe
sex is also warranted."
Department of Medicine and Department of Pathology, Mount Sinai School of
Medicine, New York, NY.
11/10/09

Reference

DS Fierer, AJ Uriel, DC Carriero, and others. Characterization of an Epidemic of
Sexually-transmitted Acute Hepatitis C Infection in HIV-infected Men in New York
City. 60th Annual Meeting of the American Association for the Study of Liver
Diseases (AASLD 2009). Boston. October 30-November 1, 2009. Abstract 82.

Other source
AASLD. New Epidemic of Sexually Transmitted Hepatitis C Infection in
HIV-infected Men in NYC. Press release. October 30, 2009

http://7thspace.com/headlines/325036/virological_pattern_of_hepatitis_b_infectio\
n_in_an_hiv_positive_man_with_fatal_fulminant_hepatitis_b_a_case_report.html

Virological pattern of hepatitis B infection in an HIV-positive man with fatal
fulminant hepatitis B: a case report

Introduction
There seem to be no published data concerning the clinical impact of populations
of hepatitis B virus (HBV) in the hepatic and extrahepatic compartments of
HIV-infected people with severe acute hepatitis.Case presentationA 26-year-old
Caucasian man presenting to our hospital with clinical symptoms suggesting acute
hepatitis was found to have an acute hepatitis B profile upon admission. He
developed fatal fulminant hepatitis and was found to be heavily
immunocompromised due to HIV-1 infection.

He had a high plasma HBV and HIV load, and analysis of the partial pre-S1/pre-S2
domain showed the presence of mixed infection with D and F genotypes. Analysis
of the point mutations within this region revealed the presence of HBV strains
with amino acid substitutions at the immunodominant epitopes involved in B or T
cell recognition.

A homogeneous population of a pre-core mutant strain harbouring the A1896G and
A1899G affecting HBeAg expression was invariably found in the liver tissue,
plasma and peripheral blood mononuclear cells despite active HBeAg secretion; it
was the dominant strain in the liver only, and was characterised by the presence
of two point mutations in the direct repeat 1 domain involved in HBV replication
activity. Taken together, these mutations are indicative of a highly replicative
virus capable of evading immune responses.

Conclusion: This case report provides clinical evidence of a possible
association between the rapid spread of highly replicative escape mutants and
the development of fulminant hepatitis in a heavily immunocompromised patient.

Virological surveillance of severe acute hepatitis B may be important in
establishing an early treatment strategy involving antiviral drugs capable of
preventing liver failure, especially in individuals for whom liver
transplantation is not accepted as a standard indication.


Author: Sabrina BagaglioLuca AlbarelloPriscilla BiswasCaterina
Uberti-FoppaClaudio FortisGiulia Morsica
Credits/Source: Journal of Medical Case Reports 2009, 3:110

http://www.infectioncontroltoday.com/hotnews/difficult-to-treat-cases-of-hepatit\
is-c.html

Patients With More Difficult to Treat Forms of Hepatitis C are Half as Likely to
Treat the Disease
11/09/2009

