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Clin Infect Dis. 2015 May 15;60(10):1569-78. doi: 10.1093/cid/civ101. Epub 2015 Feb 13.

Nonalcoholic Steatohepatitis and Hepatic Fibrosis in HIV-1-Monoinfected Adults With Elevated Aminotransferase Levels on Antiretroviral Therapy.

Author information

1
Critical Care Medicine Department, AIDS Section, National Institutes of Health (NIH) Clinical Center.
2
Laboratory of Immunoregulation.
3
Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases (NIAID).
4
Diagnostic Radiology, NIH Clinical Center.
5
Biomedical and Metabolic Imaging Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
6
Histology Core, National Eye Institute, Bethesda, Maryland.
7
Baystate Medical Center, Springfield, Massachusetts.
8
Laboratory of Infectious Disease, NIAID, Bethesda.
9
Leidos Biomedical Research, Inc, Frederick.
10
Laboratory of Pathology, National Cancer Institute.
11
Liver Diseases Branch, NIDDK, Bethesda, Maryland.

Abstract

BACKGROUND:

Persistent aminotransferase elevations are common in human immunodeficiency virus (HIV)-infected patients on antiretroviral therapy (ART), including those without hepatitis B or C coinfection, but their clinical significance is unknown.

METHODS:

HIV-infected adults with aminotransferase levels elevated above the upper limit of normal for ≥6 months while receiving ART, and without chronic viral hepatitis or other known causes of chronic liver disease, underwent a detailed metabolic assessment and liver biopsy.

RESULTS:

Sixty-two HIV-infected subjects completed the study. Forty (65%) had clinically significant liver pathology, including 34 (55%) with nonalcoholic steatohepatitis (NASH) and 11 (18%) with bridging fibrosis, 10 of whom also had NASH. Nonspecific abnormalities alone were seen in 22 (35%) subjects, including mild steatosis, mild to moderate inflammation, and evidence of drug adaptation. Insulin resistance, obesity, and the presence of either of 2 minor alleles in the PNPLA3 gene were significantly associated with increased risk of NASH and fibrosis. NASH and/or fibrosis were not associated with duration of HIV infection or ART, specific antiretroviral drugs, history of opportunistic infection, immune status, or duration of aminotransferase elevation.

CONCLUSIONS:

HIV-infected adults with chronic aminotransferase elevations while receiving ART have a high rate of liver disease. Noninvasive testing can help identify liver disease in such patients, but liver biopsy is necessary to definitively identify those at risk for liver disease progression and complications. Longitudinal follow-up of this cohort will better characterize the natural history of aminotransferase elevations in this population and identify noninvasive biomarkers of liver disease progression.

KEYWORDS:

PNPLA3; hepatotoxicity; insulin resistance; liver biopsy

PMID:
25681381
PMCID:
PMC4425826
DOI:
10.1093/cid/civ101
[Indexed for MEDLINE]
Free PMC Article

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