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September 16, 2004Pre-emptive antivirals aid living donor liver transplant recipientsBy
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Herpes zoster after liver transplantation |
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| Herpes zoster is a relatively common complication after liver transplantation, find doctors in the September issue of Liver Transplantation. | |||
| Herpes zoster is the consequence of the reactivation of latent varicella-zoster infection. Immunosuppression may be a predisposing factor for herpes zoster. In this study, doctors from Spain assessed the risk of herpes zoster, the risk factors for its occurrence, and its evolution in 209 consecutive liver transplant recipients. The team found that herpes zoster developed in 12% of patients. They calculated that the 1-, 3-, 5-, and 10-year actuarial rates of herpes zoster were 3%, 10%, 14%, and 18%, respectively. The doctors determined that the patients who developed herpes zoster were younger, received a greater number of immunosuppressive drugs, and were more frequently receiving mycophenolate mofetil or azathioprine. They found that the only factor related to herpes zoster occurrence on multivariate analysis was treatment with mycophenolate mofetil or azathioprine.
Of the patients who developed herpes zoster, 31% developed postherpetic neuralgia. Dr Ignacio Herrero and colleagues concluded, "Herpes zoster is a relatively common complication after liver transplantation". "It is related to immunosuppressive therapy." "Post-herpetic neuralgia develops in one third of patients with post-transplant herpes zoster."
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Liver Transpl 2004; 10: 1140-3
01 September 2004 |
September 2004 HCV Advocate
Post-Transplant Treatment for Hepatitis C
Liz Highleyman
Long-term liver damage related to hepatitis C is the most common reason
for liver transplants in the U.S. Unfortunately, the hepatitis C virus (HCV)
usually reinfects the new liver after a transplant. HCV recurrence typically
occurs within a few weeks and sometimes in as little as 24-48 hours after
transplantation, following an initial steep decline in HCV viral load. More
severe recurrence is associated with high pre-transplant viral load, a liver
graft from an older donor, and use of strong immunosuppressive drugs to
prevent organ rejection.
Researchers are avidly studying ways to prevent and
treat HCV recurrence after liver transplantation. Montserrat Garcia-Retortillo
and Xavier Forns reviewed the current state of knowledge in the July 2004
issue of the Journal of Hepatology.
The first approach to preventing post-transplant reinfection involves
attempting to eradicate HCV before the transplant is performed. If the virus
can be completely eliminated from the body, it cannot infect the new liver.
Unfortunately, even among people who have achieved a sustained virological
response (SVR) to treatment, HCV appears to remain in the body at very low
levels. In the June 2004 issue of the Journal of Virology, Tram
Pham and colleagues reported that HCV genetic material persists in
peripheral blood mononuclear cells (a type of immune system white blood
cell) for up to five years after spontaneous or therapy-induced HCV
"clearance." But because rapid and severe reinfection is most likely in
people with high pre-transplant viral loads, any signficant reduction in HCV
RNA is likely to prove beneficial.
Although HCV therapy can be risky in people with advanced cirrhosis,
interferon plus ribavirin is increasingly being used in HCV patients
awaiting liver transplants. For example, Gregory Everson and colleagues
treated 102 HCV positive cirrhotic patients with interferon plus ribavirin.
Although the SVR rate was low (20% overall, 11% for genotype 1), among the
32 patients who underwent transplantation, HCV did not recur in any of those
who achieved a sustained response. In another study, Forns and colleagues
found that among 30 patients on a transplant waiting list treated with
interferon plus ribavirin, HCV did not recur after transplantation in 6 of 9
patients who achieved a virological response, but did recur in all
nonresponders.
Adverse side effects are common in patients with advanced liver disease, and
in many cases therapy must be discontinued or dosages decreased (although
use of erythropoietin or filgrastim to stimulate production of red and white
blood cells, respectively, may allow some patients to stay on therapy).
While HCV treatment response rates in this population are lower than those
seen in individuals with milder disease, "antiviral therapy is a feasible
choice in HCV-infected patients with advanced liver disease," Garcia-Retrortillo
and Forns concluded.
Another approach is to use immunoglobulin (antibody) therapy starting right
before the transplant operation to prevent reinfection of the new liver. In
people with chronic hepatitis B, use of an immunoglobulin preparation called
HBIG effectively prevents HBV recurrence. In studies to date, similar use of
HCV antibodies has not prevented reinfection of the new liver. However,
studies have shown that antibodies with neutralizing activity against HCV do
exist, and research is continuing with new types of antibody preparations.
