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This is a dragon drawing!
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This is the main list and isn't in English but click on a bunch of them! COOL
PICS!
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Drawing a woman from the inside out; someone put a HUGE amount of work
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U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH
NIH News
National Center for Complementary and Alternative Medicine (NCCAM)
<http://nccam.nih.gov/
FOR IMMEDIATE RELEASE: Thursday, June 21, 2007
CONTACT: NCCAM Press Office, 301-496-7790, <e-mail: NCCAMPress@...
NCCAM WELCOMES SIX NEW MEMBERS TO ITS NATIONAL ADVISORY COUNCIL
The National Center for Complementary and Alternative Medicine (NCCAM) welcomes
six new members to the National Advisory Council for Complementary and
Alternative Medicine (NACCAM). The Council serves as the principal advisory body
to NCCAM, a component of the National Institutes of Health within the Department
of Health and Human Services.
The Council, which meets three times a year, is composed of physicians,
scientists, licensed complementary and alternative medicine practitioners, and
representatives of the public who contribute their time and expertise over a
4-year term. Council members offer advice and recommendations on the
prioritization, conduct, and support of complementary and alternative medicine
research, including research training and disseminating health information
derived from NCCAM's research.
New NACCAM members include:
-- LORI ARVISO ALVORD, M.D., Dartmouth Medical School, Hanover, NH
-- STEPHEN BARNES, PH.D., University of Alabama at Birmingham, Birmingham, AL
-- SHELDON COHEN, PH.D., Carnegie Mellon University; University of Pittsburgh
School of Medicine; and Pittsburgh Cancer Institute, Pittsburgh, PA
-- FABIO COMINELLI, M.D., PH.D., University of Virginia Health System,
Charlottesville, VA
-- MARGERY L.S. GASS, M.D., University of Cincinnati, Cincinnati, OH
-- FRANK M. TORTI, M.D., M.P.H., F.A.C.P., Wake Forest University School of
Medicine, Winston-Salem, NC
LORI ARVISO ALVORD, M.D. is the Associate Dean for Student Affairs and
Multicultural Affairs and an Assistant Professor of Surgery and Psychiatry at
Dartmouth Medical School. Her research examines surgical outcomes in American
Indians. A Navajo, her autobiography "The Scalpel and the Silver Bear"
describes her work to create culturally competent healing environments. Dr.
Alvord has received honorary degrees from Albany Medical College and Drexel
University. She has also received a Governor's Award for Outstanding Women from
the State of New Mexico.
STEPHEN BARNES, PH.D. is a Professor in the Department of Pharmacology and
Toxicology, as well as the departments of Biochemistry and Molecular Genetics,
Environmental Health Sciences, Genetics, and the Vision Sciences at the
University of Alabama at Birmingham. Dr. Barnes' research focuses on the
biochemistry, chemistry, and analysis of bile acids; the role of isoflavonoids
in preventing chronic diseases; and the application of mass spectrometry to
biomedical research. He received a Lifetime Achievement Award from the 5th
International Symposium on the Role of Soy in the Prevention and Treatment of
Chronic Disease.
SHELDON COHEN, PH.D. is the Robert E. Doherty Professor of Psychology at
Carnegie Mellon University. He is also Adjunct Professor of Pathology and of
Psychiatry at the University of Pittsburgh School of Medicine and a Member of
the Pittsburgh Cancer Institute. His research currently focuses on how
interpersonal dispositions and behaviors influence immunity and host resistance
to infectious disease. Dr. Cohen has received awards for career contributions
from the American Psychological Association, the American Psychological Society,
and the American Psychosomatic Society. He is a member of the Institute of
Medicine of the National Academies.
FABIO COMINELLI, M.D., PH.D. is the David D. Stone Professor of Internal
Medicine, Director of the Digestive Health Center of Excellence, Professor of
Microbiology and Immunology, and Chief of the Division of Gastroenterology and
Hepatology in the University of Virginia Health System. Dr. Cominelli
researches mucosal immune responses and intestinal inflammation to determine the
molecular mechanisms of intestinal inflammation and develop new therapies. He
is a member of the American Society for Clinical Investigation and the American
Association of Physicians. He has received an NIH Merit Award and the Clinical
Excellence Award from the University of Virginia Department of Medicine.
MARGERY L.S. GASS, M.D. is a Professor of Clinical Obstetrics and Gynecology and
Director of the University Hospital Menopause and Osteoporosis Center at the
University of Cincinnati Department of Obstetrics and Gynecology. Her research
areas include menopause, osteoporosis, and female sexual function. She is a
principal investigator for the Women's Health Initiative and is a past member of
the Executive Committee for the study. Dr. Gass is a past president and board
member of the North American Menopause Society and has been cited in "Best
Doctors in America".
FRANK M. TORTI, M.D., M.P.H., F.A.C.P. is the Charles L. Spurr Professor of
Medicine and Chairman of the Department of Cancer Biology at Wake Forest
University School of Medicine. He is also the Director of the Comprehensive
Cancer Center of Wake Forest University. Dr. Torti has studied the molecular
action of oxidants and cytokines (cellular messengers) and their relationship to
cancer and the balance of iron in the body. He is a noted researcher and
clinician in the area of genitourinary (GU) malignancies, and is the GU oncology
section editor of "Current Opinion in Oncology". He recently received an NIH
Merit Award.
The National Center for Complementary and Alternative Medicine's mission is to
explore complementary and alternative medical practices in the context of
rigorous science, train CAM researchers, and disseminate authoritative
information to the public and professionals. For additional information, call
NCCAM's Clearinghouse toll free at 1-888-644-6226, or visit the NCCAM Web site
at <http://www.nccam.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
<http://www.nih.gov
###
This NIH News Release is available online at:
<http://www.nih.gov/news/pr/jun2007/nccam-21.htm

CHARITY OF THE DAY
Please use this site honestly. Fraudulent searches will result in your charity
being delisted.
WHO DO YOU GOODSEARCH FOR?
HEALS of the South (Tallahassee, FL)
Search now and money will go to your designated cause.
Month Searches Amount Raised (Estimated)
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Total: Year-to-Date 695 $6.95
Total: Since Inception 858 $8.58

