What are the guideline sources, guidelines and references for Hepatic encephalopathy ?
Guideline sources The following summarized guidelines for the evaluation and management of hepatic encephalopathy (HE) are prepared by our editorial team based on guidelines from the Society of Critical Care Medicine (SCCM 2023), the European Association for the Study of the Liver (EASL 2022; 2018), the Baveno VII Consensus Workshop (Baveno VII 2022), the Italian Association for the Study of the Liver (AISF 2019), and the European Association for the Study of the Liver (EASL/AASLD 2014). 1 2 3 4 5 6 7 7 8 8 9 10 11 Definition https://web.pathway.md/diseases/reciwA55EyqDknXId 1/11 6/24/23, 12:41 PM Hepatic encephalopathy Pathway HE is a reversible neuropsychiatric abnormality found in patients with chronic liver disease and/or portosystemic shunting. 7 Epidemiology The pathophysiology of HE is multifactorial and involves agents such as ammonia, inflammatory cytokines, manganese deposition in the basal ganglia, and benzodiazepine-like compounds. Fecal microbiota and aromatic amino acids also play a role. 7 Pathophysiology In the United States, the incidence of hospital admission for HE is approximately 30 cases per 100,000 person-years. In patients with decompensated cirrhosis, the prevalence of HE is up to 20%. 8 9 Disease course HE is associated with clinical manifestations of neuronal dysfunction (delirium, seizures). If untreated, severe HE may result in brain edema, coma, and death. 10 Prognosis and risk of recurrence The in-hospital mortality of patients with HE is estimated at 14.1-15.6%. Patients with cirrhosis who develop HE have an estimated 1-year survival probability of 42% and 3-year survival probability of 23%. 8 11 CalculatorGlasgow Coma Scale GCS CalculatorWest-Haven criteria for hepatic Guidelines 1. Screening and diagnosis Screening for covert hepatic encephalopathy: As per EASL 2022 guidelines, screen patients with cirrhosis and no history of overt HE for covert HE with validated (with available experience/tools and local norms) tests. B As per AISF 2019 guidelines: Screen for covert HE using the Animal Naming Test (the number of animals listed in 60 seconds) in all patients with cirrhosis. B Screen for minimal HE using combined neuropsychological and neurophysiological indices in patients with a job and lifestyle requiring high standards of functioning. B https://web.pathway.md/diseases/reciwA55EyqDknXId 2/11 6/24/23, 12:41 PM Hepatic encephalopathy Pathway Diagnosis: As per AISF 2019 guidelines, exclude other causes of mental impairment through systematic and careful evaluation in order to diagnose type A HE. B As per AASLD 2014 guidelines, diagnose HE by excluding other causes of brain dysfunction. Obtain a diagnostic workup considering other disorders able to alter brain function and mimic HE. A Show 2 more Differential diagnosis: As per EASL 2022 guidelines: Identify alternative or additional causes of neuropsychiatric impairment in patients with suspected HE, to improve prognostic accuracy and the results of treatment. B Recognize that features of covert HE and mild cognitive impairment of an etiology other than liver dysfunction show significant overlap. B As per AISF 2019 guidelines, conduct a differential diagnosis with particular attention to dementing disorders in case of a lack of response to treatment in patients with minimal or covert HE. B 2. Classification and risk stratification Classification: As per EASL 2022 guidelines, classify HE according to the underlying condition: Situation Guidance ALF Type A Portosystemic shunt Type B Cirrhosis. B Type C Show 5 more As per AISF 2019 guidelines, classify HE according to the following criteria: Situation Guidance Type A Underlying condition Type B Type C Covert Severity of mental alteration Overt Episodic Time course of mental alteration https://web.pathway.md/diseases/reciwA55EyqDknXId 3/11 6/24/23, 12:41 PM Hepatic encephalopathy Pathway Recurrent Persistent Yes, and if so, which ones Presence of precipitating and facilitating events No. B As per AASLD 2014 guidelines, classify HE according to the type of underlying disease, severity of manifestations, time course, and precipitating factors. A Severity grading: As per EASL 2022 guidelines, use the West Haven criteria for grading the HE in patients with at least temporal disorientation (from West Haven grades 2). Add the Glasgow coma scale in patients with grades III-IV West Haven criteria. B As per AISF 2019 guidelines, consider using a combination of the West Haven criteria, the presence/absence of flapping tremor, and the Glasgow Coma Scale to grade type C, overt HE. C As per AASLD 2014 guidelines: Grade overt HE according to the