Pioglitazone for Hepatic Steatosis in HIV/HCV Co-infection.
Author(s): Matthews L(1), Kleiner D(2), Chairez C(3), McManus M(4), Nettles MJ(5), Zemanick
K(6), Morse C(7), Benator D(8), Kovacs J(9), Hadigan C(10).
Affiliation(s): Author information:
(1)National Institutes of Health, Critical Care Medicine, Bethesda, Maryland,
United States ; Lmatth3@gmail.com. (2)National Institutes of Health, National
Cancer Institute, Bethesda, Maryland, United States ; kleinerd@mail.nih.gov.
(3)National Institutes of Health, NIAID, Bethesda, Maryland, United States ;
chairezc@niaid.nih.gov. (4)National Institutes of Health, Critical Care Medicine,
Bethesda, Maryland, United States ; maryellen.mcmanus@nih.gov. (5)VAMC,
Washington DC, Infectious Diseases, Medicine, Washington, District of Columbia,
United States ; Mary.Nettles@va.gov. (6)NIH Clinical Center, Nursing, Bethesda,
Maryland, United States ; zemanickk@niaid.nih.gov. (7)NIH Clinical Center,
Critical Care Medicine, AIDS Section , 9000 Rockville Pike, Building 10/5A06 ,
MSC 1403 , Bethesda, Maryland, United States , 20892-1403 , 301-496-6028 ,
301-480-1735 ; cmorse@cc.nih.gov. (8)VAMC, Washington DC, Infectious Diseases,
Medicine, Washington, District of Columbia, United States ; debra.Benator@va.gov.
(9)NIH Clinical Center, Critical Care Medicine, AIDS Section , 9000 Rockville
Pike, Building 10/5A06 , MSC 1403 , Bethesda, Maryland, United States ,
20892-1403 , 301-496-6028 , 301-480-1735 ; jkovacs@mail.nih.gov. (10)National
Institutes of Health, NIAID , 10 Center Drive , Rm 11C103 , Bethesda, Maryland,
United States , 20892 , 301-594-5754 ; hadiganc@niaid.nih.gov.
Publication date & source: 2015, AIDS Res Hum Retroviruses. ,
Background 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) co-infection. Methods We completed a 48
week, randomized, double-blind, placebo-controlled trial of pioglitazone (45
mg/d) in 13 subjects with HIV/HCV co-infection. The primary outcome variable was
hepatic fat content, measured by magnetic resonance spectroscopy (MRS) imaging.
Results 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 towards
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. Conclusions 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
co-infection and hepatic steatosis. This small study shows that pioglitazone
helps ameliorate steatosis in the context of HIV/HCV co-infection.
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