Viral Load 1 Week After Liver Transplantation, Donor Age and Rejections
Correlate With the Outcome of Recurrent Hepatitis C
Posted 06/08/2007
Pietro Ciccorossi; Anna Maria Maina; Filippo Oliveri; Stefania Petruccelli;
Gioacchino Leandro; Piero Colombatto; Francesco Moriconi; Franco Mosca; Franco
Filipponi; Ferruccio Bonino; Maurizia Rossana Brunetto
Abstract
Background: Early identification of patients at a higher risk of rapidly
progressive recurrent hepatitis post liver transplantation (LT) could help to
tailor antiviral therapy.
Methods: We studied the correlation between early post-LT viral load and the
histological and clinical outcomes of 49 consecutive patients (34 males, median
age 55 years) in whom viraemia was monitored at days 0, 1, 7, 30, 180 and 365
after LT.
Results: Hepatitis C recurred at histology in 38 of 42 (90.5%) patients. Early
viral load after LT was higher in patients with rapidly progressive hepatitis C
recurrence (day 7 median HCV-RNA levels: 5.84 vs 4.93 Log10 IU/ml, P=0.003). Day
7 HCV-RNA levels â¥2.5 x 105 IU/ml, donor age
were independently associated with progression to cirrhosis within one year
post-LT [P=0.018, odds ratio (OR) 27.59; P=0.043, OR 13.85 and P=0.048, OR 9.95,
respectively]. Day 7 viraemia and rejection episodes were independently
associated with 5-years survival. Day 7 viraemia, in combination with acute
hepatitis and/or donor age, showed 80% sensitivity, 94% specificity and 90.5%
diagnostic accuracy to identify severe recurrence.
Conclusions: Early post-LT HCV-RNA correlates with the severity of hepatitis C
recurrence and in combination with donor age (
identifies patients with a high risk of severe recurrence and candidates of
cost-effective pre-emptive antiviral therapy.
Introduction
Liver transplantation (LT) is a life-saving option for patients with
decompensated liver disease and/or hepatocellular carcinoma (HCC) associated
with chronic Hepatitis C virus (HCV) infection.[1] Unfortunately, LT is not a
cure for hepatitis C as recurrence of viral infection is almost universal and
liver damage occurs in most cases.[1] Recurrent hepatitis C is the leading cause
of graft loss and retransplantation.[2-7] Many factors such as donor
characteristics (age, living donor and donor-recipient matching), virologic
features, acute rejection episodes and immune suppression were shown to
influence the progression of posttransplant liver disease.[8-16] Particularly,
the dynamics of HCV infection after LT appears to play a major role in the
outcome of disease recurrence and several studies reported that viraemia levels
in post transplant patients are significantly higher than before LT.[17]
However, it remains controversial whether early or late virologic events are
more relevant on disease outcome: some authors suggested that higher viraemia
levels in the early months after LT accelerate progression of liver
disease[18-20]; others showed a significant correlation between liver fibrosis
and higher viraemia levels later on during follow-up.[21,22] Thus, the current
challenge is a better understanding of HCV infection dynamics in LT patients to
optimize the management of hepatitis C recurrence by a proper timing and
tailoring of antiviral therapy in the single patient. In this study, we
investigated the relations between HCV-RNA kinetics during the first year after
LT and the severity of the outcome of recurrent hepatitis C and 5-year graft
survival.
Patients
We studied 49 consecutive anti-HCV positive patients who underwent cadaveric LT
at the Liver Transplantation Centre of the University Hospital of Pisa, Italy,
between November 1998 and March 2001. All patients were enrolled in a clinical
trial (Novartis CHI-I-04)[23] where patients received cyclosporine, azathioprine
and basiliximab with or without steroids. The inclusion criteria were: (1)
HCV-RNA positive before their first transplant, (2) absence of HBV and HIV
co-infection and (3) anti-HCV-negative donors. The protocol was approved by the
Ethic Committee of our Hospital and all procedures were performed after informed
consent. The study population consisted of 34 males and 15 females, with a
median age at transplantation of 55.5, range 34-66 years. The indications for
transplantation were end-stage cirrhosis (30 patients) or HCC (19 patients). The
Child-Pugh class was A in seven patients, B in 17 patients and C in 25 patients.
The median donor age was 55.7, range 18-84 years.
After LT, all patients received the following immunosuppression regimen: (1)
Basiliximab (20 mg/i.v.) 10 mg i.v. on the day of transplant surgery (within 6 h
after reperfusion of the graft) and 10 mg i.v. on day 4 post-LT; (2)
Cyclosporine A was initiated postoperatively at 7.5 mg/kg twice-a-day oral doses
that were adjusted to achieve and maintain the target blood trough levels of
200-400 ng/ml during weeks 1-4 and 150-250 ng/ml during months 2-12. The dosage
was also reduced in the event of drug-induced renal dysfunction; (3)
azathioprine (1-2 mg/kg) was administered for 6 months. Patients assigned to
steroids (25 patients) received i.v. methylprednisolone 500 mg
intra-operatively, 125 mg on day 1, 40 mg on day 2 and subsequently oral
prednisone 25 mg/day from day 3 to day 30, 15 mg/day from day 31 to day 60 and 5
mg/day from day 61 to day 90. Patients randomized to placebo (24 patients)
received i.v. placebo on days 0, 1 and 2 and placebo tablets from day 3 to day
90. Treatment of acute rejection episodes was based on intravenous
methylprednisolone 500 mg daily for three consecutive days. None of the patients
was treated with interferon (IFN) immediately before or in the 12 months after
transplantation. After the first year, 10 patients received IFN ± ribavirin
antiviral treatment.
Follow-up
Alanine aminotransferase (ALT), liver function tests (INR, bilirubin, albumin)
and clinical evaluation were performed at the time of LT and after
transplantation daily during the first week, weekly during the first month,
monthly during the first year and every 6 months thereafter. Serum specimens for
HCV-RNA detection (three aliquots of 0.5 ml) were collected at LT (day 0), and
days 1, 7, 30, 180 and 365 post-LT, and stored at -80°C until testing. Liver
biopsies were performed at the time of any significant ALT elevation (ALT
increase â¥3 times the upper normal value) during the first year of follow-up
and at the 12th month after LT (protocol liver biopsy). Recurrent hepatitis and
acute rejection were scored and defined according to Ishak and colleagues and
NIDDK classifications respectively.[24,25]
Definition of Hepatitis Recurrence
Hepatitis recurrence was defined by the presence of necroinflammation (Ishak's
grading â¥5) at liver histology within the 12th month after LT.
Definition of the Severity of Recurrence
In all patients, except those with graft failure, the severity of hepatitis
recurrence was evaluated at 12 months post-LT by histology and defined as: (1)
minimal when fibrosis was absent (stage 0); (2) moderate when the fibrosis stage
ranged from 1 to 2; and (3) severe when the fibrosis stage was â¥3 or in case
of graft failure.
HCV-RNA
We used three commercially available HCV-RNA assays to warrant the precise
quantification of viraemia: (a) branched-chain DNA assay (b-DNA HCV-RNA 2.0;
Chiron Corporation, Emeryville, CA, USA), sensitivity 0.2 x 106, dynamic range
0.2 x 106-1.2 x 108 genome equivalents/ml; (b) quantitative reverse
transcription polymerase chain reaction (RT-PCR) assay (Cobas Amplicor HCV
Monitor 2.0; Roche Diagnostics, Branchburg, NJ, USA), sensitivity 0.6 x 103
IU/ml, dynamic range: 0.6 x 103-5 x 105 IU/ml; and (c) qualitative RT-PCR (Cobas
Amplicor HCV Monitor 2.0), sensitivity 50 IU/ml. The results were converted to
IU/mL using conversion factors provided by the manufacturers.
All samples were tested firstly using b-DNA; if HCV-RNA was undetectable (<0.2 x
106 gen Eq/mlL), they were tested with a Cobas Monitor and samples with HCV-RNA
<0.6 x 103 IU/ml at Cobas Monitor were tested by an Amplicor qualitative assay.
The HCV genotype was assessed using a line-probe assay (Inno-LiPA; Innogenetics,
Antwerp, Belgium).
Statistical Analysis
Data were expressed as medians and ranges or in frequency tables.
Univariate analysis was performed using the Fisher's exact test for categorical
variables and the Mann-Whitney rank-sum test for continuous variables; donor age
was considered as a categorical variable after stratification of the patients
into three groups: up to 50 years, from 50 to 60 years and
compared viraemia levels between different time points using the t-test for
paired data. Viraemia levels at different time points in patients with different
outcome were studied by the analysis of variance and co-variance for repeated
measures with the test of Greenhouse Geisser for non-sphericity of
non-orthogonal components. We evaluated the independent association of viraemia
levels at single time points with progressive liver disease and confounding
factors by logistic regression analysis (forward stepwise method). P values
<0.05 were considered to be statistically significant. Receiver Operating
Characteristics (ROC) Analysis was used to define the viraemia cut-off levels
(at different time points) for the identification of patients with different
liver disease outcomes.
We used the Kaplan-Meier method to estimate survival and the log-rank test to
evaluate differences between groups. The survival corresponded to the interval
between the time of LT and the time of death caused by progression of
HCV-related liver disease or the end of follow-up. Patients who died because of
HCC recurrence were censored at the time of death. The Cox's proportional
regression model was used to estimate the independent effect on survival of
variables that showed statistical associations or trends (P<0.10) at univariate
analysis. All others were default parameters of the statistical software
package. spss for windows, version 10.0 (spss Inc., Chicago, IL, USA)
Results
For the analysis, we considered 42 of the 49 (85.7%) patients who were enrolled
in the protocol: six patients were excluded because of major events that were
not related to hepatitis C recurrence [retransplant for ischaemic-type biliary
lesions (two patients), death due to infections and multi-organ failure (four
patients)] and one patient dropped out because of incomplete monitoring.
Viraemia persisted in all the 42 patients; the HCV genotype was type 1b in 31
patients, 1a in four, 2 in four, 3 in two and 4 in one patient.
Hepatitis C Recurrence at 12 Months
During the first year of follow-up, 17 of 42 (40%) patients maintained
persistently normal or slightly elevated ALT (<3 times the upper normal values):
13 of them (76.5%) showed hepatitis C recurrence at the protocol liver biopsy.
The remaining 25 patients had more significant ALT elevation (ALT â¥3 times the
upper normal values): all these patients showed histological evidence of
hepatitis C recurrence within the 12th month.
Overall 1 year after LT, the histological evidence of hepatitis C recurrence was
present in 38 of 42 patients (90.5%) and it was graded as minimal in 16 (42.1%)
patients, moderate in 12 (31.6%) and severe in the remaining 10 (26.3%), five of
whom had clinical evidence of graft failure. Four patients with persistently
normal ALT had no signs of recurrent hepatitis at the 12th-month liver biopsy.
At the different time points, the median ALT values (U/l) in patients with
severe hepatitis recurrence as compared with the remaining patients were: 119 vs
83 at baseline; 71 vs 103 at day 7; 24 vs 18 at day 30; 66 vs 30 at month 6; and
76 vs 40 at month 12, without significant difference between the two groups.
Thirteen of 42 (31%) patients had a recurrent acute hepatitis C, defined as ALT
flare (at least five times the upper normal values) and features of hepatitis at
histology, occurring 1-6 months post-LT. Seven of 10 (70%) patients with severe
recurrence and six out of 28 (21.4%) patients with mild-moderate recurrence at
12 months (P=0.017) had an acute recurrent hepatitis C.
During the first post-LT year, acute rejection episodes were diagnosed in 16 of
42 patients (38.1%): nine patients had one episode, five patients two episodes
and two patients three episodes. Acute rejection episodes occurred in eight of
10 (80%) patients with severe recurrence and in eight of 32 (25%) patients with
absent or moderate disease (P=0.003).
Overall, the median (range) HCV-RNA (Log10 IU/ml) serum levels were: 5.65
(3.1-6.97) at baseline; 4.80 (2.48-6.91) at day 1; 5.30 (2.48-7.28) at day 7;
6.24 (2.48-7.28) at day 30; 6.65 (4.40-7.28) at month 6; and 6.47 (4.79-7.28) at
month 12. In Figure 1, we report the kinetics of HCV-RNA throughout the first
post-LT year according to the severity of hepatitis C recurrence. During the
first month post-LT, viraemia levels were significantly higher in patients with
severe recurrent hepatitis C than in the remaining patients
(Greenhouse-Geisser's test P=0.018), being 5.29 vs 4.69 Log10 IU/ml at day 1,
5.84 vs 4.93 at day 7 and 7.10 vs 6.14 at day 30; (P=0.005, 0.003 and 0.010,
respectively). Viraemia levels at months 6 and 12 were comparable in the two
groups of patients. ( Table 1 , Figure 1). HCV-RNA kinetics during the first
year were comparable in patients with or without acute hepatitis
(Greenhouse-Geisser's test P=0.413).
Figure 1. (click image to zoom)
HCV-RNA kinetics (Log10 IU/ml HCV-RNA levels; marginal expected mean
values as derived from the analysis of variance and co-variance for repeated
measures) according to the severity of hepatitis recurrence. The viraemia levels
at days 1, 7 and 30 were significantly higher in 10 patients with severe disease
recurrence 12 months after LT as compared with the remaining 32 patients
(Mann-Whitney rank-sum test).
To define the viraemia thresholds with clinical relevance at the different time
points, we ran an ROC curve analysis: HCV-RNA levels equal to or higher than 36
800 UI/ml at day 1, 239 800 UI/ml at day 7 and 4 913 400 UI/ml at day 30 showed
the highest sensitivity+specificity values for the identification of patients
with severe outcome. For further analysis, we considered rounded values (25 000
UI/ml - day 1, 250 000 UI/ml - day 7 and 5 000 000 UI/ml - day 30), which did
not significantly modify the predictive value.
At univariate analysis, severe hepatitis C recurrence was associated with donor
age
serum levels â¥25 000 IU/ml at day 1, â¥250 000 IU/ml at day 7 and â¥5 000
000 IU/ml at day 30. Genotype, baseline viral load, Child-Pugh class, steroids
in the immunosuppression and surgical features (cold ischaemia time, anhepatic
phase, duration of surgery up to reperfusion, blood products given during
surgery) did not show any statistical correlation with 12-month recurrence
severity. Baseline HCV-RNA levels
with higher HCV-RNA levels at day 7 and day 30 (P=0.007 and P<0.001
respectively).
At multivariate analysis, donor age
000 IU/ml) and rejection episodes were significantly and independently
associated with severe hepatitis recurrence (P=0.043, 0.018 and 0.048
respectively) ( Table 2 ).
Day 7 HCV-RNA serum levels â¥250 000 IU/ml were present in nine of 10 (90%)
patients with severe recurrence as compared with 10 of 32 (31.3%) patients with
absent or moderate hepatitis recurrence. Only one of 23 (4.3%) patients with
HCV-RNA <250 000 IU/ml at day 7 had a severe hepatitis recurrence that was
observed instead in nine of 19 (47.4%) patients with viraemia â¥250 000 IU/ml.
In Table 3 , we report the diagnostic performance of day 7 viraemia, donor age,
rejection episodes and acute hepatitis in the identification of patients at risk
of severe hepatitis recurrence.
Recurrent Hepatitis C-related Survival
During the post-LT follow-up (median 6.4, range: 0.3-7.1 years), nine patients
died because of graft failure caused by progressive liver disease: six of them
had an acute hepatitis C within 6 months from LT, eight had evidence of severe
hepatitis recurrence at 12 months already, five with clinical evidence of graft
failure. At univariate analysis, we found that serum HCV-RNA levels during the
early phase post-LT (days 1-7 and 30), occurrence of acute hepatitis, rejection
episodes and donor age
graft failure. Genotype, baseline viral load, Child-Pugh class, steroids in the
immunosuppression regimen and antiviral therapy after the first year post-LT did
not show any statistical correlation with HCV-related survival. At multivariate
analysis, day 7 viraemia â¥2.5 x 105 IU/ml and rejection episodes were
independently associated with HCV-related graft loss (P=0.027 and 0.040,
respectively) ( Table 4 ).
Discussion
Our study confirms that HCV viraemia relapses in all the patients with
detectable HCV-RNA in their sera at the time of LT, and histologically proven
hepatitis C recurrence one year after LT is exceedingly common (in 38 of 42
patients, 90.5%). According to previous reports showing the high variability of
liver disease progression after LT,[5] we found that liver disease was indolent
in the majority of our patients, whereas one-fourth of them showed a rapidly
progressive disease, namely severe fibrosis (â¥F3) at 1 year and <5-year
survival. A lower short-term survival had been associated with the evidence of
cirrhosis after LT: up to 42% of cirrhotics develop clinical decompensation
within 1 year and <50% of them are alive 1 year later.[26] Consistently, in our
study, eight of 10 patients who already had severe fibrosis at histology or
clinical cirrhosis within 12 months post-LT died because of graft failure during
the 5-year follow-up. Serum levels of transaminases during the first year
post-LT were not significantly different in patients with mild-moderate or
severe disease and the elevation of ALT was unspecific, unable to differentiate
the aetiology of liver damage, for instance recurrence of hepatitis from
rejection. On the contrary, persistently normal ALT were predictive of a
favourable outcome without evidence of severe hepatitis at 1-year protocol liver
biopsies.
As viraemia is the result of HCV infection dynamics, in an attempt to identify a
more reliable marker of the hepatitis C recurrence severity, we studied the
viral load kinetics after LT. The analysis showed an early decline of viral load
that, at day 1, was significantly lower than baseline (P<0.001). Thereafter,
viraemia levels increased progressively, reaching a plateau value after 1 month
that was maintained throughout the whole follow-up. At the post-LT, steady-state
viral load was 6.65 log10 IU/ml, significantly higher than pre-LT (5.65 log10
IU/ml) (P<0.001). These results are in agreement with both recent reports
describing the relapse of HCV infection as a highly dynamic process[27,28] and
previous studies reporting post-LT HCV-RNA levels significantly higher than
pre-LT levels.[17] However, these studies were not addressed to correlate the
different viraemia profiles with the outcome of hepatitis C recurrence.[27,28]
In our study, where we confirmed the high variability of viraemia patterns after
LT, we could show a correlation between early HCV-RNA levels and the outcome of
hepatitis C recurrence at 12 months (Figure 1) and we were able to define a
viraemia threshold useful to identify patients at a higher risk of rapid
progression of recurrent hepatitis C. Indeed, all but one patient (9/10) with
severe liver disease recurrence showed serum HCV-RNA levels higher than 2.5 x 05
IU/ml at day 7, whereas a poor outcome was observed in only one of the 23 (4.3%)
patients with viraemia lower than 2.5 x 105 IU/ml (negative predictive value:
95.5%). HCV-RNA serum levels higher than 2.5 x 105 IU/ml at day 7 were
significantly associated with severe hepatitis C recurrence both at univariate
(P=0.002) and multivariate (P=0.018) analyses. These results agree with those of
Gretch et al.,[18] who reported a significant association between high HCV-RNA
levels during the first weeks after LT and hepatitis C recurrence. All the data
on early HCV-RNA kinetics after LT suggest that antiviral therapy should be
started before or as soon as possible after transplantation in order to prevent
or delay the relapse of hepatitis C infection and disease. The potential
effectiveness of an early antiviral treatment in HCV-transplanted patients was
suggested by some positive results obtained with pre-emptive treatment with
standard IFN and ribavirin.[29-31] These results, however, were not confirmed in
a more recent prospective-randomized clinical trial with pegylated IFN and
ribavirin.[32] Furthermore, the tolerability of IFN and ribavirin is poor and
major adverse events may occur such as drug-induced bone marrow suppression, and
renal insufficiency. In addition, the immune-modulatory activity of IFN could
boost the immune system of the patient, favouring rejection episodes.[33]
Our data suggest that HCV-RNA serum levels as soon as 1 week after LT could help
to identify patients at risk of severe hepatitis C recurrence, reducing
significantly the number of candidates for post transplant antiviral therapy. In
our cohort, 10 of 42 (23.8%) patients had severe recurrence at 12 months and
using the day 7 HCV-RNA cut-off of 2.5 x 105 IU/ml, we achieved 90% sensitivity
and 69% specificity in their identification. Thus, we would have over-treated 10
patients with indolent recurrent hepatitis C, but on the other hand we would
have addressed an early treatment in only 19 of the 42 (45%) patients with a
consistent reduction of costs. The accuracy in the identification of patients
with severe recurrence could be improved even further by combining early
viraemia with additional factors influencing the progression of liver disease,
such as donor age, acute hepatitis C recurrence and rejection episodes ( Table 3
). In our cohort, the day 7 viraemia levels â¥2.5 x 105 IU/ml in patients whose
liver donors were older than 60 years were always associated with rapid
progression of recurrent hepatitis C. Using these two parameters, it would be
possible to select 70% of the patients with poor outcome and therefore
candidates for early treatment as early as 1 week after LT. Alternatively, by
considering day 7 viraemia, donor age and/or acute hepatitis C, we would have
identified within the first 6 months after LT eight of the 10 patients with
severe liver disease recurrence and overtreated two patients only ( Table 3 ).
Our findings confirmed previous studies where acute rejection episodes were
associated with severe recurrent hepatits C. An immune system upregulation with
an increased recognition of viral antigens or higher viral loads caused by
repeated steroid boluses could be responsible for poorer outcomes. To warrant an
appropriate treatment in patients with evidence of liver damage after LT, an
accurate differential diagnosis between acute rejection and viral hepatitis is
mandatory.[34]
In conclusion, early HCV-RNA kinetics and day 7 viraemia correlate with the
severity of hepatitis C recurrence. Therefore, monitoring the early kinetics of
viral load with quantification of day 7 HCV-RNA levels could represent a
clinically useful tool to identify post-LT patients at risk of severe hepatitis
C recurrence and candidates for a more cost-effective post transplant
pre-emptive antiviral therapy. This hypothesis prompts prospective trials to
answer the question of whether tailored antiviral therapy represents the
preferred strategy for prevention of significant histological disease after
recurrence of HCV infection post-LT.
http://www.medscape.com/viewarticle/556998?src=mp

