Details of Disease

General Information of Disease (ID: DISEAKAN)

• Disease Name: Hepatic encephalopathy
• Synonyms: encephalopathy, hepatic; Hepatoencephalopathy; portal-systemic encephalopathy
• Disease Class: DB90-DB9Z: Liver disease
• Definition: Hepatic encephalopathy is a syndrome observed in some patients with cirrhosis. It is defined as a spectrum of neuropsychiatric abnormalities in patients with liver dysfunction, when other known brain disease has been excluded.Signs and symptomsmay be debilitating, and they can begin mildly and gradually, or occur suddenly and severely. They may includepersonality or moodchanges, intellectual impairment, abnormal movements,a depressed level of consciousness, and other symptoms.There are several theories regarding the exact cause, butdevelopment of the condition isprobablyat least partiallydue to the effect of substances that are toxic to nerve tissue (neurotoxic), which are typically present with liver damage and/or liver disease. Treatment depends upon the severity of mental status changes and upon the certainty of the diagnosis.
• Disease Hierarchy:
  DIS6ZC3X: Brain disease
  DISEAKAN: Hepatic encephalopathy
• ICD Code:
  ICD-11: ICD-11: DB99.5
  Expand ICD-11: 'DB99.5
• Disease Identifiers:
  MONDO ID: MONDO_0001711
  MESH ID: D006501
  UMLS CUI: C0019151
  MedGen ID: 5513
  HPO ID: HP:0002480
  SNOMED CT ID: 13920009

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 6 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Framycetin	DMF8DNE	Approved	Small molecular drug	[1]
Glycerol phenylbutyrate	DMDGRQO	Approved	Small molecular drug	[2]
L-ornithine L-aspartate	DM41P61	Approved	Small molecular drug	[2]
Lactulose	DMSAOWQ	Approved	Small molecular drug	[3]
Phenylacetic acid	DMQ95GE	Approved	Small molecular drug	[4]
Rifaximin	DMW1TV2	Approved	Small molecular drug	[5]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 19 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
MAOA	TT3WG5C	Limited	Biomarker	[6]
MAOB	TTGP7BY	Limited	Biomarker	[6]
EPOR	TTAUX24	Strong	Biomarker	[7]
G6PD	TTKN8W0	Strong	Biomarker	[8]
GABRA1	TT1MPAY	Strong	Genetic Variation	[9]
GABRG2	TT06RH5	Strong	Genetic Variation	[9]
GLUL	TTURQ2G	Strong	Biomarker	[6]
GRIA1	TTVPQTF	Strong	Biomarker	[10]
INSR	TTCBFJO	Strong	Biomarker	[11]
LBP	TTVQJLY	Strong	Biomarker	[12]
LTA	TTP73TM	Strong	Biomarker	[13]
NOS1	TTZUFI5	Strong	Biomarker	[14]
OPRM1	TTKWM86	Strong	Biomarker	[15]
PRKDC	TTK3PY9	Strong	Biomarker	[16]
PTGS1	TT8NGED	Strong	Biomarker	[17]
SLC25A1	TTTD730	Strong	Biomarker	[18]
TSPO	TTPTXIN	Strong	Biomarker	[6]
CLCA1	TT3AF4R	Definitive	Genetic Variation	[19]
SPDEF	TT2ZUPY	Definitive	Biomarker	[20]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
GLS	DE3E0VT	Limited	Genetic Variation	[21]

This Disease Is Related to 11 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
DBI	OT884QY9	Limited	Biomarker	[22]
DGUOK	OT78HUZB	Strong	Biomarker	[23]
GABRB1	OT4L2SSB	Strong	Biomarker	[24]
GC	OTWS63BY	Strong	Biomarker	[25]
GCA	OTAJ7ZHG	Strong	Genetic Variation	[26]
GLS2	OT08MSHL	Strong	Genetic Variation	[27]
GLUD1	OTXKOCUH	Strong	Biomarker	[28]
MTFMT	OT1OIVJL	Strong	Biomarker	[29]
CLCA2	OTF191LZ	Definitive	Genetic Variation	[19]
CLCA4	OTCRR1M9	Definitive	Genetic Variation	[19]
STIL	OT9799VN	Definitive	Biomarker	[30]

References

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• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] Lactulose FDA Label
• [4] Exposures of Phenylacetic Acid and Phenylacetylglutamine Across Different Subpopulations and Correlation with Adverse Events. Clin Pharmacokinet. 2021 Dec;60(12):1557-1567.
• [5] Rifaximin FDA Label
• [6] Hepatic encephalopathy: An update of pathophysiologic mechanisms.Proc Soc Exp Biol Med. 1999 Nov;222(2):99-112. doi: 10.1046/j.1525-1373.1999.d01-120.x.
• [7] Changes in CNS cells in hyperammonemic portal hypertensive rats.J Neurochem. 2014 Feb;128(3):431-44. doi: 10.1111/jnc.12458. Epub 2013 Oct 24.
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• [10] Transport of AMPA receptors during long-term potentiation is impaired in rats with hepatic encephalopathy.Neurochem Int. 2009 Dec;55(7):514-20. doi: 10.1016/j.neuint.2009.05.006. Epub 2009 May 18.
• [11] Insulin Resistance Disrupts the Interaction Between AKT and the NMDA Receptor and the Inactivation of the CaMKIV/CREB Pathway in Minimal Hepatic Encephalopathy.Toxicol Sci. 2017 Oct 1;159(2):290-306. doi: 10.1093/toxsci/kfx093.
• [12] Posttraumatic stress disorder is associated with altered gut microbiota that modulates cognitive performance in veterans with cirrhosis.Am J Physiol Gastrointest Liver Physiol. 2019 Nov 1;317(5):G661-G669. doi: 10.1152/ajpgi.00194.2019. Epub 2019 Aug 28.
• [13] Tumor necrosis factor genomic polymorphism and outcome of acetaminophen (paracetamol)-induced acute liver failure.J Hepatol. 1998 Jul;29(1):53-9. doi: 10.1016/s0168-8278(98)80178-5.
• [14] Induction of NOS and nitrotyrosine expression in the rat striatum following experimental hepatic encephalopathy.Metab Brain Dis. 2009 Sep;24(3):395-408. doi: 10.1007/s11011-009-9154-5.
• [15] Up-regulation of central mu-opioid receptors in a model of hepatic encephalopathy: a potential mechanism for increased sensitivity to morphine in liver failure.Life Sci. 2002 Feb 22;70(14):1701-8. doi: 10.1016/s0024-3205(02)01487-x.
• [16] Perturbations in ataxia telangiectasia mutant signaling pathways after drug-induced acute liver failure and their reversal during rescue of animals by cell therapy.Am J Pathol. 2011 Jan;178(1):161-74. doi: 10.1016/j.ajpath.2010.11.001. Epub 2010 Dec 23.
• [17] Selective cyclooxygenase inhibition improves hepatic encephalopathy in fulminant hepatic failure of rat.Eur J Pharmacol. 2011 Sep;666(1-3):226-32. doi: 10.1016/j.ejphar.2011.04.060. Epub 2011 May 10.
• [18] Management of HCV-related decompensated cirrhosis with direct-acting antiviral agents: who should be treated?.Hepatol Int. 2019 Mar;13(2):165-172. doi: 10.1007/s12072-019-09933-8. Epub 2019 Feb 13.
• [19] Variations in the promoter region of the glutaminase gene and the development of hepatic encephalopathy in patients with cirrhosis: a cohort study.Ann Intern Med. 2010 Sep 7;153(5):281-8. doi: 10.7326/0003-4819-153-5-201009070-00002.
• [20] Efficacy and safety of rifaximin in Japanese patients with hepatic encephalopathy: A phase II/III, multicenter, randomized, evaluator-blinded, active-controlled trial and a phase III, multicenter, open trial.Hepatol Res. 2018 May;48(6):411-423. doi: 10.1111/hepr.13045. Epub 2018 Jan 19.
• [21] Metformin Impairs Glutamine Metabolism and Autophagy in Tumour Cells.Cells. 2019 Jan 14;8(1):49. doi: 10.3390/cells8010049.
• [22] Role of DBI in brain and its posttranslational processing products in normal and abnormal behavior.Neuropharmacology. 1991 Dec;30(12B):1425-33. doi: 10.1016/s0028-3908(11)80012-2.
• [23] Deoxyguanosine kinase deficiency: a report of four patients.J Pediatr Endocrinol Metab. 2017 May 24;30(6):697-702. doi: 10.1515/jpem-2016-0268.
• [24] Expression of gamma-aminobutyric acid A receptor subunits alpha1, beta1, gamma2 mRNA in rats with hepatic encephalopathy.World J Gastroenterol. 2005 Jun 7;11(21):3319-22. doi: 10.3748/wjg.v11.i21.3319.
• [25] Temporal profile of total, bound, and free Gc-globulin after acetaminophen overdose.Liver Transpl. 2001 Aug;7(8):732-8. doi: 10.1053/jlts.2001.26061.
• [26] Validation study associating glutaminase promoter variations with hepatic encephalopathy in East Asian populations.J Gastroenterol Hepatol. 2017 Apr;32(4):901-907. doi: 10.1111/jgh.13618.
• [27] A genetic variant in the promoter of phosphate-activated glutaminase is associated with hepatic encephalopathy.J Intern Med. 2015 Sep;278(3):313-22. doi: 10.1111/joim.12374. Epub 2015 Jun 7.
• [28] Changes in glutamate-cycle enzyme mRNA levels in a rat model of hepatic encephalopathy.Metab Brain Dis. 1988 Jun;3(2):81-90. doi: 10.1007/BF01001011.
• [29] Microbial functional change is linked with clinical outcomes after capsular fecal transplant in cirrhosis.JCI Insight. 2019 Dec 19;4(24):e133410. doi: 10.1172/jci.insight.133410.
• [30] Alogliptin abates memory injuries of hepatic encephalopathy induced by acute paracetamol intoxication via switching-off autophagy-related apoptosis.Life Sci. 2018 Dec 15;215:11-21. doi: 10.1016/j.lfs.2018.10.069. Epub 2018 Nov 1.