Ursodeoxycholic Acid Improves Bilirubin but Not Albumin in Primary Biliary Cirrhosis: Further Evidence for Nonefficacy

Abstract

Background/Aim. In randomised controlled trials (RCTs) of ursodeoxycholic acid (UDCA), although serum bilirubin is frequently reduced, its effect on disease progression and mortality is unclear. As serum albumin is an established independent prognostic marker, one might expect less deterioration of serum albumin values in a UDCA-treated group. We therefore modelled the typical evolution of serum bilirubin and albumin levels over time in UDCA-untreated patients and compared it with the observed levels in UDCA RCTs. Methods. Multilevel modelling was used to relate the evolution of serum albumin to serum bilirubin and time since patient referral. For each considered RCT, the derived model was used to predict the relationship between final mean serum albumin and bilirubin concentration, adjusted for mean serum albumin at referral and followup duration. Results. Five RCTs were eligible in terms of available data, of which two had long followup. In all trials, serum albumin did not significantly differ between UDCA- and placebo-treated patients, despite the UDCA effect on serum bilirubin. Therefore, there is no evidence over time for changes or maintenance of albumin levels for UDCA-treated patients above the levels predicted for placebo-treated patients. Conclusions. Our findings suggest that UDCA does not alter serum albumin in a way that is consistent with its effect on serum bilirubin. Therefore, reductions in serum bilirubin of UDCA-treated PBC do not parallel another validated and independent prognostic marker, further questioning the validity of serum bilirubin reduction with UDCA as a surrogate therapeutic marker.

Protective effect of ursodeoxycholic acid, resveratrol, andN-acetylcysteine on nonalcoholic fatty liver disease in rats

“…Serum glucose level was normalized in all treatment groups except for the NAC group, while serum albumin level was normalized in all treatment groups except for the UDCA + NAC group (Table 2). This comes in agreement with previous authors regarding serum glucose (Lukivskaya et al, 2004), while in disagreement of other regarding serum albumin (Tsochatzis et al, 2013). In support, it was reported that non-UDCA bile acids regulate metabolism by binding to the nuclear hormone farnesoid X receptor (FXR) and to a transmembrane bile acid receptor TGR5.…”

Defibrotide for the Treatment of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome with Multiorgan Failure

“…Based on review of the RCT evidence, the BCSH/BSBMT guideline suggests the use of UA for prophylaxis of VOD/SOS [21]; the EBMT describes clinical data for UA as 'nonconclusive' but suggestive of beneficial effect [17]. It also should be noted that UA decreases bilirubin levels via stimulation of bile acid secretion [51], however, this reduction is of uncertain benefit to hepatic function [50]. Indeed, reduction in bilirubin levels with UA may not correspond with reduction in incidence of VOD/ SOS [52], suggesting that UA has the potential to mask this key diagnostic sign of VOD/SOS.…”

Defibrotide for children and adults with hepatic veno-occlusive disease post hematopoietic cell transplantation

“…Data on prophylaxis with ursodeoxycholic acid are inconclusive; some studies found a significant benefit, and others have not found a benefit in reducing the incidence of VOD/SOS [19,25,33,34]. Of note, ursodeoxycholic acid reduces bilirubin levels via stimulation of bile acid secretion, but this change in bilirubin may not be therapeutic [35]. As discussed later in this manuscript, a pediatric phase III RCT of prophylaxis in high-risk pediatric patients found reduced incidence of VOD/SOS in patients undergoing HSCT receiving prophylactic defibrotide [26].…”