A third approach is to treat patients with interferon-based therapy soon
after liver transplantation, while their HCV viral load is still low. Among
these patients, who are typically taking high doses of immunosuppressive
drugs, adverse side effects and treatment discontinuation are common.
Although results have been mixed, some studies show that a proportion of
patients can benefit from interferon-based therapy started within the first
few weeks following transplantation. For example, in a study of 63
post-transplant patients, Vincenzo Mazaferro and colleagues reported SVR
rates of 13% among post-transplant patients treated with standard interferon
monotherapy and 33% among those treated with interferon plus ribavirin.
Studies also suggest that early treatment helps reduce the risk of
reinfection.
More commonly, HCV treatment is initiated months or years after liver
transplantation, once signs of damage to the new liver are apparent. By this
time, patients are usually healthier overall and taking lower doses of
immunosuppressive drugs, enabling them to better tolerate HCV therapy. In
general, studies have found SVR rates for this population to be around
20-25% using standard interferon plus ribavirin. Rates are somewhat higher
using pegylated interferon. In the July 2004 issue of Liver
Transplantation, for example, R. Todd Stravitz and colleagues reported
on a retrospective evaluation of interferon therapy in 23 post-transplant
patients with recurrent HCV. The subjects completed at least six months of
interferon-based therapy, 83% with Peg-Intron; however, only four were able
to tolerate ribavirin. After six months of treatment, 11 patients (48%) had
undetectable HCV RNA; of these, eight (35% of the total) achieved SVR. Liver
biopsies performed two years after HCV became undetectable showed decreased
necroinflammatory activity, and 6 of 11 patients showed histological
improvement on follow-up liver biopsies. Although SVR rates for transplant
recipients are lower than those seen in non-transplant patients, treatment
can keep HCV under control in some individuals, and those who respond may
experience decreased fibrosis progression.
Caution is necessary, however, because interferon therapy appears to
increase the risk of liver rejection. In the same issue of Liver
Transplantation, Sammy Saab and colleagues reported that five of 44 liver
transplant recipients treated with interferon (11.4%) developed acute liver
rejection, a rate higher than that seen in liver transplant patients not
receiving interferon. These five started interferon an average of 42 months
(and up to 83 months) after transplantation, and were treated for an average
of three months before rejection set in. Three were successfully treated
with intensified immunosuppressive drugs, one required a second liver
transplant, and the fifth died from sepsis. In Stravitz's study, eight (35%)
of the 23 transplant recipients treated with interferon showed evidence of
liver rejection and two required a second transplant. Further study is
needed to determine the best immunosuppressive regimens for post-transplant
patients with HCV. Whenever transplant recipients are treated for hepatitis
C, care must be taken to minimize interactions and synergistic side effects
between HCV therapy and immunosuppressive drugs.
As is true for all individuals with HCV, post-transplant patients do not
need to be treated until they show signs of liver disease progression.
"Given the low efficacy and poor tolerability of current antiviral therapy,"
Garcia-Retortillo and Forns recommend that "treatment should probably be
reserved to those individuals in whom disease progression is well
documented." However, liver damage progresses more rapidly in people with
compromised immune systems, including those taking immunosuppressive drugs.
Martín Prieto and colleagues, for example, found that HCV infection led to
cirrhosis in some 30% of transplants recipients within just five years. And
in Saab's study, two of the three patients whose acute rejection was
successfully treated progressed rapidly to cirrhosis.
For this reason, Garcia-Retortillo and Forns suggest that frequent biopsies
are indicated to monitor disease progression in the new liver.
"[A]ntiviral treatment is now fully part of the overall therapeutic strategy
post-transplantation," wrote Didier Samuel in an editorial in the July
Liver Transplantation, but "[t]he timing, the duration of treatment,
the use of pegylated interferon instead of nonpegylated interferon, and the
optimal dosage of ribavirin are still a matter of debate." As better
therapeutic regimens emerge, more research is needed to improve outcomes for
liver transplant recipients, who are among the most difficult patients to
treat but who can potentially derive considerable benefit from successful
therapy.
References:
•Everson, G. et al. Treatment of decompensated cirrhotics with a
low-accelerating dose regimen (LADR) of interferon-alfa-2b plus ribavirin:
safety and efficacy. Hepatology 32: 595, 2001.
•Forns, X. et al. Antiviral therapy of patients with decompensated
cirrhosis to prevent recurrence of hepatitis C after liver transplantation.
J. Hepatology 39: 389-396, Sept. 2003.
•Garcia-Retortillo, M. and X. Forns. Prevention and treatment of hepatitis
C virus recurrence after liver transplantation. J. Hepatology 41: 2-10, July
2004.
