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Editorial
Board:
Emmet B. Keeffe, MD (Chair); |
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HBV Watch™ |
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Timely Information for Practicing Physicians |
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February 2004
LAMIVUDINE-RESISTANT HBV
Adefovir dipivoxil therapy.
Eugene
Schiff and others from the Adefovir Dipivoxil Study 435 International
Investigators Group conducted a single-arm, multicenter study in which 324 liver
transplant (LT) patients (128 pre- and 196 post-LT) with recurrent HBV
infection and evidence of lamivudine resistance received adefovir dipivoxil 10
mg once daily. The median duration of
treatment for pre- and post-LT patients was 18.7 and 56.1 weeks,
respectively. Among patients who
received at least 48 weeks of treatment, HBV DNA became undetectable by PCR
assay (< 400 copies/mL) in the serum of 81% of pre-LT patients and 34% of
post-LT patients. ALT levels normalized
in 76% and 49% of pre- and post-LT patients, respectively, and Child-Pugh-Turcotte
scores improved in > 90% of patients in both groups. The 1-year survival rate was 84% for pre-LT
patients and 93% for post-LT patients.
No adefovir dipivoxil resistance mutations were identified in patients
after 48 weeks of therapy. The results
of this large trial confirm the findings of previous pilot studies and show the
clinical benefit of adefovir dipivoxil treatment for patients with
lamivudine-resistant HBV infection in both the pre- and post-LT settings. Fabien Zoulim, in an accompanying editorial, emphasizes that
follow-up beyond 48 weeks of treatment is needed to more fully establish the
clinical impact of adefovir dipivoxil treatment and that results of recent
trials suggest that the design of new clinical studies should evaluate
combination nucleoside therapy in order to deter the long-term development of
resistant mutations. In a second
investigation, Josef Kock and colleagues present
preclinical data demonstrating that the nucleotide analogues adefovir dipivoxil
and lamivudine (as monotherapy or combined therapy) can reduce, but not
completely block, initiation of HBV infection in primary hepatocytes. Thus,
while these drugs are potent inhibitors of viral replication, they cannot
completely eliminate HBV (cccDNA) infection of
hepatocytes. (Schiff ER et al. Hepatology 2003;38:1419-1427. Zoulim F. Hepatology 2003;38:1353-1355. Kock J et al. Hepatology 2003;38:1410-1418.)
HEPATOCELLULAR CARCINOMA (HCC)
Role of reproductive factors.
Ming-Whei Yu et al performed a multicenter case-control study
that included 218 women with HCC and 729 control women to assess the effects of
reproductive factors on HCC risk. The
risk of HCC was found to be inversely related to the number of full-term pregnancies
and to age at natural menopause (P =
0.0216 and 0.0251, respectively).
Oophorectomy at age £ 50 years was a risk for HCC (odds
ratio [OR], 2.57; 95% CI: 1.42-4.63), while the use of hormone replacement
therapy was associated with a lower risk of HCC (OR, 0.46; 95% CI: 0.27 - 0.79). Reproductive factors had a similar impact on
patients who were HBsAg-positive and HBsAg-negative except that an early
menarche (£ 12 vs ³ 16 y) increased the HCC risk in
HBsAg-positive women but had no effect in HBsAg-negative women. These data suggest that increased exposure to
estrogen during adulthood may have a protective effect against HCC. (Yu M-W et al. Hepatology 2003;38:1393-1400.)
Transplantation
Subclinical reactivation of HBV.
Manal Abdelmalek and colleagues reviewed the
outcome of liver transplant recipients with serologic evidence of past
infection with HBV. They identified 35
HBsAg-negative, anti-HBc-positive liver transplant recipients who had available
pretransplantation specimens of frozen serum and
liver tissue for HBV DNA determinations by PCR analysis among the first 693
orthotopic liver transplantations performed at the Mayo Clinic between March
1985 and May 1996. Twenty-two of the
recipients were positive for anti-HBc alone and 13 were positive for both
anti-HBc and anti-HBs; median follow-up time for the 2 groups was 94.9 and 83.2
months, respectively. HBV DNA was
detected in the serum of 6% of patients and in native liver tissue of 29% of
patients. Among the recipients whose native
liver was HBV DNA-positive pretransplantation, 40%
also had evidence of HBV DNA in posttransplantation allograft liver biopsy
specimens. This finding was more common
in patients co-infected with HCV. However, none of the patients became
HBsAg-positive or developed clinical HBV infection posttransplantation. These results suggest that prophylactic
antiviral intervention is not warranted after liver transplantation in
HBsAg-negative, anti-HBc-positive recipients.
(Abdemalek MF et al. Liver Transpl 2003;9:1253-1257.)
Lamivudine Therapy
Extended treatment following
seroconversion. HC Lee et al from the University of Ulsan College of Medicine (Seoul, Korea) conducted a study
in which 49 HBV patients who had achieved HBeAg loss/seroconversion during
lamivudine therapy were allocated according to patient preference to receive
lamivudine 100 mg/day for an additional 6 months (n = 23) or an additional 12
months (n = 26). Baseline demographic
characteristics were balanced between the 2 treatment groups. The posttreatment virological relapse rates
(PCR-based analysis) at 2 years were similar for patients in the 6-month and
12-month treatment groups (59% and 50%, respectively). Age, time to HBeAg
loss/seroconversion, and serum HBV DNA levels at the time of treatment
cessation were identified as independent predictive factors for
relapse. The results of this study
showed that extended lamivudine therapy for 12 months was not associated with a
decreased rate of posttreatment virological relapse when compared with 6 months
of therapy. (Lee HC et al. Gut 2003;52:1779-1783.)
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