title: Beneficial effects of candesartan, an angiotensin-blocking agent, on compensated alcoholic liver fibrosis - a randomized open-label controlled study.
abstract: BACKGROUND
  Recent studies have shown that the renin-angiotensin system is implicated in hepatic fibrogenesis in vitro and in vivo. However, no study was done in humans with alcoholic liver disease.
  
  
  OBJECTIVE
  To investigate the antifibrotic effect of angiotensin II type 1 receptor (AT1-R) blocking agents (ARB) in patients with alcoholic liver disease.
  
  
  METHODS
  The primary outcome was improvement in patients' histological features. Eighty-five patients with compensated alcoholic liver fibrosis (≥ F2) which was confirmed by baseline liver biopsy were randomized (intention-to-treat (ITT)) to receive either ARB, candesartan (8 mg/day) with ursodeoxycholic acid (UDCA) (600 mg/day) (n = 42) or UDCA alone (n = 43) as control for 6 months and follow-up liver biopsies were conducted.
  
  
  RESULTS
  According to the Laennec fibrosis system, candesartan showed significantly higher rates of histological improvements (ITT, 33.3% vs. 11.6%, P = 0.020). In addition, the fibrosis score was significantly reduced from 3.4 ± 1.4 to 3.1 ± 1.5 (P = 0.005) in the candesartan group. Candesartan also reduced the area of fibrosis and α-smooth muscle actin positive from 11.3 ± 6.0 to 8.3 ± 4.7 and 28.7 ± 10.5 to 23.9 ± 10.3 (%), and the hydroxyproline levels (μg/g liver tissue) from 7.8 ± 2.4 to 6.3 ± 1.7 respectively (P < 0.05). In addition, the relative expression of transforming growth factor-β1(TGF-β1), collagen-1, AT1-R, tissue inhibitor of metalloproteinase 1 (TIMP-1), metalloproteinases2 (MMP2), Rac1 and p22phox by real-time RT-PCR decreased in the candesartan group (P < 0.05). Mean arterial blood pressure in the candesartan group decreased mildly but significantly (P < 0.001). No significant complications and side effects were observed during the present study.
  
  
  CONCLUSIONS
  Administration of ARB in compensated alcoholic liver disease induces improvement of fibrosis in histological and quantitative measurements.
authors.affiliation: Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, South Korea.
authors.forename: Moon Young
authors.initials: MY
authors.lastname: Kim
authors.forename: Mee Yon
authors.initials: MY
authors.lastname: Cho
authors.forename: Soon Koo
authors.initials: SK
authors.lastname: Baik
authors.forename: Phil Ho
authors.initials: PH
authors.lastname: Jeong
authors.forename: Ki Tae
authors.initials: KT
authors.lastname: Suk
authors.forename: Yoon Ok
authors.initials: YO
authors.lastname: Jang
authors.forename: Chang Jin
authors.initials: CJ
authors.lastname: Yea
authors.forename: Jae Woo
authors.initials: JW
authors.lastname: Kim
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Sang Ok
authors.initials: SO
authors.lastname: Kwon
authors.forename: Byung Su
authors.initials: BS
authors.lastname: Yoo
authors.forename: Jang Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Min Seob
authors.initials: MS
authors.lastname: Eom
authors.forename: Seung Hwan
authors.initials: SH
authors.lastname: Cha
authors.forename: Sei Jin
authors.initials: SJ
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D001713:Biphenyl Compounds; D004359:Drug Therapy, Combination; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008104:Liver Cirrhosis, Alcoholic / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D056910:Republic of Korea; D012720:Severity of Illness Index; D013777:Tetrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D015415:Biomarkers; D001713:Biphenyl Compounds; D013777:Tetrazoles; D014580:Ursodeoxycholic Acid; C081643:candesartan