Luminary Learning Gastrointestinal Disorder- Issue 1

4  • LUMINARY LEARNING: GASTROINTESTINAL DISORDERS The prevalence of ACLF is difficult to assess given the difference in the ACLF definition. In the European multicenter study, the prevalence among hospitalized cirrhotic patients with acute decompensation was 31% [8]. A study from the U.S. Nationwide Inpatient Sample reported ACLF prevalence of 5% among hospitalizations for cirrhosis in 2011 [12]. With the increase in ACLF recognition, there is an emerging concept that differentiates hepatic encephalopathy that occurs in the setting of decompensated cirrhosis from that arising in the context of ACLF. Isolated Hepatic Encephalopathy Isolated hepatic encephalopathy occurs in a setting of decompensated cirrhosis without evidence of extrahepatic organ dysfunction. Isolated hepatic encephalopathy seems to occur in older cir- rhotic patients who are inactive drinkers. It is not clearly associated with hepatic dysfunction but rather develops in the setting of chronic diuretic use. There is no significant inflammatory reac- tion. The prognosis is good even in those requiring intensive care unit admission and mechanical ventilation for airway protection [13, 14]. Hepatic Encephalopathy Associated with Acute-on-Chronic Liver Failure Hepatic encephalopathy associated with ACLF occurs in the setting of extrahepatic organ fail- ures. It seems to occur in young cirrhotic patients who are active drinkers [14]. This type of HE is associated with hepatic dysfunction and bacterial infections. In contrast with isolated hepatic encephalopathy, HE associated with ACLF has a grave prognosis. In addition to hyperammone- mia that is observed in both types of HE, the significant inflammatory reaction found in ACLF may explain this prognostic gap [15]. Pathophysiology of Hepatic Encephalopathy in Acute-on-Chronic Liver Failure In this chapter, we focus on the pathophysiology of HE in the setting of ACLF. Jalan et al. proposed the pathophysiology of ACLF using a four-part model of predisposing event, injury resulting from precipitating event, response to injury, and organ failure (Fig. 1) [7, 16]. Predisposition is the underlying chronic liver disease. Injury can be from multiple etiologies, e.g., bacterial infection, alcohol intake, viral hepatitis, reactivation of hepatitis B, gastrointestinal bleeding, drug-induced liver injury, ischemia, infection, or surgery. The inflammatory response is important as suggested by the presence of increased C-reactive protein and an increase in leukocyte count. In the setting of bacterial translocation, lipopolysaccharide and other pathogen-associated molecular patterns (PAMPs) trigger Kupffer cells to release proinflammatory cytokines, namely IL-1, IL-6, and tumor necrosis factor alpha, which induce inflammatory reaction by leukocyte recruitment and oxi- dative stress. In addition to bacterial translocation, sterile processes such as alcohol, ischemia, or surgery can elicit an inflammatory response by damaging hepatocytes and with subsequent release of damage-associated molecular patterns (DAMPs) (Fig. 1). Organ failure is the final step