title: Acute fatty liver of pregnancy: an update on mechanisms.
abstract: Acute fatty liver of pregnancy (AFLP), characterized by hepatic microvesicular steatosis, is a sudden catastrophic illness occurring almost exclusively in the third trimester of pregnancy. Defective fatty acid oxidation in the fetus has been shown to be associated with this disease. Since the placenta has the same genetic makeup as the fetus and as AFLP patients generally recover following delivery, we hypothesized that the placenta might be involved in pathogenesis of this disease. In an animal model of hepatic microvesicular steatosis (using sodium valproate), we found that microvesicular steatosis results in mitochondrial structural alterations and oxidative stress in subcellular organelles of the liver. In placentas from patients with AFLP, we observed placental mitochondrial dysfunction and oxidative stress in subcellular organelles. In addition, defective placental fatty acid oxidation results in accumulation of toxic mediators such as arachidonic acid. Escape of these mediators into the maternal circulation might affect the maternal liver resulting in microvesicular steatosis.
authors: The Wellcome Trust Research Laboratory, Department of Gastrointestinal Sciences, Christian Medical College , Ida Scudder Road, Vellore 632004 , India.
authors: Sathish Kumar
authors: SK
authors: Natarajan
authors: The Wellcome Trust Research Laboratory, Department of Gastrointestinal Sciences, Christian Medical College , Ida Scudder Road, Vellore 632004 , India.
authors: Kavitha R
authors: KR
authors: Thangaraj
authors: The Wellcome Trust Research Laboratory, Department of Gastrointestinal Sciences, Christian Medical College , Ida Scudder Road, Vellore 632004 , India.
authors: Ashish
authors: A
authors: Goel
authors: The Wellcome Trust Research Laboratory, Department of Gastrointestinal Sciences, Christian Medical College , Ida Scudder Road, Vellore 632004 , India.
authors: C E
authors: CE
authors: Eapen
authors: The Wellcome Trust Research Laboratory, Department of Gastrointestinal Sciences, Christian Medical College , Ida Scudder Road, Vellore 632004 , India.
authors: K A
authors: KA
authors: Balasubramanian
authors: The Wellcome Trust Research Laboratory, Department of Gastrointestinal Sciences, Christian Medical College , Ida Scudder Road, Vellore 632004 , India.
authors: Anup
authors: A
authors: Ramachandran
keywords: complications; hepatology; maternal mortality; maternal–fetal medicine; metabolism