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A Possible Link
Between Hepatitis C Virus Infection and Type-2 Diabetes in Renal
Diseases and Transplantation
A link between
hepatitis C virus infection and development of
diabetes mellitus
has been suggested by many investigators; however, this remains
controversial. The mechanisms underlying the association between
hepatitis C virus and diabetes mellitus are unclear but a great
majority of clinical surveys have found a significant and
independent relationship between hepatitis C virus and diabetes
mellitus after
renal transplantation
and
orthotopic liver transplantation.
In this
retrospective study, researchers in Italy have systematically
reviewed the scientific literature to explore the association
between hepatitis C virus and diabetes mellitus in end-stage renal
disease; in addition, data on patients undergoing orthotopic liver
transplantation were also analyzed.
The unadjusted
odds ratio for developing post-transplant diabetes mellitus in
hepatitis C virus-infected renal transplant recipients ranged
between 1.58 and 16.5 across the published studies.
The rate of
anti-hepatitis C virus antibody in serum was higher among
dialysis patients
having diabetes mellitus.
Patients with
type-2 diabetes-related glomerulonephritis had the highest
anti-hepatitis C virus prevalence [19.5% (24/123) vs. 3.2%
(73/2247); P < 0.001] in a large cohort of Japanese patients who
underwent renal biopsy.
The link between
hepatitis C virus and diabetes mellitus may explain, in part, the
detrimental role of hepatitis C virus on patient and graft
survival after orthotopic liver transplantation and/or renal
transplantation.
Preliminary
evidence suggests that anti-viral therapies prior to renal
transplantation and novel immunosuppressive regimens may lower the
occurrence of diabetes mellitus in hepatitis C virus-infected
patients after renal transplantation.
Clinical trials
are under way to assess if the hepatitis C virus-linked
predisposition to new onset diabetes mellitus after renal
transplantation may be reduced by newer immunosuppressive
medications.
Division of
Nephrology and Dialysis, Maggiore Hospital, IRCCS, Milan, Italy.
03/23/05
Reference
F Fabrizi and others. Hepatitis C virus
infection and type-2 diabetes mellitus in renal diseases and
transplantation.
Alimentary Pharmacology & Therapeutics 21(6): 623-632.
March 15, 2005
http://www.hivandhepatitis.com/hep_c/news/2005/032305_b.html |
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Roche
initiates trial in post-transplant hepatitis
Roche has initiated a new study to evaluate
treatment strategies to reduce post-transplant recurrence of hepatitis C
infection with the most prescribed hepatitis C treatment combination in
the US, Pegasys and Copegus.
22 Mar 2005, 19:22 GMT - The new study will compare prophylactic
combination therapy with Pegasys (peginterferon alfa-2a) and Copegus (ribavirin,
USP), with the same combination therapy administered once hepatitis C
infection recurs histologically in the transplanted liver.
The study will enroll approximately 300 patients and include 28 trial
sites throughout the US. All patients will be evaluated at 24 months to
determine if they have experienced hepatitis C recurrence measured by
fibrosis stage two or greater and/or inflammation grade three or
greater.
"There are many questions to be answered such as how safe and effective
is hepatitis C combination therapy for patients who have received a
liver transplant, and when is treatment most effective," said Dr Michael
Charlton, associate professor of medicine and director of transplant
research at Mayo Clinic College of Medicine.
"It is our hope that this study will help determine the best strategy
for managing hepatitis C in patients who have received a liver
transplant."
| A new study on the effect
of donor age on survival and recurrence of hepatitis C after liver
transplantation found that it influenced short-term survival, but had no
long-term effect. |
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i-Newswire, 2005-03-23 - The results of this study appear in the April
2005 issue of Liver Transplantation, the official journal of the
American Association for the Study of Liver Diseases ( AASLD ) and the
International Liver Transplantation Society ( ILTS ). The journal is
published on behalf of the societies by John Wiley & Sons, Inc. and is
available online via Wiley InterScience at interscience.wiley.com/journal/livertransplantation
.
Patients who undergo liver transplantation for cirrhosis due to
hepatitis C are invariably re-infected with the virus after
transplantation. When the disease recurs it often has a more rapid and
aggressive course than in patients who have not undergone liver
transplantation. Survival rates of these patients appear to be worsening
during the past few years, but recent studies have shown conflicting
results about whether a donor's age can be associated with a poor
outcome. The current study examined the impact of donor age,
immunosuppression, and other factors on short and long term survival
after liver transplant, as well as fibrosis in these patients.
