Clinical review: The liver in sepsis

Abstract

During sepsis, the liver plays a key role. It is implicated in the host response, participating in the clearance of the infectious agents/products. Sepsis also induces liver damage through hemodynamic alterations or through direct or indirect assault on the hepatocytes or through both. Accordingly, liver dysfunction induced by sepsis is recognized as one of the components that contribute to the severity of the disease. Nevertheless, the incidence of liver dysfunction remains imprecise, probably because current diagnostic tools are lacking, notably those that can detect the early liver insult. In this review, we discuss the epidemiology, diagnostic tools, and impact on outcome as well as the pathophysiological aspects, including the cellular events and clinical picture leading to liver dysfunction. Finally, therapeutic considerations with regard to the weakness of the pertinent specific approach are examined.

Figure 1

Cellular mechanisms of sepsis-associated cholestasis. (a) Hepatocyte capture and transport of bilirubin and biliary salts. (b) Pathophysiological alterations in sepsis: (1) downregulation of sodium taurocholate cotransporting polypeptide (NTCP); (2,3) reduction of the canalicular export pumps, bile salt export pump (BSEP) and multidrug resistant-associated protein 2 (MRP2); (4) disruption of the structural and functional integrity of the tight junctions; and (5) cytoskeleton alteration surrounding the canaliculus, inducing its distension and a decrease in canalicular duct contractibility. Alb, albumin; CB, conjugated bilirubin; CYP, cytochrome P450; ER, endoplasmic reticulum; GST, glutathione transferase; LP, lipoprotein; OATP, organic anion-transporting polypeptide; UB, unconjugated bilirubin; UDP-GT, uridine diphosphate glucuronosyltransferase.