Player is loading...
Emerging treatment options for patients with PSC
Prof. Michael Trauner, Chair of Gastroenterology and Hepatology, Department of Medicine III, Medical University Clinic, Vienna, Austria
Thursday, Sept. 5, 2019 · 6:51 p.m. · 49m 04s
Embed
Transcriptions
Note: this content has been automatically generated.
00:00:00
for the invitation and also for having the courage to true slows
00:00:04
to topics and for the full room for uh uh uh those two
00:00:08
excel pick topics as you said i mean the diseases are not that common but they extremely challenging
00:00:14
and i think uh uh really uh make up more and
00:00:18
more for clean compared nulls mean academics and so these are my
00:00:23
disclosures and uh that in contrast to p. p. c.
00:00:27
where we have effective first line treatment or so and
00:00:31
also now established second line treatment with a better call
00:00:34
i guess it and vibrates based on the reasoning in trial
00:00:38
in in prime is closing contract is there's no established medical therapies reuse of
00:00:43
or so is really very controversial some countries which have the highest prevalent such as
00:00:48
for example we don't use arose at all but we of course let's say
00:00:53
in central europe probably already also feel like also is whistle from other christopher presentation
00:01:00
uh we have i. b. d. uh which has a specific uh phenotype with this uh
00:01:05
right side it uh collide this backwards i like this a rectal sparing certain is symptomatic deceased
00:01:11
and let's say i mean the i. b. d. persons i'm very much of a yeah that patients can develop p. c. but
00:01:17
i'm often surprised when i see patients who've a p. c. and
00:01:21
were followed in let's say all set of of centres that they
00:01:25
never had a call an oscar but despite the very height you murray's can really find a high rate of this places and
00:01:30
even you know cancers that the initial column ask appears in the
00:01:34
those early and patients which we have sold is a scope that
00:01:38
and uh the malignancy risk of course that's not only the call and
00:01:42
it's also mainly uh the other coming to sell a carcinoma gall bladder cancer
00:01:47
and there's a lot of clinical heterogeneity which makes is deceased uh difficult to
00:01:51
treating also so difficult to run clinical trials because it's really a very mixed fat
00:01:58
and then you actually look at the person i think this is
00:02:01
nicer reflect when you look look at liver transplant numbers i mean
00:02:05
they've kind of a level bottom in here in the u. s. u. c. p. c.
00:02:10
p. p. c. the numbers really uh i've calmed down and
00:02:13
we think this me billing to the use of or so
00:02:17
similar data from the u. k.'s big blue line here is p.
00:02:19
b. c. little in office and n. p. c. kind of uh still
00:02:24
increasing your let's say reaching higher a stable level as many other new
00:02:30
mediated diseases and then you look this is data from your nose in the
00:02:34
united states me ray at the seas searches p. c.
00:02:39
quite stately makes up about seven percent of transplant complications
00:02:43
inelastic and in some sense to slow the normal you know
00:02:47
it's twenty percent also in b. and it's in the range of fifteen percent on the one i think also in homework
00:02:52
uh if you'd look at all not p. c. long but let's see p. c. b. b. c. envelop him yet but that is the new
00:02:58
needed to this season i think it's between ten to twenty percent and that's quite a burden
00:03:03
when you think from finding effective treatments pairing organs preventing
00:03:07
with the transportation so i think we also have to think about the p. c.
00:03:12
and uh uh this also reflects our ineffective medical
00:03:16
treatment anyway saturated he sees a count of course those
00:03:19
uh good indications in every day on patients there's always the question that they already have cancer or not but
00:03:26
uh let's say it also reflects off a or ineffective will understand in treating this disease
00:03:33
so at the moment we still use arose and there was a little bit they will buy with the sole source
00:03:38
of this continuation study from poland and that was a
00:03:41
collaborative study which show that when you stop hers actually symptoms
00:03:45
and biochemistry gets worse so movie keep linda wrote the very nice editor also when it gets worse
00:03:50
when you stop it maybe it works when you between uh that's kind of complex already did an option
00:03:56
my plane but this is actually from and it tore love
00:03:58
keep linder uh who in the city guideline for some time actually
00:04:03
uh advised against the use of rose because of his ineffective or detrimental hydro study so in his
00:04:09
one of his reason and it was an actual so the current guidelines still allow
00:04:14
or in cars to use of or so and monitor elk fossil though that's not
00:04:19
that well established as a marker liking p. p. c. for example we still look
00:04:24
with the may patients so sure reduction of elk falls by more than forty percent and by that
00:04:29
this magic cup of one of one point five fold up a limit of normal we know the patients were below
00:04:35
uh that a threshold have a better programs is than those who stay a buff that some patients
00:04:41
could not hit this threshold at least also
00:04:44
patients were you should consider additional mobile experimental therapies
00:04:48
and uh consider including these patients in clinical trials
00:04:53
so what's on the horizon here at the moment
00:04:57
on the one hand we have voice like in many other colours that it this is the f. x. are
00:05:01
with us there why pixar wide and such as a
00:05:04
better call i guess it and also monster latex ally against
00:05:08
and uh the interesting thing is uh the also vibrates maybe
00:05:12
an optional goal briefly touch on that like in p. p. c.