Led by Dimitrios N. Samonakis, of the Liver Transplantation and
Hepatobiliary Unit of the Royal Free Hospital in London, the study
examined 195 transplantations due to end stage cirrhosis related to
hepatitis C that took place between 1989 and June 2003. The median donor
age was 41.5 years and 47 patients had a donor who was 30 years old or
younger. Donor age was not associated with the development of severe
fibrosis, whereas patients receiving treatment with maintenance steroids
and/or azathioprine tended not to develop severe fibrosis, even if later
discontinued; acute hepatitis C was an independent factor associated
with worse fibrosis.
"Donor age did affect survival, but only during the early critical
post-operative period, but not survival after 3 months, despite having
in our cohort 30 percent of donors over 50 years," the authors state.
They found maintenance azathioprine to be an independent factor
associated with survival advantage, overall and from 3 months. In
addition, while several studies have suggested that less
immunosuppression may seem to be a viable strategy in minimizing
progression of hepatitis C post-transplant, the authors found the
situation to be more complex. They state that "the rapid withdrawal of
steroids ( but also of azathioprine ) prevalent in recent years, may
have allowed an early reconstitution of the immune system and its
exposure to a large number of HCV [hepatitis C] infected liver cells,
leading to immune mediated severe liver damage and thus to more frequent
and severe forms of HCV recurrence."
The authors conclude that while donor age did not influence the
progression of recurrent hepatitis C, the absence of steroids and
azathioprine did play a role and maintain that these associations need
to be tested in a prospective randomized fashion.
Article: "Immunosuppression and Donor Age with Respect to Severity of
HCV Recurrence After Liver Transplantation," Dimitrios N. Samonakis,
Christos K. Triantos, Ulrich Thalheimer, Alberto Quaglia, Gioacchino
Leandro, Rosângela Teixeira, George V. Papatheodoridis, Caroline A.
Sabin, Nancy Rolando, Susan Davies, Amar P. Dhillon, Paul Griffiths,
Vincent Emery, David W. Patch, Brian R. Davidson, Keith Rolles, Andrew
K. Burroughs, Liver Transplantation; April 2005; Volume 14, Issue 4 (
Published Online: March 17, 2005 ).
John Wiley & Sons, Inc.
http://www.interscience.wiley.com
If you have questions regarding information in these press release
contact the company listed below. Please do not contact us as we are
unable to assist you with your inquiry. We disclaim any content
contained in this press release.
|
| 2005-03-23 |
http://i-newswire.com/pr11578.html
Post-Transplant HCV Treatment
Recurrence of HCV is a concern following orthoptic
liver transplantation (OLT). Among untreated patients, relapse is nearly
universal, and it sometimes occurs even in patients who previously achieved
sustained virological response to interferon-based therapy. In the February
issue of Hepatology, Naga Chalasani and colleagues reported on two
controlled post-transplant trials, one looking at prevention of HCV relapse
and the other examining treatment of recurrent hepatitis C. In the
prevention trial, 54 patients who underwent liver transplants within the
previous three weeks were randomly assigned to receive either 180 mcg
pegylated interferon (Pegasys) once weekly for 48 weeks or no antiviral
therapy. In the treatment trial, 67 patients were treated with the same
regimen, or no therapy, starting 6-60 months after transplantation. In both
studies, sustained virological response rates 24 weeks after the end of
therapy were low: 8% in the prevention trial and 12% in the treatment trial.
About one-third of treated patients in both studies (31% in the prevention
trial, 30% in the treatment trial) withdrew prematurely, but discontinuation
rates were also high for the untreated subjects (32% and 19%, respectively).
However, patients in both trials who were treated with Pegasys had
significantly lower HCV RNA levels and showed more histological improvement
than untreated subjects. The researchers concluded that pegylated interferon
therapy for 48 weeks “is safe and tolerable and offers some efficacy in the
post-OLT setting,” and recommended that further controlled studies be
conducted to look at combination therapy with pegylated interferon plus
ribavirin.
http://www.hcvadvocate.org/news/newsRev/2005/HJR-2.4.html#2
American Journal of Transplantation
OnlineEarly
doi:10.1111/j.1600-6143.2005.00812.x
Determinants of Transplant
Surgeons' Willingness to Provide Organs to
Patients Infected with HBV, HCV or HIV
Scott D. Halperna,b,c,d,*, David A. Ascha,b,d,e,f, Abraham Shakedg, Peter G.
