Interventions for primary biliary cirrhosis and osteoporosis in patients with primary biliary cirrhosis : Cochrane reviews with meta-analyses and trial sequential analyses of randomized clinical trials

Abstract

Primary biliary cirrhosis is a chronic autoimmune-mediated liver disease characterised by progressive destruction of intrahepatic bile ducts, resulting in chronic cholestasis, portal inflammation, and fibrosis that can lead to cirrhosis and, ultimately, liver failure and the need for liver transplantation. The disease primarely affects middle‐aged women and is associated with osteoporosis ‐ either postmenopausal or secondary to the liver disease. Low bone mass is an important cause of morbidity in patients with primary biliary cirrhosis, leading to an increased risk of fractures, pain, and deformity. Treatment of primary biliary cirrhosis and osteoporosis associated with primary biliary cirrhosis is complicated. A number of drugs have been evaluated for patients with primary biliary cirrhosis (glucocorticosteroids, methotrexat, azathioprine, colchicine, cyclosporin, D-penicillamine, and chlorambucil). Ursodeoxycholic acid is the only drug approved for primary biliary cirrhosis by the U.S. Food and Drug Administration. Bezafibrate may be effective for treatment of primary biliary cirrhosis. Bisphosphonates and hormone replacement may be effective treatment options for osteoporosis in primary biliary cirrhosis, but the effects have only had limited assessment in systematic reviews. Therefore, interventions based on evidence are highly warranted. Cochrane reviews with meta-analyses and trial sequential analyses of randomised clinical trials generally provide the best available evidence for health care interventions and clinical practice. Such Cochrane reviews are used to assess and summarise benefits and harms of clinical interventions. Furthermore, Cochrane reviews will also reveal lack of evidence, and define the specific need for future randomised clinical trials. Objectives To summarize the evidence from Cochrane systematic reviews on treatment options for patients with primary biliary cirrhosis and osteoporosis associated with primary biliary cirrhosis...

Primarna bilijarna ciroza je hronična autoimuna bolest jetre koju karakteriše progresivna destrukcija intrahepatičnih žučnih puteva sa posledičnom holestazom, portnom inflamacijom, i fibrozom što dovodi do nastanka ciroze jetre, i hepatičke insuficijencije sa transplantacijom jetre kao jedinom uspešnom terapijskom metodom. Više od 90% bolesnika su žene, prosečne starosti oko 50 godina. Najvažnija komplikacija bolesti vezana za holestazu je osteoporoza gde smanjenje koštane gustine dovodi do velikog rizika za nastanak preloma kostiju, bola i deformiteta. Lečenje primarne bilijarne ciroze, kao i osteoporoze u sklopu primarne bilijarne ciroze je veoma komplikovano. Za sada nema zadovoljavajuće specifične medicinske terapije koja se preporučuje za lečenje ove bolesti. Evaluirani su mnogi lekovi u terapiji ove bolesti (kortikosteroidi, metrotreksat, azatioprin, kolhicin, ciklosporin, D-penicilamin, i hlorambucil), ali do sada prikazani trajali su uglavnom bili kratki, mali i slabo kontrolisani. Ursodeoksiholna kiselina jedini je lek odobren za terapiju primarne bilijarne ciroze. U nekim kontrolisanim studijama konstatovano je da bezafibrat ima višestruka pozitivna dejstva kod bolesnika sa primarnom bilijarnom cirozom. Za bisfosfonate i supstitucionu hormonsku terapiju se očekuje da budu efikasni u terapiji osteoporoze u sklopu primarne bilijarne ciroze, ali ne postoje za sada dokazi efikasnoti u sistematskim pregledima. Kohranovi sistematski pregledi sa meta-analizama i sekvencijalnim analizama randomizovanih kliničkih studija sintetišu dokaze u cilju dobijanja pouzdanog, validnog i kompletnog pregleda proverenih dokaza o korisnim i štetnim efektima terapijskih procedura koristeći metodologiju u kojoj nema pristrasnosti u tumačenju rezultata i izvođenju zaključaka. Takođe, oni mogu ukazati na nedostatak dokaza i potrebu za budućim dobro dizajniranim randomizovanim kliničkim studijama...