•Mazzaferro, V. et al. Prospective randomized trial on early treatment of
HCV infection after liver transplantation in HCV-RNA positive patients.
Liver Transplantation 9: C-36, 2003.
•Pham, T. et al. Hepatitis C virus persistence after spontaneous or
treatment-induced resolution of hepatitis C. J. Virology 78: 5867-5874, June
2004.
•Prieto, M. et al. High incidence of allograft cirrhosis in hepatitis C
virus genotype 1b infection following transplantation: relationship with
rejection episodes. Hepatology 29: 250-256, January 1999.
•Saab, S.et al. Outcomes of acute rejection after interferon therapy in
liver transplant recipients. Liver Transplantation 10: 859-867, July 2004.
•Samuel, D. Hepatitis C, interferon, and risk of rejection after liver
transplantation. Liver Transplantation 10: 868-871, July 2004.
•Stravitz, R.T. et al. Effects of interferon treatment on liver histology
and allograft rejection in patients with recurrent hepatitis C following
liver transplantation. Liver Transplantation 10: 850-858, July 2004.
http://www.hcvadvocate.org/news/newsLetter/2004/advocate0904.html#1
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by John C. Martin |
Article
Date: 08-26-04 |
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Rising
Prevalence of Infection
While the incidence of new hepatitis infections around the world
has decreased, write Hector Rodriguez-Luna, MD, and David D. Douglas, MD,
of the Mayo Clinic in Arizona, the number of infected people "will not
peak until the year 2040." As more patients become infected, many will
remain infected for years, boosting the numbers of people with cirrhosis
in that population—a two-fold increase, in fact, by the year 2020, they
add.
The number of new hepatitis C infections in the United States has declined from an average of 240,000 in the 1980s to about 25,000 in 2001, the latest year for which statistics are available. Currently, it's estimated that about 3.9 million Americans—1.8 percent of the total population—have been infected with the virus, of whom 2.7 million have chronic, or long-term, infection.2
'An Impossible Burden'
If the current projections are accurate, Rodriguez-Luna and Douglas
maintain that "the need for
liver transplantation secondary to
chronic hepatitis C virus infection will place an impossible burden on an
already limited supply of organs." That's because hepatitis C re-infection
occurs "virtually in every post-transplant patient," they write in the
journal Current Opinion in Infectious Diseases. This re-infection happens
quickly; evidence of it begins to appear in as little as two weeks after
surgery. By 1 year post-transplantation, levels of HCV can be 10 to 20
times higher than the average
viral load prior to surgery, the two
experts explain.
"Progression of chronic hepatitis C virus is more aggressive after liver transplantation with a cumulative probability of developing graft cirrhosis estimated to reach 30% at 5 years," the authors wrote. In addition, they estimate that approximately 10 percent of patients with recurrent HCV will die or require another liver transplant within 5 years after the first transplant procedure.
According to experts, the hepatitis C virus remains in a liver transplant recipient's bloodstream after surgery, and the use of immunosuppressive drugs, which is aimed at preventing the body from rejecting the new organ, unintentionally keeps the immune system from launching a full-scale attack against the remaining virus, and it begins to make copies of itself again.3 In addition, there is a risk of recurrence if the donor is also infected.4
Managing Postoperative Recurrence
Medical experts currently recommend the use of pegylated, or
longer-lasting,
interferon and the antiviral medication,
ribavirin, as treatment for patients
whose hepatitis C infection re-occurs, and/or for those whose fibrosis
reaches a certain level in the liver. But improvements to this treatment
regimen are still needed, Rodriguez-Luna and Douglas stress.
"The major challenges that face the transplant community in the coming years include new strategies to meet the growing demand for limited organ donor supplies and improvement of treatment for those patients in whom recurrence of viral disease has occurred," they wrote. "Only with improved antiviral treatments and strategies will we make a significant impact on this problem."
Reasons for Liver Transplant
Liver transplantation is indicated for patients whose liver has
deteriorated to the point that it can no longer function normally.
Potential candidates include those who aren't able to experience a normal
quality of life, or have life-threatening liver complications as a result
of liver disease, including
cirrhosis. Postoperative survival rates
have also soared in the last several years. One-year survival odds are
estimated to be about 85% to 90%. The five-year survival rate is about
65%.5
In 2003, approximately one-third of transplants were performed for every patient waiting to undergo the procedure.6 Specifically, there were more than 5,000 liver transplants performed in the U.S. But that compares to approximately 17,000 patients on the liver transplant waiting list.
1. Rodriguez-Luna H, Douglas DD. Natural history of
hepatitis C following liver transplantation.
