{"id":7,"date":"2017-05-27T22:01:46","date_gmt":"2017-05-27T22:01:46","guid":{"rendered":"https:\/\/www.slovhep.sk\/verejnost\/clanok?uid=5f03acc282df4f389f48a59ed9e261d7"},"modified":"2017-05-27T22:01:46","modified_gmt":"2017-05-27T22:01:46","slug":"odborne-5f03acc282df4f389f48a59ed9e261d7","status":"publish","type":"post","link":"https:\/\/slovhep.sk\/en\/odborne-5f03acc282df4f389f48a59ed9e261d7","title":{"rendered":"Obeticholov\u00e1 kyselina \u2013 krit\u00e9ri\u00e1 pre lie\u010dbu pacientov s\u00a0prim\u00e1rnou bili\u00e1rnou cholangit\u00eddou"},"content":{"rendered":"<p>&nbsp;<\/p>\n<ul>\n<li>Choroba v&nbsp;&scaron;t&aacute;diu F3 alebo F4 pod\u013ea sk&oacute;re METAVIR verifikovan&eacute; histologicky alebo elastograficky,<\/li>\n<li>pri cirh&oacute;ze pe\u010dene kompenzovan&aacute; choroba Child-Pugh A 5-6 bodov, MELD &lt; 10 bodov,<\/li>\n<li>ne&uacute;spe&scaron;n&aacute; lie\u010dba ursodeoxycholovou kyselinou (UDCA) v&nbsp;&scaron;tandardnej d&aacute;vke 15 mg\/kg hmotnosti v&nbsp;d\u013a\u017eke trvania aspo\u0148 jeden rok, definovan&aacute; ako:<\/li>\n<li>progresia choroby verifikovan&aacute; histologicky alebo elastograficky, alebo<\/li>\n<li>ALP &ge; dvojn&aacute;sobok hornej hranice normy,<\/li>\n<li>celkov&yacute; bilirub&iacute;n &le; dvojn&aacute;sobok hornej hranice normy,<\/li>\n<li>predpokladan&aacute; compliance pacienta,<\/li>\n<li>re&scaron;pektovanie SPC lieku Ocaliva,<\/li>\n<li>nepr&iacute;tomnos\u0165 inej z&aacute;va\u017enej choroby pe\u010dene,<\/li>\n<li>nepr&iacute;tomnos\u0165 malignity s&nbsp;v&yacute;nimkou ohrani\u010den&eacute;ho zhubn&eacute;ho n&aacute;doru ko\u017ee,<\/li>\n<li>v&nbsp;anamn&eacute;ze nie je u\u017e&iacute;vanie drog alebo nadmern&eacute; u\u017e&iacute;vanie alkoholu.<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<p><strong>Defin&iacute;cia odpovede na lie\u010dbu obeticholovou kyselinou <\/strong>(pod\u013ea 8)<strong>:<\/strong><\/p>\n<ul>\n<li>ALP &lt; 1,67-n&aacute;sobok hornej hranice normy a&nbsp;celkov&yacute; bilirub&iacute;n &le; hornej hranice normy po 12 mesiacoch lie\u010dby.<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<p><strong>Zd&ocirc;vodnenie<\/strong><\/p>\n<p>Pod\u013ea odpor&uacute;\u010dan&iacute; EASL zv&yacute;&scaron;en&eacute; riziko komplik&aacute;ci&iacute; pri&nbsp;PBC maj&uacute; pacienti, ktor&iacute; nedosiahli biochemick&uacute; odpove\u010f na lie\u010dbu kyselinou ursodeochylol&iacute;novou (UDCA) a&nbsp;pacienti s&nbsp;cirh&oacute;zou pe\u010dene (1). Najsilnej&scaron;&iacute;m rizikov&yacute;m faktorom pre inadekv&aacute;tnu biochemick&uacute; odpove\u010f na lie\u010dbu UDCA je v\u010dasn&yacute; vek v&nbsp;\u010dase stanovenia diagn&oacute;zy (menej ako 45 rokov) a&nbsp;pokro\u010dil&aacute; choroba v&nbsp;\u010dase ur\u010denia diagn&oacute;zy (1).