Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 16-11: Cirrhosis + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Stage 1: mild confusion Stage 2: drowsiness Stage 3: stupor Stage 4: coma A revised staging system known as SONIC (Spectrum Of Neurocognitive Impairment in Cirrhosis) encompasses absent, covert, and stages 2 to 4 encephalopathy +++ General Considerations ++ A state of disordered central nervous system function resulting from failure of the liver to detoxify noxious agents of gut origin because of hepatocellular dysfunction and portosystemic shunting Ammonia is the most readily identified toxin but is not solely responsible for the disturbed mental status Precipitants of hepatic encephalopathy Gastrointestinal (GI) bleeding—increases the protein in the bowel and rapidly precipitates hepatic encephalopathy Constipation Alkalosis Potassium deficiency induced by diuretics Opioids, hypnotics, and sedatives Medications containing ammonium or amino compounds Paracentesis with consequent hypovolemia Hepatic or systemic infection Portosystemic shunts (including transjugular intrahepatic portosystemic shunts) In one study, risk factors for hepatic encephalopathy in patients with cirrhosis included a higher serum bilirubin level and use of a nonselective β-blocker, whereas a higher serum albumin level and use of a statin were protective +++ Demographics ++ Alcoholic liver disease and chronic hepatitis C are the most common etiologies of cirrhosis + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ Metabolic encephalopathy characterized by Day–night reversal Asterixis, tremor, dysarthria Delirium Drowsiness, stupor, and ultimately coma In patients with cirrhosis, may be precipitated by an acute hepatocellular insult or an episode of GI bleeding Clinical diagnosis supported by asterixis, elevated serum ammonia with exclusion of other causes of delirium Covert hepatic encephalopathy is characterized by mild cognitive and psychomotor deficits EncephalApp A smartphone app that uses the "Stroop test" (asking the patient to name the color of a written word rather than the word itself, even when the word is the name of a different color) Has proved useful for detecting covert hepatic encephalopathy +++ Differential Diagnosis ++ Metabolic encephalopathy, especially hyponatremia, hypoglycemia, or chronic kidney disease CNS infection Altered mental status from medication effects, particularly if they are hepatically metabolized + Diagnosis Download Section PDF Listen +++ +++ Laboratory Tests ++ Liver biochemical tests often consistent with advanced chronic liver disease Serum (and cerebrospinal fluid) ammonia level is generally elevated Role of neuroimaging tests (eg, cerebral positron emission tomography, magnetic resonance spectroscopy) is evolving + Treatment Download Section PDF Listen +++ +++ Medications ++ Purge blood from the GI tract with 120 mL of magnesium citrate by mouth or nasogastric (NG) tube every 3–4 hours until the stool is free of gross blood, or by administration of lactulose Lactulose Initial dose is 30 mL three or four times daily orally Titrate so that the patient produces two or three soft stools per day Administer rectally if patient cannot take orally: lactulose 200 g/300 mL in a solution of saline or sorbitol as a retention enema for 30–60 min; it may be repeated every 4–6 hours Bowel cleansing with a polyethylene glycol colonoscopy preparation is also effective in patients with acute overt hepatic encephalopathy and may be preferable Neomycin sulfate, 0.5–1 g orally every 6 or 12 hours for 7 days Controls the ammonia-producing intestinal flora Side effects include diarrhea, malabsorption, superinfection, ototoxicity, and nephrotoxicity, usually only after prolonged use Alternative antibiotics Rifaximin, 550 mg orally twice daily Metronidazole, 250 mg orally three times daily Patients who do not respond to lactulose may improve with a 1-week course of an antibiotic in addition to lactulose Probiotic agents may have some benefit Avoid opioids and sedatives metabolized or excreted by the liver If agitation is marked, oxazepam, 10–30 mg (not metabolized by the liver) may be given cautiously orally or by NG tube Correct zinc deficiency, if present, with oral zinc sulfate, 600 mg/day in divided doses Sodium benzoate, 5 g twice daily, ornithine aspartate, 9 g three times daily, and L-acyl-carnitine, 4 g orally daily, may lower blood ammonia levels, but less is known about these drugs than lactulose Flumazenil is effective in about 30% of severe hepatic encephalopathy, but the drug is short-acting and intravenous administration is required +++ Therapeutic Procedures ++ Withhold dietary protein during acute episodes When the patient resumes oral intake, protein intake should be restricted to 60–80 g/day as tolerated, and vegetable protein is better tolerated than meat protein Use of special dietary supplements enriched with branched-chain amino acids is usually unnecessary except in occasional patients who are intolerant of standard protein supplements + Outcome Download Section PDF Listen +++ +++ Complications ++ Hypernatremia can develop from intensive lactulose use +++ When to Admit ++ Inability to care for self or follow medical instructions + References Download Section PDF Listen +++ + +Adebayo D et al. Refractory ascites in liver cirrhosis. Am J Gastroenterol. 2019 Jan;114(1):40–7. [PubMed: 29973706] + +Angeli P et al. News in pathophysiology, definition and classification of hepatorenal syndrome: a step beyond the International Club of Ascites (ICA) consensus document. J Hepatol. 2019 Oct;71(4):811–22. [PubMed: 31302175] + +Asrani SK et al. Burden of liver diseases in the world. J Hepatol. 2019 Jan;70(1):151–71. [PubMed: 30266282] + +Bajaj JS et al. Acute-on-chronic liver failure: getting ready for prime time? Hepatology. 2018 Oct;68(4):1621–32. [PubMed: 29689120] + +Carey EJ et al. A North American expert opinion statement on sarcopenia in liver transplantation. Hepatology. 2019 Nov;70(5):1816–29. [PubMed: 31220351] + +Carrion AF et al. Renal dysfunction in cirrhotic patients. Am J Gastroenterol. 2019 Sep;114(9):1407–10. [PubMed: 31397680] + +European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018 Aug;69(2):406–60. [PubMed: 29653741] + +European Association for the Study of the Liver. EASL Clinical Practice Guidelines on nutrition in chronic liver disease. J Hepatol. 2019 Jan;70(1):172–93. [PubMed: 30144956] + +Kaplan DE et al; VOCAL Study Group. Effects of hypercholesterolemia and statin exposure on survival in a large national cohort of patients with cirrhosis. Gastroenterology. 2019 May;156(6):1693–706. [PubMed: 30660733] + +Martin Mateos R et al. Sepsis in patients with cirrhosis awaiting liver transplantation: new trends and management. Liver Transpl. 2019 Nov;25(11):1700–9. [PubMed: 31408581] + +O'Leary JG et al. AGA Clinical Practice Update: coagulation in cirrhosis. Gastroenterology. 2019 Jul;157(1):34–43. [PubMed: 30986390] + +Simonetto DA et al. Management of sepsis in patients with cirrhosis: current evidence and practical approach. Hepatology. 2019 Jul;70(1):418–28. [PubMed: 30516866] + +Ufere NN et al. Physicians' perspectives on palliative care for patients with end-stage liver disease: a national survey study. Liver Transpl. 2019 Jun;25(6):859–69. [PubMed: 30963669]