Frederick RT., Gastroenterol Hepatol. 2011 Apr;7(4):222-33.
HepaticEncephalopathy. Daniel Vela-Duarte, MD Int. Medicine / Neurology Loyola University Medical Center
Case 62 yo male with h/o ESLD 2/2 NASH and 1AT def, hepatorenal syndrome type II, DM II, who has presented multiple admissions for altered mental status, alternating somnolence, agitation and belligerence, diagnosed subsequently with hepatic encephalopathy and treated several times with large volume paracentesis and weekly albumin infusions. Pt was admitted for fluctuating changes in mental status, anuria, noted worsening renal function, fluid overload, hypotension and hemodialysis.
Question … What is the best treatment to prevent recurrent hepatic encephalopathy? A. Lactulose 15ml BID / daily B. Lactulose 15ml BID / daily + Rifaximin 550mg BID /daily C. Rifaximin 550mg BID / daily D. Lactulose 15ml BID during hospitalization E. Neomycin 5 g / daily + Lactulose 15ml BID /daily
Cordoba et Al, Curr Opin Crit Care. 2011 Apr;17(2):177-83.EnterobacteriaceaeProteusClostridium Urease Glutaminase Urea NH3 + CO2 Glutamine NH3 + Glutamate
Back to the Case Intravascularly depleteted 62 yo male with h/o ESLD 2/2 (Peripheral /splanchnic pooling) NASH and 1AT def, hepatorenal syndrome type II, DM II, who has presented Renin-Angiotensin-Aldost. multiple admissions for altered mental status, alternating Na / water retention somnolence, agitation and belligerence, diagnosed subsequently with hepatic encephalopathy and treated Intrarenal vasoconstriction several times with large volumeATN ? paracentesis and weekly ESLD = Alb albumin infusions. of Ammonia -Impaired detox Renal Perfusion GFR Pt was admitted for fluctuating changes in mental status, anuria, noted worsening renal function, fluid overload, hypotension and emergent hemodialysis. Schepke M, Nephrol Dial Transplant (2007) 22 [Suppl 8]: viii2–viii4
Hepatic encephalopathy Type A: Acute liver failure Type B: Portosystemic Bypass Type C: Cirrhosis - Dehydration, Na - Gi Bleeding - Infections Episodic - Constipation Impairs daily - Protein intake functioning Precipitated - Renal Failure, K Spontaneous - TIPS Health-related Recurrent: >2 / y - HCC quality of life. - Infections Persistent - Opioids Might predicts overt Mild - Benzodiazepines HE and poor Severe outcome Treatment-dependent Minimal: cognitive dysfunction (subtle motor deficits) Sundaram V, Med Clin North Am. 2009 Jul;93(4):819-36, vi
Frederick RT., Gastroenterol Hepatol. 2011 Apr;7(4):222-33.Diagnosis Asterixis: inability to maintain position. Tested by having the patient outstretch his or her arms and hold them in dorsiflexion. Elicited with tongue protrusion, dorsiflexion of the foot, or having the patient grasp the examiner’s fingers.
DiagnosisOvert Hepatic encephalopathy Impaired mental status (Conn score / West Haven criteria) 0 - 4. Impaired neuromotor function hypereflexia, rigidity. myoclonus, and asterixis Minimal Hepatic encephalopathy Subtle personality changes Altered level of consciousness Neuromuscular dysfunction No “Gold standard” to Dx.
Lactulose It improves minimal HE, cognitive functions and health-related quality of life in cirrhotic patients. Is lactulose effective decreasing recurrence of overt HE after recovery of a previous episode?
Screening of 300 pts with Cirrhosis and HE. 140 pts enrolled Exclusion: Recent EtOH HCC Meds/performanceGastroenterology, 2009 Sep;137(3):885-91, 891.e1. Epub 2009 Jun 6.
Pts were 46.8% followed up over a median of 14 months 19.6% 33.6% developed anNo difference between median time of recurrence of episode ofHE between 2 groups. overt HE. Gastroenterology, 2009 Sep;137(3):885-91, 891.e1. Epub 2009 Jun 6.
Patients with Cirrhosis and MHE. (No recurrent HE) Improvement of quality of life by measurement of SIP score (Sickness impact profile)Prasad S et Al, Hepatology. 2007 Mar;45(3):549-59.
Rifaximin Efficacy and safety of rifaximin, for the maintenance of remission from episodes of HE in outpatients with a recent hx of recurrent, overt HE (Prevention for 6m)
2 Episodes or more of overt HE during last 6 months Primary efficacy Endpoint. Conn score > 2time to the first breakthroughepisode of hepatic On Remission atEncephalopathy. enrollment. Conn score: 0-1 Secondary efficacy Endpoint. Exclusion: pts withTime to the first hospitalization precipitants.involving hepatic encephalopathy HipoK Renal Failure SBP Infection HypoNa Bass NM et Al, N Engl J Med. 2010 Mar 25;362(12):1071-81.
Results. Rate of compliance: over 80% for both 31 / 140 pts. Rifaximin group (22.1%) 73 / 159 pts. placebo group (45.9%) RRR by 58% with rifaximin vs placebo NNT: 4 19 / 140 pts Rifaximin group (13.6%) and 36 / 159 pts placebo group (22.6%). RRR by 50% with rifaximin vs placebo NNT: 9Bass NM et Al, N Engl J Med. 2010 Mar 25;362(12):1071-81.
Conclusions Rifaximin reduces the risk of a breakthrough episode of HE by 58% vs placebo (Lactulose only) during the at least 6 months of treatment. Rifaximin reduces the risk of a hospitalization involving HE by 50% vs placebo (Lactulose only) during the at least 6 months of treatment. Lactulose: 30 -60 ml / 2-3 doses, improves cognitive functions in patients with minimal HE after 3 months of treatment. Lactulose: 30 -60 ml / 2-3 doses, decreases the incidence of recurrent HE (RRR 58%)