00:05:16
uh the interesting option here is that you may also hit the cup with that because i know that have exactly very
00:05:22
importance signalling recounts did you to maintaining got integrity
00:05:26
country of control and got my corpora up and actually
00:05:29
the absence of bile acids and all the detrimental effects which you see also in advanced liver disease
00:05:35
is basically due to absence of ethics are
00:05:37
signalling and uh reduce the gap integrity and
00:05:41
increased information so maybe it's a one stop shopping for both the liver and they got
00:05:48
then of course we have strategies which treat the microbial up as
00:05:52
the noting evidence about two sparrows are also will touch on that
00:05:56
uh in a l. p. c. which is different from the two spews is which we see i. b. d.
00:06:02
and uh stretches such as frank uh my sin and also
00:06:05
other antibiotics and there's even a reason to vicki microbe realtor transportation
00:06:10
a study actually has shown some promising results and also palaces strategies such
00:06:16
as ethics are control micro products so uh this maybe you'll be fine
00:06:20
theme the question is should we treat the got to treat everyone is really got information associated
00:06:27
with a live information terms of intensity we think it is
00:06:30
not but it may be at least she up pathogenic cough works
00:06:34
this of course is very attractive uh olympus at home have
00:06:37
bad hypothesis that basically he somehow men from the got to deliver
00:06:42
maybe be very uh to go in this uh uh can be treated with uh
00:06:46
for example in to crimp walkouts with little it some up or more brought out
00:06:50
it actually some up and other strategies which basically
00:06:53
a target t. cell harming uh perhaps i would say
00:06:57
shay at inflammatory cough race in the got and in that letter
00:07:02
an interesting strategists any pretty rock which is a macrophages strategy chemo coming receptor
00:07:08
which is really necessary for a rectify show a recruitment that
00:07:12
seems to be not only important to nash but also in p. p. c. and there's an ongoing
00:07:17
clinical trial seem to sum up the locks up when he
00:07:21
did identify product track negative trial i mean one of the
00:07:24
many failures uh in the big studies which
00:07:28
below to stand in the past targeting directly
00:07:31
for pros is uh i think this tells us approach rational of targeting directly for pros is
00:07:36
in any leave it this is not only nash but also in a
00:07:39
t. c. maybe a very high aim uh which is terrific difficult to reach
00:07:46
and the study was negative and we have north of the arctic probably gas it
00:07:50
which is a very good people for also undergoing call it but diction by well
00:07:55
touch a little bit on that because that at the
00:07:57
moment is the most advanced medicinal product which is currently undergoing
00:08:01
of phase i three studies so nora so is inside change
00:08:06
short the really diversity ox a colleague asked so it's lacking
00:08:10
a method group and uh the name of more although we all know it from
00:08:13
more i turn away no more i printed for in and uh at inner frame
00:08:18
it causes a lot of confusion so people constantly makes up more also with ross or
00:08:22
and actually it's going to be changed by a real cold new recall we guess that all know little bit makes
00:08:28
it better to to keep you know are there better call it yes it this is the a. w. h. o.
00:08:34
nomenclature so no no so this uh no stands for nitrogen without credit on
00:08:38
this is all a tram in chemistry nomenclature so it's liking this methyl group
00:08:43
and this method group is exactly the group ever buy less become conjugated with price and or
00:08:50
and this makes a bile acid restricted to the enter patrick
00:08:54
circulation does conjugation so when you have to buy less it
00:08:58
which is not a conjugated this file is the champagne
00:09:02
between the bile ducts and they paddle sites within the liver process cold calling a petty chanting
00:09:08
and this call it that dick chanting is actually more
00:09:11
or so was originally synthesise down hoffman nearly thirty years ago
00:09:16
just to prove the concept of colour protection thing over conjugation resistant
00:09:21
by less than than it was sitting on the shelf for twenty years
00:09:24
and then revisiting the concept of colour protection thing and bile duct out hard
00:09:30
getting experimentally now's model such as the india to model sparrows in cullen tried this
00:09:35
uh no it's a restart was the phenotype and one of the mechanisms actually is
00:09:40
that this call it that the chanting is at generating pack up and then pick on it
00:09:45
is explained important to contact bile acid toxicity humans folk slicing contributed by
00:09:51
less it's it's as important as a uh the formation of mixed mess else
00:09:56
in addition or so also has an to proliferate differently
00:09:59
for pop again tirade anti inflammatory and we think even you
00:10:03
know model or tory effected also inhibits intro signalling in c.
00:10:07
d. four in c. d. eight uh t. cell also the
00:10:10
maybe a complex mechanism but very important feature is
00:10:14
that no worse in the long and the goes to call it that
00:10:17
fiction and things through the got but is and uh the enter patrick circulation
00:10:21
so they got but is undergoing this call hypnotic chanting
00:10:25
within the labour so a apart from generating pick cotton it
00:10:29
which is protecting the bile the good with the the um there's also in richmond
00:10:33
within the liver and i think this is a very important from a call dynamic feature
00:10:38
and in addition and uh from the concept of
00:10:41
into green a signalling uh this may be important
00:10:45
for example the bile back to be filament this is preclinical data the engine bile duct
00:10:50
is expressing a teasing molecules such as we can and also when you stimulate clench asides with yet
00:10:56
they express high levels of weekend which helps a recruitment aside to evade at
00:11:03
poses that's very nice mechanism a demonstrated but david adams and actually more or so
00:11:09
is reducing uh we can expression within the by like b. b.
