Effect of S-Adenosyl-L-Methionine on Liver Biochemistry and Quality of Life in Patients with Primary Biliary Cholangitis Treated with Ursodeoxycholic Acid. A Prospective, Open Label Pilot Study
Ewa Wunsch1, Joanna Raszeja-Wyszomirska2, Olivier Barbier3, Malgorzata Milkiewicz4, Marcin Krawczyk5,6, Piotr Milkiewicz1,2
1) Translational Medicine Group, Pomeranian Medical University, Szczecin, Poland
2) Liver and Internal Medicine Unit, Medical University of Warsaw, Warsaw, Poland
3) Laboratory of Molecular Pharmacology, CHU Quebec and Faculty of Pharmacy, Laval University, Quebec, Canada
4) Department of Medical Biology, Pomeranian Medical University, Szczecin, Poland
5) Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany
6) Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
Background & Aims: Chronic liver disease induces an acquired deficiency of S-adenosyl-L-methionine (SAMe) leading to impairment of detoxifying processes in the liver. Ursodeoxycholic acid (UDCA) represents the standard treatment in primary biliary cholangitis (PBC). As both compounds exert their hepatoprotective effects by different mechanisms, it is conceivable that when used together their effect might be additive.
The aim of this study was to analyse the effect of SAMe supplementation on liver biochemistry and health-related quality of life (HRQoL) in patients with PBC, treated with UDCA.
Methods. In this prospective pilot, proof of the principle, non-randomized and open label study we enrolled 24 patients with PBC treated with UDCA for at least 6 months. They had received both UDCA in a standard dose of 13-15 mg/kg b.w. and SAMe in the dose of 1200 mg daily over a period of 6 months. A group of 24 patients with PBC treated with UDCA served as control for liver biochemistry (Study registered on the platform ClinicalTrials.gov under ID: NCT02557360).
Results. We observed a significant decrease of ALP, GGT and total cholesterol in non-cirrhotic patients treated with SAMe. There was also a significant improvement of fatigue and pruritus in PBC-40 questionnaire and amelioration of anxiety in STAI 2 questionnaire in the SAMe group. Treatment with SAMe neither increased sulfation capacity of the liver nor had an effect on fibroblast growth factor-19 serum levels.
Conclusions. Our pilot study demonstrates a positive effect of adding SAMe to UDCA in non-cirrhotic patients with PBC.
Key words: primary biliary cholangitis − S-adenosyl-L-methionine − ursodeoxycholic acid − health-related quality of life − liver biochemistry.
Abbreviations: ALP: alkaline phosphatase; ALT: alanine aminotransferase; AST: aspartate aminotransferase; FGF-19: fibroblast growth factor-19; GGT: gammaglutamyl-transpeptidase; HADS: Hospital Anxiety and Depression Scale; HRQoL: health-related quality of life; INR: international normalized ratio; LCA: lithocholic acid; LCA-S sulfated LCA; LC-MS/MS: liquid chromatography/tandem mass spectrometry; MFIS: Modified Fatigue Impact Scale; PBC: primary biliary cholangitis; SAMe: S-adenosyl-L-methionine; SSRI: selective serotonin reuptake inhibitor; STAI: State-Trait Anxiety Inventory; UDCA: urosodeoxycholic acid.