Inflammation: A novel target of current therapies for hepatic encephalopathy in liver cirrhosis

Abstract

Hepatic encephalopathy (HE) is a severe neuropsychiatric syndrome that most commonly occurs in decompensated liver cirrhosis and incorporates a spectrum of manifestations that ranges from mild cognitive impairment to coma. Although the etiology of HE is not completely understood, it is believed that multiple underlying mechanisms are involved in the pathogenesis of HE, and one of the main factors is thought to be ammonia; however, the ammonia hypothesis in the pathogenesis of HE is incomplete. Recently, it has been increasingly demonstrated that inflammation, including systemic inflammation, neuroinflammation and endotoxemia, acts in concert with ammonia in the pathogenesis of HE in cirrhotic patients. Meanwhile, a good number of studies have found that current therapies for HE, such as lactulose, rifaximin, probiotics and the molecular adsorbent recirculating system, could inhibit different types of inflammation, thereby improving the neuropsychiatric manifestations and preventing the progression of HE in cirrhotic patients. The anti-inflammatory effects of these current therapies provide a novel therapeutic approach for cirrhotic patients with HE. The purpose of this review is to describe the inflammatory mechanisms behind the etiology of HE in cirrhosis and discuss the current therapies that target the inflammatory pathogenesis of HE.

Keywords: Hepatic encephalopathy; Inflammation; Pathogenesis; Treatment.

Figure 1

The inflammatory pathogenesis of hepatic encephalopathy in liver cirrhosis. Lactulose, rifaximin, and probiotics not only reduce the circulating levels of ammonia but also modulate intestinal flora, lower the endotoxemia and inhibit the production of pro-inflammatory cytokines. MARS treatment also decreases the circulating levels of ammonia and pro-inflammatory cytokines.