2. Centers for Disease Control and Prevention (CDC). Viral Hepatitis C.
Available at: http://www.cdc.gov/ncidod/diseases/hepatitis/c/fact.htm.
Accessed August 19, 2004.
3. Randhawa PS, Demetris AJ. Hepatitis C virus infection in liver
allografts. Pathol Annu 1995;30 Pt 2:203-206.
4.Terrault NA, Wright TL, Pereira BJ. Hepatitis C infection in the
transplant recipient. Infect Dis Clin North Am 1995
Dec;9(4):943-64.
5. Smith VJ. Liver Transplant. Available at: http://www.hepatitisneighborhood.com/content/
understanding_hepatitis/treating_hepatitisc_137.aspx.
Accessed August 19, 2004.
6.Scientific Registry of Transplant Recipients. Fast Facts About
Transplants: January 1, 2003 – December 31, 2003.
John Martin is a long-time health journalist and an
editor for Priority Healthcare. His credits include coverage of health
news for the website of Fox Television's The Health Network, and articles
for the New York Post and other consumer and trade publications.
http://www.hepatitisneighborhood.com/content/in_the_news/archive_2036.aspx
Donor age, hepatitis C virus infection and 10-year liver graft histology |
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| Donor age is a strong factor influencing the long-term histological outcome of liver grafts, find investigators in the latest issue of the Journal of Hepatology. | |||
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| Factors influencing the long-term histological outcome of liver grafts are not known. In this study, investigators from France assessed 10-year liver biopsies to identify the main factors influencing long-term graft histology. They evaluated 270 of 423 patients who still had their first functional graft 10 years after liver transplantation. All biopsy slides were reviewed by 2 pathologists. The investigators found fibrosis in 54% of patients and ductopenia in 29%. They determined that ductopenia was independently related to higher donor age.
The severity of fibrosis was influenced by hepatitis C virus (HCV) infection, hepatitis B virus (HBV) recurrence, and higher donor age. The team found that 30% of biopsies showed minimal-change lesions which were associated with the absence of HCV or HBV infection, and lower donor age. Dr Kinan Rifaia and colleagues concluded, "Post-transplant infection by HCV or HBV are main factors influencing the histological course of liver graft". "Donor age was also a strong factor in HCV infected patients as well as in HCV-negative patients". "This variable should be taken into account, particularly for candidate recipients with long life expectancy".
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J Hepatol 2004; 41(3): 446-53 27 August 2004 |
Consumption of Dietary Supplements in a Liver Transplant
Population
The extensive use of
alternative medicine products, herbal remedies, and
vitamins in large doses has reached an all time high in the
general public. Some agents are reported and advertised as immune
stimulants and may interfere with patients suffering from immune
modification, autoimmune diseases, or
transplant recipients.
In this report, researchers present an investigation into the use of herbal remedies and vitamins in their liver transplant population.
The researchers performed an investigation using a questionnaire to determine the use of herbal products and vitamins in their liver transplant population. Medical records were reviewed for each liver transplant recipient that admitted to consuming herbal products or vitamins.
Information collected included patient demographics, transplant related information, laboratory tests, outcomes, and herbs or vitamin products used. A total of 290 patients completed and returned the questionnaire.
They found 156 admitting to taking more than a standard multivitamin and/or an herbal remedy. All patients were treated with steroids for allograft rejection and experienced a recurrence of amino transaminases following the removal of steroids.
Further investigation into dietary supplements using a patient questionnaire form revealed that nearly 50% of patients admitted to using vitamins following transplantation, while 19% used herbal remedies combined with vitamins, most admitting to silymarin.
One recipient was ingesting colostrum and required admission for the management of allograft rejection, while 5 patients had consumed large amounts of echinacea or CoEnzyme Q-10 and experienced elevations in their transaminases that resolved with discontinuation of the herb.
The review also identified 4 patients with primary biliary cirrhosis and with transaminase elevation (mean values of aspartate aminotransferase and alanine aminotransferase levels of 88 and 95, respectively).
All recipients were consuming vitamins, in particular high doses of vitamin E (tocopherol), more than 1 gram per day. All of the transplant recipients were instructed to discontinue all vitamin E products and the amino transaminases resolved over the following 30 to 60 days.
"In conclusion, write the authors, "This information reveals that a significant proportion of our liver transplant recipients consumes herbal remedies. The results of this report suggest that transplant teams need to question each recipient about the use of herbal and vitamin remedies and educate them regarding the potential hazards."
Department of Medicine, Surgery and Nutrition, University of Miami, Miami, FL.
08/16/04
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Reviewed Sep 20 2004
Liver