<\/p>\n<p>Biochemick&aacute; odpove\u010f na lie\u010dbu UDCA je esenci&aacute;lny prediktor dlhodobej progn&oacute;zy pri PBC (4) a &nbsp;je rozhoduj&uacute;ca pri identifik&aacute;cii pacientov vy\u017eaduj&uacute;cich in&uacute; lie\u010dbu ako je ursodeoxychol&iacute;nov&aacute; kyselina. Jej definovanie umo\u017e\u0148uje presn&yacute; odhad rizika &uacute;mrtia alebo transplant&aacute;cie pe\u010dene u&nbsp;pacientov s&nbsp;PBC. <strong>V&nbsp;defin&iacute;cii biochemickej odpovede zohr&aacute;va k\u013e&uacute;\u010dov&uacute; &uacute;lohu zmena ALP pri lie\u010dbe UDCA<\/strong> (4). <strong>Kombin&aacute;cia ALP a&nbsp;celkov&eacute;ho bilirub&iacute;nu zvy&scaron;uje schopnos\u0165 predikova\u0165 pre\u017e&iacute;vanie pacienta <\/strong>(1, 5). EASL odpor&uacute;\u010da pou\u017e&iacute;va\u0165 kombin&aacute;ciu ALP a&nbsp;celkov&eacute;ho bilirub&iacute;nu na stratifik&aacute;ciu individu&aacute;lneho rizika progresie, &nbsp;elastografiu a&nbsp;rizikov&eacute; sk&oacute;re na defin&iacute;ciu individu&aacute;lneho rizika komplik&aacute;ci&iacute; (1). Preh\u013ead mo\u017en&yacute;ch defin&iacute;cii biochemickej odpovede a&nbsp;sk&oacute;rovac&iacute;ch syst&eacute;mov uv&aacute;dza tabu\u013eka \u010d. 1. 10-ro\u010dn&eacute; pre\u017e&iacute;vanie pri lie\u010dbe UDCA je 84 % u&nbsp;pacientov s&nbsp;ALP do dvojn&aacute;sobku hornej hranice normy a&nbsp;62 % u&nbsp;pacientov s&nbsp;ALP nad dvojn&aacute;sobok hornej hranice normy (<em>p &lt; <\/em>0,0001). Pri norm&aacute;lnej hodnote bilirub&iacute;nu je 10-ro\u010dn&eacute; pre\u017e&iacute;vanie 86 %, ak je zv&yacute;&scaron;en&yacute; bilirub&iacute;n, pre\u017e&iacute;vanie je iba 41 % (p &lt; 0,0001) (5). V&nbsp;inej &scaron;t&uacute;dii pacienti lie\u010den&iacute; UDCA s&nbsp;ALP nad dvojn&aacute;sobok hornej hranice normy mali dvojn&aacute;sobne vy&scaron;&scaron;ie riziko komplik&aacute;cie definovanej ako krv&aacute;canie z&nbsp;varixov, encefalopatia, ascites, &uacute;mrtie alebo transplant&aacute;cia pe\u010dene v&nbsp;porovnan&iacute; s&nbsp;pacientmi s&nbsp;hodnotou ALP pod dvojn&aacute;sobok hornej hranice normy (23 % versus 11 %), (p&nbsp;&lt;&nbsp;0,05) (7).&nbsp; In&iacute; autori (2, 3, 6) definuj&uacute; biochemick&uacute; odpove\u010f na lie\u010dbu UDCA e&scaron;te pr&iacute;snej&scaron;ie &ndash; ako pokles ALP pod 1,67-n&aacute;sobok hornej hranice normy. Iba 2 % pacientov v &scaron;t&aacute;diu&nbsp;Child-Pugh B pre\u017eije 7 rokov, u&nbsp;t&yacute;chto pacientov je potrebn&eacute; zv&aacute;\u017ei\u0165 zaradenie do programu transplant&aacute;cie pe\u010dene (9).<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Literat&uacute;ra<\/strong><\/p>\n<ul>\n<li>European Association for Study of the Liver. EASL Clinical Practice guidlines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol (2017)<\/li>\n<li>Hansen M, et al. Hepatology 2011; 54 (suppl 4) (Abstract 1787).<\/li>\n<li>Kumagi T, et al. Hepatology 2010(b); 52 (suppl 4) (Abstract 324).<\/li>\n<li>Lammers WJ, et al. Predicting outcome in primary biliary cirrhosis. Annals of Hepatology 2014; 13(4):316-326.