Roche initiates trial in post-transplant hepatitis

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.

Post-Transplant HCV Treatment

Determinants of Transplant Surgeons' Willingness to Provide Organs to
Patients Infected with HBV, HCV or HIV

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.

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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#