Details of Disease

General Information of Disease (ID: DIS5EZKX)

Disease Name	Acute liver failure
Synonyms	fulminant hepatic failure; acute hepatic failure
Disease Class	DB91: Acute/subacute hepatic failure
Definition	Rapid deterioration of liver function causing encephalopathy and coagulopathy. It results from damage to the liver parenchyma usually secondary to acetaminophen overdose or viral infections.
Disease Hierarchy	DISBV50J: Acute disease DISB7H4W: Hepatic failure DIS5EZKX: Acute liver failure
ICD Code	ICD-11 ICD-11: DB91
Disease Identifiers	MONDO ID MONDO_0019542 MESH ID D017114 UMLS CUI C0162557 MedGen ID 58125 HPO ID HP:0006554 Orphanet ID 90062 SNOMED CT ID 197270009

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

This Disease is Treated as An Indication in 1 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Framycetin	DMF8DNE	Approved	Small molecular drug	[1]
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This Disease is Treated as An Indication in 3 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
ELAD	DMVFDGL	Phase 3	NA	[2]
L-ornithine phenylacetate	DM0GZTD	Phase 2	Small molecular drug	[3]
Cardiotrophin-1	DM5WKU1	Phase 1	NA	[4]
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This Disease is Treated as An Indication in 1 Investigative Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
ALF-421	DM53KRA	Investigative	NA	[5]
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Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 46 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ALB	TTFNGC9	Limited	Genetic Variation	[6]
BRIP1	TTZV7LJ	Limited	Biomarker	[7]
COL1A2	TTUABC1	Limited	Biomarker	[8]
HSPA8	TTMQL3K	Limited	Biomarker	[9]
KCNJ10	TTG140O	Limited	Biomarker	[10]
LTC4S	TTW7OTG	Limited	Biomarker	[11]
PTAFR	TTQL5VC	Limited	Biomarker	[12]
THBD	TTAPV67	Limited	Biomarker	[13]
UCP2	TTSC2YM	Limited	Biomarker	[14]
TLR4	TTISGCA	moderate	Altered Expression	[15]
ABCC2	TTFLHJV	Strong	Altered Expression	[16]
AHSG	TTKF4WV	Strong	Biomarker	[17]
ALAS1	TTG1FXO	Strong	Altered Expression	[18]
ATM	TTKBM7V	Strong	Altered Expression	[19]
CASP3	TTPF2QI	Strong	Altered Expression	[20]
CASP9	TTB6T7O	Strong	Therapeutic	[21]
CD14	TT6I7DC	Strong	Biomarker	[22]
CD74	TTCMYP9	Strong	Biomarker	[23]
CSF3	TT5TQ2W	Strong	Biomarker	[24]
CYSLTR1	TTGKOY9	Strong	Biomarker	[25]
F2	TT6L509	Strong	Genetic Variation	[26]
FABP1	TTIV96N	Strong	Altered Expression	[27]
FAS	TT7LTUJ	Strong	Biomarker	[28]
FASLG	TTO7014	Strong	Biomarker	[29]
FST	TTDNM9W	Strong	Biomarker	[30]
GPNMB	TT7315J	Strong	Biomarker	[31]
HDAC2	TTSHTOI	Strong	Biomarker	[32]
HDAC6	TT5ZKDI	Strong	Biomarker	[33]
HGF	TT4V2JM	Strong	Biomarker	[34]
HMGB1	TTWQYB7	Strong	Biomarker	[35]
IL1RN	TT6GSR3	Strong	Biomarker	[36]
INHBA	TTVB30D	Strong	Biomarker	[30]
INS	TTZOPHG	Strong	Biomarker	[37]
JAK2	TTRMX3V	Strong	Genetic Variation	[38]
MAPK8	TT0K6EO	Strong	Biomarker	[39]
NOS3	TTCM4B3	Strong	Genetic Variation	[40]
PEBP1	TT1BGU8	Strong	Altered Expression	[41]
PIM3	TTCGOIN	Strong	Altered Expression	[42]
POMC	TT21AKM	Strong	Therapeutic	[43]
PPP2R5A	TTLONKX	Strong	Biomarker	[44]
SERPINC1	TT4QPUL	Strong	Biomarker	[45]
SLC17A5	TTFSUIA	Strong	Biomarker	[46]
SLC1A2	TT2F078	Strong	Biomarker	[47]
SLC6A12	TTQBMPI	Strong	Biomarker	[48]
TNF	TTF8CQI	Strong	Biomarker	[49]
OTC	TT5KIO9	Definitive	Biomarker	[50]
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⏷ Show the Full List of 46 DTT(s)