A new study by Mount Sinai researchers has for the first time found that
patients with more difficult to treat forms of hepatitis C are half as likely to
initiate treatment for the disease, when compared to patients with hepatitis C
that is easier to treat. Marital status also affected whether patients chose
treatment, as did whether or not they had other diseases. The study is published
in the Nov. 1 issue of Journal of Health Care for the Poor and Underserved.
“Overall, only about 30 percent of hepatitis C patients choose to initiate
treatment for the disease,” said Thomas McGinn, MD, senior study author and
chief of general internal medicine at Mount Sinai School of Medicine. “It’s a
huge problem that needs to be addressed. This study confirms that genotype is a
major barrier to treatment. We hope these findings will lead to changes in how
physicians approach patient care in a way that increases the rate of treatment
initiation.”
Researchers analyzed all patients referred to Mount Sinai’s Primary Care
Treatment and Screening Program for Hepatitis C between January 2003 and May
2007. The analysis included all hepatitis C clinic patients who were eligible
for treatment and to whom treatment was offered.
Of the 168 treatment-eligible patients, 41 began treatment and 127 chose not to.
Patients with genotypes 1 and 4 of the disease, which are less responsive to
treatment, were less likely to initiate treatment, as were unmarried patients
and patients with multiple diseases, or medical comorbidities. Age, gender,
language, race, and other risk factors were not found to be significant in the
study. Researchers found that:
-- Only 21 percent of individuals with genotypes 1 and 4 initiated treatment,
compared to 42 percent of patients with genotypes 2 or 3.
-- 46 percent of patients who chose treatment were married, as opposed to just
19 percent of the patients who declined treatment.
-- Patients who chose treatment had an average of 2.9 medical comorbidities,
while patients who did not treat their hepatitis C had an average of 5.2 medical
comorbidities.
“More research is needed to determine why these factors affect treatment
initiation,” said McGinn. “Because of existing studies on other diseases, we
were not surprised that marital status and comorbidities were contributing
factors to low treatment rates. However, this is the first study to associate
hepatitis C genotype with lower rates of treatment initiation.
“Duration of treatment may be a factor,” said McGinn. “Genotypes 1 and 4 of the
disease require longer treatment courses, about 9 to 12 months, versus an
average of 6 months for genotypes 2 and 3. It’s possible the longer duration
discourages patients from choosing treatment. Furthermore, patients with
genotypes 1 and 4 often need a liver biopsy, which many patients incorrectly
think are extremely painful. As a result of this study, Mount Sinai has started
a program called ‘Biopsy Buddies,’ in which a patient who has already undergone
a liver biopsy consults with a patient who needs one. We’re hopeful that by
building more support systems for patients we will increase the likelihood that
they will choose to receive treatment.”

http://news.peacefmonline.com/health/200911/31214.php

SYLiF screens 1000 people on Hepatitis 'B' in Accra

Save Your Liver Foundation (SYLiF), a Non-Governmental Organization (NGO), in
collaboration with Lord Health Care, a Herbal Clinic, has offered free screening
for 1000 people in Accra on Hepatitis B.

Mr Isaac Agyemang, Herbalist In-Charge of Lord Health Care, said apart from
offering free screening, the NGO also educated the people on health-related
matters.

"We educate the people to do the test and if you are found negative, we counsel
you, but if you are found positive, we give you supplements," he said.

Mr Agyemang said the disease had been in existence for a very long time and that
it was time now for the NGO to help fight it.

He said plans were very far advanced to extend the services into other parts of
the country.
Mr Agyemang urged the youth to take advantage of the services they offered and
have their health status checked very often.

He advised Ghanaians to desist from taking medication without doctor's advice.
Mr Dickson Adom, Ambassador of SYLif, called on the Ministry of Health to
increase awareness on the disease.

He said the NGO offered free screening on liver-related diseases for 4,000
people last month at Dome and Ashiaman in the Greater Accra Region.

http://www.springerlink.com/content/8925976141jn14j8/

Surgeon’s perspective
Journal Journal of Hepato-Biliary-Pancreatic Surgery
Publisher Springer Japan
ISSN 0944-1166 (Print) 1436-0691 (Online)
Category Topics
DOI 10.1007/s00534-009-0245-9

Topics
Hepatocellular carcinoma: Eastern and Western experiences

Single HCC between 2 and 5 cm: the grey zone
Surgeon’s perspective

Kiyoshi Hasegawa1, Norihiro Kokudo1, Keiji Sano2 and Masatoshi Makuuchi2

(1)  Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate
School of Medicine, University of Tokyo, Tokyo, Japan
(2)  Department of Hepato-Biliary-Pancreatic Surgery, Japanese Red Cross Medical
Center, 4-1-22 Hiro-o, Shibuya-ku, Tokyo 150-8935, Japan

Received: 1 August 2009  Accepted: 1 September 2009  Published online: 5
November 2009

Abstract
In the treatment of hepatocellular carcinoma (HCC), control of the tumor itself,
vascular invasion, and minute intrahepatic metastases is the main important
factor to be considered. Based on previously reported indirect evidence, liver
resection would seem to have advantages over percutaneous ablation for single
HCCs measuring between 2 and 5 cm in diameter. In conclusion, liver function
permitting, resection would be the therapeutic option of first choice. In cases
with poor liver functional reserve, liver transplantation would be a good
therapeutic option, depending on the age of the patient.
--------------------------------------------------------------------------------