Growing new blood vessels and livers
June 20, 2007 - PRESS RELEASE: BACKGROUND: Liver failure occurs when the liver
is no longer able to perform its normal synthetic and metabolic functions.
The liver is the organ responsible for filtering the blood to eliminate bacteria
or other poisonous materials. It also regulates fat storage and blood clotting
while producing vitamins and storing essential minerals. The bile produced by
the liver helps humans digest food, and the organ itself helps regulate blood
sugar levels. A few common causes of liver failure include hepatitis B,
hepatitis C, long-term excessive alcohol consumption, hemochromatosis,
malnutrition. Acute liver failure is often caused by overdoses of Tylenol,
adverse reactions to certain prescription medications, ingestion of poisonous
wild mushrooms, or viruses. Symptoms of liver failure include nausea, loss of
appetite, fatigue, diarrhea, jaundice, bleeding, abdomen swelling, mental
disorientation, sleepiness and coma.
TRADITIONAL TREATMENTS:
According to Nelson Fausto, Ph.D., chair of the Department of Pathology at the
University of Washington in Seattle, the liver is one of the only organs in the
human body that has the unique capacity to regenerate itself. When viruses cause
liver failure, supportive care is given at hospitals until the virus runs its
course and the liver has a chance to recover. When the liver is unable to
recover from failure, physicians try to keep patients alive until a donor liver
turns up and a transplant can be performed. This procedure is very successful,
but it can take days before a donor liver becomes available.
FUTURE ALTERNATIVES:
Due to the shortage of donor livers in the United States, Dr. Fausto and his
team of research scientists are trying to identify stem cells in human livers
that could be used to help patients suffering from liver failure. "If we find
the cell that is a stem cell for the liver, the idea is we can perhaps inject
those cells and repopulate livers that have been injured, particularly after
acute injury when there is a major destruction of liver cells," Dr. Fausto says.
"The idea is if you could have cells that could be introduced into the patient,
it could either be a permanent solution [to help the liver regenerate itself] or
at least serve as a bridge until transplantation can be done."
Dr. Fausto says there are several issues when it comes to implanting liver stem
cells in humans, and that scientists are still many years away from conducting
the procedure in people. "The main difficulties are immunological reactions
against the cells," he says, "because you are adding cells from another
individual into that person with the injured liver. The second difficulty is how
to introduce those cells into the liver. All of those things [still need] to be
worked out."
GROWING NEW BLOOD VESSELS!
Dr. Fausto isn't the only one conducting stem cell research that could one day
help humans. Thomas Wight, Ph.D., lead study author in the Hope Heart Program at
the Benaroya Research Institute in Seattle is attempting to grow artificial
blood vessels. "There is a need for artificial blood vessels in many different
situation," Dr. Wight says. "One of the principal needs is during kidney
dialysis, because blood vessels have to be accessed for dialysis to take place."
According to Dr. Wight, blood vessels can become damaged or destroyed when
pricked with a needle multiple times, Although blood vessels can be transplanted
from other parts of the body, new blood vessels created by scientists would be
stronger and easier to control.
REACTIONS:
Mari Jo Fraser knows first-hand what it's like to experience acute liver
failure, which is why she is excited about the scientific advancements being
made. She believes stem cells could hold the key to saving thousands of lives.
"It's just unbelievable," Fraser says. "It's exciting to know that so many
people are going to be saved. You are not going to have 18,000 or 19,000 people
waiting for a liver."
FOR MORE INFORMATION, PLEASE CONTACT:
Clare Hagerty
PRSpecialist
University of Washington
(206) 953-8532
For other medical research, visit Ivanhoe Broadcast News on the Internet at
http://www.ivanhoe.com
http://abclocal.go.com/wls/story?section=health&id=5401631

