title: Combination of branched-chain amino acid and angiotensin-converting enzyme inhibitor improves liver fibrosis progression in patients with cirrhosis.
abstract: An effective therapeutic strategy for suppressing liver fibrosis should improve the overall prognosis of patients with chronic liver diseases. Although enormous efforts are ongoing to develop anti-fibrotic agents, no drugs have yet been approved as anti-fibrotic agents for humans. Insulin resistance (IR) is reportedly involved in the progression of liver fibrosis. The aim of the present study was to evaluate the effect of combination treatment with a clinically used branched-chain amino acid (BCAA) and an angiotensin-converting enzyme inhibitor (ACE-I) on several fibrotic indices in patients with liver cirrhosis under the condition of IR. BCAA granules (Livact; 12 g/day) and/or ACE-I (perindopril; 4 mg/day) were administered, and several indices were analyzed. A 48-month follow-up revealed that the combination treatment with BCAA and ACE-I markedly improved the progression of serum fibrosis markers, whereas single treatment with either BCAA or ACE-I did not exert these inhibitory effects. The plasma level of transforming growth factor-β was significantly attenuated almost in parallel with the suppression of serum fibrosis markers. Furthermore, the combined treatment with BCAA and ACE-I improved the serum albumin level and IR, which was evaluated using the homeostasis model assessment method for IR. Taken together, since both BCAA and ACE-I are widely used with safety in clinical practice, these results indicate that this combination therapy may represent a potential new future strategy against liver fibrosis development in patients with liver cirrhosis under the condition of IR.
authors.affiliation: The Third Department of Internal Medicine, Nara Medical University, Nara 634-8522, Japan. yoshijih@naramed-u.ac.jp
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yoshiji
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Noguchi
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Ikenaka
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kaji
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Aihara
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Douhara
authors.forename: Junichi
authors.initials: J
authors.lastname: Yamao
authors.forename: Masahisa
authors.initials: M
authors.lastname: Toyohara
authors.forename: Akira
authors.initials: A
authors.lastname: Mitoro
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Sawai
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Yoshida
authors.forename: Chie
authors.initials: C
authors.lastname: Morioka
authors.forename: Masao
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Masahito
authors.initials: M
authors.lastname: Uemura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukui
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D024141:Collagen Type IV / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D007333:Insulin Resistance; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020913:Perindopril / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000597:Amino Acids, Branched-Chain; D000806:Angiotensin-Converting Enzyme Inhibitors; D024141:Collagen Type IV; D016212:Transforming Growth Factor beta; D006820:Hyaluronic Acid; D020913:Perindopril