nkhani

Masiku ano, matenda a chiwindi a Nonalcoholic mafuta (NAFLD) akhala amayambitsa matenda aakulu a chiwindi ku China komanso ngakhale padziko lapansi. Kuchuluka kwa matenda kumaphatikizapo chiwindi chosavuta cha steatohepatitis, nonalcoholic steatohepatitis (NASH) ndi matenda enaake okhudzana ndi chiwindi ndi khansa ya chiwindi. NASH imadziwika ndi kuchuluka kwamafuta ochulukirapo mu hepatocytes ndikupangitsa kuwonongeka kwa ma cell ndi kutupa, kapena popanda hepatic fibrosis. Kuopsa kwa chiwindi fibrosis kwa odwala a NASH kumagwirizana kwambiri ndi matenda a chiwindi (cirrhosis ndi zovuta zake ndi hepatocellular carcinoma), zochitika zamtima, matenda a extrahepatic, ndi imfa zonse. NASH imatha kusokoneza moyo wa odwala; komabe, palibe mankhwala kapena mankhwala omwe avomerezedwa kuti azichiza NASH.

Kafukufuku waposachedwa (ENLIVEN) wofalitsidwa mu New England Journal of Medicine (NEJM) adawonetsa kuti pegozafermin imathandizira onse chiwindi fibrosis ndi kutupa kwa chiwindi mwa odwala omwe amatsimikizira kuti si a cirrhotic NASH omwe amatsimikiziridwa ndi biopsy.

The multicenter, randomized, double-blind, two-blind-controlled, placebo-controlled Phase 2b, yoyendetsedwa ndi Pulofesa Rohit Loomba ndi gulu lake lachipatala ku yunivesite ya California, San Diego School of Medicine, adalembetsa odwala 222 omwe ali ndi biopsie-confirmed stage F2-3 NASH pakati pa September 28, 2021 ndi August 15, 2022 anapatsidwa jekeseni wa 1. mg kapena 30 mg kamodzi pa sabata, kapena 44 mg kamodzi pa masabata a 2) kapena placebo (kamodzi pa sabata kapena kamodzi pa masabata a 2). Mapeto oyambira amaphatikiza ≥ gawo 1 kusintha kwa fibrosis ndipo palibe kupita patsogolo kwa NASH. NASH idathetsedwa popanda kupita patsogolo kwa fibrotic. Kafukufukuyu adayesanso chitetezo.

Pambuyo pa chithandizo cha milungu 24, kuchuluka kwa odwala omwe ali ndi ≥ siteji 1 kusintha kwa fibrosis ndipo sikukukulirakulira kwa NASH, komanso kuchuluka kwa odwala omwe ali ndi vuto la NASH komanso osawonjezereka kwa fibrosis anali okwera kwambiri m'magulu atatu a Pegozafermin kuposa gulu la placebo, komanso kusiyana kwakukulu kwa odwala omwe amalandila 44 mg kamodzi pa sabata ziwiri zilizonse kapena 30. Pankhani ya chitetezo, pegozafermin inali yofanana ndi placebo. Zowopsa zomwe zimakhudzidwa kwambiri ndi chithandizo cha pegozafermin zinali nseru, kutsegula m'mimba, ndi erythema pamalo opangira jakisoni. Mu mayesero a gawo la 2b, zotsatira zoyamba zimasonyeza kuti chithandizo cha pegozafermin chimapangitsa chiwindi fibrosis.

pegozafermin, yogwiritsidwa ntchito mu phunziroli, ndi glycolated analogue ya human fibroblast growth factor 21 (FGF21). FGF21 ndi mahomoni a metabolic omwe amapangidwa ndi chiwindi, omwe amagwira ntchito pakuwongolera kagayidwe ka lipid ndi glucose. Kafukufuku wam'mbuyo wasonyeza kuti FGF21 ili ndi zotsatira zochizira odwala a NASH powonjezera chidwi cha insulin ya chiwindi, kulimbikitsa mafuta acid oxidation, ndi kuletsa lipogenesis. Komabe, theka lalifupi la moyo wa FGF21 (pafupifupi maola 2) limachepetsa kugwiritsidwa ntchito kwake mu chithandizo chamankhwala cha NASH. pegozafermin imagwiritsa ntchito ukadaulo wa glycosylated pegylation kukulitsa theka la moyo wachilengedwe wa FGF21 ndikuwongolera zochitika zake zachilengedwe.

Kuphatikiza pa zotsatira zabwino mu mayesero achipatala a Phase 2b, kafukufuku wina waposachedwapa wofalitsidwa mu Nature Medicine (ENTRIGUE) anasonyeza kuti pegozafermin inachepetsanso kwambiri triglycerides, cholesterol yopanda HDL, apolipoprotein B, ndi hepatic steatosis kwa odwala omwe ali ndi hypertriglyceridemia yoopsa, yomwe ingakhale ndi zotsatira zabwino pa kuchepetsa chiopsezo cha mtima wamtima zochitika kwa odwala NASH.

Kafukufukuyu akuwonetsa kuti pegozafermin, monga mahomoni okhazikika a metabolic, amatha kupereka mapindu angapo a kagayidwe kachakudya kwa odwala omwe ali ndi NASH, makamaka chifukwa NASH ikhoza kutchedwanso matenda okhudzana ndi chiwindi chamafuta mtsogolo. Zotsatirazi zimapangitsa kukhala mankhwala ofunikira kwambiri pochiza NASH. Nthawi yomweyo, zotsatira zabwino za kafukufukuyu zithandizira pegozafermin mu gawo lachitatu la mayesero azachipatala.

Ngakhale kuti chithandizo cha 44 mg kapena 30 mg pegozafermin mlungu uliwonse mlungu uliwonse chinakwaniritsa mapeto oyambirira a mayesero, nthawi ya chithandizo mu phunziroli inali masabata 24 okha, ndipo mlingo wotsatira gulu la placebo unali 7% yokha, yomwe inali yochepa kwambiri kusiyana ndi zotsatira za maphunziro achipatala am'mbuyomu omwe anakhala masabata 48. Kodi kusiyana ndi chitetezo ndizofanana? Chifukwa cha kusiyanasiyana kwa NASH, mayesero akuluakulu, apakati, azachipatala padziko lonse lapansi akufunika mtsogolomu kuti aphatikizepo odwala ambiri ndikuwonjezera nthawi ya chithandizo kuti awonetsetse kuti mankhwalawa ndi othandiza komanso otetezeka.