Anadys Pharmaceuticals Nominates ANA598, a Small-Molecule, Non-Nucleoside
Inhibitor of The NS5b Polymerase, as a Candidate for Clinical Development in
Chronic Hepatitis C Virus Infection
Wednesday June 20, 8:00 am ET
SAN DIEGO, June 20 /PRNewswire-FirstCall/ -- Anadys Pharmaceuticals, Inc.
(Nasdaq: ANDS - News), a biopharmaceutical company committed to the discovery,
development and commercialization of novel medicines for the treatment of
hepatitis and cancer, announced today that it has nominated ANA598 as a
candidate for clinical development as an orally-administered direct antiviral
for the treatment of chronic hepatitis C virus (HCV) infection.
"We have identified a small-molecule, non-nucleoside inhibitor of the NS5b
polymerase that, based on pre-clinical studies conducted to date, has shown
favorable antiviral, metabolic, pharmacokinetic, and preliminary toxicologic
properties, and is the culmination of several years of work in our HCV direct
antiviral discovery program," said Lawrence C. Fritz, Ph.D., president and chief
executive officer of Anadys. "We are now conducting additional pre-clinical
studies in anticipation of submitting an Investigational New Drug application
(IND) in the second quarter of 2008."
Preclinical Study Results
In a series of in vitro pre-clinical studies ANA598 demonstrated excellent
potency against HCV genotype 1 NS5b polymerase and potent activity in HCV
replicon assays. The compound also displayed very good in vitro metabolic
stability and did not significantly inhibit human CYP enzymes, suggesting a low
potential for drug-drug interactions. Extending these in vitro findings, in vivo
preclinical studies of ANA598 demonstrated high oral bioavailability and good
tolerability. Also, drug levels were sustained in the plasma and in the liver,
the principal site of HCV replication.
"The current standard of care is inadequate for many chronic HCV patients,
including about half of those with genotype 1 disease," said Steve Worland,
Ph.D., president, Pharmaceuticals. "We believe ANA598 possesses favorable
characteristics that may enable it to play an important role in future HCV
therapy."
About Anadys
Anadys Pharmaceuticals, Inc., http://www.anadyspharma.com, is a
biopharmaceutical company committed to advancing patient care by discovering,
developing and commercializing novel small molecule medicines for the treatment
of viral diseases and cancer. The Company's programs focus on Toll-Like
Receptor-based small molecule product candidates and direct antiviral compounds
that inhibit key steps in viral proliferation. The Company has core expertise in
medicinal chemistry coupled with structure-based drug design, and is developing
compounds for the treatment of hepatitis C infection, hepatitis B infection and
cancer.
Safe Harbor Statement
Statements in this press release that are not strictly historical in nature
constitute "forward-looking statements." Such statements include, but are not
limited to, references to the believed favorable antiviral, metabolic,
pharmacokinetic, and preliminary toxicologic properties of ANA598, the expected
timing and plans for filing an IND and the possibility that ANA598 may play an
important role in future HCV therapy. Such forward-looking statements involve
known and unknown risks, uncertainties and other factors, which may cause
Anadys' actual results to be materially different from historical results or
from any results expressed or implied by such forward- looking statements. In
particular, the results of in vitro studies and initial in vivo studies may not
be predictive of future results, and Anadys cannot provide any assurances that
any of its product candidates will not have unforeseen safety issues, will have
favorable results in future clinical trials or will receive regulatory approval.
In addition, Anadys' results may be affected by other factors. In particular,
there is no guarantee that Anadys and Novartis will be able to agree on future
development activities for ANA975, that the FDA will lift the clinical hold on
the ANA975 IND, or that the clinical development of ANA975 will be able to be
resumed. There also is no guarantee regarding Anadys' future involvement with,
or value recognition from, the ANA380 program. Anadys' results may be further
affected by risks related to its collaborative relationships with Novartis and
LG Life Sciences, competition from other biotechnology and pharmaceutical
companies, its effectiveness at managing its financial resources, its ability to
successfully develop and market products, the level of effort that its
collaborative partners devote to development and commercialization of its
product candidates, difficulties or delays in its pre-clinical studies or
clinical trials, difficulties or delays in manufacturing its clinical trials
materials, the scope and validity of patent protection for its products,
regulatory developments involving future products and its ability to obtain
additional funding to support its operations. Risk factors that may cause actual
results to differ are more fully discussed in Anadys' SEC filings, including
Anadys' Form 10-K for the year ended December 31, 2006 and the "Risk Factors"
section of Anadys' Form 10-Q for the quarter ended March 31, 2007. All
forward-looking statements are qualified in their entirety by this cautionary
statement. Anadys is providing this information as of this date and does not
undertake any obligation to update any forward-looking statements contained in
this document as a result of new information, future events or otherwise.

Great list of Signs
http://gigglesugar.com/tags/Sign+Language

Hepatitis C could be considered occupational hazard
Eric Veronikis
6/20/2007
The state House Labor Relations Committee approved a bill yesterday that would
classify hepatitis C as an occupational disease for certain law-enforcement
jobs.
Rep. James E. Casorio Jr. (D-Montgomery County) introduced House Bill 1025. The
legislation would presume that officers suffering with hepatitis C who work for
the state Fish and Boat Commission, the Department of Natural Resources and the
Port Authority contracted the disease on the job. The law would provide
automatic workers' compensation to officers with the disease, Casorio said in a
written statement.
http://www.centralpennbusiness.com/article.asp?aID=61207

GILDA IRIARTE, 60
Community leader helped residents, city work together
BY LUISA YANEZ
lyanez@...
Gilda Iriarte, a Miami mortgage broker and neighborhood activist, died Sunday at
Jackson Memorial Hospital of complications following a medical procedure, her
partner said Monday.
Iriarte had undergone a successful liver transplant four months ago and had
celebrated her 60th birthday 10 days ago with a ''gratitude party.'' She was
undergoing an outpatient procedure Wednesday to drain fluids from her lungs when
problems arose.
Iriarte was past president of the Bayside Residents Association in the largely
historic neighborhood east of Biscayne Boulevard between 60th and 72nd streets.
''She was a great community leader,'' said Louis Bourdeau, current president of
the Bayside association. ``During her tenure as our president, she was able to
get residents and the city to work together at a time when various major
enhancement projects were under way.''
Iriarte had also been active in Miami city politics and previously in citizens'
issues in Coral Gables as co-chair of Coalition to Save Coral Gables, a group
active in the late 1990s.
''Gilda approached life with great passion, whether the subject was national
politics or brewing a perfect cup of coffee,'' said Teresa Mears, her partner of
seven years, who is an assistant features editor at The Miami Herald.
''She cared deeply about things big and small, and she wasn't afraid to show
that,'' Mears said.
Iriarte began her mortgage and real estate career with Chase Manhattan Bank in
New York in 1979, where she worked as a commercial lender for large residential
and commercial projects.
Influenced by the fact that her parents had never owned a home, she decided
she'd rather work with individual home buyers, particularly first-time buyers,
and she began working in affordable housing projects in Palo Alto, Calif., in
1987.
Before moving to Miami in 1995, she worked as a residential real estate agent
and mortgage broker in Sacramento. She continued that work in South Florida,
most recently working with Infinity Mortgage in Hallandale Beach.
She was born June 7, 1947, in San Juan. She received her undergraduate degree in
economics from Marymount College in Tarrytown, N.Y., a master's degree in
economics from Boston University and an MBA from Harvard University.
In addition to Mears, she is survived by her brother, Celestino Iriarte of
Pembroke Pines, and her sister, Teresa Iriarte of California, along with several
nieces and nephews.
Instead of flowers, friends can make a donation to the Transplant Foundation
Special License Plate Marketing Fund, 701 SW 27th Ave., suite 704, Miami, FL
33135, or online at www.transplantfoundation.org.
A celebration of Iriarte's life will be held June 30, tentatively planned to be
held at Trinity Episcopal Cathedral, 464 NE 16th St.
===============
Lastly, here is a message from Gilda's partner, Teresa Mears.
Celebration of Life for Gilda Iriarte, 1947-2007
Friends --
I have tried to reach as many of you as I could personally over the last few
days to share the sad news of the passing of my beloved partner, Gilda Iriarte,
on Sunday, June 17. She had undergone a successful liver transplant just four
months ago and was doing well. She celebrated her 60th birthday a week ago with
a small "gratitude party" for some of those who had helped her out during her
surgery and recovery.
We thought we would be together for many more years. But during a routine
medical procedure last week, complications arose, she went into cardiac arrest
and, despite the heroic efforts of her transplant surgeons, she never recovered.
She was on a ventilator for several days but was conscious and alert until the
last few hours. Those of you with a spiritual bent will be interested to know
that, the day before she died, she wrote "Since I'm a new member here, I'd like
to know the requirements of the group." The last thing she asked for was the
keys.
In her honor, we will have a Celebration of Life memorial service at 11 am.
Saturday, June 30, at Trinity Episcopal Cathedral, 464 NE 16th St., Miami, with
a reception to follow. Her ashes will be spread in El Yunque, the rain forest in
her native Puerto Rico, where her cousin Robert's ashes were spread two years
ago.
Before she died, she had signed up as a volunteer for the Transplant Foundation,
which has a new organ donor license plate for Florida. If you'd like to make a
donation in her memory, you can send it to the Transplant Foundation Special
License Plate Marketing Fund, 701 SW 27th Ave., Suite 704, Miami, FL 33135 or at
www.transplantfoundation.org.
We are preparing a booklet of memories with photos and stories and also a DVD,
as well as deciding what to include in the service. If you'd like to share a
story or photo, please email it to teresamears@... or place it in the
online guestbook at www.miamiherald.com/obituaries, which should be up by
tomorrow. And if there is a piece of music or reading that you think would be
appropriate for the service, please share that with me as well.
Here is the link to her obituary online:
http://www.miamiherald.com/512/story/143995.html.
And in espanol: http://www.elnuevoherald.com/182/story/55038.html
Gilda enriched my life enormously, and I am a far better person for having loved
her.
Teresa
June 20, 2007 in Current Affairs, LGBT, Obituary | Permalink
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Mayo Clinic Study Finds Liver Transplantation Can Be Performed Safely for Obese
Patients
Wed, 06/20/2007 - 15:32 - admin
June 19, 2007 -- A new Mayo Clinic study found that liver transplantation can be
performed safely in patients who are considered medically obese. Mayo
researchers will report their findings on June 22 at the International Liver
Transplantation Society's Annual International Congress in Rio de Janeiro,
Brazil.
"Two-thirds of Americans are overweight or obese, and obesity-related liver
disease is rapidly becoming the most common reason for liver transplantation,"
says Michael Charlton, M.D., medical director of the liver transplant program at
Mayo Clinic in Rochester, and lead author of this study. "Because the majority
of liver transplant candidates are overweight or obese, it has become vital to
determine how this may affect the success of transplantation."
A previous national study conducted by the United Network for Organ Sharing
(UNOS) found that liver transplant patients who were obese had poor outcomes
following transplantation. Obesity was calculated using Body Mass Index (BMI), a
formula that uses height and weight to estimate body fat and associated health
risks. Medical providers consider a BMI of 25-29 as overweight, 30-34 as Class I
obesity, 35-40 as Class II obesity and a BMI over 40 as Class III obesity. Based
on the UNOS study, many transplant centers in the United States currently will
not perform liver transplants in patients with Class III obesity.
However, according to Dr. Charlton, the UNOS study may have been flawed because
of how BMI was calculated. A common side effect of liver disease is ascites, the
accumulation of fluid in the abdomen. The fluid weight from ascites is not
routinely subtracted from the weight calculation for BMI; thus many liver
transplant patients in the UNOS study may have been inaccurately categorized as
obese, he says.
Dr. Charlton and his team set out to determine whether obesity, based on a
revised BMI calculation after correcting for ascites, should prevent patients
from receiving a liver transplant. They evaluated data from nearly 700 liver
transplant recipients at Mayo Clinic in Rochester, the University of Nebraska
Medical Center and the University of California, San Francisco, between 1990 and
1994. Pre-transplant BMI was recalculated to correct for the amount of ascites
removed at the beginning of the patient's liver transplant. Researchers then
categorized the patients based on their adjusted obesity class and evaluated
survival at 30 days and annually to 10 years. The findings showed that outcomes
for patients who were overweight or obese (classes I, II and III ) were at least
as good as for patients who were not considered overweight.
"This study, and our experience at Mayo Clinic, demonstrates the importance of
considering each candidate for liver transplant individually and not
automatically excluding patients based on BMI," says Dr. Charlton. "Of course,
weight reduction for obese patients will always provide health benefits, but
weight alone should not be a barrier to liver transplantation."
More than 400 patients receive liver transplants at Mayo Clinic's sites in
Minnesota, Florida and Arizona each year. Mayo Clinic is the most experienced
liver transplant center in the nation, with some of the highest survival rates
in the world.
Other Mayo Clinic researchers involved in this study include Jennifer Leonard,
M.D., Julie Heimbach, M.D. and Michael Malinchoc.
For more information on liver transplantation at Mayo Clinic, please visit
www.mayoclinic.org/liver-transplant.
Source: Mayo Clinic
http://www.allamericanpatriots.com/48725320_mayo_clinic_mayo_clinic_study_finds_\
liver_transplantation_can_be_performed_safely_obese_pat

