title: Mitochondrial injury in the pathogenesis of antiretroviral-induced hepatic steatosis and lactic acidemia.
abstract: Antiretroviral medications have significantly improved the prognosis of individuals infected with the human immunodeficiency virus (HIV) by maintaining immune integrity and limiting the impact of opportunistic infections. However, these benefits have not come without a price as long-term complications of therapy are increasingly recognized as significant causes of morbidity and mortality. Many of these complications are thought to be mediated through mitochondrial injury, which appears to be the result of nucleoside analogue toxicity. A syndrome of fatty liver (steatosis) with lactic acidosis represents the most fulminant presentation of such antiretroviral toxicity, though milder variants of hepatic steatosis with or without lactate elevations have also been described in HIV-seropositive individuals. The spectrum of hepatic steatosis and hyperlactatemia is likely multifactorial and may share some features with non-alcoholic fatty liver disease (NAFLD), which is the hepatic component of the metabolic syndrome described in the general population. As antiretrovirals are also known to contribute to metabolic syndrome components including insulin resistance, hypertriglyceridemia, and central adiposity, the possibility of common pathophysiologic mechanisms underlying NAFLD and antiretroviral-associated fatty liver seem likely. However, lactate elevations are not a component of NAFLD, suggesting other factors must also be involved. A review follows which details the role of mitochondrial damage in hepatic steatosis among HIV-infected individuals and the general population, as well as the association of this damage to the pathogenesis of hyperlactatemia.
authors.affiliation: Hawaii AIDS Clinical Research Program, John A. Burns School of Medicine, University of Hawaii, 3675 Kilauea Avenue, Young Building, 5th Floor, Honolulu, HI 96816, USA. larryd@hawaii.edu
authors.forename: Larry
authors.initials: L
authors.lastname: Day
authors.forename: Cecilia
authors.initials: C
authors.lastname: Shikuma
authors.forename: Mariana
authors.initials: M
authors.lastname: Gerschenson