Management of Hepatic
Encephalopathy in the Hospital
Hospitalist Best Practice
J Rush Pierce Jr, MD, MPH
May 21, 2014
Case
• Hx: 45 year old man with cirrhosis and ascites
adm with 2 days of confusion. On lactulose for
1 year, wife doesn’t know if compliant. Wife
says no fever, abd pain, cough, diarrhea.
• PE: 100/60, 72, afebrile. Sleepy but arousable.
Spiders, jaundice, ascites, edema, 3+ reflexes
• Lab: WBC = 8,000, H/H = 11.8/34, plts = 70K.
Na = 129, K = 3.4, Cl = 103, HCO3 = 21; BUN =
7, creat = 0.9. INR = 2.5, bili = 3.9, ALT/AST sl
high. NH4 = 65. CXR and UA neg.
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Clinical questions
1. Does this patient have hepatic
encephalopathy?
2. Should I order a CT scan of head?
3. Should I do a diagnostic paracentesis to
exclude SBP?
4. Where should this patient be admitted?
5. Will initial therapy be lactulose, rifaximin, or
both?
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Classification of HE
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Source: 11th World
Congress of
Gastroenterology, 1998
4
Acute hepatic failure and HE Special considerations
• Predicts urgency for transplant
• At high risk for cerebral edema (70% for
Grade IV)
• Benefit from specific treatments of cerebral
edema
• More likely to benefit from ICU stay
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Diagnosis of HE
1. Identify underlying liver disease
– Acute with severe transaminitis
– Chronic - portal HTN
2. Ascertain neuropsychiatric sxs
– Sleep disturbance, alteration in level of
consciousness, confusion
3. Elicit neurologic signs
– Asterixis, hyperreflexia, clonus, +Babinski
4. Exclude other causes
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West Haven Clinical Severity
Grades of HE
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Pierce’s simplification of West
Haven Criteria
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•
•
•
•
Grade 0 = normal
Grade 1 = alert but squirrely
Grade 2= drowsy but awake
Grade 3 = asleep but arousable
Grade 4 = asleep and unarousable
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Asterixis
• https://www.youtube.com/watch?v=Or65nOr
cz1A
• Also seen in:
– Uremia
– Severe CO2 retention
– Dilation toxicity
– Nodding off
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Source: Adams and Victor’s
Principles of Neurology, Ch 6
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Excluding other causes
Source: J Investig Med 2013;61:695
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Serum NH4 and diagnosing HE
Source: J Hepatology
2003;38:441
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Serum NH4 and following response
to therapy of HE
Source: J Hepatology 2003;38:441
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HE management algorithm
•
•
•
•
•
Hemodynamic stabilization
Detect and treat precipitants
Lower blood ammonia
Treat cerebral edema, if present
Manage hyponatremia
Source: Curr Treat Options Neurol 2014;16:297
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Identify and treat precipitating
events
Source: Clin Liver Dis 2012;16:73–89
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Dietary recommendations for HE
Source: Hepatology 2013:58:325
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Predicting lactulose failure
Source: European J
Gastro Hepatology
2010, 22:526
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Drug treatment of HE
• Lactulose, Lactilol
– 2004 meta-analysis – superior to placebo but dop
not improve survival
– When only high quality studies included, no effect
– Widely used in practice, recommended as first line
rx
• Neomycin, metronidazole
– RCT: neomycin vs placebo – no difference
– Metonidazole, vancomyin – no RCT
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Treatment of HE - Rifaximin
Source: World J Gastroenterol 2012;18:767
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Treatment of HE - Rifaximin
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RCT – Rifaximin + lactulose vs
lactulose
• Blinded prospective RCT, one center in New Delhi,
10/2010 – 09/2011, no drug sponsorship;
• Inclusion: adults, cirrhosis and overt HE
• Exclusion: creat > 1.5, active EtOH in 4 wks, HCC,
psych illness, or major comorbidities
• All pts had rx of underlying precipitating illness
• Lactulose + rifaximin vs. lactulose + placebo;
lactulose titrated to 2 – 3 stools/day
• All meds through NG tube
Source: Am J
• Followed to discharge or death
Gastroenterol 2013;108:1458
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Source: Am J
Gastroenterol 2013;108:1458
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Main findings
• There was a significant decrease in mortality
after treatment with lactulose plus rifaximin
vs. lactulose and placebo (23.8 % vs. 49.1 % , P
< 0.05). [ARR = 25.3%, NNT = 4)
• No diff in side effects (diarrhea, abd pain)
• Pts who did not respond in each group had
higher baseline total WBC (7742 vs 6058)
• Sepsis related deaths higher in lactulose +
Source: Am J
placebo group (17 vs 7)
Gastroenterol 2013;108:1458
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Hyponatremia in HE
Source: J Hospital Med
2012;7:S14
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Mayo Clinic recommendations
Source: Mayo Clin Proc. 2014;89(2):241
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Mayo Clinic recs (contd)
Source: Mayo Clin Proc. 2014;89(2):241
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Mayo Clinic recs (contd)
Source: Mayo Clin Proc. 2014;89(2):241
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Advice on discharge (Expert
opinion)
• Home on lactulose
– All pts with Childs B/C
– Childs A and isolated episode, do test sev weeks
after discharge
• Driving
– 18 MVA’s in 167 cirrhotic patients in 1 yr
– In car driving test
Source: Mayo Clin Proc. 2014;89(2):241
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Review of clinical questions
1. Does this patient have hepatic
encephalopathy?
2. Should I order a CT scan of head?
3. Should I do a diagnostic paracentesis to
exclude SBP?
4. Where should this patient be admitted?
5. Will initial therapy be lactulose, rifaximin, or
both?
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System Questions
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Should we grade HE?
Should everyone with HE get a paracentesis?
When should we use rifaximin?
Would an HE care plan be useful?
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