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Q: Liver Transplants - Complications ( Answered 5 out of 5 stars,   0 Comments )
Subject: Liver Transplants - Complications
Category: Health
Asked by: sogoam-ga
List Price: $30.00
Posted: 06 Nov 2003 02:10 PST
Expires: 06 Dec 2003 02:10 PST
Question ID: 273105
What are the top 5 complications to liver transplants in the adult
population in the US, Western Europe, and Japan?

Request for Question Clarification by czh-ga on 06 Nov 2003 13:00 PST
Hello sogoam-ga,

I've worked on your other questions and I didn't find much to
differentiate the rate of complications based on geographic
differences among the US, Europe and Japan. Complications are much
more likely to be classified according to the type of condition
leading to the liver transplant -- especially elective vs. emergency.
Success rates (and associated complications rates) are also greatly
effected by demographic factors (age, race, gender) and the
institution performing the transplant. I'd love to help you with your
research project but the way you're asking your questions is not the
way the statistics seem to be compiled.

I look forward to your clarification.

~ czh ~

Clarification of Question by sogoam-ga on 11 Nov 2003 16:06 PST
Dear CZH,

Thank you for your excellent efforts to attempt to help.  I will try
to clarify.  I need to know the most prevelant reasons that a liver
transplant in an adult FAILS.  It is due to an artery getting blocked
off?  It is due to a lack of oxygen getting to the new organ?  Is it
due to a certain enzyme in too low a level?  What are the early
indications that a liver transplant is going to fail?  It is
interesting to know that they fail more often post emergency
transplant, but I am MOST interested in the REASON that they fail. It
is less important to know where the patients reside, and similarly
less important to know the demographic features...but I need to know
why.  Please let me know what is possible.
Subject: Re: Liver Transplants - Complications
Answered By: czh-ga on 12 Nov 2003 16:18 PST
Rated:5 out of 5 stars
Hello sogoam-ga,

Thank you for the clarification. It helped me to focus the search on
this extremely complex topic. Liver transplantation becomes the
treatment of choice for those suffering from liver failure. Liver
failure can be caused by a variety of conditions and the condition
causing the liver failure will impact the survival rate and likelihood
of complications after transplant.

Liver transplantation is most commonly performed from deceased donors
but in recent years living-donor transplantation has emerged as an
option. There isn?t very much information available yet on the
difference in complications for the recipient from living donors but
there are risk factors to consider for the donor.

The likelihood of complications is affected not only by the medical
condition causing the liver failure but also by demographic factors,
i.e., age, race, gender. The differences in risk factors and likely
outcomes because of the demographic factors are not well understood.

Liver transplantation is a very complex procedure. It requires
suppressing the immune system?s effort to reject the transplanted
organ. Suppressing the immune system is dangerous because it leads to
both bacterial and virological infections. Acute rejection of the
transplant and infections are the two primary complications in liver
transplants. Acute kidney failure, biliary problems, artery thrombosis
and bleeding are other significant complications.

Trying to collect comprehensive statistics on post-transplant
complications is extremely difficult because of the number of
variables involved. I?ve collected a sampling of articles and research
abstracts to help you get an overview of the topic. You can continue
your research at the various liver transplant resource sites I?ve
provided in this and in my two prior answers.

I hope this information will be helpful to you. 

~ czh ~

LiveR -- Post-transplant 

After the transplant operation, it is likely you will stay in hospital
for a further three weeks while you are monitored for complications. A
liver transplant is major surgery, and you should not be surprised to
experience a few small problems. Most of these will be minor and easy
to manage, but there are some more serious worries that can occur.

 Bile Duct leaks
 Biliary Tract complications
 Hepatic Artery Thrombosis
 Neurological Complications
 Primary Dysfunction

***** This site gives you a good overview of each of these possible complications.

Surgery Encyclopedia ? Liver Transplant
 -- Who is a candidate for the procedure?
 -- How is the procedure performed?
 -- What happens right after the procedure?
 -- What happens later at home?
 -- What are the potential complications after the procedure?

