title: Nonalcoholic Steatohepatitis and Hepatic Fibrosis in HIV-1-Monoinfected Adults With Elevated Aminotransferase Levels on Antiretroviral Therapy.
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.
authors: Critical Care Medicine Department, AIDS Section, National Institutes of Health (NIH) Clinical Center.
authors: Caryn G
authors: CG
authors: Morse
authors: Laboratory of Immunoregulation.
authors: Mary
authors: M
authors: McLaughlin
authors: Critical Care Medicine Department, AIDS Section, National Institutes of Health (NIH) Clinical Center.
authors: Lindsay
authors: L
authors: Matthews
authors: Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases (NIAID).
authors: Michael
authors: M
authors: Proschan
authors: Diagnostic Radiology, NIH Clinical Center.
authors: Francine
authors: F
authors: Thomas
authors: Biomedical and Metabolic Imaging Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
authors: Ahmed M
authors: AM
authors: Gharib
authors: Histology Core, National Eye Institute, Bethesda, Maryland.
authors: Mones
authors: M
authors: Abu-Asab
authors: Baystate Medical Center, Springfield, Massachusetts.
authors: Abigail
authors: A
authors: Orenstein
authors: Laboratory of Infectious Disease, NIAID, Bethesda.
authors: Ronald E
authors: RE
authors: Engle
authors: Leidos Biomedical Research, Inc, Frederick.
authors: Xiaojun
authors: X
authors: Hu
authors: Leidos Biomedical Research, Inc, Frederick.
authors: Richard
authors: R
authors: Lempicki
authors: Laboratory of Immunoregulation.
authors: Colleen
authors: C
authors: Hadigan
authors: Laboratory of Pathology, National Cancer Institute.
authors: David E
authors: DE
authors: Kleiner
authors: Liver Diseases Branch, NIDDK, Bethesda, Maryland.
authors: Theo
authors: T
authors: Heller
authors: Critical Care Medicine Department, AIDS Section, National Institutes of Health (NIH) Clinical Center.
authors: Joseph A
authors: JA
authors: Kovacs
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D001706:Biopsy; D001774:Blood Chemical Analysis; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006651:Histocytochemistry; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000453:epidemiology*; D015995:Prevalence; D000637:Transaminases / Q000097:blood*; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents; D000637:Transaminases
keywords: PNPLA3; hepatotoxicity; insulin resistance; liver biopsy