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC25A37	DTLBGTZ	Strong	Altered Expression	[51]
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This Disease Is Related to 2 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
MARS1	DE0K52I	Strong	Biomarker	[52]
UGT2B7	DEB3CV1	Strong	Biomarker	[53]
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This Disease Is Related to 46 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CASP12	OTY2W6FG	Limited	Therapeutic	[21]
FGA	OTMIHY80	Limited	Therapeutic	[54]
INS-IGF2	OTZR74BO	Limited	Biomarker	[55]
NBAS	OTW9IBRI	Limited	Biomarker	[56]
POLG2	OTDBMZJB	moderate	Genetic Variation	[57]
RINT1	OTMO19ZD	moderate	Genetic Variation	[58]
ACADM	OTA4P0FC	Strong	Genetic Variation	[59]
AFM	OTPOR8IO	Strong	Biomarker	[60]
APOA5	OTEVKLVA	Strong	Biomarker	[61]
ATRNL1	OTY5JUX2	Strong	Genetic Variation	[46]
BTBD8	OT3A3RD7	Strong	Biomarker	[62]
CAST	OTBXZZGF	Strong	Therapeutic	[63]
CCL4	OT6B8P25	Strong	Posttranslational Modification	[64]
DGUOK	OT78HUZB	Strong	Biomarker	[65]
ERO1A	OTVKOQWM	Strong	Biomarker	[66]
EVA1A	OTCY3Q2M	Strong	Biomarker	[67]
EXOSC3	OTNCF906	Strong	Altered Expression	[68]
FABP7	OTRE2H4G	Strong	Altered Expression	[69]
FAH	OTGZA1YR	Strong	Genetic Variation	[70]
FBP1	OTQBANEP	Strong	Altered Expression	[71]
GC	OTWS63BY	Strong	Genetic Variation	[72]
GFER	OTVK43OK	Strong	Altered Expression	[73]
GSDMD	OTH39BKI	Strong	Biomarker	[74]
GTF2A1L	OTDQHVAI	Strong	Biomarker	[60]
KCTD9	OTBN6ZUC	Strong	Biomarker	[75]
KRT18	OTVLQFIP	Strong	Biomarker	[76]
KRT8	OTTM4X11	Strong	Genetic Variation	[77]
MSC	OTBRPZL5	Strong	Biomarker	[24]
MST1	OTOC4UNG	Strong	Biomarker	[78]
PANX1	OTXPEDOK	Strong	Biomarker	[79]
PDLIM3	OTVXQC81	Strong	Genetic Variation	[46]
PIK3IP1	OTWE5G4T	Strong	Biomarker	[78]
POLG	OTDUCT04	Strong	CausalMutation	[80]
PPP1R11	OTSHYPPW	Strong	Biomarker	[33]
RGN	OTD04KB1	Strong	Altered Expression	[81]
RRM2B	OTE8GBUR	Strong	Biomarker	[65]
SCO1	OTC45UGB	Strong	Biomarker	[82]
SCYL1	OTQ0IN7P	Strong	Genetic Variation	[83]
SERAC1	OTWH1ULQ	Strong	Genetic Variation	[84]
SERPINF2	OTZGAF8B	Strong	Biomarker	[85]
SIGLEC9	OTZC7SIM	Strong	Biomarker	[86]
SLA2	OTNVE666	Strong	Biomarker	[52]
STON1	OT2HPUAI	Strong	Biomarker	[60]
STX18	OTW4GF3X	Strong	Biomarker	[87]
TNFAIP6	OT1SLUZH	Strong	Biomarker	[88]
TRMU	OTJ1KXM7	Strong	Genetic Variation	[89]
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⏷ Show the Full List of 46 DOT(s)