***** This is an excellent article that reviews the complete liver
transplant process.

Solid Organ Transplantation: Overview of Kidney and Liver Grafts

The most frequent complications faced by hepatic allograft recipients
in the first days to weeks post-transplant are thrombosis, infection,
and acute renal insufficiency. Thrombosis of the hepatic artery and/or
portal vein secondary to intimal injury occurs in 5% to 10% of cases
and is more frequent in pediatric recipients because of their small
vessel sizes. About 40% to 50% of liver transplant recipients will
experience an acute rejection episode. Although the majority of
centers use tacrolimus as their preferred calcineurin inhibitor, the
typical medication "cocktail" varies from center to center.74,75

Identification of the optimal regimen is challenged by the observation
that there is not a good correlation between an acute rejection
episode and outcome. In fact, the realization that patients survive on
less immunosuppression has lead to the withdrawal of a number of
agents at various time points following transplantation. The real
question comes down to which agent should be withdrawn considering the
long-term toxicities of the various agents, especially their impact on
the pediatric population.76,77

A major complication following liver transplantation is infection.78
Risk factors include extensive abdominal surgery, malnutrition, and
impaired host immunity. Also, poor early allograft function can
compromise the liver's normal function of preventing bacterial
translocation from the small bowel. Immunosuppression can also
increase the risk for post-transplant infection.79

Bleeding into the peritoneal cavity is a risk factor for bacterial or
fungal peritonitis, predominantly with gram-negative enteric flora and
Candida albicans. Persistent viremia and reinfection of the graft is a
common complication for patients undergoing transplantation for the
treatment of end-stage liver disease resulting from infection with
hepatitis B virus (HBV) or hepatitis C virus (HCV). Without effective
prophylaxis, reinfection may lead to progressive liver failure.80

Acute renal insufficiency occurs after liver transplantation in up to
40% of recipients. Contributing factors include pre-existing renal
insufficiency, poor early allograft function, and administration of
nephrotoxic drugs (including CsA or tacrolimus) in the immediate
post-transplant period.81

Chronic rejection is distinctly different from acute rejection in that
it develops slowly and is not treated effectively by intensifying
immunosuppressive therapy.82 Frequently, chronic rejection presents as
obstructive jaundice without other major liver abnormalities.
Clinically, chronic rejection of the liver allograft will present as
"Vanishing Bile Duct Syndrome."

Malignancy and disease recurrences are the major causes of late
mortality among adult orthotopic liver transplant recipients.83

Transplants -- Liver

The most common problems in the liver transplant recipient, which may
be observed in the ED, are acute graft rejection and infection.
Adverse effects of immunosuppressant drugs also may complicate the
patient's presentation. Chronic graft rejection, manifested by gradual
obliteration of small bile ducts and microvascular changes, occurs in
about 5% of patients. However, rejection generally is not an acute
presentation. Acute rejection occurs in 20-70% of cases and results in
graft dysfunction. Acute rejection is represented clinically as
jaundice with laboratory evidence of abnormal liver function tests.
Bilirubin and alkaline phosphatase rise initially, followed by
elevations in hepatocellular enzymes alanine aminotransferase (ALT)
and aspartate aminotransferase (AST).

Infection in the early posttransplant period most commonly is
bacterial. Infections frequently are intraabdominal and typically are
observed during the posttransplant hospitalization. The most common
causes of infection in the outpatient setting are the typical
community-acquired pathogens, which are treated with antimicrobials
typically prescribed for nonimmunosuppressed patients (with caution on
drug interactions). Incidence declines after 6-12 months if the
recipient is on a stable immunosuppressant regimen.

Cytomegalovirus (CMV) is the most common viral infection, occurring
most commonly between the first and third posttransplant months.
Transplant recipients may be placed on long-term pneumocystic
suppression therapy with trimethoprim-sulfamethoxazole. However, this
infection typically is a problem when immunosuppression is more
severe, such as during treatment of rejection. Fungal infections peak
in incidence 1-2 months after transplant. After that time, these
infections tend to be problematic during more intense

When recipients are on increased immunosuppression therapy for
combating rejection, other less-common opportunistic pathogens may be
involved. These include fungi (especially Candida species), herpes
simplex, herpes zoster, Pneumocystis carinii, and toxoplasmosis.
Nephrotoxicity may result from cyclosporine or tacrolimus use and may
occur at usual therapeutic levels. Hyperkalemia, hypervolemia, and
hypertension may occur.

19 Sep 1999 -- American Society of Transplant Surgeons
Causes of Late Mortality in Survivors of Liver Transplantation

This study was undertaken to determine the incidence, timing, and
causes of death in patients who have survived more than one year after
liver transplantation (LT).

Methods: A retrospective study of 686 patients who survived more than
one year after LT revealed 127 patients (18.5%) subsequently died
(median f/u = 5.2 years). The causes of death are listed in the table
below. Univariate analysis using the Cox Proportional Hazards model
was used to determine if age, gender, primary disease, and length of
survival were predictive for the causes of death.

