Serum bile acids as marker for acute decompensation and acute‐on‐chronic liver failure in patients with non‐cholestatic cirrhosis

Abstract

Serum total and individual BAs are associated with AD and ACLF in patients with cirrhosis. Assessment of total BAs could serve as additional marker for risk stratification in cirrhotic patients with respect to new onset of AD and ACLF.

Bile Acids in Hepatic Encephalopathy

“…The majority of the bile acids secreted into the duodenum from the liver are taken up by the enterocytes of the ileum via active transport, secreted into the blood stream and are recirculated back to the liver. However, in conditions where the liver is damaged, serum bile acids are known to increase, 15,16 possibly due to the release of bile acid content from damaged hepatocytes as well as an impaired reuptake of bile acids from the blood stream. The increase in total bile acid content in the serum, as a result of liver damage, occurs in many acute and chronic liver disorders to varying degrees.…”

“…The increase in total bile acid content in the serum, as a result of liver damage, occurs in many acute and chronic liver disorders to varying degrees. 15 Indeed, this increase has been suggested to have predictive value for the onset of acute decompensation and acute-on-chronic liver failure in patients with cirrhosis, 16 both of which are often associated with the development of hepatic encephalopathy. However, the development of hepatic encephalopathy is clearly a multifactorial process, and an increase in serum bile acids in the absence of other factors such as systemic inflammation and hyperammonemia is likely not enough to cause hepatic encephalopathy by itself.…”

Bile acids and cardiovascular function in cirrhosis

“…Overgrowth of intestinal bacteria and increased gut permeability due to the insufficient antimicrobial function of a depleted BA pool is followed by bacterial translocation and a potent inflammatory response that can determine decompensation of liver disease . In a recent observational prospective study, increased BA levels correlated with acute decompensation on admission of cirrhotic patients independently of sex, age and MELD score …”

“…9 In a recent observational prospective study, increased BA levels correlated with acute decompensation on admission of cirrhotic patients independently of sex, age and MELD score. 10 Carefully regulated feedback loops that promote a stable BA pool have been identified in the last decades. The most important regulatory pathway is dependent on the Farnesoid X-activated receptor (FXR) expressed in the nucleus of both terminal ileum enterocytes and hepatocytes.…”

Circulating bile acids predict outcome in critically ill patients

“…Cholestasis in critically ill patients is associated with the presence of shock, sepsis, major surgery, hepatotoxicity of drugs and parenteral nutrition [4, 6–8]. While no universal definition of cholestasis has been established [1, 6, 7, 9, 10], the complexity of cholestasis, characterized by impaired bile formation and flow and subsequent bile acid (BA) retention, may not be sufficiently reflected by bilirubin [6, 11]. Although hyperbilirubinemia and accumulation of serum BAs are frequent findings in critically ill patients, underlying molecular pathways and clinical implications are still poorly understood.…”