UPMC Transplant Surgeon to Bike across America to Help Raise Funds for Lung
Research and Awareness of Organ Donation
Brack Hattler, M.D., Ph.D., the Katherine DuRoss Ford Chair of Cardiothoracic
Transplantation and Professor of Surgery, Division of Cardiac Surgery, The
Heart, Lung and Esophageal Surgery Institute (HLESI), UPMC, will embark on a
3,300-mile bicycle journey from Seattle to Washington, D.C. beginning June 25
and ending August 11 to help raise funds for the American Lung Association (ALA)
of Washington's "Bike Ride Across America Campaign."
The McGowan Institute for Regenerative Medicine, a program of both the
University of Pittsburgh and UPMC, is sponsoring his ride and will keep an
update of his adventures on their web site at www.mirm.pitt.edu . Dr. Hattler,
who also is director of McGowan's Medical Devices and Artificial Organs research
program has been preparing for the cross-country journey by riding approximately
200 miles a week for the past four months on his Roubaix-style bike (similar to
the Trek bike that Lance Armstrong rode during the Tour de France). At 71 years
old, his goal is to complete the race and raise funds and awareness for the ALA
in support of lung disease research.
According to the ALA, lung disease is the number three killer in America and
responsible for one in seven deaths. Today, more than 35 million Americans are
living with chronic lung diseases such as asthma, emphysema and chronic
bronchitis. For those with end-stage lung disease, a transplant remains the only
option. Some diseases that cause the lungs to fail and require transplantation
include emphysema , including the form caused by the
alpha-1-antitrypsin-deficiency , pulmonary fibrosis , fibrosis, and pulmonary
hypertension. According to recent statistics provided by the United Network for
Organ Sharing, (UNOS) approximately 3,500 people in the United States are
waiting for a lung transplant, yet only 1,000 actually receive one each year.
Dr. Hattler partnered with the American Lung Association of Washington when the
family members of several of his patients made him aware that this ride was
being organized. He has ridden bikes all his life and completed 300 to 500
mile-long rides but none quite as long as this. His unique involvement with lung
transplant patients serves as his inspiration for becoming involved in this race
and gives him the courage to accept the challenge that lies before him.
"This bike ride provides me with a once in a lifetime opportunity to get out and
see parts of the country I've never seen before with fellow bikers who share the
passion of helping to raise funds for important lung disease research," says Dr.
Hattler. "I see firsthand the effects of living with lung disease, patients who
can barely breathe or walk. If I can help in some small way to bring more
quality to their lives, it makes this journey all the more worthwhile."
Dr. Hattler's wife, Jean Anne, intends to ride alongside him for portions of the
race for a total of approximately 800 of the 3,300 miles.
Prior to his arrival at UPMC, Dr. Hattler developed and patented an Intravenous
Membrane Oxygenator. This device was originally conceived and patented because
of the significant need for new forms of therapy in the treatment of reversible
lung injury. Presently, Dr. Hattler and his research personnel are focusing
their efforts on the development of the Hattler Respiratory Support Catheter,
emphasizing various means for improving gas exchange in artificial lung devices.
Dr. Hattler hopes to have the device ready for U.S.-based trials within the next
18 months. Currently, there are on-going active clinical trials in Europe.
UPMC is one of the oldest, most experienced centers in the world for lung and
heart-lung transplantation. Since 1982, UPMC transplant specialists have
performed more than 1,000 lung or heart-lung transplants, remaining one of the
most active lung transplant centers in the world, and producing outcomes that
exceed national standards. According to data released from UNOS, UPMC performed
a record 101 lung transplants in 2006, more than any other medical center in the
world.
http://www.webwire.com/ViewPressRel.asp?aId=40084

Hi, Shevi...You're right there is so very much information to absorb. Where are
you from? I live near Baltimore, MD. I was diagnosed last June 9th. Back in
April...a few months ago I got involved with a drug test study at Johns Hopkins
in Baltimore. I've been on treatment only since then (the Scherring-Plough test
drug, Ribovarin and Interferon) and my viral load has gone from 8.44 million to
30 as of a week ago. So, I know it's devastating and most of what you'll read
will be depressing but, hang in there...there are positive, uplifing and hopeful
stories out there, too.
Donna
Sharona BatShevi <hepslayerlady@...
Hello. I am Shevi or Sharona. Newly diagnosed and just
want some information and stuff. Thanks for being
here. I looked around at the messages and reports and
there is so much information. Again Thanks, Shevi

Anaesthetist remanded to prison as appeals take place in the Valencia hepatitis
case
By m.p
Jun 18, 2007 - 10:51 PM
Juan Maeso was found guilty last month of infecting 275 patients with the
Hepatitis C virus
The Spanish anaesthetist who was sentenced to 1,933 years in prison for
infecting 275 patients with the Hepatitis C virus has been ordered to prison on
remand without bail.
The preventive measure came from the Valencia High Court of Justice, the TSJA,
in Juan Maeso's appeals presented in the case. He was given 72 hours to
voluntarily enter prison, and will be arrested if he fails to meet the deadline.
He was found guilty in May of infecting patients in four Valencia hospitals over
a period between1988 and 1997.
The anaesthetist was a morphine addict, and was charged with injecting patients
with the same needle he used on himself.
The guilty sentence came almost 20 years after the Hepatitis C infections were
first detected in1988.
The first hearing in his trial was not to take place until September 2005, after
seven and a half years of court investigation.
http://www.typicallyspanish.com/news/publish/article_11033.shtml

I am an Albanian patient with detected HCV from a year now, genotype 1b. Started
last September the treatment interferon + ribavirin and have been able to
continue with full dose. Planning for a year of treatment, now my question is:
how long should my treatment continue when in the 3rd month [of treatment] I was
PCR negative. The doctor has referred to 9 months [total treatment time]. My ALT
and AST recently are in the normal range-49, 43.
On various internet sites, I see that even when the treatment result is so good
after the third month, usually the treatment continues for a full 48 weeks, and
yet my doctor is thinking of 9 months. I want the best for me. The treatment is
costly and the Ministry of Health has taken care of the cost, and I am afraid
that the financial aspect is in consideration to cut off [the treatment] soon,
with a promising result like this. The doctor did not perform a biopsy before
starting the treatment and plans to do the PCR again 6 months after the end of
treatment. Can you comment, please?
Answer by Mack Mitchell, MD
Dr. Mitchell is Director of Gastroenterology at the Johns Hopkins Bayview
Medical Center,
Baltimore, Maryland and Associate Professor of Medicine, The Johns Hopkins
University School of Medicine
If I understand correctly, you had a negative PCR at week 12 of treatment. If
that is correct, the standard is 48 weeks of treatment for genotype 1b. I was
not sure if you meant an additional 9 mos (correct) or 9 months (total treatment
time). The only way I have seen treatment shortened successfully is if the PCR
is negative at week 4.
http://www.hivandhepatitis.com/doctor/topics/hcv1.html#061907b

Sunday, June 17, 2007
Firefighter's Widow Fights for Settlement in Florida Supreme Court
On May 22, 2007, Orlando firefighter Bob Flamily died due to cardiac problems
and complications from hepatitis C after a several-year battle with these
illnesses. In 1996, Flamily retired from firefighting when he was diagnosed with
work-related cardiac problems. At the time of his retirement, he signed an
agreement with the city to receive a little over a $100,000 in workers'
compensation and full-disability pension.
However, at the time he signed the agreement, he did not know he also had the
blood-borne virus hepatitis C; Flamily had had abnormal blood test results
during his annual physicals with the city but was not told about those results.
Flamily and other firefighters sued the city and the city settled with the group
for $600,000.
Flamily then challenged his workers' compensation agreement claiming he entered
into it under false pretenses in 1996, and therefore, was entitled to get more
money. A trial court agreed, and the city was ordered to pay an additional
$140,000 to Flamily. However, the city appealed that decision and won. Now his
widow is fighting in the Florida Supreme Court; but the judges have not yet
ruled on the case.
If you or a loved one has suffered or died due to a work-related injury or
illness and feel you may be entitled to a settlement, please visit the website
of the experienced Workers' Compensation Attorneys at the Glick Law Firm, P.A.
http://www.the-injury-lawyer-directory.com/2007/06/firefighters-widow-fights-for\
.html

Comparison of 6 Non-invasive Scores for Diagnosing Liver Fibrosis Hepatitis C
Patients
By Liz Highleyman
In an effort to reduce the need for repeated liver biopsies -- which are
uncomfortable, expensive, and associated with a small risk of complications --
researchers have developed various non-invasive methods for assessing liver
fibrosis using serum biomarkers and imaging techniques.
As reported in the May 2007 Journal of Hepatology, researchers compared the
diagnostic performance of 6 non-invasive biomarker scores:
. APRI: AST-to-platelet ratio index;
. Fibrotest: an index combining a2-macroglobulin, haptoglobin, gamma
globulin, apolipoprotein, and bilirubin;
. Fibrometer: platelet count, prothrombin time, AST, a2-macroglobulin,
age, urea, and hyaluronic acid;
. Forns' index: age, platelet count, gamma-glutamyl transpeptidase (GGT),
and cholesterol;
. Hepascore: bilirubin, GGT, hyaluronic acid, a2-macroglobulin, age, and
sex;
. MP3: an index that incorporates procollagen III N-terminal peptide
(PIIINP) and matrix metalloprotease 1 (MMP1), substances involved in production
and breakdown of fibrous tissue.
The study included 180 patients with chronic hepatitis C patients. Liver
fibrosis was staged according to the METAVIR scoring system.
Results
. For distinguishing absent or mild fibrosis (stage F0-F1) versus moderate
to sever fibrosis (F2-F4), the overall diagnostic performance of the indices
determined by areas under the receiver operating characteristic curve (AUROCs)
ranged from 0.86 for Fibrometer to 0.78 for the Forns' index, a non-significant
difference.
. For discriminating between stage F0-F2 fibrosis versus stage F3-F4,
AUROCs ranged from 0.91 for Fibrometer to 0.78 for Forns' index (P < 0.02).
. Significant or extensive fibrosis was accurately predicted in 10%-86% of
patients, with positive predictive values ranging from 55% to 94%.
. Using logistic regression analysis, statistical independence was
demonstrated for MP3, Fibrotest, and APRI.
. In an evaluation of diagnostic performance of paired-combination scores,
the best combinations could accurately select one-third of patients for whom
either absence of significant fibrosis or presence of extensive fibrosis could
be predicted with more than 90% certainty.
Conclusion
In conclusion, the authors wrote, "Current non-invasive scores give reliable
information on liver fibrosis in one-third of chronic hepatitis C patients,
especially when used in combination."
This study confirms past research showing that while non-invasive tests perform
well in distinguishing between absent or mild fibrosis versus advanced fibrosis
or cirrhosis, they are not as good at distinguishing between intermediate
stages.
Such tests are gaining greater acceptance for aiding decisions about when to
start hepatitis C treatment and assessing how well treatment is working, but
some experts believe they are not yet ready for prime time.
In an accompanying editorial, Andrew Burroughs and Evangelos Cholongitas wrote
that, "Non-invasive tests for liver fibrosis have the potential to become an
important tool in clinical practice, but better validation is needed before
starting to consider [them] as established tests.It is likely that an initial
diagnostic biopsy will still be needed, but follow up for fibrosis could be
based on [non-invasive tests], providing that encouraging results [are]
published in the future."
However, an international panel of experts that recently issued guidelines for
the management of HIV-HCV coinfection* stated that, "liver biopsy is not
mandatory for considering the treatment of chronic HCV infection," given that a
combination of non-invasive methods "accurately predicts hepatic fibrosis in
most cases."
06/19/07
References
V Leroy, M-N Hilleret, N Sturm, and others. Prospective comparison of six
non-invasive scores for the diagnosis of liver fibrosis in chronic hepatitis C.
Journal of Hepatology 46(5): 775-782. May 2007.
AK Burroughs and E Cholongitas. Non-invasive tests for liver fibrosis:
Encouraging or discouraging results? Journal of Hepatology 46(5): 751-755. May
2007.
*V Soriano, M Puoti, M Sulkowski, and others. Care of patients coinfected with
HIV and hepatitis C virus: 2007 updated recommendations from the HCV-HIV
International Panel. AIDS 21(9): 1073-1089. May 31, 2007.
http://www.hivandhepatitis.com/hep_c/news/2007/061907_b.html