West-Haven criteria and the GCS. B Classify HE into various stages of severity, reflecting the degree of self-sufficiency and the need for care. B 3. Diagnostic investigations Serum ammonia levels: As per EASL 2022 guidelines, obtain serum ammonia level measurement in patients with delirium/encephalopathy and liver disease, as a normal value brings the diagnosis of HE into question. B As per AISF 2019 guidelines, obtain venous blood ammonia level measurement as part of the workup in all forms of new-onset unexplained delirium to aid in identifying unrecognized type B HE. B As per AASLD 2014 guidelines, recognize that increased blood ammonia alone does not add any diagnostic, staging, or prognostic value for HE in patients with chronic liver disease. Obtain diagnostic reevaluation in case of a normal value. B Neurophysiological testing: As per EASL 2022 guidelines, obtain a neuropsychological/neurophysiological or therapeutic test for the diagnosis of covert HE in patients with no or mild neuropsychiatric abnormalities (not meeting the criteria for the diagnosis of HE grades 2 based on the West Haven criteria). B As per AASLD 2014 guidelines, consider obtaining neurophysiological and psychometric tests by experienced examiners for the diagnosis and grading of minimal HE and covert HE. C Brain imaging: As per EASL 2022 guidelines: https://web.pathway.md/diseases/reciwA55EyqDknXId 4/11 6/24/23, 12:41 PM Hepatic encephalopathy Pathway Obtain brain CT or MRI in patients with delirium/encephalopathy and liver disease in case of diagnostic doubts or nonresponse to treatment. B Recognize that no cerebral imaging proves a diagnosis of HE. B As per AISF 2019 guidelines, obtain brain imaging to rule out alternative or coexisting causes of brain damage only in the following situations: unusual clinical profile abrupt/severe onset of symptoms focal neurological signs limited or no response to treatment of the precipitant and/or ammonia-lowering treatment over the first 12-24 hours. B Abdominal imaging: Obtain abdominal CT angiography to identify non-cirrhotic portal hypertension and portosystemic shunts in patients with hyperammonemia in the absence of significant liver damage. B Obtain Doppler ultrasound, and abdominal CT angiography if ultrasound is negative, for the assessment of spontaneous portosystemic shunts in patients with persistent or highly recurrent HE. B 4. Respiratory support Mechanical ventilation: consider intubating patients with grades III-IV HE. C 5. Medical management Setting of care: As per EASL 2022 guidelines: Admit patients with grades 3-4 overt HE to the ICU as they are at risk of aspiration. B Admit patients with HE to the ICU based on clinical judgment as there is no single marker that can identify patients who will benefit from ICU admission. B As per AISF 2019 guidelines, admit patients with high-grade overt HE at risk or unable to protect their airways to the ICU. B Management of precipitating factors: As per EASL 2022 guidelines: Assess and manage precipitating factors in patients with HE. B Attempt to control the progression of the underlying liver disease in patients with HE. B As per AISF 2019 guidelines, identify any facilitating and precipitating events once there is a working diagnosis of type C overt HE. B As per AASLD 2014 guidelines, identify and treat precipitating factors in patients with HE. A https://web.pathway.md/diseases/reciwA55EyqDknXId 5/11 6/24/23, 12:41 PM Hepatic encephalopathy Pathway Indications for treatment: As per EASL 2022 guidelines, consider initiating anti-HE treatment for the purposes of differential diagnosis and to prevent overt HE in patients with covert HE. B As per AISF 2019 guidelines, treat episodes of spontaneous or precipitated overt HE. B Show 2 more As per AASLD 2014 guidelines: Treat all episodes of overt HE, whether spontaneous or precipitated. A Treat minimal HE and covert HE episodes only on a case-by-case basis. B Nonabsorbable disaccharides: As per EASL 2022 guidelines, administer nonabsorbable disaccharides for the treatment of patients with covert HE. B As per AASLD 2014 guidelines, administer lactulose as first-line therapy for episodic overt HE. B Landmark trials: Rifaximin plus lactulose for hepatic encephalopathy In patients with overt hepatic encephalopathy, lactulose and rifaximin were superior to lactulose only with respect to complete reversal of hepatic encephalopathy. Sharma BC et al. Am J Gastroenterol. 