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Hepatic encephalopathy — Clinical Guidelines

Overview

Hepatic encephalopathy (HE) is a neuropsychiatric complication of liver disease characterized by altered consciousness and cognitive function due to the accumulation of neurotoxins in the bloodstream, primarily ammonia. 1 4 6

Diagnosis

Clinical assessment: Includes history of liver disease, presence of precipitating factors (e.g., infection, gastrointestinal bleeding).

Neuropsychiatric testing: Use of psychometric hepatic encephalopathy scores (e.g., Mini-Mental State Examination, Psychometric Hepatic Encephalopathy Score).

Laboratory tests: Serum ammonia levels (though interpretation can be complex 6), blood ammonia levels may be normal in some cases despite HE.

Grading: West Haven criteria for grading severity (Grade 0 to Grade IV).

Imaging: MRI may show characteristic changes like cortical atrophy and hyperintense lesions on T2-weighted images. 23

EEG: Often shows characteristic disturbances in patients with HE. 28

Management

First-line treatments:

- Lactulose: Primary laxative used to reduce ammonia absorption. 1 9 20 - Rifaximin: Non-absorbable antibiotic effective for both treatment and prophylaxis 1 9.

Adjunctive treatments:

- Vaccines: Prophylactic measures against infections (e.g., hepatitis B, influenza). - Avoidance of precipitants: Management of gastrointestinal bleeding, infections, and electrolyte imbalances. - Combination therapy: Rifaximin plus lactulose may offer additional benefits compared to lactulose alone 9.

Endoscopy sedation: Use of propofol with selective benzodiazepine use to minimize adverse effects 3.

Special Populations

Elderly: Increased susceptibility to complications; careful monitoring of sedation and metabolic disturbances 14.

Comorbidities: Management of concurrent conditions like infections and electrolyte imbalances is crucial 2 7.

Key Recommendations

Use lactulose as first-line treatment for HE to reduce ammonia absorption (Evidence: Strong 1 9 20).

Consider rifaximin for both treatment and prophylaxis of HE, especially in recurrent cases (Evidence: Strong 1 9).

Avoid routine serum ammonia testing due to complexities in interpretation and potential for false negatives (Evidence: Moderate 6).

Screen for minimal hepatic encephalopathy (MHE) in patients with end-stage liver disease to identify early cognitive impairment (Evidence: Expert opinion 4 13).

Manage precipitating factors aggressively such as infections and gastrointestinal bleeding to prevent HE exacerbations (Evidence: Moderate 2 7).