  Masatoshi Makuuchi
Email: makuuchi_masatoshi@...

http://www.springerlink.com/content/f432662382784369/

Journal Journal of Hepato-Biliary-Pancreatic Surgery
Publisher Springer Japan
ISSN 0944-1166 (Print) 1436-0691 (Online)
Category Topics
DOI 10.1007/s00534-009-0244-x

Topics
Hepatocellular carcinoma: Eastern and Western experiences

Single HCC smaller than 2 cm: surgery or ablation
Interventional oncologist’s perspective

Tito Livraghi1

(1)  Interventional Radiology Department, Istituto Clinico Humanitas, IRCCS, Via
Manzoni, 56, 20089 Rozzano-Milano, Italy

Received: 1 August 2009  Accepted: 1 September 2009  Published online: 5
November 2009
Abstract  In the EASL and AASLD guidelines, hepatic resection (HR) is considered
the first option for patients in stage 0 (very early HCC). This statement was
not based on randomized controlled trials (RCTs) versus other therapies, but on
the oncological assumption that HR is the better procedure for obtaining
complete tumor ablation including a safety margin. Subsequently, three RCTs
compared percutaneous radiofrequency ablation (RFA) versus HR in patients with
early HCC. All failed to demonstrate better survival in favor of HR, even though
the larger size of the early stage needs a larger area of necrosis. A recent
study focused on stage 0 demonstrated a sustained local complete response after
RFA comparable with that of HR. All these trials established that RFA is less
invasive and associated with lower complication rates and lower costs. These
data suggest that RFA can be considered the first option for operable patients
with very early HCC. Other options (HR, PEI, selective TAE/TACE) can be used as
salvage therapy for the few cases in which RFA is unsuccessful or unfeasible.

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

  Tito Livraghi
Email: lalivra@...

http://www3.interscience.wiley.com/journal/122406819/abstract


Journal of Viral Hepatitis
Volume 16 Issue 12, Pages 860 - 866
Published Online: 26 May 2009
© 2009 Blackwell Publishing Ltd


Hepatitis C virus infection is a risk factor for gallstone disease: a
prospective hospital-based study of patients with chronic viral C hepatitis

M. Acalovschi, C. Buzas, C. Radu and M. Grigorescu

3rd Medical Clinic, University of Medicine and Pharmacy, Cluj-Napoca, Romania
Correspondence to Monica Acalovschi, 3rd Medical Clinic, University of Medicine
and Pharmacy, Str. Croitorilor no. 19-23, 400162 Cluj-Napoca, Romania. E-mail:
monacal@...

Copyright © 2009 Blackwell Publishing Ltd


ABSTRACT
Summary. We evaluated the prevalence and the risk factors for gallstone disease
in patients with chronic hepatitis C infection. We investigated 453
consecutively admitted patients with chronic infection with hepatitis C virus
(HCV) (cirrhosis excluded) and 879 patients without liver disease (October
2006–April 2007). Gallstone disease was diagnosed if gallstones were present at
ultrasonography or if there had been a previous cholecystectomy. Variables
evaluated were age, gender, gallstone heredity, body mass index, waist
circumference, parity, serum lipids, fatty liver, arterial hypertension,
diabetes mellitus and metabolic syndrome (International Diabetes Federation
criteria). Informed consent was obtained from all patients. We found that 88 of
453 (19%) patients with chronic HCV hepatitis (age 50.1 ± 11.7 years) and 153 of
879 (17%) controls (age 60.6 ± 12.6 years) had gallstone disease (GD). Abdominal
obesity (OR = 2.108, 95% CI 1.287–3.452) and steatosis (OR = 3.699, 95% CI
2.277–6.008) were risk factors for GD in HCV patients. Gallstone heredity,
dyslipidaemia, type 2 diabetes mellitus and metabolic syndrome increased the
risk for GD in controls vs HCV patients. Our study shows that even HCV patients
with chronic hepatitis but not cirrhosis have an increased prevalence of
gallstones. Compared with controls, gallstones are present in HCV patients at a
younger age and are associated with central obesity and liver steatosis, but not
with gallstone heredity, dyslipidaemia, diabetes mellitus or metabolic syndrome.
Although we could not establish a temporal relationship, the association between
HCV infection and gall stone disease is real and appears to be causally linked,
at least in predisposed individuals (obese and with liver steatosis).

