Low
Risk of HBV Recurrence after Liver Transplantation in Patients Maintained on Antiviral
Therapy
After
liver transplantation, hepatitis B virus (HBV)
can infect the new liver graft if preventive measures are not employed, including
use of HBV immune globulin (HBIG) and drugs active against the virus.
As
presented at the 57th AASLD annual meeting taking place this week in Boston, researchers
conducted a study to determine whether use of anti-HBV nucleoside analogs could
prevent HBV recurrence after patients stopped HBIG.
Out of a total of 866
HBV positive patients who underwent liver transplants at the University of Michigan
at Ann Arbor, the present study included 21 individuals who received at least
7 doses of intravenous HBIG post-transplantation, experienced no HBV recurrence
while on HBIG, and eventually discontinued HBIG and were maintained on nucleoside
analogs, either lamivudine (Epivir)
or adefovir (Hepsera).
The
mean age at the time of transplantation was 49 years, 17 patients were men, 19
were Caucasians, 18 had cirrhosis, and 3 had hepatocellular carcinoma. Immediate
post-transplant prophylaxis consisted of:
HBIG + lamivudine: n = 14;
HBIG + adefovir: n = 1;
HBIG monotherapy: n = 6.
HBIG
was discontinued a median of 26.4 months (range 0.2-121) after transplantation;
all patients were HBsAg negative and had undetectable HBV DNA at the time of HBIG
was discontinuation.
4 patients discontinued HBIG during Year 1, all of whom had low or undetectable
HBV DNA at the time of transplantation.
4 discontinued HBIG in Years 2-3.
13 discontinued after Year 3.
HBV
recurrence was defined as being HBsAg positive on more than 2 occasions at least
1 month apart. A secondary endpoint was the detection of serum HBV DNA greater
than 3 log copies/mL on more than 2 occasions in the absence of detectable serum
HBsAg.
Results
The median follow-up duration after stopping HBIG was 40.2 months.
Only 1 patient experienced HBV recurrence. This individual discontinued HBIG 12
month post-transplantation, was lost to follow-up until Month 46, then presented
with fatigue and tested positive for HBsAg with elevated ALT and HBV DNA of 7.9
log copies/mL.
A second patient had HBV DNA of 3.3 log copies/mL, but with negative HBsAg 47
and 48 months after stopping HBIG.
Emergent lamivudine-resistance mutations were detected in both patients.
4 patients had 1-3 episodes of transiently detectable HBV DNA (maximum 3.8 log
copies/mL), but with negative HBsAg. All 4 had been HBV DNA and HBsAg negative
on repeat tests over a period of 1-34 months.
The cumulative probability of HBV recurrence was 0% at 2 years and 9% at 4 years
after stopping HBIG.
The probability of meeting the combined study endpoints was 0% and 22%, respectively.
Conclusion
In
conclusion, the researchers wrote, "HBIG discontinuation after 3 yrs post-[liver
transplantation] and maintenance on nucleoside analogs is associated with very
low risk of HBV recurrence in compliant HBV patients. Persistent detection of
low levels of serum HBV DNA may be an early sign of HBV recurrence. "
University
of Michigan, Ann Arbor, MI, USA.
10/31/06 Reference
S
N Wong, C Chu, C Wai, and others. Low risk of HBV recurrence post-liver transplantation
(OLT) in patients maintained on nucleoside(t)e analogue (NA)therapy after withdrawal
of hepatitis B immune globulin (HBIG). 57th AASLD. October 27-31, 2006. Boston,
MA. Abstract 782.
HBIG + lamivudine: n = 14;