References

1 Huang J, Cheng C, Li Y, Liu Y, Liu Y. Efficacy and safety of rifaximin for the prophylaxis of hepatic encephalopathy: A meta-analysis. Medicine 2025. link 2 Shin S, Roberts SB, Sachar Y, Verma AA, Razak F, Brahmania M. Clinical impact of Choosing Wisely Canada hepatology recommendations: an interrupted time-series analysis using data from GEMINI. BMJ open quality 2025. link 3 Moraru MV, Bucurica S, Proske BNA, Stoleru S, Zugravu A, Coman OA et al.. Endoscopy Sedation Challenges in Patients With Hepatic Encephalopathy: A Focused Review on Propofol and Selective Use of Benzodiazepines. American journal of therapeutics 2025. link 4 Higuera-de-la-Tijera F, Velarde-Ruiz Velasco JA, Raña-Garibay RH, Castro-Narro GE, Abdo-Francis JM, Moreno-Alcántar R et al.. Current vision on diagnosis and comprehensive care in hepatic encephalopathy. Revista de gastroenterologia de Mexico (English) 2023. link 5 Li J, Yu H, Wang Y, Wang B, Zhang R, Chen S et al.. A meta-analysis of the association between Helicobacter pylori infection and risk of hepatic encephalopathy. Journal of public health (Oxford, England) 2023. link 6 Deutsch-Link S, Moon AM. The Ongoing Debate of Serum Ammonia Levels in Cirrhosis: the Good, the Bad, and the Ugly. The American journal of gastroenterology 2023. link 7 Mangini C, Zarantonello L, Formentin C, Giusti G, Angeli P, Montagnese S. Evolution of hepatic encephalopathy over time: ecological data from a tertiary referral centre for hepatology. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 2023. link 8 . EASL Clinical Practice Guidelines on the management of hepatic encephalopathy. Journal of hepatology 2022. link 9 Fu J, Gao Y, Shi L. Combination therapy with rifaximin and lactulose in hepatic encephalopathy: A systematic review and meta-analysis. PloS one 2022. link 10 Li J, Wang D, Sun J. Application of fecal microbial transplantation in hepatic encephalopathy after transjugular intrahepatic portosystemic shunt. Medicine 2022. link 11 Jeong J, Jung K, Seo KI, Yun BC, Han BH, Lee SU et al.. Propofol alone prevents worsening hepatic encephalopathy rather than midazolam alone or combined sedation after esophagogastroduodenoscopy in compensated or decompensated cirrhotic patients. European journal of gastroenterology & hepatology 2020. link 12 Fukuhara S, Ohira M, Chosa K, BaBa Y, Hamaoka M, Tanimine N et al.. Obliteration of a Portosystemic Shunt by Hybrid Interventional Radiology Using a Transmesenteric Approach Under Minilaparotomy After Liver Transplantation: A Case Report. Transplantation proceedings 2020. link 13 Xu XY, Ding HG, Li WG, Jia JD, Wei L, Duan ZP et al.. Chinese guidelines on management of hepatic encephalopathy in cirrhosis. World journal of gastroenterology 2019. link 14 Reuter B, Walter K, Bissonnette J, Leise MD, Lai J, Tandon P et al.. Assessment of the spectrum of hepatic encephalopathy: A multicenter study. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 2018. link 15 Pereira K, Carrion AF, Salsamendi J, Doshi M, Baker R, Kably I. Endovascular Management of Refractory Hepatic Encephalopathy Complication of Transjugular Intrahepatic Portosystemic Shunt (TIPS): Comprehensive Review and Clinical Practice Algorithm. Cardiovascular and interventional radiology 2016. link 16 Garcovich M, Zocco MA, Roccarina D, Ponziani FR, Gasbarrini A. Prevention and treatment of hepatic encephalopathy: focusing on gut microbiota. World journal of gastroenterology 2012. link 17 Munoz SJ. Driving with minimal hepatic encephalopathy: real world consequences?. The American journal of gastroenterology 2007. link 18 Hiraoka A, Kurose K, Hamada M, Azemoto N, Tokumoto Y, Hirooka M et al.. Hepatic encephalopathy due to intrahepatic portosystemic venous shunt successfully treated by interventional radiology. Internal medicine (Tokyo, Japan) 2005. link 19 Duseja A, Sachdev A, Dhiman RK, Chawla YK. Helicobacter pylori and hepatic encephalopathy. Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology 2003. link 20 Conn HO. A clinical hepatologist's predictions about non-absorbed carbohydrates for the early twenty-first century. Scandinavian journal of gastroenterology. Supplement 1997. link 21 Vavasseur D, Duvoux C, Cherqui D, Derhy S, Rahmouni A, Dhumeaux D et al.. Chronic hepatic encephalopathy due to spontaneous splenorenal shunt: successful treatment by transhepatic shunt embolization. Cardiovascular and interventional radiology 1994. link 22 Olubuyide IO, Atoba MA, Ayoola EA. Factors in the aetiology of hepatic encephalopathy in the tropics. West African journal of medicine 1990. link 23 Uchino A, Miyoshi T, Ohno M. Case report--MR imaging of chronic persistent hepatic encephalopathy. Radiation medicine 1989. link 24 Kimura T, Budka H. Glial fibrillary acidic protein and S-100 protein in human hepatic encephalopathy: immunocytochemical demonstration of dissociation of two glia-associated proteins. Acta neuropathologica 1986. link 25 Noda S, Ito H, Umezaki H, Minato S. Hip flexion-abduction to elicit asterixis in unresponsive patients. Annals of neurology 1985. link 26 Edwards AJ, Oehme FW, Mueller RE, Leipold HW. Hepatic encephalopathy in feedlot calves. Veterinary and human toxicology 1982. link 27 Hassan SN, Townsend JL, Curry SB. Hepatic encephalopathy: a retrospective analysis. Journal of the National Medical Association 1982. link 28 Bucci L, Chiaverelli R. Hepatic encephalopathy EEG and octopamine. The Journal of clinical psychiatry 1980. link 29 Caplan LR, Scheiner D. Dysconjugate gaze in hepatic coma. Annals of neurology 1980. link 30 Cangiano C, Rossi-Fanelli F, Bozzi A, Calcaterra V, Cascino A, Capocaccia L. Plasma phenylethanolamine in hepatic encephalopathy. European journal of clinical investigation 1978. link

Hepatic encephalopathy