--------------------------------------------------------------------------------
Received December 2008; accepted for publication February 2009
DIGITAL OBJECT IDENTIFIER (DOI)
10.1111/j.1365-2893.2009.01141

http://sti.bmj.com/cgi/content/abstract/sti.2009.036590v1

Sex Transm Infect. Published Online First: 26 October 2009.
doi:10.1136/sti.2009.036590
Copyright © 2009 by the BMJ Publishing Group Ltd.
Sex Transm Infect 2009;0:sti.2009.036590
© 2009 BMJ Publishing Group Ltd

Hepatitis C testing in sexual health services in England, 2002-2007: results
from sentinel surveillance

Emily J Tweed1,*, Lisa J Brant1, Martin Hurrelle2, Paul Klapper3, Mary E Ramsay1

1 Health Protection Agency Centre for Infections (Immunisation Department),
United Kingdom;
2 Health Protection Agency Leeds laboratory, United Kingdom;
3 Manchester Medical Microbiology Partnership, United Kingdom
Correspondence to: Emily J Tweed, University of Oxford, c/o Lisa Brant, Health
Protection Agency Centre for Infections, 61 Colindale Avenue, Colindale, London,
NW9 5EQ, United Kingdom; emilytweed43@...


ABSTRACT

Objectives: To describe testing for hepatitis C virus in sexual health services
in England between 2002 and 2007, using data from a sentinel surveillance study
of hepatitis testing.

Methods: Data on all anti-HCV tests carried out between 2002 and 2007 were
collected from 20 participating laboratories. Test requests originating in
sexual health services were identified, allowing analysis of the demographic and
clinical characteristics of individuals tested in this setting. KC60 statutory
returns data were used to estimate the proportion of new GUM clinic attendees
tested for hepatitis C each year.

Results: 90,424 individuals were tested for anti-HCV in 100 sexual health
clinics: 3.2% (n=2,858) were found to be positive. Multivariable analysis showed
anti-HCV status to be associated with male sex and reported history of injecting
drug use. In those clinics for which data on trends were available, testing for
anti-HCV increased over the study period and the percentage testing positive
decreased. KC60 data suggested that most clinics tested less than 20% of new
patients for anti-HCV, though the proportion of patients tested increased over
time.

Conclusions: Sexual health services have become increasingly important locations
for hepatitis C testing in England, although the proportion of patients testing
positive is low compared to other settings. We suggest that testing in this
setting could be better targeted to those most at risk of infection by thorough
investigation of risk factors among service users.

http://www3.interscience.wiley.com/journal/122379188/abstract?CRETRY=1&SRETRY=0

Journal of Internal Medicine
Volume 266 Issue 6, Pages 537 - 546
Published Online: 8 May 2009
2007 Blackwell Publishing Ltd


Original Article
Predictive value of on-treatment response during full-dose antiviral therapy of
patients with hepatitis C virus cirrhosis and portal hypertension

E. G. Giannini 1*, M. Basso 2*, V. Savarino 1 & A. Picciotto 2

  From the 1Gastroenterology Unit ; and   2 Viral Hepatitis Unit, Department of
Internal Medicine, University of Genoa, Genoa, Italy
Correspondence to Antonino Picciotto MD, Centro per le Diagnosi e Terapia delle
Epatiti, Dipartimento di Medicina Interna, Università di Genova, Viale
Benedetto XV, no.6, 16132, Genova, Italia.
(fax: +390103538992; e-mail: picciott@...).
   *Both authors equally contributed to the manuscript.

Copyright © 2009 Blackwell Publishing Ltd

J Intern Med 2009; 266 537–546.

ABSTRACT

  Abstract.
Objective. Therapy with full-dose pegylated interferon (PEG-IFN) and
weight-based ribavirin has been evaluated in limited series of patients with
hepatitis C virus (HCV) and advanced disease. In this study, we evaluated the
efficacy and tolerability of full-dose antiviral therapy in patients with
compensated, fully developed cirrhosis, and assessed the predictive value of
on-treatment virological response.

