Diagnosis
Acute liver failure
The inability of the liver to perform its normal synthetic, metabolic and storage function:
Synthetic: bile, cholesterol, albumin, blood clotting, CRP
Metabolic: hemoglobin, ammonia, drugs
Storage: glucose, vitamins, minerals
Acute liver failure:
PT-INR ≥1.5 and altered mental status without cirrhosis or preexisting liver disease.
Pediatric acute liver failure:
Prothrombin time ≥ 20 seconds, PT-INR ≥ 2
or PT 15 - 20 seconds, PT-INR 1.5-1.9 + Hepatic Encephalopathy
Also known as: Fulminant hepatic failure
Etiology
Cause of acute liver failure [zft][skt][9ih][oos][avk][rid]
Indeterminate 31%
Dug-induced 24%: (most common cause in USA and Europe)
Antibiotics (ampicillin-clavulanate, ciprofloxacin, doxycycline, erythromycin, isoniazid, nitrofurantoin, tetracycline)
Antidepressants (amitriptyline, nortriptyline)
Antiepileptics (phenytoin, valproate)
Anesthetic agents (halothane)
Lipid-lowering medications (atorvastatin, lovastatin, simvastatin)
Immunosuppressive agents (cyclophosphamide, methotrexate)
NSAIDs
Salicylates (Reye syndrome)
Others (disulfiram, flutamide, gold, propylthiouracil)
Ginseng
Pennyroyal oil
Teucrium polium
Chaparral or germander tea
Kawakawa
Toxin:
Amanita phalloides mushroom toxin
Bacillus cereus toxin
Cyanobacteria toxin
Organic solvents (eg, carbon tetrachloride)
Yellow phosphorus
Infection 11% (HEV in India/Pakistan, HBV in Africa)
Cytomegalovirus
Hemorrhagic fever viruses
Herpes simplex virus
Paramyxovirus
Epstein-Barr virus
Dengue virus
Metabolic 11%
Alpha1-antitrypsin deficiency
Fructose intolerance
Galactosemia
Lecithin-cholesterol acyltransferase deficiency
Reye syndrome
Tyrosinemia
Wilson disease
Vascular/ischemic
Ischemic hepatitis (severe hypotension or chemoembolization)
Hepatic vein thrombosis (Budd-Chiari syndrome)
Hepatic veno-occlusive disease
Portal vein thrombosis
Hepatic arterial thrombosis
Infiltrative/malignancy
Immunedysregulation
Cause of chronic (or acute-on-chronic) liver failure:
Infection: viral hepatitis A, B, C, EBV, CMV, HSV
Inflammation: Autoimmune hepatitis, Primary sclerosing cholangitis, Primary biliary cirrhosis, Preeclampsia
Toxic: alcoholism, paracetamol, antibiotics, antidepressants, antiepileptics, anesthetics, statin, immunosuppressive, NSAIDs, salicylates, herb, mushroom, ecstasy, cocaine
Vascular: Ischemic hepatitis, Hepatic vein thrombosis (Budd-Chiari syndrome), Portal vein thrombosis, Hepatic arterial thrombosis
Metabolic: Malnutrition, Hemochromatosis, Alpha1-antitrypsin deficiency, Fructose intolerance, Galactosemia, Lecithin-cholesterol acyltransferase deficiency, Tyrosinemia, Wilson disease
Malignancy: metastasis, hepatocellular carcinoma, cholangiocarcinoma
May lead to cytotoxic and vasogenic cerebral edema causing intracranial hypertension and increased mortality.
