Acquired liver injury in the intensive care unit.

T HE liver plays a key role in the synthesis of proteins, metabolism of toxins and drugs, and in modulation of immunity. In critically ill patients, hypoxic, toxic, and inflammatory insults can affect hepatic excretory, synthetic, and/or purification functions, leading to systemic complications such as coagulopathy, increased risk of infection, hypoglycemia, and acute kidney injury. In severe cases, hepatic encephalopathy or brain dysfunction (acute liver failure) may occur. Because of the lack of specificity of standard laboratory investigations, identifying liver injury or dysfunction in critically ill patients remains a significant challenge. In addition, the great heterogeneity of criteria used to define the consequences of liver insults increases the difficulties for the clinician to properly interpret hepatic biochemical abnormalities. In this review, we choose to define liver injury as an elevation in serum concentrations of routinely measured hepatic enzymes, including aminotransferases (aspartate aminotransferase [AST]; alanine aminotransferase, [ALT]), alkaline phosphatase (ALP), or -glutamyl transpeptidase. Hepatic dysfunction refers to derangement of pathways related to synthetic or clearance function, including international normalized ratio (INR) and bilirubin. Hepatotoxicity refers to hepatic injury and dysfunction caused by a drug or another noninfectious agent. Acute liver failure designates liver injury that results in life-threatening hepatic synthetic dysfunction and brain dysfunction (encephalopathy) (fig. 1). Here we review the causes, mechanisms, and clinical implications of intensive care unit (ICU)-acquired liver injury and dysfunction in patients without previous known hepatobiliary disease on ICU admission. Consequently, this review will not cover liver injury caused by chronic liver disease; viral, metabolic, vascular, or autoimmune liver disease; pregnancyrelated liver injury; or postoperative hepatic resection.