Design and subjects. We studied 85 HCV-positive cirrhotic patients (82
Child-Pugh class A; 41 treatment-naïve) who were treated with PEG-IFN α-2a
(1.5 μg kg−1week−1) or α-2b (180 μg week−1) and weight-based ribavirin
for 24 (genotype 2–3) or 48 (genotype 1–4) weeks. Forty-three patients were
genotype 1 (51%), and HCV-RNA was>600 000 IU mL−1 in 53 patients (62%).
Prevalence of portal hypertension and diabetes was 81% and 18% respectively.

Results. Sustained virological response (SVR) was obtained in 22 patients (26%).
Positive serum HCV-RNA at week 4 and week 12 of therapy predicted nonresponse
(NR) in 85% (52/61) and 100% (38/38) of patients, respectively. Treatment was
discontinued due to adverse events in 14 patients (16%). Genotype 1–4 (P =
0.02) and HCV-RNA>600 000 IU mL−1 (P = 0.02) were the baseline parameters
significantly associated with lack of SVR, whilst positive serum HCV-RNA at week
12 was the only parameter independently associated with NR (100% negative
predictive value).

Conclusion. Full-dose antiviral therapy with PEG-IFN and ribavirin can be safely
carried out even in patients with compensated, fully established cirrhosis and
portal hypertension. Selecting patients on the basis of HCV genotype and viral
load, and application of on-treatment stopping rule may help rationalize
treatment in patients who are unlikely to obtain SVR.

--------------------------------------------------------------------------------
DIGITAL OBJECT IDENTIFIER (DOI)
10.1111/j.1365-2796.2009.02130

http://www.freep.com/article/20091108/BUSINESS06/911080704/1002/BUSINESS/Giving-\
back-Greenview

Posted: Nov. 8, 2009
Giving back: Greenview

Facebook Twitter Digg
TODAY'S SUBJECT: Debbie and Ted Green, founders of the Greenview Foundation's
Hepatitis C Research Fund


THE CAUSE: A venture of Ann Arbor-based technology company Greenview Data, the
Greenview Foundation's Hepatitis C Research Fund raises money for medical
research at the University of Michigan to improve the diagnosis and education of
Hepatitis C patients worldwide. The foundation was established in 2006 by Debbie
Green and her husband, Ted, who is the president and founder of Greenview Data.
BACKGROUND: The Greens were compelled to start the fund because a young woman
they love contracted hepatitis C through a blood transfusion while being treated
for cancer at the age of 7. She was told that by the time she needed treatment
for the hepatitis, science would come to the rescue. Now, 20 years later,
progress in hepatitis C research is still lagging and education about available
treatments is insufficient.
RESULTS: The first goal of the Hepatitis C Research Fund was reached in 2007
when the organization donated $10,000 to the University of Michigan Hospitals.
This was enough to seed the foundation's research project of creating an online
system available worldwide to patients and doctors to estimate treatment
effectiveness based on a patient's medical and lifestyle parameters. An
additional $20,000 was raised in 2008, mostly through the sale of the
foundation's cookbook "Cooking Around the World," donations and a golf outing.
The goal for 2009-10 is to raise $40,000. The foundation aims over time to raise
the full $150,000 required for the online system.
ON GIVING: The annual death toll of hepatitis C in the United States is
estimated to be 8,000-12,000. The Greens' foundation aims to save lives by
raising awareness of hepatitis C and existing treatment options, providing seed
money for research grants, and raising money for research.
INFORMATION: Learn more about the Greenview Foundation's Hepatitis C Fund by
contacting Debbie Green at: Debbie@... or 734-223-8400.
Giving Back recognizes philanthropy and volunteerism in the Michigan business
community. To nominate your company, boss, colleague or employee, e-mail Randy
Essex, ressex@....

