PEGINTERFERON ALPHA-2B IS SAFE

AND EFFECTIVE IN HBEAG-POSITIVE

CHRONIC HEPATITIS B PATIENTS WITH
ADVANCED FIBROSIS
Erik H. C. J. Buster, Bettina E. Hansen, Maria Buti, Jean Delwaide, Claus Niederau, Peter P.
Michielsen, Robert Flisiak, Pieter E. Zondervan, Solko W. Schalm, and Harry L. A. Janssen

Anastasia P.
Dr.dr.A.M.Luthfi P.Sp.PD,K-GEH
Hepatitis B virus (HBV) is one of the most prevalent viral pathogens in
humans.

Third of the worlds population having evidence of infection with HBV and
about 400 million people chronically infected.

Higher response rates have been reported for peginterferon (PEG-IFN)

therapy in hepatitis B e antigen (HBeAg)positive chronic HBV patients.

This study investigated the response to and safety of PEG-IFN alpha-2b

(PEG- IFN--2b) alone or in combination with lamivudine in patients with
HBeAg-positive chronic hepatitis B and advanced fibrosis.
 Patients and Methods
The study investigated the efficacy and safety of 52 weeks of PEG-IFN-2b alone or
in combination

All patients had been positive for hepatitis B s antigen (HBsAg) for at least 6
months prior to randomization, Patients were eligible if they tested HBeAg positive
on 2 occasions less than 8 weeks prior to randomization, serum ALT level that was
more than 2 up to 10 times the upper limit of normal (ULN), and had serum HBV
DNA greater than 1.0x105 copies/ml.
exclusion criteria
antiviral therapy less than 6 months prior to randomization;
serum antibodies to hepatitis C virus, hepatitis
D virus, or human immunodeficiency virus;
preexisting leukopenia (white blood cell count 3,000/
mm3, neutrophil count 1,800/mm3) or thrombocytopenia
(platelets 100,000/mm3); or decompensated
liver disease.
 Patients and Methods
Follow-up after discontinuation of therapy lasted 26 weeks. The primary outcome
measure was loss of HBeAg at week 78.

Improvement of liver histology was defined as a reduction of at least 2

points in necroinflammatory score (range 018) or 1 point in fibrosis score
(06).
 Patients were randomized at a 1:1 ratio to receive PEG-
IFN--2b (100 g weekly) with placebo or with lamivudine
(100 mg daily) for 52 weeks.
After 32 weeks, PEG-IFN--2b dosage was lowered to 50 g
per week to prevent side effects and early treatment
discontinuation.
Follow-up after discontinuation of therapy lasted 26 weeks.
The primary outcome measure was lossof HBeAg at week
78.
 Results
Of the 239 patients in this
study, 70 had advanced fibrosis
(29%) and 24 had cirrhosis
(10%).

Patients with advanced fibrosis

were older than those without
and more often had acquired
their infection via sexual or
parenteral transmission.
 Results
Response to Treatment
Treatment allocation did not
influence response rates in
patients with, nor in those
without advanced fibrosis.

Although not statistically

significant, the rate of HBsAg
seroconversion was twice as
high in patients with advanced
fibrosis compared to those
without.
Response to Treatment
(cont.)

Response rates in the subgroup of patients

with cirrhosis were similar to those in the
group of patients with advanced fibrosis.

HBV genotype was found to influence

outcome at the end of follow-up.
Logistic Regression Analysis
of actors Predicting Response
at Week 78.
Increasing age, sexual or parenteral
transmission, presence of advanced
fibrosis or cirrhosis, and high HAI score
were found to be associated with
increased likelihood of virologic
response
 Safety
Most adverse events
occurred equally in
patients with and without
advanced fibrosis
Safety (cont.)

The higher rate of thrombocytopenia

in patients with advanced fibrosis did
not result in an increase in significant
bleeding problems.

Epistaxis tended to occur more often

in patients with advanced fibrosis
 PEG-IFN dose reduction was
comparable for patients with
advanced fibrosis and without
advanced fibrosis as well as
premature discontinuation of
therapy.

The reason for dose reduction

of PEG-IFN in patients with
advanced fibrosis was more
often thrombocytopenia than in
patients without advanced
fibrosis
 Discussion
In this study of the use of PEG-IFN therapy, virologic
response, defined as HBeAg seroconversion and HBV
DNA 10,000 copies/ml at the end of follow-up, occurred
significantly more often in patients with advanced fibrosis
than in those without.

The rate of HBsAg seroconversion was twice as high in

patients with advanced fibrosis, although this difference
was not statistically significant.
 The higher response rates of patients with advanced
fibrosis in our study might have been a result of the
antiviral drug used (PEG-IFN versus standard IFN), the
longer duration of therapy (1 year versus 4 months), or
the predominant HBV genotypes.

Multivariateanalysis showed no relation between

presence of advanced fibrosis and response to PEG-IFN--
2b.
 Nucleos(t)ide analogs are often considered preferential over
PEG-IFN in patients with advanced fibrosis as prolonged
treatment with these drugs may reduce progression to
decompensated liver disease and development of
hepatocellular carcinoma in patients with advanced fibrosis.

However, improved survival and decreased incidence of

HCC have also been observed in patients with and without
preexisting cirrhosis who responded to IFN therapy.
 CONCLUSION
Our findings show that PEG-IFN--2bis at least as effective in
patients with advanced fibrosis as in those without.

Although patients with cirrhosis more often require dose

reduction or early discontinuation of therapy, treatment is safe
and outcome is similar to patients without cirrhosis.

Therefore, when aiming for sustained off-treatment response,

patients with advanced fibrosis and well-compensated liver
disease
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