00:11:13
c. and so it also maybe another level apart from having direct
00:11:17
uh and probably for the v. effects on on t. cells that also the recruitment
00:11:22
to the bile duct tape if the limit the maintenance of uh uh lymphocytes closed to the public the p. t. loom
00:11:28
may be interrupted at least based on a preclinical data
00:11:33
and you uh probably way off the face to data showing it those dependent
00:11:37
reduction of alkaline of foster basis primary readout
00:11:42
uh compared to placebo with different those is really
00:11:46
is often more so with the about or twenty
00:11:49
five percent with the highest those within twelve weeks and then or so was discontinued that was a relapse
00:11:56
of liver enzymes and then this effect occurred independent of the
00:12:00
previous response through the arctic probably guess its own this trials
00:12:03
the patients who've been top or so but there there there's a respond as in previous as a non responders and both
00:12:09
responded equally which is i think an important feature because no h. so good safety profile and
00:12:16
based on the state to a phase three trial has been initiated a long time trial which
00:12:21
we'll have a combined and point of reduction pelican foster days
00:12:26
and a stabilisation of a liberal histology uh uh basically it's it
00:12:32
makes the a square or uh and it includes biochemical he's the logical
00:12:37
and also clinical endpoints with about three hundred patients to be recruited
00:12:41
another think they're fifths it's we've sent dozens with so and so
00:12:45
y'all recruit actively to this trial really need to have updated
00:12:50
every patient counting those p. c. trials it's really fight for every
00:12:54
in the little patience because uh it's really really yeah the seats
00:12:59
so i should point out that no uh so which also
00:13:01
may be effective in another colour static diseases which are not yet
00:13:05
a test that the moment we published a reason thoughts while in nash that was it
00:13:11
so they import the thing is that no it's it's not a a like and for
00:13:15
the classic bile acid receptor such as f. x. are in teacher five and this is
00:13:20
but we can't resting another strategy which is
00:13:23
currently holding those uh nuclear receptor targeted therapies
00:13:27
targeting efforts are or for example of uh people are in the
00:13:31
case of vibrates and the interesting thing with those nuclear receptor is ah
00:13:35
that nuclear receptor satellite and activated transcription factors
00:13:39
which are for example activated by by last it
00:13:42
well by a fatty acid or white rock which of course is high affinity
00:13:47
and this then in uses utterance workshop program which
00:13:50
is really very part so they have a very productivity
00:13:54
the control metabolism not only by less it but also clue clothes and lip metabolism
00:13:59
and they also control inflammation immunity and fibrosis in t. should repay
00:14:05
so i would see those nuclear receptor is is immune water it rocks
00:14:09
which control both metabolism in this case bile acid metabolism and information
00:14:15
and and that applies to both affix our and and keep our
00:14:19
and these nuclear receptor targeted strategies now have emerged the second
00:14:24
line therapy in p. p. c. is you're probably way off
00:14:27
with a stairwell uh f. x. out like an such sabbatical i guess it with the new england paper
00:14:33
people lie against the the reason pacified with data
00:14:36
from the french trial by a crystal for copy show
00:14:40
and also took a copy good reset to specify is more than just an immune to suppress if it's of course
00:14:46
a are too quick to reset dragon is but it
00:14:48
also you come and uses a or or modify spout composition
00:14:54
and that was the reason try was put as a night uh uh in in
00:14:57
p. c. so the question is could those tracts also be effective in p. c.
00:15:02
there are trials with a better call i guess it announced or what life exile against
00:15:07
and know that the french uh based on you know small case here is that that's a fibre it was
00:15:13
also effective in p. c. also initiated phase three trial
00:15:17
similar to the p. p. c. trial in the french network
00:15:21
and put last night the questions i know that homework and we all may have some discussion
00:15:26
i think is using steroids in in p. s. c. and it always depends a little bit
00:15:31
you know it's of course in overlaps income christopher's talked about that that's a clear indication first their rates
00:15:37
and then uh it depends do you really look for
00:15:40
information in liver histology usually do it in the context
00:15:44
of having a suspicion of overlaps income and then you see inflammation their interface
00:15:48
appetite is of course your going to treat it right so see and treat
00:15:53
inflammation than others in yeah raise the overlap but i touchy
00:15:56
for the ten percent of the p. c. patients have elevated
00:16:01
she for level so there is a they overlap with i. g. forty seasoned op immune hepatitis about
00:16:07
ten percent of patients and those uh certainly candidates a formula suppresses treatment
00:16:12
and the question is at least and you see and uh inflammatory infiltrate
00:16:17
only the histology there's one opinion that this is the consequence of colour spaces
00:16:22
because colours diesels isn't using opinion phenomenal so you wait
00:16:26
what is colour static therapy doing for example to trends
00:16:29
i mean is is are you treated right away that i think there's a we can discuss that later sissy country
00:16:35
information also is a topic in a college steady little diseases such as in p. f. c.
00:16:42
so uh what about those nuclear receptor is uh i mentioned
00:16:45
earlier that this may be a a stretch either you basically
00:16:50
to read both the lever and the cap and their stated
00:16:53
both affix ah and for people of course first there it
00:16:57
that you are going to hit both the liver and they
00:17:00
get and then this is i think an interesting concept especially
00:17:03
the ethics ally against but also for vibrates we also know that there
00:17:07
was a strategies treating i. b. p. with people or a small molecules
00:17:12
which i've got restricted and uh recently a uh
00:17:17
face to trial that'll better call the gas it the second line treatment in p. p. c.
00:17:22
was also contacted in p. c. s. s. u. c. with much lower those is then in p. b. c.
00:17:28
it was effective in reducing outlined faster pace but even with a low
00:17:31
doses of this is point five to three and five to ten really plan
00:17:36
you see very high rate of pride 'cause my inspiration is it's even higher then e. p. p. c.