Diabetes Treatment May Improve Response to Pegylated Interferon/Ribavirin, and
HCV Eradication in Turn May Reduce Insulin Resistance
By Liz Highleyman
Researchers have yet to fully understand the complex relationship between
hepatitis C virus (HCV) infection, liver fibrosis and steatosis (fat
accumulation), and metabolic abnormalities such as elevated blood lipids and
insulin resistance (which can progress to diabetes).
Two studies presented at the recent Digestive Disease Week 2007 conference last
month in Washington, DC, shed further light on this issue, with one showing that
treatment for type 2 diabetes may help improve response to interferon-based
therapy for chronic hepatitis, while the other suggested that effective HCV
eradication can reduce insulin resistance.
Diabetes Treatment
H.M. Elgouhari and colleagues from Cleveland conducted a study to assess the
rate of sustained virological response (SVR) in hepatitis C patients with and
without diabetes mellitus, and to evaluate the safety of combining
insulin-sensitizing agents (ISAs) with pegylated interferon plus ribavirin.
The investigators employed a case-controlled retrospective analysis of
prospectively collected data. They identified 61 patients with HCV and diabetes
who were treated with standard doses of pegylated interferon plus ribavirin
between 2002 and 2004; 21 subjects also received ISAs. A control group of 61 HCV
patients without diabetes matched for HCV genotype and ethnicity treated during
the same time period was selected.
Descriptive statistics were performed to characterize both groups, and a
univariate analysis was done to compare variables of interest. Logistic
regression was performed to identify independent factors associated with
treatment failure.
Results
. Patients with diabetes had a higher mean body mass index (BMI) than those
without diabetes (32.4 vs 28.5).
. Diabetes patients were also more likely to have advanced liver fibrosis (56%
vs 28%; P = 0.003).
. SVR was observed in 14 of 61 patients with diabetes (23%) compared to 31 of
61 subjects without diabetes (51%) (P = 0.001).
. By univariate analysis, diabetes (P = 0.001), genotype 1 HCV (P = 0.005),
and African-American ethnicity (P = 0.03) were associated with lack of SVR.
. Multivariate logistic regression identified diabetes (OR 3.9) and genotype 1
(OR 3.7) as independent predictors of treatment failure.
. This association remained significant after adjusting for other relevant
variables including ethnicity and presence of advanced fibrosis.
. Among patients with diabetes, the SVR rate was higher in patients who were
using ISAs (29%) compared to those who were not (20%), but this difference did
not reach statistical significance.
. The rates of serious adverse events, early treatment discontinuation, and
ALT flares were similar between patients receiving and not receiving ISAs.
"Diabetes mellitus is a predictor of treatment failure in HCV patients treated
with [pegylated interferon]/ribavirin," the investigators concluded. "Based on
this limited assessment, ISAs appear to be safe when combined with [pegylated
interferon]/ribavirin in diabetic HCV patients."
HCV Eradication
In the second study, researchers from Kurume University School of Medicine in
Japan looked at the impact of hepatitis C treatment on insulin resistance.
As background, they noted that they had previously shown that HCV down-regulates
hepatic expression of insulin receptor substrate (IRS) 1 and 2 -- key molecules
involved in insulin signaling -- through up-regulation of suppressor of cytokine
signaling 3. Thus, they wrote, "HCV itself seems to play an important role for
the development of insulin resistance."
The aim of the current study was to examine the effects of HCV eradication on
hepatic expression of IRS-1/2 and insulin resistance. The investigators analyzed
80 subjects with biopsy-proven chronic HCV infection. Patients received
interferon-alfa with or without ribavirin for 6 months, and were classified into
3 groups 6 months after the completion of therapy:
. Sustained responders (n = 26);
. Relapsers (n = 11);
. Non-responders (n = 43).
Insulin resistance was assessed using the homeostasis model assessment method
(HOMA-IR). Hepatic expression of IRS-1/2 was evaluated by immunoblotting and
immunostaining in 14 sustained responders.
Results
. Among non-responders, BMI decreased significantly from 22.9 to 21.5 at the
end of follow-up (P < 0.05).
. However, there were no significant changes in HOMA-IR values at the end of
follow-up compared with those before starting antiviral therapy (3.9 vs 3.7).
. Among relapsers, no significant differences were seen in BMI (21.9 vs 22.0)
or HOMA-IR values (3.5 vs 3.6) at the end of follow-up compared with those
before starting therapy.
. Among sustained responders, there was no significant difference in BMI at
the end of follow-up (22.3 s. 22.1), but HOMA-IR values decreased significantly
from 3.2 to 2.3 (P < 0.01).
. Immunoblotting showed a 3-fold increase in hepatic expression of IRS-1/2
after HCV eradication.
. Immunostaining revealed that increased IRS-1/2 expression occurred in
hepatocytes, but not in non-parenchymal cells.
In conclusion, the researchers wrote, "We demonstrated that eradication of HCV
improves hepatic expression of IRS-1/2 and insulin resistance."
06/19/07
References
HM Elgouhari, I Hanouneh, CO Zein, and others. Diabetes Mellitus is a Predictor
of Treatment Failure in hepatitis C Patients Treated with Peg IFN and RBV.
Digestive Disease Week 2007 (DDW 2007). Washington, DC. May 19-24, 2007.
Abstract M1800.
T Kawaguchi, T Ide, E Taniguchi, and others. Eradication of HCV Improves Hepatic
Expression of Insulin Receptor Substrate 1/2 and Insulin Resistance. DDW 2007.
Abstract 361.
http://www.hivandhepatitis.com/2007icr/ddw/docs/061907_a.html

Lawmaker recalls late father in vote today
Assemblyman Kenneth Zebrowski Jr., D-New City, spoke about his late father in
voting this afternoon for legislation to set up a statewide hepatitis C advisory
council. His dad, former Assemblyman Kenneth Zebrowski, died March 18 from liver
and kidney failure after a battle with hepatitis C.
"It's very important. It's a disease that a lot of people don't know about,"
said Kenneth Zebrowski Jr., who was elected last month to the district his
father served.
Under the bill, the panel would advise the state health commissioner about
implementation of a comprehensive hepatitis C program and would evaluate and
report to the Legislature and governor on the state's system for screening and
detecting hepatitis C. Assemblywoman Ellen Jaffee, D-Suffern, Rockland County,
is the lead sponsor.
Zebrowski his father had a brain tumor removed in 1973. Decades later, in the
1990s, he was diagnosed with hepatitis C.
The bill passed unanimously and now goes to the Senate, where it is sponsored by
Sen. Thomas Morahan, R-New City, Rockland County.
http://polhudson.lohudblogs.com/2007/06/18/lawmaker-recalls-late-father-in-votin\
g-for-bill/

NATAP http://natap.org/
Federal budget reductions mean S. Florida HIV/AIDS patients to lose services
By Bob LaMendola
South Florida Sun-Sentinel
Posted June 19 2007
Every week, Oakland Park HIV patient Peter Giraldo goes for acupuncture and
therapeutic massage to lessen severe nerve pain in his extremities caused by his
medications and diabetes.
But the therapies will vanish next month, and other services used by thousands
of South Florida HIV/AIDS patients will shrink dramatically as a result of
federal budget cuts now coming to a head, county health officials said.
Substance abuse treatment, nutritional counseling and other programs stand to be
cut.
For a second straight year, local HIV budget planners said they are struggling
to stretch declining grants from the federal Ryan White Program.
"The money keeps getting smaller but the number of patients keeps getting
larger," said Kathleen Cannon, a funding co-chairman on the Broward County HIV
Health Services Planning Council, which allocates Ryan White money.
Broward is receiving a grant of $13.1 million, down from $15 million last year.
Palm Beach County is getting $7.7 million, down from the sharply cut $8.3
million received last year. Each county hopes to get another million dollars in
a final allotment in August, but because more cities are competing for money
this year, the amounts may be only a few hundred thousand, officials said.
"Something has to give," said David Begley, chairman of the Palm Beach County
HIV Care Council. "There are going to be some clients who are going to go
without."
Ryan White money goes to local and state agencies to help pay for medical care
and services for HIV/AIDS patients with no health coverage.
Last year, when Congress reauthorized the program, it let more cities get grants
even though the pool of money has been declining since 2003. Also, new federal
rules require spending three-fourths of the grants for medical care and
counseling, squeezing money earmarked for support services.
To cope, Cannon said Broward's planning council is considering cutting off
services to about 75 people with incomes above three times the federal poverty
level, such as a single person making more than $30,630. A decision is expected
June 28.
"It's a very painful decision, but we're going to have to have limits because we
just don't have the money," Cannon said. Also, $1.3 million was trimmed for
medicine and dental care.
Palm Beach County had taken a hard hit a year ago, when paperwork problems
resulted in its grant plunging from $9.5 million down to $8.3 million. Some cuts
were made then, but the blow was cushioned by one-time gifts of $350,000 from
the state and county.
This year, that cushion is gone. Begley said the result is that money to help
HIV patients buy groceries would drop by two-thirds, to $135,000. Help for
patients with financial emergencies would be cut by $100,000, or 40 percent.
Money for case managers would drop by $1 million, or one-third.
"We're talking about food here. But we don't have many choices," Begley said.
The new federal rules more tightly restrict using Ryan White money to treat HIV
patients for substance abuse and to provide transportation. That forced local
cuts.
Also, the grants can no longer be spent for complementary care such as
acupuncture, chiropractors and therapeutic massage. Giraldo, who has been
HIV-positive for 20 years, said he fears his health and mental state will worsen
without the pain-relieving therapies.
"These services help me manage the virus so I don't get sick and I don't use the
emergency room," he said.
Bob LaMendola can be reached at blamendola@... or 954-356-4526 or
561-243-6600, ext. 4526.