Stockh and Emily Blumberga
The common provision of organs to patients infected with hepatitis B virus
(HBV) and hepatitis C virus (HCV), but not to those infected with human
immunodeficiency virus (HIV), has been attributed to perceived or real
differences in transplantation efficacy among these populations. However,
other explanations remain possible. We surveyed all active U.S. transplant
surgeons to identify determinants of their views of the propriety of
transplantation among HBV-, HCV-, and HIV-infected patients. The 347
surgeons (56.1%) returning completed questionnaires believed that HCV- and
HIV-infected patients have similar post-transplant survival (p = 0.9), but
that both groups fare worse than HBV-infected patients (p < 0.00001 for both
comparisons). Most transplant surgeons considered HBV- and HCV-infected
patients to be appropriate transplantation candidates (p = 1.0 for this
comparison), whereas one-third considered HIV-infected patients to be
appropriate candidates (p < 0.00001 when compared with HBV- or HCV-infected
patients). That surgeons are generally willing to transplant HCV-infected
patients but not HIV-infected patients, and yet believe these groups will
have similar post-transplant survival, suggests that survival estimates
alone do not explain surgeons' choices. HIV-infected patients should have
equal access to organs unless or until evidence emerges that they fare
substantially worse than other potential recipients.
From Alimentary Pharmacology & Therapeutics
A Comparison of Liver
Transplantation Outcomes in the Pre- vs Post-MELD Eras
F. Kanwal; G.S. Dulai; B.M.R. Spiegel; H.F. Yee; I.M. Gralnek
Summary and Introduction
Summary
Background: The model for end stage liver disease (MELD)-based organ
allocation system is designed to prioritize orthotopic liver transplantation
(OLT) for patients with the most severe liver disease. However, there are no
published data to confirm whether this goal has been achieved or whether the
policy has affected long-term post-OLT survival.
Aim: To compare pre-OLT liver disease severity and long-term (1 year)
post-OLT survival between the pre- and post-MELD eras.
Methods: Using the United Network of Organ Sharing database, we compared two
cohorts of adult patients undergoing cadaveric liver transplant in the
pre-MELD ( n = 3857) and post-MELD ( n = 4245) eras. We created
multivariable models to determine differences in: (i) pre-OLT liver disease
severity as measured by MELD; and (ii) 1-year post-OLT outcomes.
Results: Patients undergoing OLT in the post-MELD era had more severe liver
disease at the time of transplantation (mean MELD = 20.5) vs. those in the
pre-MELD era (mean MELD = 17.0). There were no differences in the unadjusted
patient or graft survival at 1 year post-OLT. This difference remained
insignificant after adjusting for a range of prespecified recipient, donor,
and transplant centre-related factors in multivariable survival analysis.
Conclusions: Although liver disease severity is higher in the post- vs.
pre-MELD era, there has been no change in long-term post-OLT patient or
graft survival. These results indicate that the MELD era has achieved its
primary goals by allocating cadaveric livers to the sickest patients without
compromising post-OLT survival.
Introduction
Although the model for end stage liver disease (MELD)-based organ allocation
system is designed to prioritize orthotopic liver transplantation (OLT) for
patients with the most severe liver disease, there are no published data to
confirm that this goal has been achieved. Specifically, there has been no
previous attempt to measure whether liver disease severity at the time of
OLT is higher in the post- vs. pre-MELD era. Nonetheless, assuming that the
MELD era has indeed allowed sicker patients to be transplanted sooner,[1,2]
a plausible assumption would be that post-OLT outcomes are now worse
compared with the pre-MELD era. However, recent data do not bear this out as
they demonstrate unchanged 3-month patient and graft survival in the post-
vs. pre-MELD eras.[1] Given that pre-OLT liver disease severity is the most
important determinant of post-OLT outcomes,[3,4] there appears to be a
disconnect between the purported increase in pre-OLT severity and the lack
of change in post-OLT outcomes. The source of this apparent disconnect is
unclear. Potential explanations might include: (i) pre-OLT liver disease
severity is not a predictor of post-OLT outcomes; (ii) transplant recipients
are, in fact, not sicker in the post- vs. pre-MELD eras; (iii) post-OLT
outcomes have indeed worsened but have not yet been detected as reported
outcomes have been limited to only 3-month post-OLT.