00:17:41
and uh the setback occurred independent of the previous response or use of or so
00:17:47
and having the i think also that phase uh to be you or perhaps
00:17:51
even face re trial is planned for better call i guess it at the moment
00:17:57
uh recently a a a study with the not sure
00:18:00
what life excel like endless i love facts uh was performed
00:18:04
which also showed with that have outlined pasta baseball thing uh so exposed us in these patients also
00:18:10
channel up and if i brought a gun point one battery marcus will improve then the important thing is
00:18:16
that these non story life excel lie against it not decorate
00:18:19
right so it may be the no longer look like bile acids
00:18:23
but maybe something to build a compound has a power structure not that they didn't use the sprite does
00:18:29
and also here face at three trial is already on the way
00:18:34
so basically when you think of affix ah kind of policies i would see then
00:18:39
s. stairway to hormones which circulate between the liver and they got that
00:18:43
all sink use other factors in the intestine such as active nineteen which also
00:18:48
control by less at home is stacey is so in addition
00:18:51
to affix ah and the ice display g. of having those morale
00:18:55
not restricted or even got selective non suffer with latex out
00:18:59
like in such a set of facts which worked mainly the got
00:19:02
or having more broad compounds such as a better call i guess it would even
00:19:06
and they're going to babbitt separation because they are by less iterate the if the continue
00:19:12
to circulate within the enter patrick circulation and uh stimulate both the
00:19:17
liver and uh they got the in a continuous way i mean
00:19:20
they're both arguments for both i mean it also has a danger
00:19:24
of course menu from oracle circulating around all the time in the think
00:19:28
you all the way up there all the dozing issue instead what the patient this happens when you have a compound which is kind of
00:19:34
trapped inventor patrick circulation so i would say it's safer to just hit the got and have a comp what which man is gone
00:19:40
and maybe from the concept in p. c. tweaking the let's really
00:19:44
caught me by modify my proper order this is still conceptual speculation
00:19:49
shoes this could be a way how to approach indices such as p. c.
00:19:55
in addition uh to uh f. x. ah we also had f. chief nineteen
00:20:00
which is a whole morning cues benefits are repressed as powerless censuses and also
00:20:04
look at synthesis and you may have heard of f. t. f. nineteen
00:20:08
agony is in uh the feel of a nash the same also applies
00:20:13
two p. c. and p. c. they're very current ching face to
00:20:17
date in p. p. c. with a reduction of alkaline foster days
00:20:21
eighteen q. c. interestingly alkaline phosphate days has not improved as a lot of discussion at
00:20:27
the moment is alpine foster is a good market are in p. c. we know that
00:20:32
a significant proportion of patients have normal act one
00:20:35
fall off apace despite having c. viewer probably injured graphic
00:20:39
at the melodies there's a lot of fluctuation and actually in the
00:20:43
study an improvement of opposes mark that's non invasive marcus actors poses three
00:20:48
and alf test was seen without improvement of alkaline phosphate they so they
00:20:53
hit a direct and departed effect of active nineteen which also was seen
00:20:58
in nash trial i think this is an interesting concept it's an intractable part so
00:21:03
we'll see whether this is accepted by patients is with p. c. as long term treatment
00:21:09
then in addition we also can interfere at up points invented that dick
00:21:13
circulation which is basically still preclinical data but they also for example by last
00:21:19
entry block us into the little you know that they uh my absolute
00:21:23
takes a they had but that is your that but that is the rock
00:21:27
basically a n. t. c. p. the palace transport the volume tower coloured coat transporter
00:21:33
uh taking up by lessons into the new ways to popping side for the hepatitis b. virus and
00:21:38
block us off this um viral entry also blocked by less up take of course
00:21:43
and there's preclinical data that this may uh reduce the buttons of
00:21:47
bile acids by interrupting their interpublic circulation and you also can do that
00:21:52
uh in the in testing either with raisins or with more uh more selective
00:21:57
re uptake inhibitors indian testing such as a speedy inhibitors and this is going
00:22:03
to a shift at the signalling in they got by
00:22:06
also model lighting the micro broader because if increased exposure
00:22:10
often been testing in this case the colon to buy less it's the question is do you want to have that in the context of i.
00:22:16
p. d. and potential cancer it's it could be posted could be anti
00:22:19
inflammatory or it could be per customer training we don't know what that is
00:22:24
at the interesting aspect is that didn't uses she'll be want production and she'll be one not only has
00:22:30
those well known metabolic defects but is also complains you're protected actually probably
00:22:35
clinically we could demonstrate that you can fuel bile back injury bind using she'll
00:22:41
be one production for example by giving is p. d. inhibitors arises we
00:22:45
get a concept of chewing the labour through the got maybe this is something
00:22:49
which will follow us in the future that also i think uh have apologised have to
00:22:54
have a comprehensive view of pestering probity and have apology and also always look at the cup
00:23:01
and they have more so which is a totally different concept i mean this is a comment that take a a
00:23:06
track which is undergoing this colour but the chanting but not
00:23:10
targeting within the entered but except collections a lot of options
00:23:14
and let it would visit the got little access that day and i've mentioned this particular p. c. i.
