Ursodeoxycholic Acid Decreases Incidence of Primary Biliary Cholangitis and Biliary Complications After Liver Transplantation: A Meta‐Analysis

Abstract

After liver transplantation (LT), the role of ursodeoxycholic acid (UDCA) is not well characterized. We examine the effect of UDCA after LT in the prophylaxis of biliary complications (BCs) in all‐comers for LT and the prevention of recurrent primary biliary cholangitis (rPBC) in patients transplanted for PBC. Two authors searched PubMed/MEDLINE and Embase from January 1990 through December 2018 to identify all studies that evaluate the effectiveness of UDCA prophylaxis after LT for BCs in all LT recipients and rPBC after LT in patients transplanted for PBC. Odds ratios (ORs) were calculated for endpoints of the BC study. Pooled recurrence rates were calculated for rPBC. The study was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta‐Analysis guidelines. A total of 15 studies were included, comprising 530 patients in the analysis for BCs and 1727 patients in the analysis for rPBC. UDCA was associated with decreased odds of BCs (OR, 0.70; 95% confidence interval [CI], 0.52‐0.93; P = 0.01) and biliary stones and sludge (OR, 0.49; 95% CI, 0.24‐0.77; P = 0.004). Prophylactic use of UDCA did not affect the odds of biliary stricture. For patients transplanted for PBC, the rate of rPBC was lower with the prophylactic use of UDCA (IR 16.7%; 95% CI, 0.114%‐22.0%; I2 = 36.1%) compared with not using prophylactic UDCA (IR 23.1%; 95% CI, 16.9%‐29.3%; I2 = 86.7%). UDCA after LT reduces the odds of BC and bile stones and sludge in all‐comer LT recipients and reduces or delays the incidence of rPBC in patients transplanted for PBC. UDCA use after LT could be considered in all LT recipients to reduce the odds of BC and may be particularly beneficial for patients transplanted for PBC by reducing the incidence of rPBC.

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“…UDCA solubilizes cholesterol from the surface and core of gallstones. Moreover, it seems to have a cytoprotective activity by decreasing the bile-acid/phospholipid ratio of the secreted bile, and by an anti-oxidant, anti-apoptotic and membrane-stabilizing effect [ 27 ]. A recent meta-analysis of two retrospective studies and one randomized controlled trial (RCT) have demonstrated that UDCA did significantly reduce the risk of post-LT biliary stones and sludge but did not have any significant impact on the risk of biliary strictures [ 27 ].…”

“…Moreover, it seems to have a cytoprotective activity by decreasing the bile-acid/phospholipid ratio of the secreted bile, and by an anti-oxidant, anti-apoptotic and membrane-stabilizing effect [ 27 ]. A recent meta-analysis of two retrospective studies and one randomized controlled trial (RCT) have demonstrated that UDCA did significantly reduce the risk of post-LT biliary stones and sludge but did not have any significant impact on the risk of biliary strictures [ 27 ]. On the other hand, a meta-analysis of four high-quality RCTs has shown that UDCA, as an adjuvant treatment, was not able to prevent acute cellular rejection or steroid-resistant rejection after LT [ 28 ].…”

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“…They included 12 studies that comprised 1727 patients. They showed that UDCA prophylaxis decreased the rate of rPBC (13.3%, CI: 7.2-19.4%) compared to not using prophylactic UDCA (33.8%, CI: 28.7-38.9%) [71]. The second meta-analysis by Li et al evaluated the role of prophylactic UDCA as a potential risk factor for PBC recurrence.…”

Ursodeoxycholic Acid Decreases Incidence of Primary Biliary Cholangitis and Biliary Complications After Liver Transplantation

“…This article summarizes a recent 2021 meta‐analysis by Pedersen et al 5 evaluating the effects of UDCA on the incidence of BCs, and rPBC after LT.…”