izindaba

Namuhla, isifo sesibindi esinamafutha e-Nonalcoholic (NAFLD) sesiyimbangela eyinhloko yesifo sesibindi esingapheli e-China ngisho nasemhlabeni. I-spectrum yesifo ihlanganisa i-hepatic steatohepatitis elula, i-nonalcoholic steatohepatitis (NASH) kanye ne-cirrhosis ehlobene nomdlavuza wesibindi. I-NASH ibonakala ngokunqwabelana kwamafutha amaningi kuma-hepatocyte kanye nokulimala kwamaselula nokuvuvukala, noma ngaphandle kwe-hepatic fibrosis. Ubunzima be-fibrosis yesibindi ezigulini ze-NASH buhlotshaniswa eduze nokubikezelwa kwesibindi esibi (i-cirrhosis kanye nezinkinga zayo kanye ne-hepatocellular carcinoma), izenzakalo zenhliziyo nemithambo yegazi, i-extrahepatic malignancies, kanye nayo yonke imbangela yokufa. I-NASH ingathinta kabi izinga lempilo yeziguli; Nokho, azikho izidakamizwa noma izindlela zokwelapha ezivunyelwe ukwelapha i-NASH.

Ucwaningo lwakamuva (ENLIVEN) olushicilelwe ku-New England Journal of Medicine (NEJM) lubonise ukuthi i-pegozafermin ithuthukise kokubili i-fibrosis yesibindi nokuvuvukala kwesibindi ezigulini ze-NASH eziqinisekisiwe ze-biopsy ezingezona i-cirrhotic.

Isivivinyo somtholampilo se-multicenter, esingahleliwe, esingaboni kabili, esilawulwa yi-placebo esilawulwa yi-placebo, esilawulwa nguSolwazi Rohit Loomba kanye nethimba lakhe lomtholampilo eNyuvesi yaseCalifornia, eSan Diego School of Medicine, sabhalisa iziguli ezingama-222 ezinesigaba esiqinisekisiwe se-biopsie F2-3 NASH phakathi kukaSepthemba 28, 2021 no-Agasti 15, 2022 zanikezwa umjovo we-pecuza 2022 ngokungahleliwe. mg noma 30 mg kanye ngesonto, noma 44 mg kanye njalo emavikini angu-2) noma i-placebo (kanye ngeviki noma kanye njalo emavikini angu-2). Iziphetho eziyinhloko zihlanganisa ≥ ukuthuthukiswa kwesigaba 1 ku-fibrosis futhi akukho ukuqhubeka kwe-NASH. I-NASH ixazululwe ngaphandle kokuqhubeka kwe-fibrotic. Lolu cwaningo lwenze nokuhlola ukuphepha.

Ngemuva kwamaviki angama-24 okwelashwa, inani leziguli ezine-≥ isigaba 1 sokuthuthuka kwe-fibrosis futhi elingekho ukuwohloka kwe-NASH, kanye nenani leziguli ezine-NASH futhi elingekho ukuwohloka kwe-fibrosis laliphezulu kakhulu emaqenjini amathathu ethamo le-Pegozafermin kuneqembu le-placebo, nomehluko obaluleke kakhulu ezigulini ezelashwa nge-44 mg kanye njalo emavikini amabili noma ama-30. Mayelana nokuphepha, i-pegozafermin yayifana ne-placebo. Izehlakalo ezimbi ezivame kakhulu ezihlobene nokwelashwa kwe-pegozafermin kwakuyisicanucanu, isifo sohudo, ne-erythema endaweni yomjovo. Kulolu cwaningo lwesigaba 2b, imiphumela yokuqala iphakamisa ukuthi ukwelashwa nge-pegozafermin kuthuthukisa i-liver fibrosis.

I-pegozafermin, esetshenziswe kulolu cwaningo, iyi-analogue ye-glycolated esebenza isikhathi eside ye-human fibroblast growth factor 21 (FGF21). I-FGF21 iyi-hormone ye-metabolic engapheli ekhishwa isibindi, edlala indima ekulawuleni i-lipid kanye ne-glucose metabolism. Ucwaningo lwangaphambilini lubonise ukuthi i-FGF21 inemiphumela yokwelapha ezigulini ze-NASH ngokwandisa ukuzwela kwe-insulin yesibindi, ivuselela i-fatty acid oxidation, nokuvimbela i-lipogenesis. Kodwa-ke, isigamu sempilo emfushane ye-FGF21 yemvelo (cishe amahora angu-2) ikhawulela ukusetshenziswa kwayo ekwelashweni komtholampilo kwe-NASH. I-pegozafermin isebenzisa ubuchwepheshe be-glycosylated pegylation ukuze inwebe uhhafu wempilo ye-FGF21 yemvelo futhi ithuthukise umsebenzi wayo webhayoloji.

Ngaphezu kwemiphumela emihle yalolu cwaningo lomtholampilo lweSigaba 2b, olunye ucwaningo lwakamuva olushicilelwe ku-Nature Medicine (ENTRIGUE) lubonise ukuthi i-pegozafermin iphinde yehlisa kakhulu i-triglycerides, i-cholesterol engeyona i-HDL, i-apolipoprotein B, kanye ne-hepatic steatosis ezigulini ezine-hypertriglyceridemia enzima, engase ibe nomthelela omuhle ekunciphiseni ingozi ye-cardiovascular events ezigulini ezine-NASH.

Lolu cwaningo luphakamisa ukuthi i-pegozafermin, njenge-hormone ye-metabolic engapheli, ingahlinzeka ngezinzuzo eziningi ze-metabolic ezigulini ezine-NASH, ikakhulukazi ngoba i-NASH ingase iqanjwe kabusha ngokuthi isifo sesibindi esihlobene ne-metabolic esikhathini esizayo. Le miphumela ikwenza kube umuthi ongaba namandla obaluleke kakhulu ekwelapheni i-NASH. Ngesikhathi esifanayo, le miphumela emihle yocwaningo izosekela i-pegozafermin ibe yisigaba sesi-3 sokuhlolwa komtholampilo.

Nakuba kokubili masonto onke ama-44 mg noma iviki ngalinye ukwelashwa kwe-pegozafermin okungu-30 mg kufinyelele isiphetho esiyinhloko se-histological yocwaningo, ubude besikhathi sokwelashwa kulolu cwaningo lwalungamaviki angu-24 kuphela, futhi izinga lokuthobela eqenjini le-placebo lalingu-7% kuphela, elaliphansi kakhulu kunemiphumela yocwaningo lomtholampilo lwangaphambilini olwathatha amaviki angu-48. Ingabe umehluko nokuvikeleka kuyafana? Uma kubhekwa ukuhlukahluka kwe-NASH, ukuhlolwa kwemitholampilo emikhulu, emaphakathi, amazwe ngamazwe kuyadingeka esikhathini esizayo ukuze kufakwe isibalo esikhulu seziguli kanye nokwelula ubude besikhathi sokwelashwa ukuze kuhlolwe kangcono ukusebenza nokuphepha komuthi.