00:23:20
b. d. phenotype i personally think this is an separate type of i. b. d. maybe the third or fourth
00:23:26
depending determine it polite is uh not uh it's in
00:23:30
independent type of a call like this i would say
00:23:34
and you have basically the concept of despair houses and the loss
00:23:37
of got the area function which may be a pathogenic and they are
00:23:42
it's a lot of uh uh let's say that a good rationale to target the cat litter axes
00:23:47
e. p. c. i've talked about the lymphocytes homing i mentioned disposes
00:23:52
if it changes in micro brought up but of course he they are that the clinical
00:23:56
course of p. c. and i did the is the second the most explains an on and
00:24:01
its manifestation of p. c. after collect i mean this is actually not
00:24:05
better and i was very surprised seeing this speech data that two hundred five
00:24:10
out of two thousand five hundred a p. c. i. b. p. patients develop you
00:24:14
see after collector i mean of course this is about back knows is a manifestation
00:24:20
it's not the same thing but i think it's not a rare thing there's certainly a disconnect
00:24:25
i think yeah i'd be the pipeline of products is very
00:24:28
inspiring i think those guys trying draw it doesn't have apologised realist
00:24:32
look what's going on in room apology in term apology
00:24:36
or step apologises was going on in the i. t. field
00:24:39
who's taking you know they do sticking on lap although it was disappointing
00:24:43
in p. d. c. there will be a pool in alternative politely so
00:24:47
although most of what you showed with the th seventeen x.
00:24:50
that type of opinion hepatitis but i think in p. c.
00:24:54
it plays a role they don't eat some not the uh the into playing partners is an interesting approach
00:25:00
and i think we also have to keep in mind that the and the colours that big rocks the f. excel
00:25:04
likens it even that vibrates also work on crap information
00:25:08
or in the case of ethics are on my copy op
00:25:11
so there's this help like one of i. b. d. marks
00:25:14
which continuously all was still in the uh uh p. c. field
00:25:19
and to an actually the the recent example above middle it somehow
00:25:23
and that was a bit disappointment i must say i mean there's no perspective trial
00:25:27
unfortunately probably based on those more discouraging results
00:25:32
from three retrospective series from the shit ted
00:25:35
uh and also from the international p. c. a study group and also
00:25:40
i uh mayo clinic and and australian experience basically the take home message
00:25:45
is that there's no improvement of act one faster pace in some serious
00:25:49
a significant proportion of patients even showed deterioration so we don't know is this the natural fluctuation
00:25:55
of elk fascinate rock which is not that effective and it comes
00:25:59
back to the discussion is alkaline faster these it good weed out
00:26:03
to town for example or stop a t. c. track i think this is an interesting question at the moment
00:26:09
but perhaps too many potentially a effective treatment options account because that didn't
00:26:15
work on out fast because for example don't look sufficiently uncle enjoyed brands
00:26:20
or on opposes markets but basically delete some not disappointing
00:26:25
uh no all changes so my outline faster pace but
00:26:28
in terms of id activity of course in p. c. i. b. d.
00:26:32
it's effective and this is for example the international p. c. study group
00:26:37
a recently published by caitlin she see there's basically no change in liver enzymes
00:26:43
still like answered is intriguing i mentioned uh uh uh actually it some of which a
00:26:48
little bit well uh the inhibiting beat the seven also another intake when i saw forms
00:26:53
and uh of course not delete some up is not an issue because the side effects and the net can walk past
00:26:59
uh the tosca trial positive and also just collide this i think
00:27:03
locking net can resting between partner also maybe an option e. p. c.
00:27:08
and the the interesting candidate is bad want which is a bit enhance
00:27:12
sign which basically in uses indirectly net can expression and the interesting thing is
00:27:18
that uh uh this enzyme uses big the already arrived and
00:27:22
nine says substrates which basically drive this process the maybe the link
00:27:26
between the cat micro papa microbial product promoting net can
00:27:31
expression and perhaps the up whitey some homing in this approach
00:27:35
uh it's still has a number that's it i try which is currently contacted by the pending in university
00:27:41
and uh the study still recruiting in a that one and monoclonal antibody
00:27:46
a little bit elite sum up a study the the randomised controlled through a trial was the strongest and
00:27:51
then you look at biological seem to sum up i mentioned earlier there and if a product like negative
00:27:57
and send it to a rock actually is on the horizon with a a pass size trials
00:28:02
yeah i don't know whether of the data basically could be because i think they should have data
00:28:08
at the moment and the interesting thing is that a cynic critter ah you'll probably
00:28:12
oh like they have to pay to nash but also in colour spaces there's recent interest
00:28:18
that macrophages infiltration of brown cloud parts plays a key role
00:28:22
so it's not just about lymphocytes also about in that community
00:28:26
is about known aside to write macrophages and with this this
00:28:29
year to see see five blah you basically bach marker fashion
00:28:33
recruitment to the liver and to parasites trial was actually
00:28:36
completed some perhaps uh we're going to see data here
00:28:40
very soon as well and then you remember the nash baited had burned and different topic
00:28:45
than anti inflammatory signatures i'm very curious to see what that means for a p. c.
