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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 Watch™ |
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Timely Information for Practicing Physicians |
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APRIL
2004
ADEFOVIR
DIPIVOXIL
Results of
treatment in lamivudine-resistant HBV infection. The emergence of viral mutations in the YMDD motif of the
HBV DNA polymerase gene has been reported to occur in 16%-32% of patients after
52 weeks of lamivudine treatment and to increase to 67% by 4 years of
therapy. Robert Perrillo and colleagues
conducted a study that evaluated the efficacy and safety of adding adefovir
dipivoxil to the treatment of chronic HBV patients who were receiving ongoing
lamivudine therapy for at least 6 months and had YMDD mutant HBV. Adefovir is a synthetic nucleotide analogue
that has shown potent anti-HBV activity.
HBV resistance to this compound has not been observed in up to 48 weeks
of therapy. In the current study, 95
patients with compensated HBV (Group A) were randomized to receive adefovir 10
mg daily or placebo while continuing lamivudine. A second group of 40 HBV patients (Group B)
who had decompensated liver disease or were post-liver transplantation were
given adefovir in addition to their lamivudine therapy. In Group A, HBV DNA responses occurred in 85%
of patients treated with combination therapy compared with 11% of patients
treated with placebo plus lamivudine.
Normalization of serum ALT occurred in 31% of patients receiving combination
therapy versus 6% of patients receiving placebo plus lamivudine. In Group B, 92% of patients had an HBV DNA
response associated with improved liver chemistries. In a second study, Marion Peters and others
randomized 59 HBeAg-positive patients with lamivudine-resistant HBV and
compensated liver disease to receive either adefovir alone (10 mg daily),
lamivudine alone (100 mg daily), or adefovir plus ongoing lamivudine. Rapid reductions in serum HBV DNA levels were
seen in all adefovir-treated patients.
The time-weighted average change from baseline in serum HBV DNA level by
week 16 was -2.45 and -2.46 log10 copies/mL in the combination therapy
and adefovir monotherapy groups, respectively, compared with -0.07 log10
copies/mL in the lamivudine monotherapy group.
The median changes in serum HBV DNA level from baseline at week 48 were
0.0, -3.59, and -4.04 log10 copies/mL in the lamivudine monotherapy,
combination therapy, and adefovir monotherapy groups, respectively. Furthermore, normalization of serum ALT
levels was observed in 5%, 53%, and 47% of lamivudine monotherapy, combination therapy,
and adefovir monotherapy patients, respectively. The results of these studies demonstrated
that adefovir alone or in combination with ongoing lamivudine therapy provides
effective viral suppression in patients with lamivudine-resistant HBV. In an accompanying editorial, Tim Shaw et al
concluded that continuation of lamivudine after adefovir rescue has been initiated
was of little benefit in patients with compensated liver disease. However, hepatitis flares were more common
during the first 12 weeks among the patients who received adefovir only. Whether an overlap period of combination
therapy is needed for patients with decompensated liver disease remains to be
determined. (Perrillo R et al. Gastroenterology
2004;126:81-90. Peters MG et al. Gastroenterology 2004;126:91-101. Shaw T et al. Gastroenterology 2004;126:343-347.)
HEPATOCELLULAR
CARCINOMA (HCC)
Occult HBV as
a possible risk factor for HCC. Teresa Pollicino and colleagues
studied the impact of occult HBV infection in cases of HCC. They analyzed tumor and liver tissues from
107 HBsAg-negative cirrhotic patients with HCC and 192 HBsAg-negative patients
with chronic hepatitis. HBV DNA was
detected in 63.5% of the patients with HCC and 32.8% of the patients with
chronic hepatitis. Both integrated viral
DNA and covalently closed circular HBV genomes were detected in the patients
with occult HBV. The authors suggested
that this significant association of occult HBV with HCC is evidence that
occult HBV infection is a risk factor for the development of HCC. In an accompanying editorial, Jorge Marrero
and Anna Lok discussed whether the presence of occult HBV infection in patients
with HCC means that HBV is an innocent bystander, a cofactor, or a sole
causative agent. They maintained that
the role of HBV in this clinical setting remains unclear and identified
critical issues that need to be addressed by future studies before the testing
of all HBsAg-negative patients with HCC for occult HBV infection can be
recommended. (Pollicino T et
al. Gastroenterology
2004;126:102-110. Marrero JA, Lok ASF. Gastroenterology 2004;126:347-349.)
CHILDHOOD
CHRONIC HBV
Current
therapeutic approaches. B Dikici and coworkers from the
department of pediatrics at Dicle University prospectively randomized 182
children with HBV infection to 3 treatment groups for 6 months of therapy: (1)
interferon alfa-2b 10 MU/m2 thrice weekly (high-dose IFN); (2) IFN 5
MU/m2 thrice weekly plus lamivudine (LAM) 4 mg/kg up to 100 mg/day; or
(3) LAM initiated 2 months prior to starting IFN 5 MU/m2 thrice
weekly. Mean decrease in serum ALT at
the end of treatment for the high-dose IFN group was less than that observed
for treatment groups 2 and 3. However,
no differences between treatment groups were found for HBeAg clearance,
anti-HBe seroconversion, or achievement of complete response (normalization of
serum ALT, clearance of HBV DNA, and anti-HBe seroconversion). Thus, high-dose IFN therapy achieved a
similar complete response rate to that of combination IFN plus LAM therapy in
children with chronic HBV infection.
(Dikici B et al. J Gastroenterol
Hepatol 2004;19:127-133.)
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