Download Treatment with Peg-Interferon α-2b for HBeAg

Treatment with Peg-Interferon α-2b
for HBeAg-Positive Chronic Hepatitis B
: HBsAg Loss Is Associated with HBV Genotype
Hajo J. Flink, M.Sc.,1 Monika van Zonneveld, M.D., Ph.D., Bettina E. Hansen, M.Sc.,
Robert A. de Man, M.D., Ph.D., Solko W. Schalm, M.D., Ph.D., Harry L.A. Janssen,
M.D., Ph.D.,
for the HBV 99-01 Study Group
Am J Gastroenterol
2006;101:297–303
INTRODUCTION
• Chronic HBV infection
:defined as HBsAg positivity for > 6 mo.
ass. with risk ↑ of developing cirrhosis, hepatic
decompensation, hepatocellular carcinoma
• Loss of HBsAg
: improved long-term outcome risk ↓ of hepatic
decompensation & hepatocellular carcinoma
• Purpose of therapy for chr. hepatitis B is serum HBsAg
negativity.
INTRODUCTION
• nucleoside or nucleotide analogues
: reactivation after Tx termination
HBV variants in continuous Tx
• lamivudine : < 2% loss of HBsAg
adefovir dipivoxil : 1.6% loss of HBsAg
INTRODUCTION
: Tx with PEG INF α-2b is effective for HBeAg(+) HBV.
Combination with lamivudine not superior to monotherapy.
→to investigate incidence of & factors predicting HBsAg
loss due to treatment with Peg-IFN α-2b alone or with
lamivudine
PATIENTS
• 266 pt were analyzed
• Inclusion : >16 yr
(+) for HBsAg & HBeAg for > 6 mo.
elevated ALT levels (2 time ULN)
•
Exclusion : antiviral or immune modulatory treatment
anti-HCV,HDV,HIV Ab , pregnancy
decompensated liver disease
drug or alcohol abuse, HCC
inadequate hematological levels
serum AFP > 50 ng/mL
hypo-,hyperthyroidism, contraIx for IFN α.
Study Design
100 ug/wk Peg-IFN
α-2b for 32 wk with
placebo
50 ug/wk Peg-IFN α2b ,32~52 wk with
placebo
Post F/U
26wks
100 ug/wk Peg-IFN
α-2b for 32wk with
Lamivudine 100mg
50 ug/wk Peg-IFN α2b ,32~52wk with
Lamibudine 100 mg
RESULTS
Figure 1. Course of serum HBeAg, HBsAg, and PCRnegativity (<400 copies/mL) during Tx & F/U.
Table 1. Pt Data on Nonresponders, HBeAg Responders,
HBsAg Responders
Figure 2. HBV DNA response & ALT normalization at end of
F/U in HBeAg(+) HBeAg(-), HBsAg(-) pt at the end of F/U.
Table 2. Baseline Characteristics and Geographical
Distribution of pt with HBV Genotype A, B, C, D
Figure 3. Proportion of HBeAg and HBsAg clearance
at end of F/U according to genotype
Genotype A versus D (p=0.006)
CONCLUSIONS
• Peg-IFN α-2b for HBeAg-positive pt led to HBsAg loss
in 7% , higher than for lamivudine or adefovir .
• treatment with Peg-IFN α-2b , best therapy to achieve
HBsAg clearance in pt with genotype A.