00:28:51
what about moderation of not microbial i i mentioned the antibiotics
00:28:55
most of the data out there for bank uh my scene
00:28:58
but we have to keep in mind that might come bank uh my son is not just an on
00:29:02
it all the way antibiotic it's also very potent immutable
00:29:05
auditory bracket model it's you read a activity in composition
00:29:10
it's it's interesting to see that uh then you look at antibiotics and mean a metal night
00:29:16
assault tetris cycling positive trial from finland but but a lot of side effects i don't think
00:29:22
this is going to be uh they it's interesting to
00:29:25
see that's office hours nine see some revival there's no
00:29:29
oh that tool randomised controlled trials in the us so this is basically this whole file a cellphone i might
00:29:35
uh and mess on asylum mine component combine so maybe
00:29:39
you can anti inflammatory antibiotic got michael brought the model waiting
00:29:44
approach and actually a my experience and i've talked
00:29:48
about that with with other investigators there are individual patients
00:29:52
who respond to uh to the l. p. c. i. b. c. right back
00:29:55
out to the old fashioned sort of our sign i don't know whether you've made
00:29:59
similarly experience and that's also data that's all purcell assigned also sent in to port and they enter
00:30:04
and get a pop topic in the liver so it's also very all right but very interesting product
00:30:10
which is where was that at the moment with tax i mean was disappointing and actually there's a lot of tape down
00:30:16
by one ally in p. c. i think this is basically
00:30:19
just the signature of little so roses or advanced liver disease
00:30:23
and they're a new address for example so little mice in is about an ally
00:30:28
uh the specific antibiotics which which uh maybe tried in the future
00:30:33
i think no interest isn't the clips it gets a love story at the moment which is a pool forming tapes yellow
00:30:39
a species which was identified in p. c. i. b.
00:30:42
d. patients basically contributing to got permeability and a little information
00:30:48
uh but yeah except been disappointing and josh course and make a from how they actually
00:30:53
recently completed a f. m. t. trial which was safe
00:30:56
and a very small proportion you know intend passions you can't
00:30:59
say much showed an improvement of outline faster this but i think you see the the feel this going in the moment
00:31:06
so at the end it then we we think of p. c. you know we
00:31:10
have this information with this structuring and then you look at the combine chip ran
00:31:14
you have to see the inflammation in structuring
00:31:17
actually combine geographical it looks or colin just copy
00:31:21
collate it looks more think phones theses so i would say it's the currencies of the got
00:31:26
associated with polite is maybe this is telling us something
00:31:29
but uh personally i think that a new clothes all healing
00:31:34
isn't important uh aspect but then you see this really
00:31:38
by look into the paper thingy i'm i'm wondering how
00:31:41
can a few and imply mayor pro or anti inflammatory approach
00:31:46
we still have lacked integrity so i think in the future when you think about combination simply iffy
00:31:52
we not only will have any colour static kind
00:31:55
of bile duct protective attracts which maybe the backbone
00:31:59
but uh we don't have to add a email mulatto it lacks probably we
00:32:03
have to uh diagnosed disease early i think many of them you know mahler tori
00:32:08
biologics did not work because we're just simply diagnosing the disease much too late
00:32:13
basically when it is for product and giving this colin should graphics a clearance
00:32:18
and adding appropriate channel differ perhaps also santa let the cracks because in essence and this was a question
00:32:24
a different context yeah they spy objects in essence probably
00:32:28
con computing to bile duct uh it it's sealed best
00:32:32
and as analytic tracks of course the question all this is with
00:32:35
this height you more receipt risky you really want to stimulate regeneration
00:32:39
it's actually the season maybe things like g. l. p. one
00:32:43
through the got the kind of mild form of approaching that
00:32:47
of course uh out there a lot of uh you know concepts
00:32:51
for combination therapies but when you look at those diapers basically it's
00:32:55
combining everything at the same time i think this doesn't make sense probably we need
00:32:59
sequential therapy depending on t. c. stages or individual acerbic
00:33:04
depending whether a part that protected in one the model editorial perhaps probably generative
00:33:10
and if the product approaches make more sense i think the key question one of the key questions is by that
00:33:17
clicking the cat is really instrumental in terms of treating p. c. than says we don't really
00:33:23
know because it appears to be a a slightly disconnected and this is hey it i think with
00:33:29
many conceptually it peeling approaches i think the near future will be nora so
00:33:35
and affix ah like ends and people likens vibrates perhaps also the f.
00:33:39
f. nineteen men ethics which are most advanced in clinical trials at the moment
00:33:45
yeah i think the michael brown is promising with frank um i seen the the tragedy with frank uh
00:33:50
my son is that the hotly would control trials a
00:33:53
lot of small or partly very large case the rest
00:33:57
but no control trials i think email model of tori tracks
00:34:01
ah interesting they have so far been disappointing for the question
00:34:05
which we have to ask is the concept wrong or i'll be
00:34:08
too late in the the seasons out diagnosis i think the late uh
00:34:12
is the case and as i mentioned uh i think one of the enigmatic questions is
00:34:17
whether we really have to treat underline i. b. d. we're just simply to reach up
00:34:21
passes in the live when they got which i think also would be good i think
00:34:25
but that knows is essential we have learned a lot
00:34:28
from the scandinavian trial putting you know i. b. d. patients
00:34:32
in this can and basically detecting high prevalence of p.
