Management of Hepatic Encephalopathy Atif Zaman, MD MPH Oregon Health & Science University Professor of Medicine Division of Gastroenterology and Hepatology
Disclosure 1. The speaker Atif Zaman, MD MPH have no relevant financial relationships to disclose. 2. The speaker/planner Lauren Myers, MMSc, PA-C have no relevant financial relationships to disclose.
Hepatic Encephalopathy Discuss diagnosis and prognosis Nomenclature (minimal vs overt) Treatment options
Pathophysiology of Hepatic Encephalopathy Ammonia Upregulation of astrocytic peripheral benzodiazepine receptors (PBR) Neurosteroid production Modulation of GABA A receptor Hepatic encephalopathy
Hepatic Encephalopathy Is A Clinical Diagnosis Clinical findings and history important Ammonia levels are unreliable Measurement of ammonia not necessary Measurement of ammonia levels may be supportive when diagnosis is in doubt
Stages of Hepatic Encephalopathy Stage Mental state Neurologic signs 1 Mild confusion: limited attention Incoordination, tremor, span, irritability, inverted sleep impaired handwriting pattern 2 Drowsiness, personality changes, Asterixis, ataxia, dysarthria intermittent disorientation 3 Somnolent, gross disorientation, Hyperreflexia, muscle marked confusion, slurred speech rigidity, Babinski sign 4 Coma No response to pain, decerebrate posture
Minimal Hepatic Encephalopathy Occurs in 30-70% of cirrhotic patients without overt hepatic encephalopathy Detected by psychometric and neuropsychological testing May improve with lactulose or synbiotics (probiotics and fermentable fiber)
Treatment of Hepatic Encephalopathy Identify and treat precipitating factor Infection GI hemorrhage Prerenal azotemia Sedatives Constipation Protein restriction should be avoided
Treatment of Hepatic Encephalopathy Lactulose (adjust to 2-3 bowel movements/day) Long-term therapy assessment Higher likelihood of recurrent encephalopathy Assessment of need for liver transplantation
Current HE Treatment Options Drug Name Drug Class Indication Lactulose Rifaximin Neomycin Metronidazole Vancomycin Poorly absorbed disaccharide Non-aminoglycoside semi-synthetic, nonsystemic antibiotic Aminoglycoside antibiotic Synthetic antiprotozoal and antibacterial agent Aminoglycoside antibiotic Decrease blood ammonia concentration Prevention and treatment of portal-systemic encephalopathy Reduction in risk of overt hepatic encephalopathy (HE) recurrence in patients 18 years of age. Adjuvant therapy in hepatic coma Ototoxicity and nephrotoxicity Not approved for HE Peripheral neurotoxicity Not approved for HE Bacterial resistance and renal toxicity Mullen KD et al. Semin Liver Dis. 2007;27(suppl 2):32-47.
Lactulose Currently the mainstay of therapy of HE; ~70% to 80% of patients with acute and chronic HE improve with lactulose treatment Administered orally, by mouth or through a nasogastric tube or via retention enemas Adjust to 2-3 bowel movements/day Principal side effects include abdominal distension, cramping, diarrhea, electrolyte changes, and flatulence Bajaj JS. Aliment Pharmacol Ther 2010;31:537-547
Rifaximin Minimally absorbed (<0.4%) oral antibiotic No clinical drug interactions reported No dosing adjustment required in patients with liver disease or renal insufficiency In registration trials, 91% of patients were given lactulose concomitantly 58% reduction in risk of recurrent hepatic encephalopathy (NNT=4) 50% reduction in risk of hospitalizations (NNT=9) Bass NM et al. N Engl J Med. 2010;362:1071-1081.
Take Home Points Hepatic Encephalopathy Clinical diagnosis Identify precipitating factors Identify and then treat patients with recurrent encephalopathy