Epidemiology
Incidence per 100.000 [skt][mmz][zhn][ous][qnz]
Symptoms & findings
Symptoms
Anorexia, Asterixis, Bradycardia, Coma, Decreased consciousness, Diarrhea, Fatigue, Hematemesis, Hematochezia, Hepatomegaly, Hypertension, Hypotension, Icterus, Lethargy, Melena, Nausea, Seizure, Spider nevus, Tachycardia
Clinical findings
Acidosis, Alkalosis, ANA, Anti-SMA, Ascites, Decreased Albumin, Decreased Magnesium, Decreased Phosphate, Elevated ALAT, Elevated ALP, Elevated Ammonia, Elevated ASAT, Elevated Creatinine, Elevated Intracranial Pressure, Elevated Lactate, Elevated PT-INR, Gynecomastia, Hypoglycemia, Hypokalemia, Hypoxemia, Jaundice, Papilledema, Thrombocytopenia
Anamneses
Localized findings
Approach
Blood test: ASAT, ALAT, PT-INR, Bilirubin, ammonia, creatinine, copper, Viral serology, toxicology, Antinuclear antibody (ANA), anti-smooth muscle antibody (ASMA), and immunoglobulin levels
Blood gas: Lactate
Blood culture
Ultrasound abdomen
CT abdomen
Liver biopsy
CT caput
Electroencephalography
Treatment
Identify conditions that have specific medical treatments [zft][rid]
Antidote: N-acetylcysteine
Encephalopathy and Cerebral Edema:
Frequent mental status check, ICU, Barbiturate agents (thiopental or pentobarbital)
ICP-measurement, mannitol (bolus dose of 0.5-1 g/kg)
Coagulopathy:
Fresh frozen plasma
Platelet transfusion
Vitamin-K
Determine the likelihood of either spontaneous native liver recovery or death
Emergency Liver Transplantation remains the only definitive treatment
Kings College Criteria:
Paracetamol:
pH < 7.3
OR combination of the following:
Hepatic encephalopathy grade ≥ 3
PT-INR > 6.5
Lactate > 3
Non-paracetamol
Hepatic encephalopathy and PT-INR ≥ 6.5
OR any three of the following:
PT-INR > 3.5
Bilirubin ≥ 300 μmol/L
Age < 10 or > 40 years
Unfavorable cause: Drug-Induced Liver Injury, indeterminate
Differential diagnoses
Alcoholic liver disease, Budd-Chiari syndrome, Cirrhosis, Drug-induced liver injury, Eclampsia, Heart failure, Nonalcoholic fatty liver disease, Preeclampsia, Primary biliary cirrhosis, Sepsis, Shock, Spontaneous bacterial peritonitis, Viral hepatitis
References
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[2] Devarbhavi H, Asrani SK, Arab JP, Nartey YA, Pose E, Kamath PS. Global burden of liver disease: 2023 update. J Hepatol. 2023 Aug;79(2):516-537.
[3] Lee WM. Acute liver failure in the United States. Semin Liver Dis. 2003 Aug;23(3):217-26.
[4] Acharya SK, Batra Y, Hazari S, Choudhury V, Panda SK, Dattagupta S. Etiopathogenesis of acute hepatic failure: Eastern versus Western countries. J Gastroenterol Hepatol. 2002 Dec;17 Suppl 3:S268-73.
[5] Bernal W, Auzinger G, Dhawan A, Wendon J. Acute liver failure. Lancet. 2010 Jul 17;376(9736):190-201.
[6] http://emedicine.medscape.com/article/177354 (2014-01-02); [Medscape]
[7] Bower WA, Johns M, Margolis HS, Williams IT, Bell BP. Population-based surveillance for acute liver failure. Am J Gastroenterol. 2007 Nov;102(11):2459-63.
[8] Bretherick AD, Craig DG, Masterton G, Bates C, Davidson J, Martin K, Iredale JP, Simpson KJ. Acute liver failure in Scotland between 1992 and 2009; incidence, aetiology and outcome. QJM. 2011 Nov;104(11):945-56.
[9] Ho CM, Lee CH, Wang JY, Lee PH, Lai HS, Hu RH. Nationwide longitudinal analysis of acute liver failure in taiwan. Medicine (Baltimore). 2014 Jun;93(4):e35.
[10] Qin G, Shao JG, Zhu YC, Xu AD, Yao JH, Wang XL, Qian YK, Wang HY, Shen Y, Lu P, Wang LJ. Population-representative Incidence of Acute-On-Chronic Liver Failure: A Prospective Cross-Sectional Study. J Clin Gastroenterol. 2016 Sep;50(8):670-5.