• Je něco špatně v tomto záznamu ?

Prolonged fibroblast growth factor 19 response in patients with primary sclerosing cholangitis after an oral chenodeoxycholic acid challenge

SJ. Zweers, EM. de Vries, M. Lenicek, D. Tolenaars, DR. de Waart, KV. Koelfat, AK. Groen, SW. Olde Damink, U. Beuers, C. Ponsioen, PL. Jansen, FG. Schaap,

. 2017 ; 11 (1) : 132-140. [pub] 20160930

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc17023659

BACKGROUND: Bile salts likely contribute to liver injury in patients with primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC). Fibroblast growth factor 19 (FGF19) is a bile salt-induced enterokine with hepatoprotective potential as it suppresses de novo bile salt synthesis. Here, we evaluated the bile salt receptor FXR/FGF19 gut-liver axis in PSC and PBC patients. METHODS: Fasted patients with PSC (n = 12) and PBC (n = 10), and healthy controls (HC; n = 10) were orally challenged with the natural FXR agonist chenodeoxycholic acid (CDCA 15 mg/kg). Blood was sampled hourly until 8 h afterwards. Serum FGF19 and bile salt excursions were determined. Serum levels of 7α-hydroxy-4-cholesten-3-one (C4), reflecting bile salt synthesis, were measured as a biomarker of FGF19 response. RESULTS: Baseline serum FGF19 levels were comparable between groups, while fasted bile salt levels in PSC patients were elevated. Upon CDCA challenge, HC and PBC patients showed a serum FGF19 peak after 4 h followed by a decline. PSC patients showed a prolonged and elevated serum FGF19 response up to 8 h, combined with a sustained serum elevation of CDCA and other bile salts. In general, C4 levels declined following FGF19 elevation. In PSC patients with less favorable prognosis, baseline C4 levels were drastically suppressed and did not further decline. CONCLUSION: Following an oral CDCA challenge, PSC patients showed an impaired clearance of CDCA and a prolonged serum FGF19 response. FXR agonist therapy in PSC could cause prolonged exposure to elevated levels of FGF19, and we propose careful monitoring for detrimental side effects in patient studies.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc17023659
003      
CZ-PrNML
005      
20170908100755.0
007      
ta
008      
170720s2017 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1007/s12072-016-9769-7 $2 doi
035    __
$a (PubMed)27696157
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Zweers, Serge J $u Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands.
245    10
$a Prolonged fibroblast growth factor 19 response in patients with primary sclerosing cholangitis after an oral chenodeoxycholic acid challenge / $c SJ. Zweers, EM. de Vries, M. Lenicek, D. Tolenaars, DR. de Waart, KV. Koelfat, AK. Groen, SW. Olde Damink, U. Beuers, C. Ponsioen, PL. Jansen, FG. Schaap,
520    9_
$a BACKGROUND: Bile salts likely contribute to liver injury in patients with primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC). Fibroblast growth factor 19 (FGF19) is a bile salt-induced enterokine with hepatoprotective potential as it suppresses de novo bile salt synthesis. Here, we evaluated the bile salt receptor FXR/FGF19 gut-liver axis in PSC and PBC patients. METHODS: Fasted patients with PSC (n = 12) and PBC (n = 10), and healthy controls (HC; n = 10) were orally challenged with the natural FXR agonist chenodeoxycholic acid (CDCA 15 mg/kg). Blood was sampled hourly until 8 h afterwards. Serum FGF19 and bile salt excursions were determined. Serum levels of 7α-hydroxy-4-cholesten-3-one (C4), reflecting bile salt synthesis, were measured as a biomarker of FGF19 response. RESULTS: Baseline serum FGF19 levels were comparable between groups, while fasted bile salt levels in PSC patients were elevated. Upon CDCA challenge, HC and PBC patients showed a serum FGF19 peak after 4 h followed by a decline. PSC patients showed a prolonged and elevated serum FGF19 response up to 8 h, combined with a sustained serum elevation of CDCA and other bile salts. In general, C4 levels declined following FGF19 elevation. In PSC patients with less favorable prognosis, baseline C4 levels were drastically suppressed and did not further decline. CONCLUSION: Following an oral CDCA challenge, PSC patients showed an impaired clearance of CDCA and a prolonged serum FGF19 response. FXR agonist therapy in PSC could cause prolonged exposure to elevated levels of FGF19, and we propose careful monitoring for detrimental side effects in patient studies.
650    _2
$a aplikace orální $7 D000284
650    _2
$a dospělí $7 D000328
650    _2
$a senioři $7 D000368
650    _2
$a studie případů a kontrol $7 D016022
650    _2
$a purgativa $x aplikace a dávkování $7 D002400
650    _2
$a kyselina chenodeoxycholová $x aplikace a dávkování $7 D002635
650    _2
$a sklerozující cholangitida $x krev $x farmakoterapie $x metabolismus $7 D015209
650    _2
$a cholestenony $x krev $7 D002783
650    _2
$a klinické protokoly $7 D002985
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a fibroblastové růstové faktory $x krev $x metabolismus $7 D005346
650    _2
$a lidé $7 D006801
650    _2
$a střeva $x metabolismus $7 D007422
650    _2
$a játra $x metabolismus $7 D008099
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a lidé středního věku $7 D008875
655    _2
$a časopisecké články $7 D016428
700    1_
$a de Vries, Elisabeth M $u Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
700    1_
$a Lenicek, Martin $u Department of Clinical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
700    1_
$a Tolenaars, Dagmar $u Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands.
700    1_
$a de Waart, D Rudi $u Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands.
700    1_
$a Koelfat, Kiran V K $u Department of Surgery, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, PO BOX 616, 6200 MD, Maastricht, The Netherlands.
700    1_
$a Groen, Albert K $u Departments of Pediatrics, Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
700    1_
$a Olde Damink, Steven W M $u Department of Surgery, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, PO BOX 616, 6200 MD, Maastricht, The Netherlands.
700    1_
$a Beuers, Ulrich $u Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands. Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
700    1_
$a Ponsioen, Cyriel $u Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
700    1_
$a Jansen, Peter L M $u Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands. Department of Surgery, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, PO BOX 616, 6200 MD, Maastricht, The Netherlands.
700    1_
$a Schaap, Frank G $u Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands. frank.schaap@maastrichtuniversity.nl. Department of Surgery, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, PO BOX 616, 6200 MD, Maastricht, The Netherlands. frank.schaap@maastrichtuniversity.nl.
773    0_
$w MED00163696 $t Hepatology international $x 1936-0541 $g Roč. 11, č. 1 (2017), s. 132-140
856    41
$u https://pubmed.ncbi.nlm.nih.gov/27696157 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20170720 $b ABA008
991    __
$a 20170908101356 $b ABA008
999    __
$a ok $b bmc $g 1239340 $s 984572
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2017 $b 11 $c 1 $d 132-140 $e 20160930 $i 1936-0541 $m Hepatology international $n Hepatol Int $x MED00163696
LZP    __
$a Pubmed-20170720

Najít záznam

Citační ukazatele

Možnosti archivace