title: Toxic effects of nucleoside reverse transcriptase inhibitors on the liver. Value of electron microscopy analysis for the diagnosis of mitochondrial cytopathy.
abstract: Nucleoside reverse transcriptase inhibitors (NRTIs) induce mitochondrial toxic effects resulting in multiple organ disorders. Liver involvement has been associated mainly with severe lactic acidosis and massive steatosis. However, patients with HIV infection who are receiving antiretroviral treatment frequently have mildly abnormal liver test results that, to date, have not been linked unambiguously to the toxic effects of NRTIs. Thirteen patients with HIV infection treated with NRTI-based regimens had low-grade abnormal liver test results associated with digestive and nonspecific general symptoms. Histologic examination of liver samples showed diffuse steatosis in only 6 cases and mild steatosis in the remaining cases, associated with megamitochondria, mild lobular inflammation and necrosis, Mallory bodies, and perisinusoidal fibrosis. In all cases, ultrastructural study disclosed mitochondrial abnormalities. Our work demonstrates that NRTI-induced toxic effects in the liver may occur as indolent nonspecific disease with variable histologic features and emphasizes the diagnostic value of electron microscopy, particularly when diffuse steatosis is absent.
authors.affiliation: Department of Pathology, European Georges Pomoidou Hospital, INSEM U430, Broussais Hospital, Paris, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Duong Van Huyen
authors.forename: Alain
authors.initials: A
authors.lastname: Landau
authors.forename: Christophe
authors.initials: C
authors.lastname: Piketty
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Bélair
authors.forename: Dominique
authors.initials: D
authors.lastname: Batisse
authors.forename: Gustavo
authors.initials: G
authors.lastname: Gonzalez-Canali
authors.forename: Laurence
authors.initials: L
authors.lastname: Weiss
authors.forename: Raymond
authors.initials: R
authors.lastname: Jian
authors.forename: Michel D
authors.initials: MD
authors.lastname: Kazatchkine
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruneval
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D005234:Fatty Liver / Q000139:chemically induced / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects* / Q000648:ultrastructure; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects*
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors