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Hepatic Encephalopathy - 8/8/2012

posted Aug 8, 2012, 5:18 PM by Rohit Das   [ updated Dec 27, 2012, 7:16 AM by Purnema Madahar ]

Today, we had our first Chief of Service with Dr. Wolkoff, Chairman of the GI/Hepatology Department. Cynthia Armand did an excellent job presenting a case of a 60 year old woman with Hepatitis C-related cirrhosis who has had repeated admissions for confusion and altered mental status, most likely attributable to hepatic encephalopathy (HE). Of note, she has had other complications of cirrhosis, including refractory ascites, for which she received a TIPS (a mode of relieving portal hypertension via artificial systemic shunting) in 2011.

First off, HE is common – it occurs in 20-35% of patients with cirrhosis, and occurs after cirrhosis has ensued for 10-15 years, enough time for severe hepatic failure to occur.

  • HE is a clinical diagnosis, with a variable array of symptoms and severity. As Dr. Wolkoff mentioned, HE can be very subtle, and often requires history from friends and family to make the diagnosis.
  • Serum ammonia is actually nonspecific, and not required for a diagnosis of HE.
  • There generally is an inciting factor, including volume depletion, electrolyte abnormalities, bleeding, infection…to name a few.
  • Of note, TIPS can lead to HE due to portosystemic shunting. The incidence is around 30%, and generally occurs a few weeks after TIPS insertion.

Dr. Wolkoff paid particular attention to the pathophysiology of HE. Attached is a very recent review of the mechanisms potentially responsible for HE. Ammonia is certainly implicated, but overall, it’s not as simple as just good ol’ NH3

  • Normally, the liver and kidney act intimately to metabolize ammonia. In the absence of intact liver function, extra-hepatic pathways to metabolize ammonia are utilized – including astrocyte’s glutamine synthetase. Accumulation of the subsequent metabolite – glutamate – leads to astrocyte swelling and dysfunction…yea, that’s bad.        
  • There are also some studies suggesting that the blood brain barrier may be compromised in HE, allowing unwanted compounds into bad places…    
  • Even Manganese, which is generally excreted via the billiary tract, is also believed by some authors to be implied in the pathogenesis of HE…

Regarding management, Dr. Wolkoff went over the mechanism behind Lactulose and Rifaximin, which are the mainstays of treatment for HE. Dr. Wolkoff also mentioned the potential synergy between the two, which has been shown in terms of clinical outcomes. In a randomized, blinded study in 2010, 299 patients with a history of HE (of which 91-92% were taking Lactulose, in both arms) were given either Rifaximin or Placebo. Assessing for time to first “breakthrough” HE episode in 6 months of follow up:         

  • Hazard ratio for Rifaximin was 0.42, which was highly significant        
  •  Hazard ratio for time to first HE-related hospitalization, a secondary outcome,  was 0.5, which also significant         
  • Overall, to prevent one episode of HE within 6 months, the number needed to treat with Rifaximin was 4.

 Food for thought…        

  •  Cynthia mentioned her patient’s MELD score…how is that calculated, and why is it important aside from prioritizing transplant status? For what purpose was the MELD score initially created?         
  • How many grades of HE are there, and what is the symptomatology of each (see the review article...)?         
  • Oh, and I keep talking about hazard ratios…what are they? How are they different from relative risk ratios…?

Until next time...

Hepatic encephalopathy: A review
Lizardi-Cervera et. al., Annals of Hepatology 2003, 2(3): 122-130

Perazzo et. al., World Journal of Hepatology 2012, 4(3): 50-65

Bass et. al., NEJM 2010, 362: 1071-1081
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