00:34:35
c. in patients with spoke when normal out point faster pace
00:34:39
the think the current strategy baking until at one foster these races
00:34:43
at least in high risk patients such as i. b. t. pages long we have to treat
00:34:48
the disease really maybe we have to do we define the disease that defining the disease
00:34:53
on complains your colouring geography which basically is proposes in scaring
00:34:58
my commands refers to this liver cirrhosis of the of the bile duct and would be like
00:35:02
defining upper rank come up with a disease based on the fact that there's a
00:35:06
rose is just simply doesn't make sense i think we have to redefine the disease
00:35:10
tweak it earlier and want issue is and
00:35:13
this is a unifying a perspective basically fall a
00:35:17
pack the pinnacle bile duct diseases is that when you have purposes and you've lost the facts
00:35:23
it's difficult to get the ducks back and this is totally different
00:35:26
for example from viral hepatitis and nash where you can get ripped off
00:35:30
uh they propose and still have the uh architecture which
00:35:34
with the rich works in p. c. and in even more
00:35:37
in p. p. c. uh when you lose the bile back
00:35:40
to have a disconnect and even getting rid of the prototype roses
00:35:44
probably won't help service complimentary and synergistic options and i think a complex disease
00:35:51
such as p. c. very likely will need a combination therapy
00:35:56
but it's not combining everything we have at the same time
00:35:59
but it's more a sequential therapy the problem will be hard to really test that clinically
00:36:04
in patients which in terms of number a slightly a
00:36:09
limited supplies recruit to clinical trials i think that's the most
00:36:13
important take home message thank you very much yeah
00:36:21
oh
00:36:28
i ah yes
00:36:38
yeah
00:36:45
oh
00:36:51
oh
00:36:53
yeah
00:36:55
ah
00:36:57
right
00:37:02
yeah
00:37:06
yeah i think it's fibrosis and probably non invoice aggressive approaches marcus
00:37:11
i think in terms of imaging we're not good good enough to really
00:37:15
you know quantified reliably or even though what we're looking at should we look at bile duct volume should
00:37:20
we look at a you know a stiffness or
00:37:23
should we look at the information in a diffusion sequences
00:37:28
but i think at the moment would be be probably have
00:37:30
made the mistake of not integrating for pros is enough yeah
00:37:34
i mean the compromises that at least in the ongoing phase
00:37:38
three trials we have those accomplice it endpoints improvement of colour spaces
00:37:42
at least without deterioration in some studies even improvement of approaches a little bit
00:37:48
like what you know from national improvement of nephew thought deterioration
00:37:52
of approaches or improvement of for profit without the duration of match
00:37:56
and this is uh this is really a problem also
00:37:59
in terms of uh uh encouraging industry in engaging in
00:38:03
large files and we have i think the little form next week or are these rules will be discussed i think
00:38:08
i think mandate effect potentially effective products has been killed
00:38:13
because the didn't reduce alkaline phosphates i think this was one of the
00:38:16
mistakes which would probably made in the past we do agree on that or
00:38:23
ah
00:38:29
uh_huh
00:38:38
yeah
00:38:40
the problem is that those markers i mean it's great you know to to
00:38:44
to a face to trial showing proof of concept pocket the cage with everything
00:38:48
then you go with the same concept to the phase three and this or they ask what's
00:38:53
the evidence that this is linked i'll come and then you have to say we don't know
00:38:56
and then you're back to the start this is this is the real problem uh
00:39:00
no but we just simply don't have the evidence at the moment but it really those
00:39:06
sorrow get parameters that linked all upcoming p. c. it's even more
00:39:09
an issue like a game you know of a national another liberties so
00:39:17
which
00:39:20
oh
00:39:25
yeah
00:39:29
right
00:39:32
yeah
00:39:35
yeah
00:39:37
yeah
00:39:42
oh yeah
00:39:48
uh_huh
00:39:52
because i'm reminded that i have to repeat the question not show was a
00:39:56
endoscopy of the bile duct where the the use your common interest copy also
00:40:01
in terms of requiring samples i mean the problem is uh the invasive next yeah otherwise we would be much more
00:40:07
advanced we would do it like an i. b. d. kind of also isn't really also from the convent we could do
00:40:14
colin joss could be as easily and safely like on oscar p. b. would run a lot filed
00:40:19
with nicole for healing and just see what works within or or eight weeks or something like that
00:40:24
that would be the perfect endpoint the product by hope is that in the chain
00:40:29
maybe good enough you know a high resolution m. r.
00:40:33
uh also with the fusion imaging and things like that
00:40:36
uh but i think it the you answer the question
00:40:39
itself clinical practised it will remain humour surveillance that human suspicion
00:40:43
and uh i didn't mention that the list and a
00:40:46
trial because it was focusing on a pharmacological therapy basically
00:40:51
pilot aviation uh with outstanding is uh by the same if because the
00:40:56
ratings less side effects and complications and drop them stand yeah but we
00:41:00
still do it's in some cases for the think it from stereo and
00:41:03
it was only or in patients who who were who haven't if if
00:41:16
yeah
00:41:18
e.
00:41:21
uh_huh
00:41:26
oh
00:41:30
oh right yeah
00:41:36
uh_huh
00:41:40
it's
00:41:43
oh absolutely absolutely
00:41:48
i mean the humble groove based on many studies also directed looking at the bile
00:41:53
including microbial up our also i'll six o. also help protect and i think you know
00:41:58
that may actually be a mark i think which is on the estimated because you often have the phenomenon
00:42:03
of having those sky high cal protecting levels
00:42:07
with hardly any endoscopy delusions and then we've
00:42:10
uh uh ask maybe it's his logical information i think this is coming from the bile duct
00:42:15
and i think cal protecting could be i mean certainly you know uh
00:42:19
they also put use a lot of or help protect it could be
00:42:23
maybe it should be studied more i know that uh for colours to do in your
00:42:28
directing file put you interviewed surviving behold to passage maybe that's a good income that information mark
00:42:36
sure
00:42:38
or from the u. c. p. a right of course that's what the above come through through e. e.
00:42:47
uh_huh
00:42:51
right
00:42:53
oh okay oh yeah
00:42:58
but you know
00:43:00
yeah
00:43:03
yeah yeah yeah yeah i mean quite honestly i think we should
00:43:09
put every i. b. d. patients i. b. d. more than a ten
00:43:12
years uh in the sky or even five years in the scanner i
00:43:16
mean it's easy to do in the centre but let's say to the
00:43:19
in the centre that's that's approach which i convinced my i. p. t. call work to do
00:43:25
and based on the scandinavian paper you detect a lot of abnormalities but here the question is is it really
00:43:31
p. c. so you have a normal colour ensure granting the patient has normal uh kind of off the base
00:43:37
but they also data suggest that there's radiological progression so
00:43:41
it's suggested that this may able to full blown p. c.
