|
Outcomes among Patients with End-Stage Liver Disease Who Are Coinfected
with HIV and Hepatitis C Virus
Coinfection
with hepatitis C virus (HCV) and HIV is common in at-risk populations
because of shared routes
of transmission. In some high-risk populations, such as injection
drug users, rates of concordance between HIV and HCV infection as high
as 60% 80% have been observed.
In
the years before HAART was available, death from
opportunistic
infections caused by AIDS was the leading concern for HIV-infected patients. The
advent of HAART, however, has allowed patients infected
with HIV to restore and retain immune function,
increasing life span and enabling the emergence
of morbidity
and mortality due to other causes.
Bica
et al. demonstrated that, by the late 1990s, end-stage liver
disease (ESLD)
or cirrhosis
was the underlying
cause of nearly 50% of deaths observed in
HIV-infected populations.
Cirrhosis
is a serious liver condition characterized by
irreversible scarring of the liver that can lead
to liver failure and death. Progression to ESLD
in HCV-monoinfected patients typically takes 2030 years after
initial infection.
With
HIV coinfection, this process is accelerated. The mechanisms underlying
this process are unclear, although HAART-related hepatotoxicity, concomitant alcohol
use, and immune
reconstitution have been implicated.
HIV-HCV Coinfected Patients and Liver Transplantation
Given
their faster rates of progression and relatively
poor rates of response to treatment for HCV
infection, coinfected patients with ESLD are now
increasingly being considered as candidates for orthotopic
liver transplantation in several transplantation centers.
Survival
results in HIV-infected patients with ESLD,
in general, appear promising, although improving survival
in patients coinfected with HCV and
HIV remains a challenge.
It
has been predicted that the prevalence of coinfected
patients with decompensated cirrhosis will increase
over the next several years and further strain
the limited resources of institutions that perform
liver transplantation.
In
this article, the authors evaluate the medical and ethical
aspects of liver transplantation, treatment of
cirrhosis in coinfected patients, and the importance
of a team approach with the management of
liver disease in the population of coinfected patients.
HAART-related
toxicities have been implicated, especially when
given to patients with viral hepatitis. Rates of
response to treatment for HCV infection in coinfected
patients continue to lag behind those in monoinfected
patients, even with the advent of pegylated
interferons.
Liver
transplantation has been approached with caution in
this population because of concern about the sequelae
of
immunosuppression and HAART-related hepatotoxicity,
and results have been conflicting.
Progression of Cirrhosis
The duration of the advance of cirrhosis
from compensated to decompensated is often asked
by patients but remains very difficult to
predict. Patients with chronic hepatitis C without
coinfection tend to progress to ESLD over the
course of 2030 years,
whereas coinfected patients have increased rates of
progression. Time is of the essence when
defining which coinfected patients should undergo transplantation
quickly and which can be maintained with treatment.
The key point is that a greater proportion
of coinfected than monoinfected patients is likely
to advance to ESLD and that this will occur
more quickly in the coinfected population.
Assessment of Liver Transplantation to Date in HIV Positive
Patients
Reports from the University of Pittsburgh
and the University of Miami in the HAART era
reveal a marked improvement in survival, considerably
fewer issues with post-transplantation morbidity,
and a better appreciation of complex drug interactions
with the HAART regimens. These results suggested that
HIV should no longer be considered an absolute
contraindication for orthotopic liver transplantation
in coinfected patients.
The Pittsburgh group has the most experience
to date in orthotopic liver transplantation
in coinfected patients, with 26 patients over an
8-year period. They report that 1 survivor
is nearly 6 years removed from time of transplantation
and that the 1-year patient survival rate
(85%) is very similar to that among non-HIV-infected
patients.
However, the King's College group reported
very poor graft and patient survival among patients
coinfected with HCV and HIV. It should be
noted that survival rates among HCV-monoinfected transplant
recipients also differ between centers. An important
point of difference may be the different antiviral
therapies used to treat recurrence of HCV among
the various centers.
A multicenter, National Institutes of Healthsponsored
trial led by the University of California, San
Francisco transplantation team is investigating
treatment outcomes and survival in coinfected patients
undergoing orthotopic liver transplantation or
kidney transplantation.
This trial has several objectives, including
proving safety and efficacy of liver transplantation
for coinfected patients with ESLD. The study anticipates
enrolling 150 kidney transplant recipients and
125 liver transplant recipients over the course
of 3 years, with 25 years of
follow-up.
It is hoped that this ambitious study
will offer a clearer perspective on the outcomes
that should be expected when coinfected patients
undergo transplantations and will give important
insights as to how HAART regimens interact with
immunosuppressive medications.
Conclusions
In conclusion the authors write, In conclusion,
as immunosuppression protocols, antiretroviral treatments,
and diagnostic tests for cirrhosis improve, the
outlook for transplantation in coinfected patients
can only improve as well.
A multidisciplinary approach involving hepatologists,
HIV specialists, and surgeons in the clinical management
of coinfected patients undergoing liver transplantation
will help prevent unnecessary drug interactions.
This setting revealed improved long-term
post-transplantation survival, as has been shown at
the University of Miami.
Future studies will be required to assess
quality of life and long-term outcomes in coinfected
transplant recipients.
06/17/05
Reference
G
W Neff, N J Shire and S M Rudich.
Outcomes among Patients with End-Stage Liver Disease Who Are Coinfected
with HIV and Hepatitis C Virus. Clinical Infectious Diseases 41(1):
Supp 50-55. July 2005.
|
