Toxic effects of nucleoside reverse transcriptase inhibitors on the liver. Value of electron microscopy analysis for the diagnosis of mitochondrial cytopathy.
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.
Duong Van Huyen
Jean-Paul
JP
Department of Pathology, European Georges Pomoidou Hospital, INSEM U430, Broussais Hospital, Paris, France.
Landau
Alain
A
Piketty
Christophe
C
Bélair
Marie-France
MF
Batisse
Dominique
D
Gonzalez-Canali
Gustavo
G
Weiss
Laurence
L
Jian
Raymond
R
Kazatchkine
Michel D
MD
Bruneval
Patrick
P
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*
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors