Pioglitazone to Treat Fatty Liver in Patients With HIV and Hepatitis C Infections

Summary

This study will evaluate the effectiveness of pioglitazone in reducing liver fat content in patients with HIV and hepatitis C virus (HCV) infections. Fatty liver and accompanying insulin resistance in patients with HIV and HCV co-infections is associated with inflammatory changes, liver fibrosis and a poorer response to HCV treatment. Pioglitazone is a drug that helps to reduce the body's resistance to insulin. It is approved by the Food and Drug Administration to treat diabetes. Patients with HIV and HCV co-infections who have hepatic steatosis (fatty liver) may be eligible for this study. Candidates are screened with a medical history and physical examination, blood and urine tests, magnetic resonance imaging (MRI) of the liver to measure liver fat and, if needed, a liver biopsy to confirm the diagnosis of liver steatosis. * Participants are randomly assigned to take either pioglitazone therapy or placebo for 48 weeks. This is followed by a second 48-week treatment period in which all participants take pioglitazone. * There are approximately 12 visits during the 96 weeks of the study. Participants will receive a physical assessment, blood and urine tests at each visit. In addition, periodic assessments of dietary habits, body composition, oral glucose tolerance testing, and health related quality of life questionnaires will be completed. * A repeat MRI of the liver is performed at 48 weeks and at the end of the study to evaluate any potential changes in liver fat and inflammation. In addition, there is a follow-up liver biopsy at 48 weeks and an optional liver biopsy at 96 weeks.

Timeline

Start

2008-08

Primary completion

2013-01

Completion

2013-01

Publications

• Background Jain MK, Skiest DJ, Cloud JW, Jain CL, Burns D, Berggren RE. Changes in mortality related to human immunodeficiency virus infection: comparative analysis of inpatient deaths in 1995 and in 1999-2000. Clin Infect Dis. 2003 Apr 15;36(8):1030-8. doi: 10.1086/368186. Epub 2003 Apr 2.
• Background Sulkowski MS, Mast EE, Seeff LB, Thomas DL. Hepatitis C virus infection as an opportunistic disease in persons infected with human immunodeficiency virus. Clin Infect Dis. 2000 Apr;30 Suppl 1:S77-84. doi: 10.1086/313842.
• Background Sulkowski MS, Mehta SH, Torbenson M, Afdhal NH, Mirel L, Moore RD, Thomas DL. Hepatic steatosis and antiretroviral drug use among adults coinfected with HIV and hepatitis C virus. AIDS. 2005 Mar 24;19(6):585-92. doi: 10.1097/01.aids.0000163935.99401.25.
• Background Matthews L, Kleiner DE, Chairez C, McManus M, Nettles MJ, Zemanick K, Morse CG, Benator D, Kovacs JA, Hadigan C. Pioglitazone for Hepatic Steatosis in HIV/Hepatitis C Virus Coinfection. AIDS Res Hum Retroviruses. 2015 Oct;31(10):961-6. doi: 10.1089/AID.2015.0093. Epub 2015 Aug 24.

Drugs

Indications