View PDF Version - RePub - Erasmus Universiteit Rotterdam
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Summary and conclusion 233<br />
The model strongly supports individual decision making on treatment discontinuation<br />
in patients with HBeAg positive chronic hepatitis B. It is recommended to stop PEG-IFN<br />
treatment by 24 weeks if HBV DNA declined less than 2log10.<br />
In Chapter 2.4 statistical methods are presented that enable dynamic updates of the<br />
prediction of a signifi cant clinical event.<br />
If biomarkers change during follow-up, the clinical prognosis changes along. Our aim<br />
was to incorporate longitudinal profi les of these markers in a dynamic model to repeatedly<br />
update the individual prediction of the event. The general concept is presented<br />
specifi cally in the setup when the clinical event has a bivariate outcome.<br />
First a direct approach is proposed, extending the usual logistic regression of baseline<br />
variables with the observed repeated measurements of the markers. The model is<br />
designed to update the prognosis of the outcome each time new information becomes<br />
available. Instead of entering the observed marker values the behaviour of the markers<br />
can also be used. Proceeding this way fi rst linear mixed modelling is applied to fi t the<br />
subject specifi c patterns of the markers and afterwards entering the random effects in<br />
the logistic regression while adjusting for the estimation error of the random effects.<br />
Secondly an indirect prediction method using multivariate mixed effects models is<br />
applied. The patterns of the markers are allowed to vary depending on the outcome<br />
variable. Thereafter, the empirical Bayes estimates are used to obtain posterior probabilities<br />
that are subsequently used to update the probability of the outcome variable<br />
each time new information becomes available.<br />
The different methods were applied to data on treatment of chronic hepatitis B patients.<br />
We conclude that the prediction of response obtained at baseline can be signifi cantly<br />
improved with all of the above mentioned methods and may be useful tools to update<br />
the prognosis for the individual patients.<br />
PEG-IFN alfa-2a results in a sustained response in a minority of HBeAg-negative chronic<br />
hepatitis B patients. In Chapter 2.5 the role of on-treatment quantitative HBsAg and<br />
HBV DNA levels in the prediction of sustained response in HBeAg-negative patients<br />
receiving PEG-IFN alfa-2a is assessed.<br />
HBV DNA and HBsAg were quantifi ed at baseline, during treatment and follow-up in<br />
the sera from 107 patients who participated in an international multicenter trial. Overall,<br />
22% of patients achieved sustained response (serum HBV DNA