The first explanation is unlikely given the extensive validation to the
contrary.[3,4] The remaining two explanations are plausible and have not
been systematically appraised. The MELD based system prioritizes patients
with more severe liver disease. The MELD system also prioritizes patients
with renal insufficiency, and patients with hepatocellular carcinoma. All
these factors are associated with decreased patient and graft survival.[3-6]
In light of these, our aim was to reassess the contention that sicker
patients are receiving cadaveric livers and that the post-OLT outcomes are
stable in the post-MELD era. We therefore sought to test the hypotheses
that: (i) pre-OLT liver severity is higher; and (ii) post-OLT patient and
graft survival are lower in the post- vs. pre-MELD era. To test our first
hypothesis, we performed a multivariable analyses in over 8000 orthotopic
liver transplant recipients using the United Network of Organ Sharing (UNOS)
liver transplant database to determine whether the mean pre-OLT liver
disease severity increased in the post-MELD era compared with the pre-MELD
eras. To test our second hypothesis, we conducted a multivariable survival
analysis to determine whether 1-year patient and graft survival worsened in
the post-MELD era compared with the pre-MELD eras.
FULL TEXT:
http://www.medscape.com/viewarticle/498545_1
Biochemical marker aids prognosis in liver transplant patients
20 Feb 2005
A new study on whether the model used to identify patients most in need of a
liver transplant can be improved upon found that measuring serum sodium in
potential transplant patients helps to better predict those with a poor
prognosis.
The results of this study appear in the March 2005 issue of Liver
Transplantation, the official journal of the American Association for the
Study of Liver Diseases (AASLD) and the International Liver Transplantation
Society (ILTS). The journal is published on behalf of the societies by John
Wiley & Sons, Inc. and is available online via Wiley InterScience at
http://www.interscience.wiley.com/journal/livertransplantation.
Since 2002, liver allocation in the U.S. has been based on a patient's score
on the Model for End-Stage Liver Disease (MELD), which uses levels of three
biochemical markers (serum bilirubin, serum creatinine, and prothrombin time
expressed as INR) to predict three-month mortality in patients with
cirrhosis of the liver listed for transplantation. The current study
examined whether factoring serum sodium and hyponatremia (low sodium level
in the blood), as additional markers would increase the accuracy of the MELD
score to predict risk of death on the waiting list.
Led by Andres E. Ruf, M.D., of the Liver Unit of the Fundacion Favaloro in
Buenos Aires, Argentina, the study included 262 patients with cirrhosis who
were listed for liver transplantation at Fundacion Favaloro between June
1995 and January 2003. INR, serum bilirubin, creatinine and sodium were
measured at the time of listing and used to calculate a MELD score. The
efficacy of serum sodium, hyponatremia (defined by serum sodium less than or
equal to 130 mEq/L) and MELD to predict death within 3 and 6 months of
listing was analyzed with two different statistical methods. Results of the
study showed that when added to the MELD, serum sodium and hyponatremia
significantly increased the accuracy of the score in predicting short-term
mortality.
"In our study, the prevalence of hyponatremia was significantly higher in
patients who died within 3 months (63 percent) than in those who survived 3
months (13 percent)," the authors note. "Similarly, patients with
hyponatremia had significantly more advanced liver failure compared to those
with normal serum sodium." They add that although hyponatremia ultimately
reflects renal impairment, it appears to be a more accurate and early marker
of poor outcome than serum creatinine in transplant candidates with advanced
cirrhosis.
According to the study, serum sodium, like bilirubin, INR, and creatinine,
is an objective, quantitative and reproducible laboratory test, and is
therefore a good candidate for inclusion in the mathematical formula of the
MELD score. While serum sodium can be decreased with the use of diuretics
and can therefore be manipulated, this disadvantage also applies to serum
creatinine. The authors conclude that the study "shows that hyponatremia is
an excellent predictor of outcome in patients with advanced cirrhosis and
significantly increases the efficacy of MELD to predict waitlist mortality."
The work outlined in this news alert was supported by the Foundation for
Research and Education in Liver Diseases in Buenos Aires, Argentina.
------------------
Article: "Addition of Serum Sodium Into the MELD Score Predicts Waiting List
Mortality Better Than MELD Alone," Andres E. Ruf, Walter K. Kremers, Lila L.
Chavez, Valeria I. Descalzi, Luis G. Podesta, Federico G. Villamil, Liver
Transplantation, 11:3, March 2005 (DOI: 10.1002/lt.20329).
Contact: David Greenberg
dgreenbe@wiley.com
John Wiley & Sons, Inc.
http://www.medicalnewstoday.com/medicalnews.php?newsid=20199#
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