2013 Sep. Oral branched-chain amino acids: Consider administering oral branched-chain amino acid supplementation to achieve and maintain recommended nitrogen intake in patients intolerant to dietary protein. C Consider administering oral branched-chain amino acids as an alternative or additional agent for the treatment of patients with HE not responding to conventional therapy. B Intravenous L-ornithine L-aspartate: consider administering IV L-ornithine L-aspartate as an alternative or additional agent in patients with HE not responding to conventional therapy. B Dopaminergic agents: administer dopaminergic agents for the treatment of patients with cirrhosis-related Parkinsonism. B Antibiotic therapy: consider administering neomycin C or metronidazole as an alternative option in patients with HE. C Landmark trials: Rifaximin plus lactulose for hepatic encephalopathy In patients with overt hepatic encephalopathy, lactulose and rifaximin were superior to lactulose only with respect to complete reversal of hepatic encephalopathy. Sharma BC et al. Am J Gastroenterol. 2013 Sep. https://web.pathway.md/diseases/reciwA55EyqDknXId 6/11 6/24/23, 12:41 PM Hepatic encephalopathy Pathway Diuretic therapy: avoid diuretic therapy in patients with persistent overt HE. D Discontinuation of treatment: consider discontinuing anti-HE therapy on an individual basis in patients with a history of overt HE, improved liver function and nutritional status, and controlled precipitant factors. C 6. Inpatient care Serial clinical assessment: assess for signs of intracranial hypertension at regular intervals and monitor for intracranial pressure and manage according to available pertinent guidelines. B 7. Nonpharmacologic interventions Dietary modifications: As per EASL 2022 guidelines, consider replacing animal protein with vegetable and dairy protein in patients with recurrent/persistent HE, taking into account the patient's tolerance, provided that overall protein intake is not compromised. C As per AISF 2019 guidelines: Do not reduce protein intake/administration. D Do not replace meat with vegetables (pulses) and/or dairy protein, except in patients truly intolerant to meat protein. D As per AASLD 2014 guidelines: Ensure a daily energy intake of 35-40 kcal/kg of ideal body weight and a daily protein intake of 1.2-1.5 g/kg. B Offer small meals or liquid nutritional supplements evenly distributed throughout the day and a late-night snack. B Vitamin and micronutrient supplements: As per EASL 2022 guidelines: Treat demonstrated or suspected vitamin/micronutrient deficiencies in patients with HE as they can compound HE. B Do not administer zinc supplementation routinely in patients with HE. D As per AISF 2019 guidelines: Treat vitamin and micronutrient deficiencies as they may worsen mental function and confound the diagnosis of HE. B Consider initiating zinc supplementation in patients with type C, overt HE with documented zinc deficiency. C 8. Therapeutic procedures https://web.pathway.md/diseases/reciwA55EyqDknXId 7/11 6/24/23, 12:41 PM Hepatic encephalopathy Pathway Albumin dialysis: consider performing albumin dialysis to ameliorate HE in patients with liver failure and overt HE. C Occlusion of portosystemic shunts: As per EASL 2022 guidelines, consider performing obliteration of accessible portosystemic shunts in stable patients with cirrhosis with recurrent/persistent HE (despite adequate medical treatment) with a Model for End-stage Liver Disease score < 11. C As per AISF 2019 guidelines: Perform surgical shunt reduction/obliteration in patients with persistent or highly recurrent type C, overt HE. B Assess the feasibility, pros and cons of shunt obliteration in patients with type B HE as this has the potential to cure the disease. B Liver support system: do not use liver support systems for the treatment of patients with type A HE. D Fecal microbiota transplantation: do not perform fecal microbiota transplantation routinely in patients with recurrent/persistent HE. D 9. Perioperative care Pre-TIPS prophylaxis: Consider administering rifaximin for prophylaxis of HE before non-urgent TIPS placement in patients with cirrhosis and previous episodes of overt HE. B Assess for the presence and/or history of overt and covert HE in patients scheduled for a non- urgent TIPS placement. Recognize that one single episode of HE is not an absolute contraindication, especially if precipitated by bleeding. B 10. Surgical interventions Liver transplantation: As per EASL 2022 guidelines, consider performing liver transplantation in patients with recurrent/persistent HE. Refer patients promptly to a center for evaluation in case of the first episode of overt HE. B Show 2 more As per AISF 2019 guidelines, use a combination of clinical and imaging criteria examined by a multidisciplinary expert team to recognize irreversible brain damage in patients with severe coma, in order to avoid futile liver transplantation. B Show 2 more As per AASLD 2014 guidelines, evaluate