ANALYST'S VIEW
Need for new drugs to tackle 'superbugs'
Antibacterials used to treat hospital-acquired infections, mostly targeting
gram-positive organisms such as MRSA, generate revenues of approximately $1.5
billion annually in the US alone. Although MRSA has grabbed the headlines, more
worrying is the emergence of MDR gram-negative organisms, resistant to almost
all currently available drugs - highlighting a crucial unmet need in the market.
Nosocomial infections are infections acquired by patients in the hospital
setting. Across the US and Europe it is thought approximately five to 10% of
hospitalized patients develop a nosocomial infection during their stay, and
these infections often result in significant morbidity and mortality.
Datamonitor estimates that up to 3.7 million patients develop nosocomial
infections in an average year in the US alone.
Bacterial pathogens are the most common cause of nosocomial infections,
contributing significantly to the hospital antibacterial market's sales of $6.7
billion in 2005. Among the 21 different classes of antibacterial drugs, the
classes that have clearly dominated in terms of both sales and volume use
include parenteral cephalosporins and parenteral broad-spectrum penicillins,
accounting for 21% and 15% of total sales in 2005, respectively.
Rise in multi-drug resistant bacterial strains
Overuse of broad-spectrum antibiotics, improved survival of critically ill
patients, the rising population of immuno-compromised patients and the rise in
use of indwelling medical devices have all contributed to the emergence of
difficult to treat strains such as methicillin resistant staphylococcus aureus
(MRSA) and vancomycin resistant enterococcus (VRE). In 2004 the National
Nosocomial Infections Surveillance system found that MRSA strains accounted for
almost 63% of all S. aureus infections in ICUs in the US. Increases in MRSA
rates have also been reported in Europe, with the highest rates - 44% - being
observed in the UK.
At the same time, Enterococcal infections have also become increasingly
difficult to treat. In addition to their intrinsic resistance to beta-lactam
antibiotics, the prevalence of VRE and aminoglycoside resistant E. faecalis
strains has also been on the increase. Furthermore, these organisms are becoming
increasingly resistant to most of the available antimicrobial agents, as
illustrated by the recent emergence of vancomycin-intermediate/resistant strains
of S. aureus. Clostridium difficile has also emerged as an important nosocomial
pathogen. New, more virulent strains, such as BI/NAP1, which affects mainly
Canada and the US, and a similar strain known as O27, observed in the UK, are
spreading faster and have a higher mortality rate than the previously known
strains.
While gram-positive organisms account for the majority of hospital acquired
infections, there has been a significant increase in multi-drug resistant
gram-negative bacteria such as extended-spectrum beta lactamase producing
Escherichia coli and Klebsiella pneumoniae. Worryingly, some strains of
Pseudomonas aeruginosa and Acinetobacter baumannii have become resistant to all
currently available antimicrobials. Since gram-negative organisms exhibit
intrinsic resistance to several antibiotics, additionally acquired resistances
leave very few options for treatment.
For patients who have acquired a nosocomial infection, empirical treatment is
initiated depending on the site of infection and the suspected organism.
Vancomycin in combination with agents to cover for potential gram-negative
organisms is the preferred choice of therapy, since gram-positive organisms such
as S. aureus and in particular MRSA account for the majority of surgical site
infections, blood stream infections and hospital acquired pneumonia. On the
other hand, urinary tract infections, which are predominantly caused by gram
negative organisms such as E. coli, are usually treated with monotherapy.
Datamonitor estimates that the annual antibiotic spend for nosocomial infections
in the US ranges from $550 million for urinary tract infections, to $250 million
for bloodstream infections.
Lack of effective products
Due to the rising rates of multi-drug resistant gram positive bacterial
infections, the majority of newly introduced products and products in late stage
development target bacteria such as MRSA. Among the antibacterials introduced
since 2000 targeting such pathogens, linezolid (Zyvox) has been the most
successful, owing to its parenteral and oral formulations.
However, the MRSA market is likely to become increasingly crowded with drugs
such as daptomycin, launched in 2003, tigecycline, launched in 2005, as well as
dalbavancin and telavancin, both expected in 2007, intensifying the competition.
Tigecycline has generated much enthusiasm due to its ability to target both
gram-positive and gram-negative organisms; its disadvantage being the lack of
coverage for pseudomonas infections.
Although these new agents targeting gram-positive organisms have been welcomed
by the infectious disease community, there is a significant opportunity for new
antibacterials which can treat multi-drug resistant gram-negative organisms - a
crucial unmet need for the hospital market. Among pharma companies active in the
market for systemic antibiotics, Johnson & Johnson appears to be the first to
have spotted this gap. It looks best positioned here with two in-licensed
compounds, doripenem from Shionogi and ceftobiprole from Basilea, both of which
have already been filed for approval with the FDA.
Related research: Stakeholder Opinions: Nosocomial Infections - The need for new
gram-negative drugs priced $3,800

My prayers are with her and the family during this very trying time. Please
accept my sincerest condolences and thank you for letting the Hep C Community
know. We all mourn each passing.

SHC orders quick treatment of Hep B/C prisoners
Staff Report
KARACHI: The Superintendent of Central Prison Khairpur was directed by a
division bench of the High Court of Sindh (SHC) here Monday to expedite the
treatment of over a hundred jail inmates suffering from the life-threatening
diseases Hepatitis B and C and adjourned the hearing till July 6.
The widespread disease was diagnosed after a sampling of prisoners, jail
authorities and other staff under the Prime Ministers National Programme for
Prevention and Control of Hepatitis.
In all 12 members of prison hospital staff, jail officials numbering 28 and 749
prisoners were tested for Hepatitis. Nineteen of the jail inmates refused to be
tested. Out of the tested prisoners 15 were tested HBVC +ve (positive) and 135
tested HCV positive. Interesting, none of the persons associated with jail,
other than prisoners were found infected.
When this public interest litigation came up for hearing, the respondents on
notice including the Civil Surgeon of Civil Hospital Khairpur, Sindh Secretary
Health and IG prisons were represented by sub-ordinate officials. Abbas Ali,
Additional Advocate General Sindh, represented the state.
The court was informed that the delay in treatment was caused due to a delay in
reports from the laboratory located in Lahore. The bench adjourning the matter
and asked the Jail Superintendent to take measures and expedite the matter so
that prisoners were properly treated for the deadly disease. The bench has
already observed that "a prisoner does not shed his basic rights at the prison
gate and as long as he is in custody, his health and well being are the
responsibility of the state".
http://www.dailytimes.com.pk/default.asp?page=2007%5C06%5C19%5Cstory_19-6-2007_p\
g12_10

FIB-4: An inexpensive and accurate marker of fibrosis in HCV infection.
comparison with liver biopsy and fibrotest.
Vallet-Pichard A, Mallet V, Nalpas B, Verkarre V, Nalpas A, Dhalluin-Venier V,
Fontaine H, Pol S.
Université Paris-Descartes, Paris, France.
To optimize the management of patients with chronic hepatitis C virus (HCV)
infection, noninvasive tests to determine the degree of hepatic fibrosis have
been developed. The aims of this study were (1) to validate a simple,
inexpensive, noninvasive test called FIB-4, which combines standard biochemical
values (platelets, ALT, AST) and age, in a series of 847 liver biopsies
performed in HCV-monoinfected patients; and (2) to compare the results of 780
FIB-4 and FibroTests performed the same day in a series of 592 HCV-infected
patients. The FIB-4 index enabled the correct identification of patients with
severe fibrosis (F3-F4) and cirrhosis with an area under the receiver operating
characteristic curve of 0.85 (95% CI 0.82-0.89) and 0.91 (95% CI 0.86-0.93),
respectively. An FIB-4 index <1.45 had a negative predictive value of 94.7% to
exclude severe fibrosis with a sensitivity of 74.3%. An FIB-4 index higher than
3.25 had a positive predictive value to confirm the existence of a significant
fibrosis (F3-F4) of 82.1% with a specificity of 98.2%. Using these ranges, 72.8%
of the 847 liver biopsies were correctly classified. The FIB-4 index was
strongly correlated to the FibroTest results for a score <1.45 or
0.561, P < 0.01). A FIB-4 value <1.45 or
concordant with FibroTest results in 92.1% and 76%, respectively. Conclusion:
For values outside 1.45-3.25, the FIB-4 index is a simple, accurate, and
inexpensive method for assessing liver fibrosis and proved to be concordant with
FibroTest results. (HEPATOLOGY 2007.).
PMID: 17567829 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=175678\
29&dopt=Abstract

Predictors of response of U.S. veterans to treatment for the hepatitis C virus.
Backus LI, Boothroyd DB, Phillips BR, Mole LA.
Center for Quality Management in Public Health, Veterans Affairs Palo Alto
Health Care System, Palo Alto, California.
The currently recommended treatment for hepatitis C virus (HCV) infection is
pegylated interferon alfa (PEG-INF) and ribavirin, which can be difficult to
tolerate. More information about predicting sustained virologic response (SVR)
may allow more informed treatment decisions to be made. This retrospective
observational cohort study identified predictors of SVR to PEG-INF and ribavirin
in routine medical practice at 121 Department of Veterans Affairs facilities.
Among 5,944 patients infected with HCV genotypes 1, 2, or 3 who had been treated
with PEG-INF and ribavirin, SVR rates were 20%, 52%, and 43%, respectively, and
discontinuation rates were 68% (prior to 48 weeks), 34% (24 weeks), and 41% (24
weeks), respectively. In multivariate analysis, significant predictors of
decreased likelihood of genotype 1 patients having an SVR were being African
American, clinical liver disease, diabetes, low cholesterol, low hemoglobin, low
platelet count, and treatment at a low-volume facility. Predictors of increased
likelihood of genotype 1 patients having an SVR were low-level HCV viremia,
elevated ALT quotient, and receiving PEG-INF 2A (rather than 2B). For genotype 2
patients, increasing body mass index, prior use of interferon, and low platelet
count were negative predictors; only low-level HCV viremia was a positive
predictor. For genotype 3 patients, only receiving PEG-INF 2A affected the
likelihood of an SVR; its effect was positive. Conclusion: Among patients for
whom HCV treatment is initiated during routine medical care, multiple factors
including form of PEG-INF received affect the SVR rate for genotype 1 patients.
Few of these factors affect the rate for genotype 2 patients, and even fewer do
so for genotype 3 patients. (HEPATOLOGY 2007.).
PMID: 17567830 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=175678\
30&dopt=Abstract

On-Demand Webcast Now Available!
If you missed our satellite symposium in Washington, DC, on May 20, see it now
from the comfort of your home or office. Who Moved My PEG? The Changing Future
of Anti-HCV Therapy, a free 90-minute CME webcast, features audio and slides
from the symposium.
Listen to the expert faculty panel, chaired by Eugene R. Schiff, MD, as they
discuss these and other important topics:
a.. Hepatitis C virus (HCV) epidemiology and disease burden
b.. The role of HCV in the development of hepatocellular carcinoma
c.. Goals for treatment success and methods for minimizing treatment
resistance
d.. Current and emerging approaches to anti-HCV therapy, including STAT-C
(protease and polymerase inhibitors) and the potential role these agents may
play in the future
Presentation slides and activity syllabus are available for download.
Take advantage of this free educational opportunity-at any time, at your
convenience. Click here to view the webcast today!