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AASLD: Treating Before Transplant Cuts HCV Recurrence
By John Gever, Senior Editor, MedPage Today
Published: November 06, 2009
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner  Earn CME/CE credit
for reading medical news




BOSTON -- In patients with advanced liver disease related to hepatitis C, a
course of pegylated interferon and ribavirin (Rebetol) before liver transplant
may help them avoid recurrence of infection, a researcher said here.
Nearly 30% of patients receiving the drugs showed no signs of the hepatitis C
virus (HCV) three months after receiving a new liver, reported Gregory T.
Everson, MD, of the University of Colorado in Denver.
He presented results of a prospective, semirandomized component of a larger
study called A2ALL at the American Association for the Study of Liver Diseases
meeting.
"This experience supports the concept that pretransplant therapy can prevent
allograft reinfection," he said.
Action Points
--------------------------------------------------------------------------------
”Explain to interested patients that hepatitis C virus infection can persist
after liver transplant.


”Explain that the pretransplant drug regimen used in this study had significant
toxicities and did not benefit all patients.


”Note that this study was published as an abstract and presented at a
conference. These data and conclusions should be considered preliminary until
published in a peer-reviewed journal.

Not surprisingly, the best results were achieved in patients whose HCV viral
loads were reduced to undetectable levels at the time of transplant, Everson
reported. Among 14 patients in whom this was achieved, eight remained virus free
at the post-transplant evaluation.
Duration of the pretreatment regimen was also a significant predictor of
post-transplant response, Everson reported.
Some 44% of patients who received the interferon-ribavirin treatment for more
than 15 weeks before transplant had a postprocedure response, compared with 18%
of those treated for 10 to 15 weeks and 15% of those getting the drugs for less
than 10 weeks (P=0.04).
Other factors -- such as baseline HCV viremia, viral genotype, type of donor
(live versus dead), and toxicity-related dose limitations -- were not
significantly associated with post-transplant response, although the study may
not have been powered adequately to detect such associations.
Of the 79 patients enrolled in the trial, 47 with HCV genotypes 1, 4, 5, or 6
were randomized in a 2:1 ratio to receive the pretransplant drug regimen or no
treatment. All of the 32 other patients with HCV genotypes 2 or 3 received the
treatment.
The treatment consisted of starting doses of 0.75 mcg/kg/week of pegylated
interferon-alfa-2b (PEGIntron) and 600 mg/day of ribavirin, which were both
escalated as tolerated over several weeks to standard target levels.
Median treatment duration was 11.4 weeks for the 44 dead-donor candidates and
14.6 weeks for the 35 able to receive live-donor organs.
Transplant was actually performed in 41 patients, 25 of whom were dead-donor
candidates.
Everson characterized the effectiveness of the pretransplant drug regimen as
"limited."
He said it should be considered only for selected patients, particularly those
with relatively less severe disease.
In the trial, those were the patients who were live-donor candidates along with
the dead-donor candidates who received a so-called MELD upgrade because of
hepatocellular carcinoma.
"If you take all the patients with HCV going to liver transplant, many of them
are too sick to treat with [pegylated interferon] and ribavirin," he said.
Data from the study indicated that the treatment was significantly toxic.
Three-quarters of the treated patients suffered serious adverse events, compared
with half of untreated patients (P=0.04). These were seen both before and after
transplant.
However, mortality rates were the same in treated and untreated patients, at
about 15%.
Everson said it might be possible in the future to try pretreatment in sicker
patients when direct antiviral drugs for HCV become available.
In the meantime, he said, patients who can tolerate the treatment need to stay
on it for at least 12 weeks.
The study was funded by the National Institutes of Health.
Everson reported relationships with Schering-Plough and Ortho Biotech. Other
co-authors reported relationships with Roche, Salix, Gilead, Vertex, Pfizer,
GlaxoSmithKline, Amgen, Bayer, Novartis, and Human Genome Sciences, among
others.

Primary source: Hepatology
Source reference:
Everson G, et al "Interim analysis of a controlled trial of pretransplant
peginterferon alfa-2b/ribavirin (PEG/RBV) to prevent recurrent hepatitis C virus
(HCV) infection after liver transplantation (LT) in the Adult-to-Adult Liver
Transplantation (A2ALL) Study" Hepatology 2009; 50: 302A.