Results: The 10-year actuarial survival was 71% (based on 100%
survival at one year). The four most common causes of death were graft
failure, malignancy, recurrent disease and cardiac disease. Age and
male gender were the only risk factors affecting cause of death.

What is the most common cause for organ (liver) rejection?
JSG: Organ rejection is a very complex problem. It is due to
overstimulation of the immune system, which in turn sets off a chain
reaction of events within the liver, which ultimately leads to liver

What are the odds of rejecting a transplanted liver?
JSG: Seventy-five percent of all patients coming to liver
transplantation survive the first year after transplantation. Most
centers report that over 95% of their patients who survive the first
year survive each year after the first. However, rejection occurs in
as many as 50-to-80 percent of all those undergoing liver
transplantation, and must be managed. The early cases of rejection can
be easily treated with appropriate medications. The loss of the liver
due to severe damage will occur in 5 to 10 percent of the cases.

Organ transplant recipients face serious kidney-failure risk, study finds
Anti-rejection drugs and pre-transplant health problems both play a role
3-SEP-2003 -- University of Michigan Health System

Kidney Failure a Major Problem in Transplants
Drugs that fight rejection increase risk

WEDNESDAY, Sept. 3 (HealthDayNews) -- Kidney failure is a disturbingly
high risk for all transplant patients, says the largest survey ever
Ironically, the major cause of those kidney failures is an unavoidable
side effect of the rejection-suppressing drugs that made
transplantation possible, experts say.
"The five-year risk of chronic renal [kidney] failure after
transplantation of a non-renal organ ranges from 7 to 21 percent,
depending on the type of organ transplanted," says a report in the
Sept. 4 issue of the New England Journal of Medicine by transplant
specialists at the University of Michigan.

Biliary tract complications following liver transplantation.
Transplant Proc. 2003 Sep;35(6):2316-7

INTRODUCTION: Biliary tract complications, which occur in 5.8% to
24.5% of adult liver transplant recipients, remain one of the most
common problems following transplantation. The aim of this study was
to evaluate these problems and analyze methods of treatment.

Liver Diagnosis Categories

Transplantation Proceedings 
Volume 34, Issue 1, February 2002, Pages 290-291
Recipient factors analysis in long-term allograft survival of liver

Liver allograft survival can be influenced by several factors that
could participate in transplant outcome, independently of other
elements such as HLA matching. Indeed, influences on transplant
outcomes are complex: the role of a single factor can be confounded by
many considerations other than immunosuppression. Therefore, not all
recipients should be considered to be at equal risk at the time of
liver transplant. Additional risk factors have been reported in
several studies, including transplantation for primary sclerosing
cholangitis,[1] for autoimmune diseases such as primary biliary
cirrhosis, [2] for certain patterns of HLA mismatch between donor and
recipient, [3, 4, 5 and 6] accompanied by cytomegalovirus infection,
[7] between donor and recipient of different ethnic origins, [8] in
the absence of azathioprine in the immunosuppressive regimen, [9]
based on donor age and gender, [10 and 11] and in retransplants. [12]

Results and discussion
The primary indications for liver transplant lead to differential
outcomes: recipients with fulminant hepatitis as a cause of liver
failure showed reduced survival rates in contrast to other recipients
(33% v 59%, P = .047) (Fig 1A). Although primary sclerosing
cholangitis and primary biliary cirrhosis[1 and 2] have also been
reported as risk factors in liver transplantation, we did not identify
this factor due to its low frequency in our recipients. The different
immunosuppressive regimens did not seem to influence allograft
survival (61% CsA vs. 51% CsA+OKT3, P = .59). Neither did recipient
gender appear to play a role on survival (59% female vs. 57% male, P =
.84). With respect to recipient age, 40 to 50 year age group showed
the lowest survival (49%), followed by the 50 to 60 year (52%) and the
over 60 year groups (61%). The highest survival was observed among
recipients of 30 to 40, 0 to 20, and 20 to 30 years (76%, 73%, and
70%, respectively), but the differences were not statistically
significant (P = .42) (Fig 1B), probably because the large number of
groups masked the actual role that could be discovered in a layer
series. The presence of viral infection (VHB, VHC, CMV) itself did not
seem to significantly influence survival rates (54% infection vs 63%
noninfection, P = .78), although it can be important in relation to
partial HLA class I matching as a cause to trigger acute rejection
such as we have recently described.[13] Additionally, in our series
the occurrence of all acute rejection episodes did not clearly
predispose to a reduced long-term allograft survival rate (58%
nonacute rejection vs 57% acute rejection, P = .79), even if recipient
morbidity was seriously affected.

