Hypoxic-Ischemic Encephalopathy-Associated Liver Fatty Degeneration and the Effects of Therapeutic Hypothermia in Newborn Piglets

Abstract

Background: Although liver can be injured under the hypoxic-ischemic encephalopathy (HIE) condition, there is currently no histopathological evidence. Therapeutic hypothermia is used to protect the brain; however, the therapeutic potential for concomitant liver injury is unknown. Objectives: This study aimed to histopathologically prove HIE-associated liver injury and to investigate the influence of therapeutic hypothermia in a newborn piglet HIE model. Methods: Eighteen newborn piglets were divided into 3 groups: control (n = 4), HIE (n = 8), and therapeutic hypothermia (n = 6) groups. The hypoxic insult was induced by decreasing the fraction of inspiratory oxygen from 21 to 2-4% over 40 min while monitoring cerebral blood volume and cerebral hemoglobin oxygen saturation. For therapeutic hypothermia, whole-body cooling at 33-34°C was administered for 24 h after the hypoxic insult. We hematologically and histopathologically investigated the liver injury in all groups. Results: Alanine transaminase and lactate dehydrogenase levels in the HIE group were significantly elevated compared with those in the control group. Micro-lipid droplet accumulation in the periportal zone, but not in the perivenous zone, was significantly greater in the HIE group than in the control group and significantly smaller in the therapeutic hypothermia group than in the HIE group. Conclusions: We demonstrated that micro-lipid droplet accumulation in the cytoplasm of hepatocytes in the periportal zone occurs under the HIE condition and that this accumulation is suppressed by therapeutic hypothermia.