title: Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial.
abstract: The only currently recommended treatment for nonalcoholic fatty liver disease (NAFLD) is lifestyle modification. Preliminary studies of silybin showed beneficial effects on liver function. Realsil (RA) comprises the silybin phytosome complex (silybin plus phosphatidylcholine) coformulated with vitamin E. We report on a multicenter, phase III, double-blind clinical trial to assess RA in patients with histologically documented NAFLD. Patients were randomized 1:1 to RA or placebo (P) orally twice daily for 12 months. Prespecified primary outcomes were improvement over time in clinical condition, normalization of liver enzyme plasma levels, and improvement of ultrasonographic liver steatosis, homeostatic model assessment (HOMA), and quality of life. Secondary outcomes were improvement in liver histologic score and/or decrease in NAFLD score without worsening of fibrosis and plasma changes in cytokines, ferritin, and liver fibrosis markers. We treated 179 patients with NAFLD; 36 were also HCV positive. Forty-one patients were prematurely withdrawn and 138 patients analyzed per protocol (69 per group). Baseline patient characteristics were generally well balanced between groups, except for steatosis, portal infiltration, and fibrosis. Adverse events (AEs) were generally transient and included diarrhea, dysgeusia, and pruritus; no serious AEs were recorded. Patients receiving RA but not P showed significant improvements in liver enzyme plasma levels, HOMA, and liver histology. Body mass index normalized in 15% of RA patients (2.1% with P). HCV-positive patients in the RA but not the P group showed improvements in fibrogenesis markers. This is the first study to systematically assess silybin in NAFLD patients. Treatment with RA but not P for 12 months was associated with improvement in liver enzymes, insulin resistance, and liver histology, without increases in body weight. These findings warrant further investigation.
authors.affiliation: Department F. Magrassi e A. Lanzara, Second University of Naples, 80131 Napoli, Italy. carmelina.loguercio@unina2.it
authors.forename: Carmela
authors.initials: C
authors.lastname: Loguercio
authors.forename: Pietro
authors.initials: P
authors.lastname: Andreone
authors.forename: Ciprian
authors.initials: C
authors.lastname: Brisc
authors.forename: Michaela Cristina
authors.initials: MC
authors.lastname: Brisc
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bugianesi
authors.forename: Maria
authors.initials: M
authors.lastname: Chiaramonte
authors.forename: Carmela
authors.initials: C
authors.lastname: Cursaro
authors.forename: Mirela
authors.initials: M
authors.lastname: Danila
authors.forename: Ilario
authors.initials: I
authors.lastname: de Sio
authors.forename: Annarosa
authors.initials: A
authors.lastname: Floreani
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Freni
authors.forename: Antonio
authors.initials: A
authors.lastname: Grieco
authors.forename: Marzia
authors.initials: M
authors.lastname: Groppo
authors.forename: Roberta
authors.initials: R
authors.lastname: Lazzari
authors.forename: Salvatore
authors.initials: S
authors.lastname: Lobello
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Lorefice
authors.forename: Marzia
authors.initials: M
authors.lastname: Margotti
authors.forename: Luca
authors.initials: L
authors.lastname: Miele
authors.forename: Stefano
authors.initials: S
authors.lastname: Milani
authors.forename: Lajos
authors.initials: L
authors.lastname: Okolicsanyi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palasciano
authors.forename: Piero
authors.initials: P
authors.lastname: Portincasa
authors.forename: Patrizia
authors.initials: P
authors.lastname: Saltarelli
authors.forename: Antonina
authors.initials: A
authors.lastname: Smedile
authors.forename: Francesco
authors.initials: F
authors.lastname: Somalvico
authors.forename: Aldo
authors.initials: A
authors.lastname: Spadaro
authors.forename: Ioan
authors.initials: I
authors.lastname: Sporea
authors.forename: Paolo
authors.initials: P
authors.lastname: Sorrentino
authors.forename: Raffaela
authors.initials: R
authors.lastname: Vecchione
authors.forename: Concetta
authors.initials: C
authors.lastname: Tuccillo
authors.forename: Camillo
authors.initials: C
authors.lastname: Del Vecchio Blanco
authors.forename: Alessandro
authors.initials: A
authors.lastname: Federico
mesh_terms: D015992:Body Mass Index; D005234:Fatty Liver / Q000188:drug therapy*; D006801:Humans; D010713:Phosphatidylcholines / Q000008:administration & dosage / Q000627:therapeutic use*; D012383:Romania; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage / Q000627:therapeutic use*; D014810:Vitamin E / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D010713:Phosphatidylcholines; D012838:Silymarin; D014810:Vitamin E; D000077385:Silybin