Liver transplant in primary sclerosing cholangitis: Current trends and future directions

Table 3 Overview of important clinical trials and meta-analysis assessing medications used in management of primary sclerosing cholangitis

Ref.	Year	Type	Objective	Results
				Death	Symptoms (fatigue, pruritus)	Liver transplantation	Histological improvement	Marker values (bilirubin, GGT, ALP, ALT or AST)	Cholangiographic changes	Cholangiocarcinoma	Adverse events
Ursodeoxycholic acid
Shi et al[74]	2009	Meta-analysis of RCT (8 RCT, 465 patients)	Evaluate the effect and safety of UDCA in PSC	No significant effect	No significant effect	No significant effect	Significant difference	No significant effect	No significant effect on improvement	No significant difference on incidence	No significant difference on incidence
Othman et al[61]	2012	Meta-analysis of RCT (7 RCT, 553 patients)	Investigate the efficacy of UDCA in PSC	No significant effect	No significant effect	No significant effect	No significant effect	Significantly decrease ALP, GGT, bilirubin, ALT or AST	No significant effect on improvement	No significant difference on incidence	No significant difference on incidence
Poropat et a[62]	2011	Meta-analysis of RCT (8 RCT, 592 patients)	Assess the beneficial and harmful effects of BA for patients with PSC	No significant effect	No significant effect	No significant effect	No significant effect	Significantly decrease ALP, GGT, bilirubin or AST. Not significant effect on albumin	No significant effect on improvement	No significant difference on incidence	No significant difference on incidence
Triantos et al[63]	2011	Meta-analysis of RCT (8 RCT, 567 patients)	Evaluate if UDCA is useful for PSC	No significant effect	No significant effect	No significant effect	No significant effect	Not reported	Not reported	No significant difference on incidence	Not reported
Immunosuppressive therapies: glucocorticoids, cyclosporine, tacrolimus, methotrexate and mycophenolate mofetil
Peng et al[69]	2017	Meta-analysis of RCT (7 RCT, 266 patients)	Evaluate the safety and efficiency of IA for the treatment of PSC	No significant effect	Not reported	No significant effect	Not reported	No significant improvement on liver biochemistry except AST	Not reported	Not reported	Significant increase on incidence
Liu et al[70]	2022	Meta-analysis (7 RCT and 14 observational, 737 patients)	Assess the efficacy and adverse effects of immunomodulators in adult patients with PSC	Not reported	Not reported	Not reported	Not reported	Significantly decrease ALP. Not significant effect on bilirubin and AST	Not reported	Not reported	16.1% of patients had severe AEs1
Antibiotics
Shah et al[75]	2019	Meta-analysis of clinical trials (3 RCT and 2 open labeled trials, 124 patients)	Assess the effect of antibiotic therapy (vancomycin, metronidazole, rifaximin and minocycline) in PSC with or without inflammatory bowel disease	Not reported	Not reported	Not reported	Not reported	Significant reduction in ALP and bilirubin	Not reported	Not reported	8.9 % of patients had severe AEs1
Probiotics
Vleggaar et al[76]	2008	RCT that included 14 patients	Assess potential beneficial effects of probiotics in PSC	Not reported	No significant effect	Not reported	Not reported	No significant effect on bilirubin, ALP, GGT, AST, ALT, prothrombin, albumin or bile salts	Not reported	Not reported	Not reported
Newer drugs
Fickert et al[72]	2017	RCT that included 161 patients	Evaluate the safety and efficacy of three doses of oral nor UDCA compared with placebo in patients with PSC	Not reported	No significant effect	Not reported	Not reported	Significantly decrease ALP, GGT, ALT or AST	Not reported	Not reported	14 patients had severe AE1

¹Results of this outcome were not included in the meta-analysis. It was derived from the assessment of individual studies. GGT: Gamma-glutamyl; ALP: Alkaline phosphatase; AE: Adverse effects; RCT: Randomized controlled trial; AST: Aspartate Aminotransferase; ALT: Alanine transaminase; PSC: Primary sclerosing cholangitis; UDCA: Ursodeoxycholic acid; BA: Bile acids.