interplay of genotype and phenotype of the host and the bacteria respectively. The
phenotype of the host is primarily expressed through immunological mechanisms
and variations in the type of inflammatory mediators, in contrast to the expression
of bacterial virulence factors and membrane proteins (CagA, VacA, BabA).^21
Triple therapy (two antibiotics + proton pump inhibitor) is the mainstay of
H. pylorieradication protocols, but its effectiveness depends on the activity of all
three components. An important parameter of decreased effectiveness has been the
increasing bacterial resistance to antibiotics, which led to the last modification of
the guidelines, where areas with high (>15–20 %) and low (<15 %) bacterial
resistance to clarithromycin were defined. Full personalization of the algorithm is
implemented after two unsuccessful attempts of bacterial eradication when
esophagogastroduodenoscopy andH. pylorisusceptibility testing are indicated.^22
The activity of the third triple therapy component (proton pump inhibitor, PPI)
depends on the function of hepatic microsomal enzymes, particularly CYP2C19, an
enzyme that breaks down all known PPIs. According to the level of CYP2C19
activity, one can be a rapid, moderate or slow PPI metabolizer.^23 The effect of
CYP2C19 activity on clinical effectiveness of PPIs is not fully elucidated, although
the results of studies suggest a need for higher doses in rapid metabolizers.^24
3 The Potential of Personalized Medicine
Contemporary medicine often uses imprecise, nonspecific and broad-spectrum
drugs to treat diseases, which increases the risk of side effects and reduces the
effectiveness of treatment. Precise treatment of diseases with a low incidence of
side effects and complications can be achieved by discovering and targeting key
pathogenetic mechanisms. Due to the genotype and phenotype conditioned
interindividual diversity in patients suffering even the same disease, personalized
medicine is closest to achieving this utopian goal.
The optimal approach to the treatment pyramid of inflammatory bowel diseases
is currently being waged by the supporters of the ascending (step up) and
descending (top down) approach. Thestep upapproach starts with milder drugs
(with fewer side effects and complications) and gradually introduces stronger drugs
until clinical response is achieved. Thetop downapproach, on the contrary, starts
with‘heavy artillery’(biologics) being replaced by milder drugs when clinical
remission is induced.^25 Although both approaches are currently being used,step up
in mild andtop downin severe forms of the disease, due to the unpredictability and
(^21) Wen et al. ( 2007 ) and Dossumbekova et al. ( 2006 ).
(^22) Malfertheiner et al. ( 2012 ).
(^23) Chong and Ensom ( 2003 ) and Hagymasi et al. ( 2011 ).
(^24) Ozawa et al. ( 2004 ) and Hunfeld et al. ( 2008 ).
(^25) D’Haens et al. ( 2008 ).
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