00:43:44
but the two and says we don't know whether that's true yeah but you
00:43:48
see early changes uh in i. b. d. patients with totally normal upon faster pace
00:43:53
and even you know patients who have a more local ensure grams we have some diffusion perry
00:43:58
portable correcting signals and the i mean something is going on in liver that maybe early p. c.
00:44:08
yeah
00:44:10
yeah that's the other downside yeah that's yeah
00:44:16
yeah that that's true i mean yeah
00:44:22
and probably should name it differently yeah we should i mean i i do not tell the patient
00:44:27
you have early p. c. because then they're just cool remote disputes yelled at a a uh huh
00:44:37
the it's a it's a difficult decision but i think at the end we we we need to have the courage
00:44:42
to change the definition of the disease otherwise you know remote window right now
00:44:53
yeah it's just so should survival benefit from i mean is that it's
00:44:59
a good for everybody really but this is right the this is the information
00:45:02
rich you seem to get there and the for profit and the cussing which
00:45:06
ended and the anti inflammatory i mean they're not directly into colours that it
00:45:10
actually um my group and was back in crowds or we're
00:45:13
running a a very early stepping trial in t. p. c. d.
00:45:17
because we thought it would be and the colours that approaches show that it's safe and that it's
00:45:22
lowering the profiles and there's the data from scandinavia the pages on staten switch you see
00:45:27
that's better outcomes due to those multi factorial steady effects i would
00:45:32
i would say i would not prescribe standards for p. c. but when there is the
00:45:36
slightest indication force that in user would encourage the use of stallions in such patients huh
00:45:43
even though you know that they have a increased prevalence or i. b.
00:45:46
p. patients of increased that the prevalence or don't know about you see
00:45:50
i don't think somebody showed the paper that maybe i think we you had one of your slides i think
00:45:57
we neglected many of our patients have all from ash and there will be on top of the immune or whatever
00:46:11
ah okay then
00:46:15
you know your i. e.
00:46:22
yes uh_huh
00:46:25
uh_huh
00:46:28
oh
00:46:34
right i i think that
00:46:38
i think the evidence is that patients uh whether significant elevation
00:46:43
of a l. t. in addition to the out far off
00:46:46
also improve without your key to go with the with the oak for some also for example yeah
00:46:53
so i think those are second i mean but we for example in p.
00:46:55
p. c. it's better defined as as active t. b. c. or this interface
00:47:00
uh activity not plastic appetite is in p. p. c.
00:47:05
which purport to associate with pull a prognosis i mean
00:47:08
it's it's actually this let's say there's good preclinical beta
00:47:13
that by less it's in this medium range of about fifty
00:47:17
hundred mike from all you know fire away from this toxic detergent activity
00:47:22
isn't using it th seventeen response and ever yeah directly from the battle sites which for example but
00:47:28
use and c. p. one uh this is indeed you're one mediator of a of an ominous i'm wondering
00:47:34
whether it i would say from a clinical perspective those patients would interface activity
00:47:40
in p. p. c. uh don't automatic all you know if the don't fulfil
00:47:44
the fool or criteria of overlaps and numbers biochemical in several logical a lot of
00:47:50
i would i break i mean nowadays we don't put little histology in p. p. c. or in
00:47:55
p. c. outside of clinical trials but a lot of that interface activity i think a secondary phenomena
00:48:02
work clinically would wait until the p. l. p. improves i think that maybe
00:48:06
a take home message i think if that goes of overlaps animals made much of
00:48:10
i i'm shop you know even all uh institution how many overlaps syndromes are
00:48:16
in let us or diagnosis just because somebody's indigo p. with p. b.
00:48:20
c. which then goes down with us agreed but that's not a lot of
00:48:25
and um i think those are secondary phenomena and you could say it's file as a
00:48:29
proxy city or in a more more than him a logical few which i'm sure you
00:48:34
uh have high affinity to i would i would think about the new mechanisms by less of a totally new
00:48:40
remote whatever you clocks i think this is or agents
00:48:44
this is some this is a concept which i think we'll
Conference Program
Autoimmune Hepatitis: Current and Emerging Treatment Options
Prof. Christoph Schramm, Senior physician, Medical Specialist in Internal Medicine and Gastroenterology, Center for Internal Medicine I, Medical University Clinic Hamburg Eppendorf, Hamburg, Germany
Sept. 5, 2019 · 6:06 p.m.
289 views
Emerging treatment options for patients with PSC
Prof. Michael Trauner, Chair of Gastroenterology and Hepatology, Department of Medicine III, Medical University Clinic, Vienna, Austria
Sept. 5, 2019 · 6:51 p.m.
233 views
Recommended talks
Anticoagulation treatment for portal vein thrombosis in patients with cirrhosis: DOACs – are we still far from using them?
Prof. Dr. med. Andrea De Gottardi, Hepatology, Inselspital, University Hospital Bern
June 21, 2018 · 7:30 p.m.
628 views
NIPMAP: Niche Phenotype Mapping of Multiplex Histology Data by Community Ecology.
Dr. Jean Hausser, Assistant Professor, Karolinska Institute, Sweden
Jan. 25, 2023 · 10:21 a.m.
132 views