You have been asked to review a 53-year-old female with known alcoholic liver disease. She has had a progressive fall in her conscious level over the last 24 hours and the medical team are concerned she is developing hepatic encephalopathy (HE).
a) List four alternative diagnoses to HE that you would consider in this circumstance. (10% marks)
b) List six clinical signs that would be suggestive of HE. (30% marks)
c) Discuss the specific management of severe HE in this setting. (60% marks)
• Drug or alcohol effects
• Seizure disorder
• Traumatic injury
• Septic encephalopathy
• Hypoglycaemia and other electrolyte disorders
• Basic principles of management include:
Excluding other causes of altered mentation
HE is a diagnosis of exclusion (part [a] of question 10). Serum ammonia levels should not be used as a diagnostic tool or to monitor response to treatment.
Identifying and treating precipitating cause
• Increased nitrogen load (GI bleed, excess protein intake, infection)
• Decreased toxin clearance (hypovolaemia, renal failure, constipation, port-systemic shunt, medication non-compliance, acute on chronic liver failure)
• Altered neurotransmission (sedating medications, alcohol, hypoxia, hypoglycaemia)
Reducing nitrogen load in the gut/Ammonia formation
• Non-absorbable disaccharidases- Lactulose is metabolized by bacteria in the colon to acetic and lactic acid, which reduces colonic pH, decreases survival of urease producing bacteria in the gut, and facilitates conversion of ammonia (NH3) to ammonium (NH4+), which is less readily absorbed by the gut. The cathartic effect of these agents also increases faecal nitrogen waste.
• Antibiotics-Rifaximin is a minimally absorbed oral antibiotic with broad spectrum activity against gram-positive and gram-negative aerobic and anaerobic bacteria. Oral neomycin and metronidazole have been used to treat hepatic encephalopathy in the past but due to concerns of toxicity and side effects, rifaximin is now the preferred antibiotic.
Second line- (all not required to score full marks)
• Probiotics- As gut bacteria play a central role in producing ammonia it has been theorized that altering gut flora using probiotics may be beneficial in HE.
• Polyethylene Glycol- Commonly used, safe and highly effective laxative that has recently been proposed as a possible agent for HE
• Flumazenil- benzodiazepine antagonist at GABA receptors. Can result in clinical improvement but no mortality benefit
• Ammonia scavengers- increase ammonia clearance and reduce systemic concentrations by providing an alternative pathway for renal ammonia clearance.
• L-ornithine l-aspartate (LOLA)- increases glutamine synthase and urea excretion. Similar clinical improvement when compared to lactulose.
• Zinc- Low zinc is associated with impairment of urea cycle enzymes leading to elevated ammonia levels.
• Porta-systemic shunts- Medically refractory HE should raise suspicion of a spontaneous splenorenal shunt and patients who have undergone TIPS should be considered for shunt reversal if severe HE persists
Management of cerebral oedema-Lactulose or rifaximin can be beneficial for the treatment of gradual-onset encephalopathy in patients with prior cirrhosis, but additional, aggressive treatment of brain edema with osmotic diuretics is required in new, fulminant forms to prevent secondary, permanent brain-stem damage and to sustain patients through liver transplantation.
Nutrition - plays a key role in managing HE and preventing recurrence. Optimal daily energy intake should be 35 to 40 kcal/kg ideal body weight with daily protein intake of 1.2 to 1.5 g/kg ideal body weight.Multivitamin should be considered with the addition of specific treatments for clinically apparent vitamin deficiencies.
Assessing the need for long term therapy and liver transplant evaluation
Liver transplant evaluation should be considered in appropriate candidates once a diagnosis of overt hepatic encephalopathy is made
Possible causes of unconsciousness in the middle-aged alcoholic could be anything, considering also that we are not given any better description of it (i.e. it could represent merely confusion rather than coma).
The top four would have to be:
Other possibilities include:
Clinical signs which might suggest HE can be extracted from this ancient grading system which was developed by Conn and Lieberthal (1979)
Specific steps in the management of hepatic encephalopathy should consist of specific therapies targeted at reducing the hepatic toxin load and management of the precipitating cause. The excellent college answer offers some detailed discussion, which is difficult to improve upon.
J.S. Bajaj (2010) offers a detailed exploration of the modern management of hepatic encephalopathy. Another excellent review is from Riggio et al (2015). From these, the following approach has been concocted, to easily recall and regurgitate in an exam setting:
Specific management of hepatic encephalopathy
Management of the precipitating cause
Supportive management of the encephalopathic patient
Chapter 49 (pp. 549) Disorders of consciousness by Balasubramanian Venkatesh
Chapter 44 (pp. 501) Liver failure by Christopher Willars and Julia Wendon
Blei, Andres T., and Juan Córdoba. "Hepatic encephalopathy." The American journal of gastroenterology 96.7 (2001): 1968-1976.
Ferenci, Peter, et al. "Hepatic encephalopathy—definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998." Hepatology 35.3 (2002): 716-721.
Prakash, Ravi, and Kevin D. Mullen. "Mechanisms, diagnosis and management of hepatic encephalopathy." Nature Reviews Gastroenterology and Hepatology7.9 (2010): 515-525.
Nabi, Eiman, and Jasmohan S. Bajaj. "Useful Tests for Hepatic Encephalopathy in Clinical Practice." Current gastroenterology reports 16.1 (2014): 1-8.
Guillén, Juan C. Quero, and Juan M. Herrerías Gutiérrez. "Diagnostic methods in hepatic encephalopathy." Clinica chimica acta 365.1 (2006): 1-8.
Shawcross, Debbie L., and Julia A. Wendon. "The neurological manifestations of acute liver failure." Neurochemistry international 60.7 (2012): 662-671.
Conn, Harold O., and Milton M. Lieberthal. The hepatic coma syndromes and lactulose. Williams & Wilkins, 1979. - this is a book, and not available for free online.