Ursodeoxycholic Acid in the Therapy for Primary Biliary Cirrhosis: Effects on Progression and Prognosis

Abstract

The effects in clinical studies of UDCA on the endpoints "death" or "pre-transplantation survival" can only be shown when UDCA therapy is started in an early disease phase, preferably in stage I but no later than stage II, and is then continued into stages III/IV, or preferably stage IV. The reasons for this lie in the observation that, in stages I/II, no patient suffers from progressive disease that irrevocably leads to death or transplantation, while a measurable effect of UDCA, as is true for other drugs and other hepatic diseases, continues to dwindle and finally disappears as patients progress through the fibrotic and cirrhotic stages III and IV. Hence, administration of UDCA must begin in the phase of progressive inflammation (stages I and II) and the outcome documented after many years of long-term therapy. This requires very large, probably unattainable, patient collectives. Whether it is justified to administer placebo to one-half of these patients over such an extended period of time represents a profound ethical dilemma. Because these arguments were not considered in the two meta-analyses cited above or in any other study, they do not allow a definitive statement on the life expectancy of patients on UDCA therapy. On the other hand, it is possible using generally accepted, independent prognostic variables and mathematical models, whose limitations are well-known and must be considered, to predict with a high degree of accuracy the disease course of treated and untreated patients and calculate their life expectancy and/or pre-transplantation survival. Because UDCA exerts a significant positive effect on the most important prognostic markers for PBC, such as serum bilirubin, piecemeal necroses, histological disease progression, ascites and edema, and apparently the scores for pruritus and fatigue, this permits us to demonstrate not only a decrease in the incidence of transplantation but also to calculate a prolongation in life expectancy.

Was der (Viszeral-)Chirurg als neue Erkenntnisse über die Gallensäuren und deren Zusammenspiel mit dem Darmmikrobiom wissen sollte

“…So wird die in der menschlichen Galle nur zu 3 % vorkommende Ursodesoxycholsäure (lat. ursus = Bär) zur Auflösung kleiner Gallensteine und als Apoptosehemmer zur Behandlung der primären biliären Cholangitis eingesetzt [5,60].…”

Primary biliary cirrhosis and liver transplantation

“…The only currently established treatment for PBC is UDCA 13-15 mg/kg a day (119). UDCA was shown to improve serum biochemical markers such as bilirubin, ALP, GGT, cholesterol, and IgM levels (120-125).…”

Therapie cholestatischer Lebererkrankungen

“…Tab. 3) und der Transplantationsindikation [9] sowie bei frühzeitigem Therapiebeginn zu einer signifikanten Lebensverlängerung [19,32]. [23] 55 Gebessert Unverändert Fraglich Poupon et al 1991Poupon et al ,1994 146 Gebessert Gebessert Gebessert Lindor et al 1994Lindor et al , 1996 178 Gebessert Gebessert Unverändert Heathcote et al 1994 [9] 222 Gebessert Gebessert Gebessert Turner et al 1994 [35] 46 Gebessert Gebessert n. s. Combes et al 1995 [5] 149 Gebessert Gebessert Gebessert [20] 105 Gebessert Gebessert Unverändert Mitchell et al 1997 [22] 24 Gebessert Gebessert Gebessert…”