Friday, 25 January, 2002, 12:11 GMT 
'Race role in liver transplants'

An American study has found that race could be a key factor in a
patient's chances of surviving a liver transplant.  The study,
published in The Lancet on Friday, found that African Americans and
Asians did not fare as well as white Americans and Hispanic patients. 
And the study suggests that the rate of graft failure - due to organ
rejection - was nearly twice as high among African Americans  But the
study has not yet been able to pinpoint the reasons for the difference
in recovery rates.


Thomas E. Starzl, MD and colleagues at the University of Pittsburgh
School of Medicine studied 462 liver transplants in order to identify
what donor characteristics increase the risk of failed surgery. Female
sex, in addition to increasing age, boosted the likelihood of an
unsuccessful transplant. An average of 59.5 percent of patients who
received female livers were alive two years later compared with an
average of 75 percent of male organ recipients. Subsequent research
has confirmed this phenomenon.

Instead, variations in the immune system are probably fundamental to
understanding sex-specific responses to transplants. Numerous studies
have confirmed that women wage a much stronger immune response than
men. ?There is an actual difference at the cellular level between how
a woman and a man mount an immune response,? said Dr. Foegh, ?But
beyond sex hormones we still don?t know what accounts for that

Gender Plays Part in Transplant Success
Organs from female donors more likely to be rejected, study finds

FRIDAY, Nov. 8 (HealthDayNews) -- If you are facing a transplant, you
might want to ask about the gender of the donor organ.

A German study found that people given organs from female donors are
more likely to reject the organ and have higher death rates compared
to people who get organs from male donors. The report appears in a
recent issue of the Journal of the American Society of Nephrology.
The study also suggests that female transplant patients have a higher
organ rejection rate than men.

The study says that gender may also be a factor in the success of
liver transplants, but the results were unclear. When they analyzed
data from around the world, the researchers found no gender
difference. But they did find a gender difference in North America,
where men who received livers from female donors had a greatly reduced
chance of success.

The researchers say it's not known how gender affects organ
transplants. One theory is that there are differences in male and
female immune systems.

2003-02-26  -- Complications in liver donors said fairly common

NEW YORK (Reuters Health) - Liver-tissue transplants from living
donors are increasing in the US, and although deaths among donors are
rare, complications are "not uncommon," researchers reported

Their study of US liver-transplant programs found that the number of
adult-to-adult transplants involving a living donor jumped from one in
1997 to 266 in 2000.

During this period, one of 449 donors died, while 14.5% suffered a
complication, more than half of whom needed to be rehospitalized. Bile
leakage from the "cut edge" of the donor's liver, which sometimes
requires surgery, was the most common problem.

Medline Plus Health Information -- Liver Transplantation

***** This is an excellent source for current articles and lots of
background information.


Manual of Liver Transplant Medical Care
ISBN 1-57749-115-7
Spiral bound $30.00 
To order, call Fairview Publications at 1-800-544-8207. 
Or visit our Web Site at

Written by the University of Minnesota Physicians Transplant Program
and Fairview Health Services, the Manual of Liver Transplant Medical
Care is an essential reference for referring and primary care
physicians. It outlines the optimal procedures to follow in the care
of the liver transplant recipient beginning prior to the time of first
referral and continuing through the rest of the recipient's
postoperative life.

***** See especially Chapters 3 and 4. The links provide brief
summaries of all topics included in the table of contents.

Transplant Living is a project of the United Network for Organ Sharing
(UNOS), a nonprofit organization that maintains the national Organ
Procurement and Transplantation Network (OPTN) under contract with the
Health Resources and Services Administration of the U.S. Department of
Health and Human Services.
Organ Facts ? Liver

***** This is a new website from UNOS offering a wide variety of
resources for transplant patients.

Scientific Registry of Transplant Recipients

Transplant Statistics: Annual Report : Data by Category

Liver Transplant Results at Mayo Clinic in Rochester

Mayo Clinic's results with liver transplantation are among the best in
the world. The results of a transplant program can be measured in many
ways. The most common comparative numbers include:
 -- The number of transplants performed. 
 -- The percentage of transplant recipients who are alive at specific
time points after surgery.


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sogoam-ga rated this answer:5 out of 5 stars
Great sources - will certainly be of value!

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