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The Ultimate Gift
A
newsletter from the transplant team
at Rhode Island Hospital
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Hepatitis C in Renal Transplantation
by Angelito Yango, Jr., MD
Hepatitis C virus (HCV) is highly prevalent among patients with
end stage renal disease (ESRD) affecting as much as 10-20% of patients
on hemodialysis. This is significantly higher than in the general
population and as a result, a considerable number of patients referred
for transplant evaluation are infected with hepatitis C with a prevalence
ranging from 12-40%. In fact, HCV infection has now emerged as the
leading cause of chronic liver disease in renal transplant patients.
Pre-transplant hepatitis C infection is associated with an increased
risk of developing post transplant liver disease. Twenty to 60%
of patients have sustained elevations in serum transaminases, and
in a majority of patients, there is a sustained viremic state. Histologic
evidences of disease progression have also been documented in some
series of patients undergoing liver biopsies. There is however no
correlation between the degree of transaminitis, viral titers and
extent of liver disease so that in most cases, a liver biopsy is
required to fully asses the extent of the disease as well as to
establish prognosis.
The natural history of hepatitis C infection in renal transplant
recipients remains inadequately defined and its effects on patients
and graft survival controversial. Conflicting results may in part
be due to differences in study design, length of follow up and mode
of HCV screening. Perreira et al reported a 1.41 relative risk of
death from all causes and a 2.39 relative risk of death due to liver
disease or infection among HCV positive recipients compared to HCV
negative recipients (Pereira BJ. KI 51:981,1997). Similarly, Hanufasa
et al have shown a decline in survival rate post transplantation
among HCV positive recipients compared to HCV negative patients
(63.9% vs. 87.9%) (Hanufasa T. Transplantation 66: 471, 1998). This
poor survival rate was mainly due to liver disease but was apparent
only after the second decade post transplantation.
Graft survival is another area of concern among HCV positive transplant
patients. Whether HCV infection confers an independent risk for
acute rejection is a controversial issue. Correll et al reported
a significantly lower rate of acute rejection in HCV positive patients
which was ascribed to a reduction in naive T helper cells in HCV
positive patients (Corell A. Lancet 346: 1497, 1995). In most other
studies including more recent series, there seems to be a trend
towards lower graft survival especially after a sustained follow
up of greater than 5 years suggesting that the deleterious effects
of HCV on patient and graft survival occur after an extended follow
up.
Despite suboptimal long-term results of kidney transplantation
in HCV positive patients, kidney transplantation remains a viable
option for HCV positive patients with ESRD. Knoll et al recently
showed better survival outcomes for HCV positive renal transplant
recipients compared to HCV positive patients who were acceptable
transplant candidates but had not yet received a kidney transplant
(Knoll G. AJKD 29: 608, 1997). Similarly, Roth et al demonstrated
excellent short term results in a small cohort of HCV positive renal
transplant patients who were followed prospectively for ~12 months
with no episodes of fulminant or subfulminant liver failure (Roth
D. Transplantation 61: 886. 1996). Therefore, at least on a short
term, HCV positive patients with ESRD stand to benefit from kidney
transplantation.
There is at present insufficient data to guide decision making
for HCV positive patients with ESRD who are being evaluated for
transplantation. Because serum transaminases are insensitive markers
in identifying significant liver disease, a liver biopsy should
be strongly considered part of the pre-transplant evaluation. Patients
with mild inflammation and fibrosis may be listed for transplantation
while patients with significant cirrhosis should be advised against
transplantation because immunosuppression may significantly increase
the risk of progression of liver disease, HCV positive patients
awaiting transplantation may benefit from a trial of interferon
alfa 2a (IFN) treatment. IFN treatment in combination with ribavarin
has been shown to induce biochemical and virologic response in as
high 40% of patients. However, sustained response is limited with
relapse rates as high as 50%. Side effects are also poorly tolerated
often leading to discontinuation of treatment in a significant number
of patients.
Recently, use of peginterferon alpha-2a has been shown to induce
a higher rate of virologic response compared to unmodified interferon
alpha 2a. Treatment response is also influenced to a large extent
by viral genotype. Patients infected with genotype I show poor response
to IFN therapy compared to those with genotypes 2 or 3.
Experience with the use of IFN in renal transplant has been disappointing
mainly due to its limited efficacy in sustaining virologic response
as well as an unacceptably high risk of rejection and graft loss
(25-37%). Because therapy for hepatitis C is limited, management
of HCV positive renal transplant recipients poses a challenge. HCV
positive transplant patients should be followed closely for virologic,
biochemical and clinical evidences of active hepatitis. HCV serologies
and RNA levels should be monitored at least twice a year or more
frequently if clinically indicated. A liver biopsy should be considered
inpatients with chemical or virological evidence of active hepatitis
and information from this should guide in the modulation of immunosuppression.
Whenever possible, immunosuppression should be kept at a minimum
to decrease the risk of infection. Inpatients with rapidly declining
liver function, a liver biopsy should be performed as soon as possible
and therapy with interferon may be considered with provisions for
active surveillance for allograft rejection.
In summary, HCV infection remains highly prevalent among
patients on hemodialysis and may have a negative impact on long-term
transplant outcomes. Limited data not only show that HCV infection
does not affect patient and graft outcomes in the first 10 years
post transplant but also show that transplantation confers better
survival rate than similar patients who remain on dialysis. Therefore,
the presence of HCV infection should not be a contraindication for
kidney transplantation. Because there is, at present, no effective
treatment for HCV in renal transplant recipients, management of
these patients involves close follow up to detect deterioration
in liver function, viral reactivaton and allograft dysfunction as
well as minimizing immunosuppression to prevent infectious complications.
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