After
liver transplantation, hepatitis B virus (HBV) can recur if preventive measures
are not employed, including use of HBV immune globulin (HBIG) and drugs active
against the virus.
Previous
studies have shown that HBV DNA can be detected in biopsies of the new liver in
patients who had transplants due to hepatitis B, despite the absence of serological
markers of HBV recurrence. However, quantification of HBV DNA was not performed
and the presence of covalently closed circular (ccc) DNA was not analyzed in most
transplant studies.
As
presented at the 57th AASLD annual meeting taking place this week in Boston, researchers
aimed to quantify intrahepatic total and ccc HBV DNA in explants (old removed
livers) and new livers after transplantation, and to determine its association
with HBV recurrence.
Explant
livers from 18 patients and post-transplant biopsies from 26 patients were analyzed.
Total and ccc HBV DNA were quantified using real time PCR. Serum HBV DNA was quantified
using the COBAS Amplicor assay.
Results
Among the 18 patients whose explant livers were assessed, 7 were HBeAg positive,
8 had detectable serum HBV DNA, and 10 were receiving antiviral therapy prior
to transplantation.
Total HBV DNA was detected in 17 and ccc DNA in 16 of these patients.
HBeAg positive patients had higher concentrations of ccc DNA (-1.87 vs -3.27 log
copies/cell; P = 0.037) and higher ratios of ccc to total HBV DNA (11.7% vs 3.1%;
P = 0.04) compared with HBeAg negative patients.
After a median follow-up of 18 months (range 5-35), 2 patients (11%) had HBV recurrence.
In these
individuals, the mean serum HBV DNA level at the time of transplantation was higher
than in patients without recurrence (8.79 vs 5.2 log copies/mL; P = 0.046).
Concentrations of total and ccc HBV DNA were also higher in these 2 patients,
but the difference was not statistically significant.
51 biopsies from 26 patients collected between 7 days and 48 months post-transplantation
were studied.
8 patients had detectable total (16/16 biopsies) and ccc (12/16 biopsies) HBV
DNA in their biopsy samples; among these patients, 2 experienced HBV recurrence.
14 patients
had detectable total (27/30 biopsies) but not ccc (0/30 biopsies) HBV DNA; one
of these experienced HBV recurrence.
4 patients had no detectable total or ccc HBV DNA in any of their biopsy samples;
none experienced HBV recurrence.
The concentrations of total and ccc DNA in post-transplant biopsies were 2.7 and
1.2 log lower than in explant livers.
All 3 patients with HBV recurrence were HBeAg positive prior to transplantation,
compared to only 3 of 20 patients without recurrence (P = 0.001).
All 3 patients with HBV recurrence had detectable total HBV DNA in their post-transplant
biopsies, compared to 19 of 23 patients without HBV recurrence.
2 of the 3 patients with HBV recurrence had detectable ccc DNA in their post-transplant
biopsies compared to 6 of 23 without HBV recurrence (P = 0.215).
Conclusion
"Total
and ccc HBV DNA could be detected in the explant livers of most patients with
hepatitis B, including those who had undetectable HBV DNA in serum," the
researchers wrote in conclusion. "Total but not ccc HBV DNA could be detected
in post-[transplant] liver biopsies of most patients despite undetectable serum
HBV DNA and HBsAg. Detection of HBV DNA in explant liver or post-[transplant]
biopsies does not predict HBV recurrence [after transplantation]." Internal
Medicine, University of Michigan, Ann Arbor, MI; University of Florida, Gainesville,
FL; Mount Sinai Medical Center, New York, NY; Virginia Commonwealth University,
Richmond, VA.
10/31/06 Reference M
Hussain, C Soldevila-Pico, S Emre, and others. Presence of intrahepatic (total
and ccc) HBV DNA is not predictive of HBV recurrence after liver transplant (OLT).
57th AASLD. October 27-31, 2006. Boston, MA. Abstract 786.
After
liver transplantation, hepatitis B virus (HBV) can recur if preventive measures
are not employed, including use of HBV immune globulin (HBIG) and drugs active
against the virus. 
Among the 18 patients whose explant livers were assessed, 7 were HBeAg positive,
8 had detectable serum HBV DNA, and 10 were receiving antiviral therapy prior
to transplantation. 
