Ursodeoxycholic Acid and S-adenosylmethionine for the Treatment of Intrahepatic Cholestasis of Pregnancy: A Meta-analysis

An optimal therapeutic strategy has not yet been identified for the pharmacological treatment of intrahepatic cholestasis of pregnancy (ICP). The aim of this study was to evaluate the efficacy and safety of ursodeoxycholic acid (UDCA) and S-adenosylmethionine (SAMe) in the treatment of ICP, both individually and in combination. A meta-analysis of all randomized controlled trials (RCTs) comparing UDCA, SAMe, and combination therapy was performed. We carried out a literature search using pubmed, embase, the cochrane register of controlled trials, and the science citation index of web of science. The maternal clinical and biochemical responses, including pruritus scores, total bilirubin, total bile acids, alanine aminotransferase, and aspartate transaminase, were evaluated. Safety assessments, including preterm delivery, cesarean section, and meconium-stained amniotic fluid, were also analyzed. Five RCTs including 311 patients were evaluated. In comparison to SAMe, UDCA significantly reduced the pruritus score (OR = -0.45, 95% confidence interval [CI]: -0.66 to -0.25, P < 0.0001) and improved the levels of total bile acids (TBAs; OR = -0.59, 95% CI: -0.99 to –0.30, P < 0.0001) and alanine aminotransferase (ALT; OR = -0.38, 95% CI: -0.66 to -0.09, P = 0.01). UDCA was associated with significantly lower preterm delivery rates than SAMe (RR = 0.48, 95% CI: 0.32–0.72, P = 0.0004). Interestingly, combination therapy significantly reduced total bilirubin (TB; vs. SAMe, OR = -0.41, 95% CI, -0.74 to -0.08, P = 0.02), aspartate transaminase (AST; vs. UDCA, OR = -0.40, 95% CI, -0.74 to –0.06, P = 0.02), and the rate of preterm delivery (vs. SAMe, OR = 0.62, 95% CI, 0.42 - 0.91, P = 0.02), in comparison with either drug administered alone. UDCA decreased the pruritus score, TBA, and ALT levels more effectively than SAMe, reducing the rate of preterm delivery for ICP.