Literature DB >> 35814520

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

Siddheesh Rajpurohit1, Balaji Musunuri1, Pooja Basthi Mohan1, Shiran Shetty1.   

Abstract

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.
© 2022 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.

Entities:  

Keywords:  ALC, acetyl-L-carnitine; BCAA, branched-chain amino acid; BD, twice a day; BDI, Beck Depression Inventory; BUN, blood urea nitrogen; CHESS, Clinical Hepatic Encephalopathy Staging Scale; CLDQ, Chronic Liver Disease Questionnaire; ECT, estimated completion time; EEG, electroencephalogram; FMT, fecal microbiota transplantation; GPB, glycerol phenylbutyrate; HESA, Hepatic Encephalopathy Scoring Algorithm; HRQOL, health-related quality of life; IV, intravenous; MED, Modified Encephalopathy Scale; MELD, Model for End-stage Liver Disease; MMSE, Mini-Mental State Examination; NTZ, nitazoxanide; Nal, naloxone; OD, once a day; ORT, object recognition test; PEG, polyethylene glycol; QID, four times a day; QOL, quality of life; RBNS, Repeatable Battery for the Assessment of Neuropsychological Status; RCT, randomized control trial; RT-qPCR, real-time quantitative polymerase chain reaction; TID, three times a day; VSL#3, high concentration probiotic preparations; hepatic encephalopathy; liver cirrhosis; novel drugs; treatment outcome

Year:  2022        PMID: 35814520      PMCID: PMC9257922          DOI: 10.1016/j.jceh.2022.01.012

Source DB:  PubMed          Journal:  J Clin Exp Hepatol        ISSN: 0973-6883


  82 in total

1.  AST-120 (spherical carbon adsorbent) lowers ammonia levels and attenuates brain edema in bile duct-ligated rats.

Authors:  Cristina R Bosoi; Christian Parent-Robitaille; Keith Anderson; Mélanie Tremblay; Christopher F Rose
Journal:  Hepatology       Date:  2011-06       Impact factor: 17.425

2.  Characterization of fecal microbial communities in patients with liver cirrhosis.

Authors:  Yanfei Chen; Fengling Yang; Haifeng Lu; Baohong Wang; Yunbo Chen; Dajiang Lei; Yuezhu Wang; Baoli Zhu; Lanjuan Li
Journal:  Hepatology       Date:  2011-06-26       Impact factor: 17.425

3.  Ammonia control in children with urea cycle disorders (UCDs); phase 2 comparison of sodium phenylbutyrate and glycerol phenylbutyrate.

Authors:  Uta Lichter-Konecki; G A Diaz; J L Merritt; A Feigenbaum; C Jomphe; J F Marier; M Beliveau; J Mauney; K Dickinson; A Martinez; M Mokhtarani; B Scharschmidt; W Rhead
Journal:  Mol Genet Metab       Date:  2011-05-05       Impact factor: 4.797

4.  Probiotic VSL#3 reduces liver disease severity and hospitalization in patients with cirrhosis: a randomized, controlled trial.

Authors:  Radha K Dhiman; Baldev Rana; Swastik Agrawal; Ashish Garg; Madhu Chopra; Kiran K Thumburu; Amit Khattri; Samir Malhotra; Ajay Duseja; Yogesh K Chawla
Journal:  Gastroenterology       Date:  2014-08-27       Impact factor: 22.682

5.  Naloxone in the management of hepatic encephalopathy.

Authors:  Q Jiang; G Jiang; T E Welty; M Zheng
Journal:  J Clin Pharm Ther       Date:  2010-06       Impact factor: 2.512

Review 6.  Probiotics for people with hepatic encephalopathy.

Authors:  Rohan Dalal; Richard G McGee; Stephen M Riordan; Angela C Webster
Journal:  Cochrane Database Syst Rev       Date:  2017-02-23

7.  Normal protein diet for episodic hepatic encephalopathy: results of a randomized study.

Authors:  Juan Córdoba; Juan López-Hellín; Mercé Planas; Pilar Sabín; Francesc Sanpedro; Francisco Castro; Rafael Esteban; Jaume Guardia
Journal:  J Hepatol       Date:  2004-07       Impact factor: 25.083

8.  Ammonia control and neurocognitive outcome among urea cycle disorder patients treated with glycerol phenylbutyrate.

Authors:  George A Diaz; Lauren S Krivitzky; Masoud Mokhtarani; William Rhead; James Bartley; Annette Feigenbaum; Nicola Longo; William Berquist; Susan A Berry; Renata Gallagher; Uta Lichter-Konecki; Dennis Bartholomew; Cary O Harding; Stephen Cederbaum; Shawn E McCandless; Wendy Smith; Gerald Vockley; Stephen A Bart; Mark S Korson; David Kronn; Roberto Zori; J Lawrence Merritt; Sandesh C S Nagamani; Joseph Mauney; Cynthia Lemons; Klara Dickinson; Tristen L Moors; Dion F Coakley; Bruce F Scharschmidt; Brendan Lee
Journal:  Hepatology       Date:  2013-01-03       Impact factor: 17.425

9.  Studies of osmotic diarrhea induced in normal subjects by ingestion of polyethylene glycol and lactulose.

Authors:  H F Hammer; C A Santa Ana; L R Schiller; J S Fordtran
Journal:  J Clin Invest       Date:  1989-10       Impact factor: 14.808

10.  Polyethylene Glycol and Lactulose versus Lactulose Alone in the Treatment of Hepatic Encephalopathy in Patients with Cirrhosis: A Non-Inferiority Randomized Controlled Trial.

Authors:  Mohammadreza Naderian; Heshmatollah Akbari; Morteza Saeedi; Amir Ali Sohrabpour
Journal:  Middle East J Dig Dis       Date:  2017-01
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