References

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2	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3	ClinicalTrials.gov (NCT01634230) Emergency Use of OCR-002 in Acute Liver Failure. U.S. National Institutes of Health.
4	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4906).
5	Secretion of a TNFR:Fc fusion protein following pulmonary administration of pseudotyped adeno-associated virus vectors. J Virol. 2004 Nov;78(22):12355-65.
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31	Expression of osteoactivin in rat and human liver and isolated rat liver cells.J Hepatol. 2005 Apr;42(4):565-72. doi: 10.1016/j.jhep.2004.12.021.
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33	Histone deacetylase 6 inhibitor ACY1215 offers a protective effect through the autophagy pathway in acute liver failure.Life Sci. 2019 Dec 1;238:116976. doi: 10.1016/j.lfs.2019.116976. Epub 2019 Oct 18.
34	Cellular and functional loss of liver endothelial cells correlates with poor hepatocyte regeneration in acute-on-chronic liver failure.Hepatol Int. 2019 Nov;13(6):777-787. doi: 10.1007/s12072-019-09983-y. Epub 2019 Sep 12.
35	HMGB1 is a Central Driver of Dynamic Pro-inflammatory Networks in Pediatric Acute Liver Failure induced by Acetaminophen.Sci Rep. 2019 Apr 12;9(1):5971. doi: 10.1038/s41598-019-42564-5.
36	Amniotic-fluid-derived mesenchymal stem cells overexpressing interleukin-1 receptor antagonist improve fulminant hepatic failure.PLoS One. 2012;7(7):e41392. doi: 10.1371/journal.pone.0041392. Epub 2012 Jul 23.
37	A cohort study of the incidence of serious acute liver injury in diabetic patients treated with hypoglycemic agents.Arch Intern Med. 2003 Mar 24;163(6):728-34. doi: 10.1001/archinte.163.6.728.
38	Direct intrahepatic portocaval shunt for treatment of portal thrombosis and Budd-Chiari syndrome.Ann Hepatol. 2016 Jan-Feb;15(1):127-30. doi: 10.5604/16652681.1184288.
39	Endoplasmic Reticulum Stress-Induced Upregulation of STARD1 Promotes Acetaminophen-Induced Acute Liver Failure.Gastroenterology. 2019 Aug;157(2):552-568. doi: 10.1053/j.gastro.2019.04.023. Epub 2019 Apr 25.
40	Role of nitric oxide synthase genes in hepatitis E virus infection.J Viral Hepat. 2014;21(9):671-9. doi: 10.1111/jvh.12186. Epub 2013 Nov 11.
41	Inhibition of RKIP aggravates thioacetamide-induced acute liver failure in mice.Exp Ther Med. 2018 Oct;16(4):2992-2998. doi: 10.3892/etm.2018.6542. Epub 2018 Jul 30.
42	Downregulation of microRNA-124 prevents the development of acute liver failure through the upregulation of PIM-3.Exp Physiol. 2020 Jan;105(1):108-119. doi: 10.1113/EP087963. Epub 2019 Dec 9.
43	Single injection of naked plasmid encoding alpha-melanocyte-stimulating hormone protects against thioacetamide-induced acute liver failure in mice.Biochem Biophys Res Commun. 2004 Sep 10;322(1):153-61. doi: 10.1016/j.bbrc.2004.07.091.
44	Functional genetics-directed identification of novel pharmacological inhibitors of FAS- and TNF-dependent apoptosis that protect mice from acute liver failure.Cell Death Dis. 2016 Mar 17;7(3):e2145. doi: 10.1038/cddis.2016.45.
45	Antithrombin III is associated with acute liver failure in patients with end-stage heart failure undergoing mechanical circulatory support.J Thorac Cardiovasc Surg. 2017 Jun;153(6):1374-1382. doi: 10.1016/j.jtcvs.2017.01.053. Epub 2017 Feb 9.