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AASLD: Liver Reserve Measured in Breath Test
By John Gever, Senior Editor, MedPage Today
Published: November 06, 2009
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine,
Harvard Medical School, Boston.  Earn CME/CE credit
for reading medical news



Action Points
--------------------------------------------------------------------------------
”Explain to interested patients that liver health in patients potentially in
line for liver transplant is measured with a system called MELD, or Model of
End-Stage Liver Disease.


”Explain that the test described in this study is not FDA approved and is
currently available only in a clinical trial setting.


”Note that this study was published as an abstract and presented at a
conference. These data and conclusions should be considered preliminary until
published in a peer-reviewed journal.
BOSTON -- A simple breath test gives a good overall measure of liver function in
patients with chronic viral hepatitis and could help in evaluating potential
liver transplant candidates, a researcher said here.


The test, which measures exhaled carbon dioxide following an oral dose of
isotopically labeled methacetin, accurately predicted survival of 395 patients
with chronic viral hepatitis during a median of five months of follow-up,
reported Gadi Lalazar, MD, of Hadassah Hebrew University in Jerusalem.
The test predicted death with a sensitivity of 82% and specificity of 89% in the
prospective study, Lalazar told attendees at the American Association for the
Study of Liver Diseases meeting.
Although the findings still need additional validation, Lalazar said, it also
appeared that the test could improve survival predictions for patients within
specific ranges of Model of End-Stage Liver Disease (MELD) scores.
MELD is now the basis for allocating liver transplants, but is known to be an
imperfect predictor of survival, Lalazar explained.
The breath test, tradenamed Breath ID, is based on the fact that methacetin is
metabolized in the liver to produce acetaminophen and carbon dioxide. The speed
of that reaction declines with impaired hepatic function.
The test uses methacetin containing 13C carbon atoms, such that the exhaled
carbon dioxide is also labeled with this isotope. Therefore, Lalazar said, the
amount of 13C-labeled carbon dioxide in breath correlates closely with hepatic
function.
The technology, being developed by an Israeli company called Exalenz, translates
the carbon dioxide measurement into a hepatic impairment score (HIS). For
purposes of the study, scores were grouped into tertiles reflecting low, medium,
and high risk.
Patients in the study had mean MELD scores of 8.2, with about 80% having scores
below 10, indicating relatively mild liver disease. Close to 90% had hepatitis C
virus infection; the remainder had hepatitis B. About 30% had cirrhosis.
Eleven patients died during follow-up, which ranged from two to 24 months.
Nine of the deaths occurred in patients with high-risk HIS values; the other two
occurred in the medium-risk group.
Lalazar said the risk of death increased by 34% with each log10 unit increase in
the HIS (P<0.0001).
The accuracy remained strong in patients with normal levels of alanine
aminotransferase (ALT), he said.
Six of the deaths occurred in patients with normal ALT but who were determined
to be at high risk on the basis of breath-test results. Two deaths occurred in
medium-risk patients with normal ALT, and none in the low-risk patients.
Four patients with MELD scores under 15 died during the study; three of them
were identified as high-risk on the basis of HIS scores.
Lalazar said only one death was recorded among 10 patients with MELD scores of
15 or higher whose HIS results indicated low risk.
He said that breath test results were associated with mortality risk, even among
patients in a relatively narrow two-point range in MELD scores.
John Hoefs, MD, of the University of California Irvine, commented that
quantitative tests of liver health such as this appear to be more accurate than
the usual clinical measures.
"Quantitative liver function tests trump fibrosis and other measures in
predicting clinical outcomes," he said.
Hoefs, who was not involved in the study, was part of a group that had reported
here on a separate trial involving a panel of other quantitative tests, such as
choline and antipyrine clearance and perfused hepatic mass. It also accurately
predicted outcomes in patients with chronic viral hepatitis.
"We think this [methacetin breath test research] supports that effort," he said.
Lalazar noted that the study was limited by the low proportion of cirrhotic
patients and the small number of deaths. "A validation study is required," he
said.
The study was funded by Exalenz, developer of the methacetin breath test.
Lalazar reported no potential conflicts of interest other than the research
funding. One co-author reported relationships with Alcobra, Immuron, Enzo
Biochem, and ChiasmaPharma.
Hoefs reported relationships with Roche and Gilead.

