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Editorial Board: Emmet B. Keeffe, MD (Chair); Anna Lok, MD; Brian McMahon,
MD; Albert Min, MD; Myron Tong, MD; Naoky Tsai, MD; Bruce Tung, MD |
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HBV
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Timely Information for Practicing Physicians |
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MARCH 2005
CHRONIC HEPATITIS B AND KIDNEY
TRANSPLANTATION ― Guest Editorial, Brian McMahon, MD
Since the 1977 release of guidelines
from the Centers for Disease Control and Prevention (CDC) to prevent
transmission of hepatitis B virus (HBV) infection in dialysis units, the
incidence of chronic hepatitis B in patients with end-stage renal disease has
significantly declined. However, the
management of HBV infection in patients with kidney failure remains an
important clinical issue, since the presence of chronic hepatitis B is
associated with decreased patient survival after kidney transplantation (Mathurin P. Hepatology 1999;29:257-263). Although chronic hepatitis B is
not a contraindication for kidney transplantation, all potential kidney
transplant recipients with HBV infection should undergo complete evaluation,
which may include liver biopsy to assess the severity of liver disease. Patients
with underlying cirrhosis should be considered for combined liver-kidney
transplantation, if liver failure and criteria for liver transplantation are
present, as isolated kidney transplantation may be associated with hepatic
decompensation or complications of portal hypertension. Generally, patients
with compensated cirrhosis can be followed carefully and only considered for
liver transplantation when they meet the classical minimal listing criteria. There is no consensus on the optimal choice
of antiviral medication and the timing or duration of therapy in kidney
transplant recipients with chronic hepatitis B.
The risk of significant hepatic injury after kidney transplantation
correlates with the HBV DNA titer pretransplant. Therefore, patients with
chronic hepatitis B and active disease―based on elevated alanine
aminotransferase (ALT) levels, high HBV DNA titers, and active disease on liver
biopsy―should be treated with antiviral agents before proceeding to
transplantation. Lamivudine is the best-studied
medication in this setting, having been shown to be safe and effective in
preventing liver injury after kidney transplantation (Fabrizi F, et al. Transplantation
2004;77:859-864). In post–kidney transplant patients, interferon therapy
is associated with a high risk of precipitating rejection of the renal
allograft and should generally be avoided.
Most transplantation centers recommend initiating lamivudine therapy in
the pretransplant or early post-transplant period to prevent reactivation of
hepatitis B. Nonrandomized studies have suggested that early lamivudine
therapy, starting in the pretransplant or early post-transplant period, improves
survival, as compared with delaying therapy until active hepatitis B develops (Chan T, et al. Hepatology 2002;36:1246-1252). Although the rate of
development of lamivudine-resistant mutations appears to be even higher in
kidney transplant recipients than in immunocompetent patients, the development
of resistance does not always lead to clinically significant events (Thabut D,
et al. Eur J Gastroenterol Hepatol
2004;16:1367-1373). All patients should
be closely monitored so that additional therapy can be implemented if
clinically indicated. To date, there are no data on the use of adefovir or
entecavir in the setting of kidney transplantation, but these are areas that
deserve further study.
HBV in renal transplant
recipients. The prevalence of HBV infection is
higher in renal transplant recipients than in the general population, and HBV
is a significant cause of mortality and morbidity after renal
transplantation. Recent studies indicate
that lamivudine is an effective treatment for HBV in patients who have
undergone renal transplantation, but there is little information regarding its
long-term use in this population. Dominique Thabut and colleagues report the
long-term follow-up of 14 consecutive renal transplant patients treated with
lamivudine for chronic HBV in their hepatogastroenterology unit (Hôpital Pitié-Salpétrière,
LAMIVUDINE THERAPY
Treatment of acute, severe hepatitis
B. Hemda Schmilovitz-Weiss and coworkers
investigated the safety and efficacy of lamivudine for the treatment of acute,
severe HBV infection in a pilot study of 15 patients. Lamivudine 100 mg daily was started 3–12
weeks after the onset of infection and continued for 3–6 months. All patients had severe coagulopathy (mean
INR, 4.5), with mean ALT 3738 U/L and total bilirubin 18 mg/dL, and 5 patients
had grade 1–4 encephalopathy. Therapy was well tolerated, and 13 patients responded
to treatment. Virologic response
(undetectable serum HBV DNA) was associated with improvement of coagulopathy,
resolution of encephalopathy, and normalization of liver enzyme levels. The results of this small study suggest that
lamivudine may prevent the progression of severe, acute hepatitis B. Further large, prospective studies are
warranted. (Schmilovitz-Weiss H, et al. Liver Int 2004;24:547-551)
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