AG&M annual report 2018

AG&M Science Impressions 2018
Ulrich Beuers and Jorrit van Niekerk
A common symptom of cholestatic liver diseases is
pruritus which may reduce quality of life tremendously.
The search for a particular pruritogen in cholestasis has
been ongoing since decades. It has been inferred that
potential pruritogens are made in the liver and excreted
in bile; as a result of cholestasis, they might accumulate
in the body and trigger the sensation of itch at itch
neurons. Recent findings of the PhD fellows Andreas
Kremer, Ruth Bolier and Jacqeline Langedijk supervised
by Prof. Ronald Oude Elferink and Ulrich Beuers indicate
that Lysophosphatidic acid (LPA), a potent neuronal
activator, and autotaxin, the enzyme which forms LPA
and the nonspecific cation channels TRPA1 and TRPV1,
which are also activated by LPA and responsible for pain
and itch sensing are involved. All together they may
form a key element of the long-sought pruritogenic
signaling cascade in cholestatic patients.
The identification and characterization of a biliary
‘factor X’ is at this moment the major focus of this
research line. A multicenter international clinical trial,
the FITCH trial (‘fibrates for itch’) resulting from the
experimental work above, organized by the PhD fellows
Elsemieke de Vries and Ruth Bolier and supervised by
Ulrich Beuers, was just successfully finished; results
will be reported later this year and might change
international guideline recommendations.
27