title: A Phase II Randomized, Controlled Trial of S-Adenosylmethionine in Reducing Serum α-Fetoprotein in Patients with Hepatitis C Cirrhosis and Elevated AFP.
abstract: In animal models of hepatocellular carcinoma (HCC), deficiency of S-adenosylmethionine (SAMe) increased the risk of HCC whereas administration of SAMe reduced HCC. The aim of this trial was to determine whether oral SAMe administration to patients with hepatitis C cirrhosis would decrease serum α-fetoprotein (AFP) level, a biomarker of HCC risk in hepatitis C. This was a prospective, randomized, placebo-controlled, double-blind trial of SAMe, up to 2.4 g/d, for 24 weeks as compared with placebo among subjects with hepatitis C cirrhosis and a mildly elevated serum AFP. Primary outcome was change in AFP between baseline and week 24. Secondary outcomes included changes in routine tests of liver function and injury, other biomarkers of HCC risk, SAMe metabolites, markers of oxidative stress, and quality of life. One hundred ten subjects were randomized and 87 (44 SAMe and 43 placebo) completed treatment. There was no difference in the change in AFP during 24 weeks among subjects receiving SAMe as compared with placebo. Changes in markers of liver function, liver injury, and hepatitis C viral level were not significantly different between groups. Similarly, SAMe did not change markers of oxidative stress or serum glutathione level. SAMe blood level increased significantly among subjects receiving SAMe. Changes in quality of life did not differ between groups. Overall, this trial did not find that SAMe treatment improved serum AFP in subjects with advanced hepatitis C cirrhosis and a mildly elevated AFP. SAMe did not improve tests of liver function or injury or markers of oxidative stress or antioxidant potential.
authors.affiliation: Medical Healthcare Group, VA Long Beach Healthcare System, Long Beach, California. Department of Medicine, Division of Gastroenterology, University of California, Irvine, California. timothy.morgan@va.gov.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Morgan
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, University of California, Irvine, California.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Osann
authors.affiliation: Institute of Metabolic Disease, Baylor Research Institute, Dallas, Texas.
authors.forename: Teodoro
authors.initials: T
authors.lastname: Bottiglieri
authors.affiliation: Medical Healthcare Group, VA Greater Los Angeles Healthcare System, Los Angeles, California.
authors.forename: Neville
authors.initials: N
authors.lastname: Pimstone
authors.affiliation: Department of Medicine, Department of Medicine, University of California, Irvine, California.
authors.forename: John C
authors.initials: JC
authors.lastname: Hoefs
authors.affiliation: Department of Medicine, Division of Gastroenterology, University of California, Irvine, California.
authors.forename: Ke-Qin
authors.initials: KQ
authors.lastname: Hu
authors.affiliation: Department of Medicine, Division of Hepatology, University of California, San Diego, California.
authors.forename: Tarek
authors.initials: T
authors.lastname: Hassanein
authors.affiliation: Liver Research Institute and Department of Medicine, University of Arizona, Tucson, Arizona.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Boyer
authors.affiliation: Research Pharmacy, University of California, Irvine, California.
authors.forename: Lorene
authors.initials: L
authors.lastname: Kong
authors.affiliation: Chao Family Comprehensive Cancer Center, University of California, Irvine, California.
authors.forename: Wen-Pin
authors.initials: WP
authors.lastname: Chen
authors.affiliation: Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland.
authors.forename: Ellen
authors.initials: E
authors.lastname: Richmond
authors.affiliation: Research Healthcare Group, VA Long Beach Healthcare System, Long Beach, California.
authors.forename: Rachel
authors.initials: R
authors.lastname: Gonzalez
authors.affiliation: Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland. Department of Surgery, Walter Reed National Military Medical Center, Bethesda, Maryland.
authors.forename: Luz M
authors.initials: LM
authors.lastname: Rodriguez
authors.affiliation: Departments of Medicine, Biological Chemistry, Public Health and Epidemiology and Chao Family Comprehensive Cancer Center, University of California, Irvine, California.
authors.forename: Frank L
authors.initials: FL
authors.lastname: Meyskens
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006526:Hepatitis C / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D011446:Prospective Studies; D011788:Quality of Life; D012436:S-Adenosylmethionine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D000509:alpha-Fetoproteins / Q000378:metabolism*
chemical_list: C097353:AFP protein, human; D000975:Antioxidants; D015415:Biomarkers; D000509:alpha-Fetoproteins; D012436:S-Adenosylmethionine