Open-label study of ademetionine for the treatment of intrahepatic cholestasis associated with alcoholic liver disease

BACKGROUND: The effect of oral and/or parenteral ademetionine (500 mg intravenous [IV] and tablet formulation) on clinical symptoms and biochemical markers of intrahepatic cholestasis (IHC) was investigated in subjects with alcoholic liver disease (ALD) and compensated liver function. METHODS: Prospective, multicenter, open-label study consisting of a screening period and an 8-week treatment period and performed in subjects (18-75 years) with compensated ALD and confirmed IHC. Subjects with a baseline serum coniugated bilirubin value above normal range were initially treated with IV ademetionine for two weeks (500-800 mg daily) and continued with oral ademetionine 1500 mg daily for a further six weeks. Subiects with a baseline serum coniugated bilirubin value within normal range were treated with oral ademetionine for eight weeks. RESULTS: A total of 72 subjects were treated; 41 initially with IV ademetionine and 31 with oral ademetionine. Clinical symptoms status improved from baseline to end of treatment with an increase in the proportion of subiects with no symptoms. Ademetionine showed significant improvements in primary efficacy parameters alkaline phosphatase (ALP) and y-glutamyltransferase (yGT) (P<0.0001). Although decreases of ALP were higher for subjects initially treated with IV ademetionine, these subjects also had higher baseline values. No safety concerns with ademetionine arose with respect to the severity or frequency of adverse events (AEs) during the treatment period, laboratory parameters, and vital signs. CONCLUSIONS: Administration of oral or IV/oral ademetionine step-therapy for 8 weeks to subjects with IHC due to ALD was safe and provided a significant improvement of disease burden. © 2018 EDIZIONI MINERVA MEDICA.

Ivashkin V.T.1 , Maevskaya M.V.1 , Kobalava Z.D. 1 , Uspenskiy Y.P.3 , Fominih J.A.3 , Rozanov A.V. 4 , Tolkacheva V.V. 2, 5 , Sotnikova T.I.6 , Alikhanov B.A.7 , Gorbacheva I.A.8 , Ershova O.B.9 , Znakhyrenko A.A.10 , Sokolov K.A.1 , Sander-Struckmeier S.11
Edizioni Minerva Medica
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  • 1 I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
  • 2 Peoples Friendship University of Russia, Moscow, Russian Federation
  • 3 Hospital of the Holy Martyr Elizabeth, Saint Petersburg, Russian Federation
  • 4 Moscow Hospital of the Russian Academy of Sciences (Troitsk), Peoples' Friendship University of Russia, Moscow, Russian Federation
  • 5 Affiliate Hospital of the Russian Academy of Sciences, Troitsk, Russian Federation
  • 6 City Clinical Hospital named after S.P. Botkin, Moscow, Russian Federation
  • 7 Central Clinical Hospital, Russian Academy of Sciences, Moscow, Russian Federation
  • 8 St. Petersburg State Health Institution Clinical Hospital of St. Luke, Saint Petersburg, Russian Federation
  • 9 Clinical Emergency Hospital named NV Solovyov, Yaroslavl, Russian Federation
  • 10 Autonomous Nonprofit Organization Petersburg Metro Polyclinic, Saint Petersburg, Russian Federation
  • 11 Abbott Laboratories, LLC, Lake Bluff, IL, United States
Ключевые слова
Alcoholic; Cholestasis; Liver diseases; S-adenosylmethionine
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