Novel Drugs for the Management of Hepatic Encephalopathy: Still a Long Journey to Travel

Hepatic encephalopathy (HE) is one of the reversible complications of chronic liver disease, associated with a higher mortality rate. In current clinical practice, treatment with rifaximin and lactulose/lactitol is the first line of treatment in HE. With the advance in pathophysiology, a new class of ammonia lowering drugs has been revealed to overcome the hurdle and disease burden. The mechanism of the novel agents differs significantly and includes the alteration in intestinal microbiota, intestinal endothelial integrity, oxidative stress, inflammatory markers, and modulation of neurotoxins. Most of the trials have reported promising results in the treatment and prevention of HE with fecal microbiota transplantation, albumin, probiotics, flumazenil, polyethylene glycol, AST-120, glycerol phenylbutyrate, nitazoxanide, branched-chain amino acid, naloxone, and acetyl-L-carnitine. However, their clinical use is limited due to the presence of major drawbacks in their study design, sample size, safety profile, bias, and heterogenicity. This study will discuss the novel therapeutic targets for HE in liver cirrhosis patients with supporting clinical trial data. ( J CLIN EXP HEPATOL 2022;12:1200-1214)

Automated summary

Hepatic encephalopathy (HE), a reversible complication of chronic liver disease, has a higher mortality rate. Current first-line treatments include rifaximin and lactulose/lactitol. However, novel drugs targeting the reduction of ammonia levels have shown promising results in clinical trials. These drugs act through various mechanisms, such as altering intestinal microbiota, preserving intestinal endothelial integrity, reducing oxidative stress and inflammation, and modulating neurotoxins. Despite their potential, major drawbacks in study design, sample size, safety profile, bias, and heterogeneity limit their clinical use.