View PDF Version - RePub - Erasmus Universiteit Rotterdam

Chapter 2.2
54
PEG-IFN, the proportion of patients achieving sustained response after treatment with
this drug can probably be increased.
Most studies investigating IFN-based therapy in HBeAg-positive chronic hepatitis B
found that high baseline ALT, low baseline HBV DNA and HBV genotype A or B were
associated with of response. 10, 25, 26, 35 In addition to these factors, we identifi ed sex and
age as predictors of response to PEG-IFN. It should be mentioned that in both studies
more men than women were included. We found that the infl uence of sex, age, HBV
DNA and previous IFN therapy was signifi cantly different across HBV genotypes. HBV
genotype thus has great infl uence on the outcome of PEG-IFN therapy. Therefore, contrary
to a statement on this topic in the newest guidelines from the European Association
for the Study of the Liver (EASL), 27 we believe that determination of HBV genotype
is essential in all patients in whom sustained off-treatment response is pursued. Other
potential approaches to tailor PEG-IFN therapy in chronic hepatitis B include quantifi cation
of serum HBeAg and HBsAg. 36 These approaches are still being validated and not
routinely available to most physicians. Because of limited availability in clinical practice,
we also chose not to include liver histology.
Previously we presented a model based on 266 HBeAg-positive patients participating
in a single randomised trial. 37 However, the vast majority of these patients were
infected with HBV genotype A or D, only a small proportion of patients harboured HBV
genotype B or C. To gain a good prediction model for all HBeAg positive patients, we
now combined the data of the two largest randomised trials investigating PEG-IFN in
HBeAg-positive chronic hepatitis B. We showed that a model based on readily available
baseline factors can provide an adequate prediction of sustained response. Ideally, a
large confi rmatory group would have been used for external validation. Such a group
is unfortunately not available. Clinical trials that are currently still ongoing may allow for
further validation of the model in the near future.
Since substantial viral replication may persist despite HBeAg loss in some patients, a
combined endpoint of HBeAg clearance from serum and low HBV DNA is crucial in
HBeAg positive chronic hepatitis B. Particularly patients with HBV genotype non-A infection
can develop mutations in the precore or core promoter region and may still be at
risk for progressive liver disease despite HBeAg loss. 6, 38 Both clearance of HBeAg and
suppression of HBV replication are key events in the natural course and during antiviral
therapy in HBeAg positive chronic hepatitis B. HBeAg loss after IFN-based therapy was
associated with reduced progression to cirrhosis and HCC, and improved survival. 5, 39
In addition, large population studies have established a clear link between HBV viremia
and the risk for HBV-related complications. 40, 41 Serum HBV DNA was the strongest
predictor of progression to cirrhosis and HCC, with a signifi cantly higher risk for patients