Primary source: Hepatology
Source reference:
Lalazar G, et al, "The noninvasive 13c methacetin breath test accurately
predicts long term survival in patients with chronic viral hepatitis and may
serve as an adjunctive tool to MELD: Results of a 395 patient clinical trial"
Hepatology 2009; 50: 349A

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ASN: HCV Changes Dialysis Treatment Needs
By Todd Neale, Staff Writer, MedPage Today
Published: October 30, 2009
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner  Earn CME/CE credit
for reading medical news



Action Points
--------------------------------------------------------------------------------
”Explain to interested patients that this study unexpectedly found that HCV
infection was associated with a lower requirement for epoetin in patients on
dialysis.


”Note that this study was published as an abstract and presented at a
conference. These data and conclusions should be considered preliminary until
published in a peer-reviewed journal.
SAN DIEGO -- Patients on dialysis need less epoetin to treat their anemia if
they are infected with hepatitis C (HCV), a researcher reported here.

HCV-positive patients also needed a lower dose of IV iron than their noninfected
counterparts, even though they had similar hemoglobin levels, according to David
Goodkin, MD, of the Arbor Research Collaborative for Health in Ann Arbor, Mich.
This is a "surprising, unusual finding," Goodkin said at the American Society of
Nephrology meeting, because most inflammatory diseases, which interfere with the
signal the bone marrow sends to make more red blood cells, would result in the
need for a higher dose of epoetin.
"We speculate that it may be that this viral infection is actually stimulating
the liver to make this hormone erythropoietin," Goodkin said, although he
admitted that he doesn't know why the virus would activate the
erythropoietin-producing cells.
He said the finding would probably not affect clinical practice because patients
on dialysis have their epoetin doses adjusted regularly anyway.
"The doctors are still going to follow the hemoglobin level and adjust the EPO
dose," Goodkin said. "This is just a clue that if it's hepatitis C-positive,
they'll need less EPO, on average, than people who are hepatitis C-negative."
Goodkin said he decided to investigate after he saw the results of a small
case-control study from 2008, involving 66 patients, showing that those on
dialysis who were infected with HCV needed significantly lower doses of
erythropoietin (P<0.01). There was also a trend toward lower IV iron
requirements (P<0.07).
To explore the issue on a larger scale, he turned to the prospective Dialysis
Outcomes and Practice Patterns Study (DOPPS).
The current analysis included 36,245 patients in 12 countries who were on
hemodialysis, 7.8% of whom were positive for HCV.
After adjusting for age, sex, race, years of hemodialysis, country, and 14
comorbidities, he and his colleagues found that the weekly epoetin dose was
significantly lower in the HCV-positive patients (7,737 versus 8,210 Units,
P=0.02).
IV iron dose was also significantly lower in the infected patients (89.2 versus
96.4 mg/month, P=0.02).
Hemoglobin concentration was not significantly different in the two groups
(P=0.46).
The odds ratios for not receiving epoetin or IV iron therapy among HCV-positive
patients were 1.15 (P=0.002) and 1.19 (P=0.0002), respectively.
Hepatitis B infection, on the other hand, offered no advantage.
In addition to the unexpected effect of HCV infection on the epoetin dose,
another surprising finding was that only seven infected patients in the study
received antiviral treatment, including interferon.
Goodkin speculated that clinicians might have been sparing the patients the
adverse effects of antiviral therapy because most HCV-positive patients do not
develop cirrhosis and liver failure, and patients on dialysis, many of whom are
older, have a limited lifespan.
DOPPS is funded by Amgen, Kyowa Hakko Kirin, and Genzyme.
Goodkin reported relationships with Affymax, AMAG Pharmaceuticals, Amgen,
FibroGen, Keryx, Seattle Life Sciences, Xenon Pharmaceuticals, and Urodynamix
Technologies.

Primary source: American Society of Nephrology
Source reference:
Goodkin D, et al "Epoetin and IV iron dose requirements are reduced by hepatitis
C infection in hemodialysis patients in the Dialysis Outcomes and Practice
Patterns Study" ASN 2009; Abstract TH-PO276.