patients with intractable overt HE and liver failure for liver transplantation. A https://web.pathway.md/diseases/reciwA55EyqDknXId 8/11 6/24/23, 12:41 PM Hepatic encephalopathy Pathway 11. Specific circumstances Patients with acute-on-chronic liver failure: consider administering nonabsorbable disaccharides in critically ill patients with acute-on-chronic liver failure and overt HE. C Show 4 more 12. Patient education General counseling: counsel patients with a history of overt HE episode about the risks associated with driving and the appropriateness of formal driving assessment with the relevant authorities. B 13. Preventative measures Avoidance of precipitating factors: Avoid worsening/decompensation of the underlying liver disease, if possible, for the prevention of overt HE. D Avoid and manage precipitants, such as infection, constipation, and dehydration, for the prevention of overt HE. D Primary prevention: As per EASL 2022 guidelines, consider removing the blood from the gastrointestinal tract promptly with lactulose or mannitol by nasogastric tube, or lactulose enemas to prevent HE in patients presenting with gastrointestinal bleeding. B As per AISF 2019 guidelines, do not offer primary prophylaxis for the prevention of overt HE, with the exception of rapid removal of blood from the gastrointestinal tract after an upper gastrointestinal bleeding. D Secondary prevention: As per Baveno VII 2022 guidelines: Administer rifaximin for the secondary prophylaxis of HE. A Consider administering rifaximin for prophylaxis of overt HE in patients with previous overt HE undergoing elective TIPS placement. C As per EASL 2022 guidelines: Initiate lactulose as secondary prophylaxis after the first episode of overt HE, and titrate to obtain 2-3 bowel movements per day. A Initiate rifaximin as an adjunct to lactulose for secondary prophylaxis after 1 additional episode of overt HE within 6 months of the first one. B As per AISF 2019 guidelines, address the recurrence of HE as it is frequent, costly, and potentially preventable. B Show 3 more https://web.pathway.md/diseases/reciwA55EyqDknXId 9/11 6/24/23, 12:41 PM Hepatic encephalopathy Pathway Likelihood Ratios Pertinent positives The following findings increase the probability of hepatic encephalopathy in adults. 1 1 Finding LR+ Value Increased serum arterial ammonia 1.3 Increased serum venous ammonia 1.1 Pertinent negatives The following findings decrease the probability of hepatic encephalopathy in adults. 1 1 Finding LR- Value serum arterial ammonia not increased 0.4 serum venous ammonia not increased 0.9 References 1. Sara Montagnese, Francesco Paolo Russo, Piero Amodio et al. Hepatic encephalopathy 2018 A clinical practice guideline by the Italian Association for the Study of the Liver AISF . Dig Liver Dis. 2019 Feb;51 2 190 205. Open 2. Vilstrup H, Amodio P, Bajaj J et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014 Aug;60 2 715 35. Open 3. European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of hepatic encephalopathy. EASL. 2022 Jun. Open 4. Roberto de Franchis, Jaime Bosch, Guadalupe Garcia-Tsao et al. Baveno VII Renewing consensus in portal hypertension. J Hepatol. 2022 Apr;76 4 959 974. Open 5. Rahul Nanchal, Ram Subramanian, Waleed Alhazzani et al. Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU Neurology, Peri-Transplant Medicine, Infectious Disease, and Gastroenterology Considerations. Crit Care Med. 2023 May 1;51 5 657 676. Open 6. 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 2 406 460. Open 7. Elwir S, Rahimi RS. Hepatic Encephalopathy: An Update on the Pathophysiology and Therapeutic Options. J Clin Transl Hepatol. 2017 Jun 28;5 2 142 151. Open 8. Stepanova M, Mishra A, Venkatesan C et al. In-hospital mortality and economic burden associated with hepatic encephalopathy in the United States from 2005 to 2009. Clin Gastroenterol Hepatol. 2012 Sep;10 9 1034 41.e1. Open 9. Acharya C, Bajaj JS. Current Management of Hepatic Encephalopathy. Am J Gastroenterol. 2018 Nov;113 11 1600 1612. Open https://web.pathway.md/diseases/reciwA55EyqDknXId 10/11 6/24/23, 12:41 PM Hepatic encephalopathy Pathway 10. Wijdicks EF. Hepatic Encephalopathy. N Engl J Med. 2016 Oct 27;375 17 1660 1670. Open 11. Bustamante J, Rimola A, Ventura PJ et al. Prognostic significance of hepatic encephalopathy in patients with cirrhosis. J Hepatol. 1999 May;30 5 890 5. Open 12. American Association for the Study of Liver Diseases. Choosing Wisely AASLD recommendations. Choosing Wisely. 2014. Open 13. Karin Weissenborn. Hepatic Encephalopathy: Definition, Clinical Grading and Diagnostic Principles. Drugs. 2019 Feb;79 Suppl 1 5 9. Open https://web.pathway.md/diseases/reciwA55EyqDknXId 11/11