46	Outcomes of Acute Liver Injury in Adults Due to Wilson's Disease: Is Survival Without Transplant Possible?.Liver Transpl. 2020 Mar;26(3):330-336. doi: 10.1002/lt.25703.
47	Expression of astrocytic genes coding for proteins implicated in neural excitation and brain edema is altered after acute liver failure.J Neurochem. 2014 Mar;128(5):617-27. doi: 10.1111/jnc.12511. Epub 2013 Nov 14.
48	Betaine/GABA transporter-1 (BGT-1) deficiency in mouse prevents acute liver failure in vivo and hepatocytes apoptosis in vitro.Biochim Biophys Acta Mol Basis Dis. 2020 Mar 1;1866(3):165634. doi: 10.1016/j.bbadis.2019.165634. Epub 2019 Dec 9.
49	Atractylodin ameliorates lipopolysaccharide and d-galactosamine-induced acute liver failure via the suppression of inflammation and oxidative stress.Int Immunopharmacol. 2019 Jul;72:348-357. doi: 10.1016/j.intimp.2019.04.005. Epub 2019 Apr 24.
50	AAV gene therapy corrects OTC deficiency and prevents liver fibrosis in aged OTC-knock out heterozygous mice.Mol Genet Metab. 2017 Apr;120(4):299-305. doi: 10.1016/j.ymgme.2017.02.011. Epub 2017 Mar 2.
51	Functional secretome analysis reveals Annexin-A1 as important paracrine factor derived from fetal mesenchymal stem cells in hepatic regeneration.EBioMedicine. 2019 Jul;45:542-552. doi: 10.1016/j.ebiom.2019.07.009. Epub 2019 Jul 12.
52	Molecular Adsorbent Recirculating System Effectively Replaces Hepatic Function in Severe Acute Liver Failure.Ann Surg. 2017 Oct;266(4):677-684. doi: 10.1097/SLA.0000000000002361.
53	Acute liver failure enhances oral plasma exposure of zidovudine in rats by downregulation of hepatic UGT2B7 and intestinal P-gp.Acta Pharmacol Sin. 2017 Nov;38(11):1554-1565. doi: 10.1038/aps.2017.54. Epub 2017 Aug 3.
54	Therapy with interleukin-22 alleviates hepatic injury and hemostasis dysregulation in rat model of acute liver failure.Adv Hematol. 2014;2014:705290. doi: 10.1155/2014/705290. Epub 2014 Apr 1.
55	Characterization of the molecular mechanisms involved in the increased insulin secretion in rats with acute liver failure.Biochim Biophys Acta. 2007 Jan;1772(1):60-5. doi: 10.1016/j.bbadis.2006.10.001. Epub 2006 Oct 4.
56	SOPH syndrome in three affected individuals showing similarities with progeroid cutis laxa conditions in early infancy.J Hum Genet. 2019 Jul;64(7):609-616. doi: 10.1038/s10038-019-0602-8. Epub 2019 Apr 24.
57	Whole exome sequencing identifies a homozygous POLG2 missense variant in an infant with fulminant hepatic failure and mitochondrial DNA depletion. Eur J Med Genet. 2016 Oct;59(10):540-5. doi: 10.1016/j.ejmg.2016.08.012. Epub 2016 Aug 31.
58	RINT1 Bi-allelic Variations Cause Infantile-Onset Recurrent Acute Liver Failure and Skeletal Abnormalities. Am J Hum Genet. 2019 Jul 3;105(1):108-121. doi: 10.1016/j.ajhg.2019.05.011. Epub 2019 Jun 13.
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84	Individual exome analysis in diagnosis and management of paediatric liver failure of indeterminate aetiology.J Hepatol. 2014 Nov;61(5):1056-63. doi: 10.1016/j.jhep.2014.06.038. Epub 2014 Jul 10.
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