Ministry terminates contracts of hepatitis teachers
Published Date: June 20, 2007
KUWAIT: Education Ministry yesterday terminated the contracts of Egyptian
teachers with hepatitis and gave noninfectious carriers an opportunity until
announcing the results of high-school exams.
Education Undersecretary Jassem Al-Omar said in cooperation with Egyptian
embassy and consulate, the teachers' financial rights were settled. In the
future, the ministry will apply stricter measures when conducting medical
checkups of expatriate teachers, he noted.
The liability is shared between Education Ministry, Kuwaiti Health Ministry's
health office in Egypt and a private Egyptian hospital, he explained. The issue
of hepatitis emerged in 2003 when the ministry delegated the issue of medical
checkups of Egyptian teachers to the office in Cairo, he said.
Between 2003-2005, the ministry hired 3,500 male and female teachers, and the
infection was discovered by coincidence four months ago when it was found out
that a single case was not tested by the office and the private hospital, he
noted.
All Egyptian teachers hired since 2003 will go through full medical checkups,
said Al-Omar who added that 48 cases were discovered so far and they range from
contagious to noninfectious. Both hepatitis B and C are only contracted through
surgical instruments and blood transfusion. Type B is also contracted through
sexual contact.
Earlier this month, Kuwaiti cabinet approved hiring 2,600 expatriate teachers by
Education Ministry for school year 2007-2008. --- KUNA
http://www.kuwaittimes.net/read_news.php?newsid=MzU5MTM2NA==

Hello. I am Shevi or Sharona. Newly diagnosed and just
want some information and stuff. Thanks for being
here. I looked around at the messages and reports and
there is so much information. Again Thanks, Shevi

Occult hepatits C virus persistence: identification and
characteristics
Medical Laboratory Observer, Feb, 2006 by Tram N.Q. Pham, Tomasz
I. Michalak
Hepatitis C virus (HCV) is a single-stranded RNA virus of the
Flaviviridae family that replicates by making the so-
called "negative" strand. The virus infects at least 180 million
people worldwide, and up to 85% of the inflicted become carriers of
the virus having chronic liver disease. The current standard
antiviral treatment with pegylated interferon-alpha (IFN-alpha) and
Ribavirin is effective in only about 50% of chronically infected
patients. There is no vaccination against HCV; and with thousands of
new infections each year, this virus will remain a significant social
and economical burden for many years to come.
It has been presumed that resolution of hepatitis C, as evidenced by
normalization of liver function tests and negativity of serum HCV
RNA, determined by the current standard laboratory assays, reflects
viral eradication. Recent evidence from our laboratory and others,
however, indicates that by employing more sensitive nucleic acid
detection tests, low levels of HCV RNA can be identified in sera,
lymphoid cells, and hepatic tissue for years after apparent complete
recovery from hepatitis C. (1-6) This review will focus on recent
identification of occult HCV infection and characteristics of its
persistence.
Natural course of HCV infection
In the majority of newly infected patients, hepatitis C is a
clinically asymptomatic disease characterized by the appearance of
HCV RNA in serum, which is detectable in one to three weeks after
exposure to virus by current clinical laboratory assays. Elevation
for up to eight times in serum alanine aminotransferase (ALT) level,
which is the hallmark biochemical indicator of liver injury, may be
seen two to eight weeks after infection. Symptoms of the acute
hepatitis, which are observed in one-third of the patients and may
include malaise, weakness, jaundice, and abdominal pain, tend to
subside as the ALT levels decline. (7) Antibodies to HCV (anti-HCV)
are detectable by commercially available enzyme-linked immunoassays
in 50% to 70% of patients at the onset of symptoms, increasing to
more than 90% after three months, and completely disappearing 10 to
20 years after resolution of hepatitis. (8) Spontaneous recovery and
apparently complete clearance of HCV RNA occur in 15% to 50% of
patients with acute disease.
In contrast to transient acute hepatitis, chronic hepatitis C
infection is defined by the persistence of HCV RNA in serum for at
least six months. HCV RNA and ALT levels may fluctuate considerably,
especially during the transition from the acute to chronic phase of
the disease. Most patients with chronic hepatitis have an HCV RNA
load between 1[0.sup.4] to 1[0.sup.6] international units (IU)/mL or 1
[0.sup.5]-1[0.sup.7] virus genome equivalents (vge) per mL of plasma.
Two-thirds of them may have persistently elevated ALT of
approximately four times the normal upper limit level. The most
clinically important outcome of chronic hepatitis is progressive
liver fibrosis leading to cirrhosis in 5% to 20% of the patients over
a 20- to 25-year period. HCV-positive cirrhotic patients are at a
higher risk of developing end-stage liver disease (30% over 10 years)
and hepatocellular carcinoma (a risk of 1% to 2% per year). (9) In
addition to these clinically and laboratory well-defined forms of HCV
infection, recent studies revealed the existence of an asymptomatic
HCV infection which continues for years after resolution of
symptomatic hepatitis and is characterized by carriage of serum HCV
RNA at levels normally not detectable by the assays currently used
for laboratory diagnosis.
HCV RNA detection assays
Several tests have been developed for the detection and
quantification of HCV RNA. Among them are the FDA-approved manual and
semiautomatic qualitative assays, such as Amplicor and Cobas Amplicor
HCV version 2 from Roche, which have limits of detection of 50 IU/mL
or 50 vge/mL to 135 vge/mL, as well as the transcription-mediated
amplification (TMA) assay, such as VERSANT HCV from Bayer, which has
a sensitivity of 10 IU/mL or approximately 50 vge/mL. In addition,
measurement of HCV RNA levels, which is important in predicting the
likelihood of response to therapy, has been made possible by
quantitative assays employing either TMA or signal amplification
(branched DNA) techniques. Currently, VERSANT HCV RNA version 3.0
assay from Bayer, which has a dynamic range of 615-7.7 X 1[0.sup.6]
IU/mL, is the only one with FDA approval.
Recently, research assays applying reverse transcription of viral RNA
to cDNA followed by two sequential rounds of polymerase chain
reaction (RT-PCR) with HCV gene-specific primers, and validating the
amplified products by nucleic acid hybridization (NAH) with
recombinant HCV DNA as a probe, were developed. (1) These RT-PCR/NAH
assays detect HCV RNA positive (vegetative) and negative
(replicative) strands with a sensitivity of [less than or equal to]10
vge/mL (<5 IU/mL) and ~100 vge/mL (~50 IU/mL), respectively. Due to
their extreme sensitivity, rigorous protocols ensuring the
authenticity of HCV RNA amplification have to be followed. In
addition, a quantitative, real-time RT-PCR detecting HCV RNA at a
sensitivity of ~100 vge/mL was also recently established. (1), (3)
Application of these new detection methods has uncovered previously
unknown facts about the natural history of HCV infection, including
identification of occult HCV persistence. (1)
Lymphotropism of HCV
Although HCV is considered to be primarily hepatotropic, accumulated
evidence clearly indicates that the virus also invades and replicates
in the immune system. In fact, the presence of both HCV RNA positive
and negative strands has been demonstrated in lymphoid cells in both
in vivo and in vitro settings. For example, T cells, B cells,
monocytes, and dendritic cells from patients with chronic hepatitis C
have all been shown to carry HCV genomes. (2), (10-12) Most recently,
by applying assays of superior sensitivity mentioned above,
replication of HCV has been seen to persist in lymphoid cells for
years after spontaneous recovery or a sustained virological response
to IFN-alpha/Ribavirin therapy. (1-3) In addition, low levels of HCV
RNA in lymphoid cells have been detected in a significant proportion
of patients with persistently elevated liver enzyme levels of unknown
etiology. (13), (14) Along the same line, susceptibility of T and B
cell lines as well as primary human T cells and macrophages to HCV
infection have also been documented. (15-18)
Occult HCV infection
In our studies, using the highly sensitive RT-PCR/NAH assays,
conclusive evidence was obtained for the presence of replicating HCV
in persons who apparently completely recovered from hepatitis C and
whose sera were repeatedly negative for HCV RNA by standard assays.
We found that more than 80% of these individuals were serum HCV RNA
positive at levels usually not exceeding 1[0.sup.2] vge/mL and that
30% to 40% of them also carried HCV RNA in circulating lymphoid cells
at levels between 10 and 1[0.sup.4] vge per 1[0.sup.7] cells (see
Figure 1). (1), (19)
[FIGURE 1 OMITTED]
However, when the cells, including those apparently negative for HCV
RNA, were ex vivo treated with mitogens known to activate different
immune cell subsets, e.g., phytohemagglutinin (PHA) to stimulate T
cells, pokeweed mitogen (PWM) to induce B and T cells, and
lipopolysaccharide (LPS) to activate monocytes and B cells, HCV RNA
was detected in all of the individuals. (1), (2), (19) Interestingly,
in the majority of the cases, synergistic stimulation of T and B
cells and monocytes with mitogen cocktails led to a more pronounced
upregulation of HCV RNA expression than did single mitogen
treatments, suggesting that all three cell subsets are reservoirs of
the virus (see Figure 2). This propensity was also found when the
same cell subsets purified from hepatitis C patients were analyzed.
(2), (19) Overall, the ex vivo synergistic mitogen stimulation of
peripheral lymphoid cells allows for a more precise detection of
silent HCV infection than by testing either sera or naive (untreated)
lymphoid cell samples alone. Our original identification of commonly
occurring occult HCV infection has been corroborated by recent data
from several other laboratories. (3), (4), (6) This collective
evidence challenges the previous notion that resolution of hepatitis
C reflects complete virus eradication. Further, the invariable
detection of replicating HCV genomes in lymphoid cells from
individuals with either occult or symptomatic infection attests to
the existence of an extrahepatic compartment for HCV replication.
[FIGURE 2 OMITTED]
In addition to consistent identification of HCV RNA in ex vivo
stimulated peripheral lymphoid cells, HCV RNA has also been detected
in liver tissue of asymptomatic individuals with a sustained response
to antiviral treatment. (3), (5) Although these patients generally
exhibit histologically apparent improvement after IFN-alpha/Ribavirin
therapy, including partial regression of fibrosis, liver biopsies
from many of them show evidence of persistent minimal inflammation or
even of active chronic hepatitis. (3), (5)
Implications of occult HCV infection
Although investigations on clinical relevance of occult HCV infection
have just begun, the data available at this point could help explain
sustained HCV-specific T-cell responses observed in individuals
decades after recovery from hepatitis C. (8), (20) In this regard,
the presence of low amounts of the replicating virus could provide
continuous antigenic stimuli beneficial to immunocompetent
individuals in maintaining an effective antiviral immune response and
keeping the occult infection under control. On the other hand, virus
persisting at very low levels may provide a means for reactivation of
infection when the host's immune system becomes compromised due to a
disease or therapy. Indeed, reactivation of HCV infection has been
documented in patients receiving immunosuppressive treatment. (21),
(22) Along the same line, HCV RNA was also detected in sera of anti-
HCV positive patients weeks after acquiring HCV-negative kidney (23)
or bone marrow (24) transplants and immunosuppressive therapy. With
respect to commonly observed HCV reinfection of liver allografts in
patients with end-stage diseases caused by chronic hepatitis C,
migration of lymphoid cells, including those carrying not readily
detectable quantities of replicating virus, may constitute a main
mechanism by which the transplanted liver becomes infected.
In summary, occult HCV infection is a common, if not an invariable,
consequence of resolution of hepatitis C when measured by highly
sensitive assays established recently in some research laboratories.
The availability of assays detecting HCV RNA with a comparable
sensitivity in clinical laboratories would improve the precision with
which HCV is detectable among patients and in the general population.
Furthermore, the persistence of traces of replicating HCV in lymphoid
cells, from which viral infection may potentially rebound under
favorable conditions, suggests that future treatments aimed at HCV
elimination should take into consideration that both the liver and
the lymphatic system are the sites of virus propagation.
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