title: Pioglitazone for Hepatic Steatosis in HIV/Hepatitis C Virus Coinfection.
abstract: Chronic hepatitis C infection frequently coexists with human immunodeficiency virus (HIV) and together are associated with increased hepatic steatosis. Steatosis is a risk factor for progression of liver disease and may persist despite a sustained virologic response to hepatitis C treatment. Therefore, therapies to target hepatic steatosis are important for individuals with HIV and hepatitis C virus (HCV) coinfection. We completed a 48-week, randomized, double-blind, placebo-controlled trial of pioglitazone (45 mg/day) in 13 subjects with HIV/HCV coinfection. The primary outcome variable was hepatic fat content, measured by magnetic resonance spectroscopy (MRS) imaging. Individuals randomized to pioglitazone had a significant decrease in hepatic fat content measured by MRS from baseline (15.1 ± 7.0%) to week 48 (7.6 ± 3.9%), with a mean difference of -7.4% (p = 0.02, n = 5). There was no significant change in hepatic fat content with placebo. Glycemic control as measured by oral glucose challenge improved significantly with pioglitazone (p = 0.047). Though not statistically significant, there were trends toward improved alanine aminotransferase (ALT) and histopathologic grade of steatosis in subjects who received pioglitazone. Pioglitazone was well tolerated and no one discontinued due to side effects. This study demonstrates that 48 weeks of pioglitazone therapy, and not placebo, results in significant reductions in hepatic fat content as measured by MRS in subjects with HIV and HCV coinfection and hepatic steatosis. This small study shows that pioglitazone helps ameliorate steatosis in the context of HIV/HCV coinfection.
authors.affiliation: 1 Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health , Bethesda, Maryland.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Matthews
authors.affiliation: 2 Laboratory of Pathology, National Cancer Institute, National Institutes of Health , Bethesda, Maryland.
authors.forename: David E
authors.initials: DE
authors.lastname: Kleiner
authors.affiliation: 3 Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Chairez
authors.affiliation: 4 Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc. (formerly SAIC-Frederick, Inc.), Frederick National Laboratory for Cancer Research , Frederick, Maryland.
authors.forename: Maryellen
authors.initials: M
authors.lastname: McManus
authors.affiliation: 5 Infectious Diseases Section, Medical Service, Veterans Affairs Medical Center , Washington, District of Columbia.
authors.forename: Mary Jane
authors.initials: MJ
authors.lastname: Nettles
authors.affiliation: 6 NIH Clinical Center Nursing Department, National Institutes of Health , Bethesda, Maryland.
authors.forename: Kira
authors.initials: K
authors.lastname: Zemanick
authors.affiliation: 1 Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health , Bethesda, Maryland.
authors.forename: Caryn Gee
authors.initials: CG
authors.lastname: Morse
authors.affiliation: 5 Infectious Diseases Section, Medical Service, Veterans Affairs Medical Center , Washington, District of Columbia.|7 Division of Infectious Diseases, The George Washington University Medical Center , Washington, District of Columbia.
authors.forename: Debra
authors.initials: D
authors.lastname: Benator
authors.affiliation: 1 Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health , Bethesda, Maryland.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Kovacs
authors.affiliation: 3 Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland.
authors.forename: Colleen
authors.initials: C
authors.lastname: Hadigan
mesh_terms: D000328:Adult; D060085:Coinfection / Q000188:drug therapy; D004311:Double-Blind Method; D005234:Fatty Liver / Q000188:drug therapy*; D005260:Female; D015658:HIV Infections / Q000150:complications*; D019698:Hepatitis C, Chronic / Q000150:complications*; D006651:Histocytochemistry; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008099:Liver / Q000000981:diagnostic imaging / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D010919:Placebos / Q000008:administration & dosage; D011859:Radiography; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D010919:Placebos; D045162:Thiazolidinediones; D000077205:Pioglitazone