Editorial Board:
Anna Lok,
MD; Brian McMahon, MD; Albert Min, MD; Myron
Tong, MD; Naoky Tsai, MD; Bruce Tung, MD
HBV Watch™
Timely Information for Practicing Physicians
MARCH 2003
LAMIVUDINE THERAPY
Compassionate use. H-W Hann and colleagues of the US Lamivudine
Compassionate Use Study Group conducted a multicenter study in which 75
patients with decompensated HBV-related cirrhosis were treated with lamivudine
100 mg daily. Ninety-three percent of
these patients were not candidates for liver transplantation. At baseline, all patients were
HBsAg-positive, 62% were HBeAg-positive, and 64% were HBV DNA-positive by the
branched chain DNA assay. The median
duration of lamivudine therapy was 12.7 months (range, 0.5-33 months). Among HBV DNA-positive patients, 64% became
HBV DNA-negative during lamivudine treatment.
Serum ALT levels normalized in 48% of patients, and the median
Child-Pugh score improved from 10 at baseline to 8 during therapy. Virologic breakthrough was detected in 8
(18%) of 41 patients treated for a median of 13.1 months (YMDD variant HBV was
found in 3 of 4 patients tested). These
findings demonstrate that lamivudine treatment of patients with HBV-related
decompensated cirrhosis can result in meaningful improvements. (Hann H-W L, et al. Liver Transpl 2003;9:49-56)
Histological outcomes. J Dienstag
et al evaluated liver biopsy specimens from 63 patients with chronic HBV
infection at baseline and after 1 and 3 years of lamivudine treatment. After 1 year of therapy, 36 patients (57%)
had ³2 point improvement in Histological Activity Index (HAI)
scores, and 24 patients (38%) had no change in necroinflammatory activity. After 2 additional years of therapy, 12
patients (19%) continued to improve and 38 patients (60%) remained stable. Among 11 patients with cirrhosis at baseline,
8 patients (73%) showed improvement (HAI score decreased from 4 to £3)
during lamivudine therapy, and only 1 (2%) of the remaining 52 patients
progressed to cirrhosis. In addition,
bridging fibrosis improved (³1 level) in 12 (63%) of 19 evaluable
patients. Worsening HAI scores occurred
in similar proportions of patients with and without YMDD variants; however,
patients with YMDD variants for >2 years were less likely to experience
improved scores. These results show that
long-term lamivudine therapy is associated with improvements in histological
outcomes for most patients with chronic HBV infection, but the emergence of
YMDD variants blunts histological responses.
(Dienstag JL, et al. Gastroenterology 2003;124:105-117)
ANTIBODY TO HEPATITIS
B SURFACE ANTIGEN (Anti-HBs)
Development of anti-HBs after liver transplantation.
C-M Lo and colleagues at the University of Hong Kong Medical Center
observed that 21 (42%) of 50 patients with chronic HBV infection receiving
prophylactic lamivudine therapy without hepatitis B immune globulin after liver
transplantation developed anti-HBs.
Seroconversion to anti-HBs was detected at a median of 8 days after
transplantation (range, 1-43 days), and the anti-HBs titer increased to a
maximum within 3 months. The presence of
anti-HBs was associated with a more rapid clearance of serum HBsAg (p =
0.011). Anti-HBs disappeared in 12
patients at a median of 201 days (range, 24-214 days). Logistic regression
analysis identified an HBV-immune donor as the only independent predictor of
anti-HBs production, suggesting the possibility of adoptive immunity transfer
through the liver graft. These findings
demonstrate anti-HBs may develop spontaneously in patients receiving lamivudine
prophylaxis following liver transplantation for chronic HBV infection. (Lo C-M,
et al. Hepatology 2003;37:36-43)
NOSOCOMIAL HBV
INFECTION
HBV and HCV infection in a pediatric ward.
U Dumpis et al reported that 106 pediatric
patients cared for on a hematology oncology ward were infected with HBV or HCV
from 1996 to 2000. Serum samples from 32
patients were positive for HBV DNA or HCV RNA by PCR analysis, and 10 samples
were positive for both markers. Fifteen
of 19 HBV and 17 of 23 HCV core gene sequences were clustered together,
indicating nosocomial transmission and suggesting that the spread of infection
was probably due to inadequate infection control measures on the ward,
especially with the use of multidose vials.
No new cases of HBV and only 3 anti-HCV seroconversions occurred over a
19-month period following the introduction and strict maintenance of prevention
measures including stopping the use of multidose vials and routine hand hygiene
procedures. (Dumpis
U, et al. J Med Virol
2003;69:331-338)
HBeAg
CLEARANCE
Correlation with serum HBV DNA levels. C-J Chu and
coworkers retrospectively analyzed HBV DNA levels by PCR-based assay in
sequential serum samples of 165 Chinese patients with different stages of chronic
HBV infection. Although HBV DNA levels decreased by a mean of 3 log10
in patients with clearance of HBeAg, 51% of patients still had HBV DNA levels
>105 copies/mL when HBeAg became undetectable. HBV DNA levels at
the time of HBeAg loss were similar in patients with and without anti-HBe
seroconversion, and in patients with and without selection of precore variant.
While HBV DNA values >105 copies/mL excluded all inactive
carriers, 45% of patients with HBeAg-negative chronic hepatitis B had HBV DNA
levels that were intermittently <105 copies/mL. The authors
concluded that it is not possible to define a single cut-off HBV DNA value to
distinguish inactive carriers from patients with HBeAg-negative chronic
hepatitis B. (
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