<\/li>\n<li>Lammers WJ, et al. Levels of alkaline phosphatase and bilirubin are surrogate end points of outcomes of patients with primary biliary cirrhosis: an international follow-up study. 2014; 147(6):1338&ndash;49.<\/li>\n<li>Meaney MJ, et al. J Hepatol 2011; 54:S364-534(Abstract 1296).<\/li>\n<li>Momah N, et al. Optimizing biochemical markers as endpoints for clinical trials in primary biliary cirrhosis. Liver International 2012; 32: 790-795.<\/li>\n<li>Nevens F, et al. A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis. N Engl J Med. 2016; 375(7):631-43.<\/li>\n<li>Reisman Y, et al. Survival probabilities of Pugh-Child-PBC classified patients in the euricterus primary biliary cirrhosis population, based on the Mayo clinic prognostic model. Euricterus Project Management Group. 1997; 44(16):982-9. <strong><br \/> <\/strong><\/li>\n<\/ul>\n<p><strong>Tabu\u013eka 1: Hodnotenie odpovede na lie\u010dbu UDCA u&nbsp;pacientov s&nbsp;prim&aacute;rnou bili&aacute;rnou cholangit&iacute;dou <\/strong>(pod\u013ea 1)<\/p>\n<p><strong>&nbsp;<\/strong><\/p>\n<table style=\"border-color: #000000;\" border=\"2\">\n<tbody>\n<tr>\n<td style=\"width: 160.243px;\">\n<p><strong>Kvalitat&iacute;vna defin&iacute;cia<\/strong><\/p>\n<\/td>\n<td style=\"width: 116.91px;\">\n<p><strong>\u010cas (mesiace)<\/strong><\/p>\n<\/td>\n<td style=\"width: 333.576px;\">\n<p><strong>Zlyhanie lie\u010dby<\/strong><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"width: 160.243px;\">\n<p>Rochester<\/p>\n<\/td>\n<td style=\"width: 116.91px;\">\n<p>6<\/p>\n<\/td>\n<td style=\"width: 333.576px;\">\n<p>ALP &ge; 2x ULN alebo<\/p>\n<p>Mayo sk&oacute;re &ge; 4,5<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"width: 160.243px;\">\n<p>Barcelona<\/p>\n<\/td>\n<td style=\"width: 116.91px;\">\n<p>12<\/p>\n<\/td>\n<td style=\"width: 333.576px;\">\n<p>Pokles ALP &nbsp;&le; 40 % alebo<\/p>\n<p>ALP &ge; 1x ULN<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"width: 160.243px;\">\n<p>Paris I<\/p>\n<\/td>\n<td style=\"width: 116.91px;\">\n<p>12<\/p>\n<\/td>\n<td style=\"width: 333.576px;\">\n<p>ALP &nbsp;&ge; 3x ULN alebo<\/p>\n<p>AST &ge; 2x ULN alebo<\/p>\n<p>Bilirub&iacute;n &gt; 17,1 umol\/l<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"width: 160.243px;\">\n<p>Rotterdam<\/p>\n<\/td>\n<td style=\"width: 116.91px;\">\n<p>12<\/p>\n<\/td>\n<td style=\"width: 333.576px;\">\n<p>Bilirub&iacute;n &ge; 1x ULN alebo<\/p>\n<p>Album&iacute;n &lt; 1x ULN<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"width: 160.243px;\">\n<p>Toronto<\/p>\n<\/td>\n<td style=\"width: 116.91px;\">\n<p>24<\/p>\n<\/td>\n<td style=\"width: 333.576px;\">\n<p>ALP &gt; 1,67x ULN<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"width: 160.243px;\">\n<p>Paris II<\/p>\n<\/td>\n<td style=\"width: 116.91px;\">\n<p>12<\/p>\n<\/td>\n<td style=\"width: 333.576px;\">\n<p>ALP &ge; 1,5x ULN alebo<\/p>\n<p>AST &ge; 1,5x ULN alebo<\/p>\n<p>Bilirub&iacute;n &gt; 17,1 umol\/l<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"width: 160.243px;\">\n<p>Ehime<\/p>\n<\/td>\n<td style=\"width: 116.91px;\">\n<p>6<\/p>\n<\/td>\n<td style=\"width: 333.576px;\">\n<p>Pokles GMT &le; 70 % a GMT &ge; 1xULN<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"width: 160.243px;\">\n<p><strong>Kontinu&aacute;lne sk&oacute;rovacie syst&eacute;my<\/strong><\/p>\n<\/td>\n<td style=\"width: 116.91px;\">\n<p><strong>\u010cas (mesiace)<\/strong><\/p>\n<\/td>\n<td style=\"width: 333.576px;\">\n<p><strong>Sk&oacute;rovacie parametre<\/strong><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"width: 160.243px;\">\n<p>UK-PBC<\/p>\n<\/td>\n<td style=\"width: 116.91px;\">\n<p>12<\/p>\n<\/td>\n<td style=\"width: 333.576px;\">\n<p>Bilirub&iacute;n, ALP a&nbsp;AST v&nbsp;12. mesiaci, album&iacute;n a&nbsp;trombocyty na za\u010diatku lie\u010dby<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"width: 160.243px;\">\n<p>GLOBE<\/p>\n<\/td>\n<td style=\"width: 116.91px;\">\n<p>12<\/p>\n<\/td>\n<td style=\"width: 333.576px;\">\n<p>Bilirub&iacute;n, ALP, album&iacute;n, trombocyty v&nbsp;12. mesiaci, vek na za\u010diatku lie\u010dby<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n","protected":false},"excerpt":{"rendered":"<p>&nbsp; Choroba v&nbsp;&scaron;t&aacute;diu F3 alebo F4 pod\u013ea sk&oacute;re METAVIR verifikovan&eacute; histologicky alebo elastograficky, pri cirh&oacute;ze pe\u010dene kompenzovan&aacute; choroba Child-Pugh A 5-6 bodov, MELD &lt; 10 bodov, ne&uacute;spe&scaron;n&aacute; lie\u010dba ursodeoxycholovou kyselinou (UDCA) v&nbsp;&scaron;tandardnej d&aacute;vke 15 mg\/kg hmotnosti v&nbsp;d\u013a\u017eke trvania aspo\u0148 jeden rok, definovan&aacute; ako: progresia choroby verifikovan&aacute; histologicky alebo elastograficky, alebo ALP &ge; dvojn&aacute;sobok hornej hranice [&hellip;]<\/p>\n","protected":false},"author":2,"featured_media":2304,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_et_pb_use_builder":"","_et_pb_old_content":"","_et_gb_content_width":"","inline_featured_image":false,"footnotes":""},"categories":[5],"tags":[28],"class_list":["post-7","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-pre-clenov","tag-ochorenia"],"_links":{"self":[{"href":"https:\/\/slovhep.sk\/en\/wp-json\/wp\/v2\/posts\/7","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/slovhep.sk\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/slovhep.sk\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/slovhep.sk\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/slovhep.sk\/en\/wp-json\/wp\/v2\/comments?post=7"}],"version-history":[{"count":0,"href":"https:\/\/slovhep.sk\/en\/wp-json\/wp\/v2\/posts\/7\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/slovhep.sk\/en\/wp-json\/wp\/v2\/media\/2304"}],"wp:attachment":[{"href":"https:\/\/slovhep.sk\/en\/wp-json\/wp\/v2\/media?parent=7"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/slovhep.sk\/en\/wp-json\/wp\/v2\/categories?post=7"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/slovhep.sk\/en\/wp-json\/wp\/v2\/tags?post=7"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}