Hepatic Encephalopathy: A Case Study in Patient Management
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Transcript of Hepatic Encephalopathy: A Case Study in Patient Management
Hepa%c Encephalopathy: A Case Study in Pa%ent Management
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Case Presentation: Mr. C
• Initial presentation
– 67 year-old man admitted to hospital with confusion, hypoxia
– Diagnosed with pneumonia and treatment initiated – Confusion persists despite clinical improvement in
pneumonia
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History, PE & Labs: Mr. C
• Past Medical History – Hypertension
• Medications – HCTZ 25 mg daily
• Habits – Tobacco: 1 ppd – Alcohol: 6-12 beers/wk – Drug use: none
• Social History – Married, retired truck
driver
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• Physical exam – Lungs: â breath sounds right
base – Abd: BS+, soft, NT/ND – Ext: 1+ LE edema – Neuro: lethargic, + asterixis
• Laboratory – WBC 15K, plt 92,000 – AST 76, ALT 34 – alk phos 102, t bili 2.3 – Albumin 3.2 – PT-INR 1.5
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Case Presentation : Mr. C
• New diagnosis of cirrhosis; evaluation included: – positive anti-HCV antibody – HCV viral load of 1,520,000 IU/mL
• Wife reports that Mr. C seemed more forgetful for several days prior to admission
Diagnoses: Cirrhosis, possible hepatic encephalopathy
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Natural History of Chronic Liver Disease
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Chronic liver disease
Cirrhosis
Hepatocellular carcinoma
(liver cancer)
Decompensated cirrhosis Portal hypertension
Hepatic encephalopathy
Ascites Varices
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Challenges to Diagnosing Cirrhosis • Liver disease is quiet
– Often asymptomatic until dramatic end-stage presentations – Early signs may include
• Low platelet count • Lower extremity edema
• Low threshold to evaluate for chronic liver disease – Most common disorders
• HCV: screen all baby boomers born 1945-1965 • Fatty liver disease: obesity, diabetes • Alcohol abuse
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Hepatic Encephalopathy
• Hepatic encephalopathy (HE) or portosystemic encephalopathy (PSE)
– A reversible syndrome of impaired brain function occurring in patients with advanced liver failure
– Risk of HE • Incidence: 20% per year among patients with cirrhosis • Prevalence: 30%-45% of patients with cirrhosis
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Overt vs. Minimal HE
• Overt HE – Clinical presentation with neuropsychiatric signs and
symptoms of HE
• Minimal HE – Abnormal psychometric tests – Essentially normal clinical neuropsychiatric examination
• Consider in the patient with vague, intermittent symptoms
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Overt vs. Minimal HE • Overt HE
– Clinical presentation with neuropsychiatric signs and symptoms of HE
– Consider HE if any of the following:
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Sleep disturbances (trouble sleeping, sleeping too much, day/night reversal)
Anxiety
Difficulty with concentration Inappropriate behavior
â attention Lethargy
â reaction time Somnolence
Memory problems Slurred speech
Euphoria Disorientation
Depression symptoms Confusion
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• Portal hypertension
– Majority will have cirrhosis – Less common: Portal hypertension but no
liver disease
• Acute liver failure – Acetaminophen toxicity most common cause
Conditions Associated with HE
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Pathogenesis of HE
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Why Does HE Happen?
Number of theories; likely multifactorial • Neurotoxins
– Ammonia • Impairment of neurotransmission • Alteration of the blood brain barrier • Cerebral edema • Altered brain energy metabolism • Systemic response to infection and inflammation
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Moroni F. Lancet 1998 James JH. Science 1998
Mans AM. J Neurochem 1983 Bode C. J Hepatol 1987
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Where Do Ammonia and Other Toxins Come From?
• GI tract is the primary source of ammonia – Produced by cells lining small
intestine from glutamine – Colonic bacteria breaking down
nitrogen sources like ingested protein
• Enters the circulation via the portal vein – Intact liver clears almost all
ammonia and other toxins
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Moroni F. Lancet 1998
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Impact of Portal Hypertension
• Major impact from portal hypertension – Blood going to liver through
portal vein meets up with resistance from scarring in liver
– Blood seeks other paths around liver to heart
• varices – Blood bypassing the liver
doesn’t get detoxified
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Clinical Features of Portal Hypertension
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• Clinical features – Ascites, spontaneous
bacterial peritonitis (SBP) – Hepatic hydrothorax – Bleeding gastric or
esophageal varices – Portal gastropathy
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Precipitants of HE: Overview
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Drugs ammonia Dehydra0on Shunts Vascular occlusion
Hepatocellular carcinoma
Alcohol Cons%pa%on Diarrhea TIPS Hepa%c vein thrombosis
Benzodiazepines Electrolyte disturbances
Diure%cs Surgical shunts
Portal vein thrombosis
Narco%cs Excess dietary protein
GI bleeding
GI bleeding Vomi%ng
Infec%on Paracentesis
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Precipitant of HE: Drugs
• Drugs – Alcohol – Benzodiazepines – Narcotics – Anything mood altering if advanced disease…
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Precipitant of HE: Infections
• Infection – Any infection – Ascites infection = SPB
• Spontaneous bacterial peritonitis
– Pneumonia • Pneumococcal vaccine
recommended – Influenza
• Vaccine recommended
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Precipitant of HE: TIPS
• TIPS – Transjugular intrahepatic
portosystemic shunt – Indications
• Uncontrolled variceal bleeding
• Refractory ascites – Risk of HE
• 10%-44%
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Diagnosis of HE
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Spectrum of HE
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Normal Minimal HE I II III IV
Overt HE Stages
Conn HO. Gastroenterology 1978 Bajaj, J.S. Hepatology 2009
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Stages of HE: West Haven or Conn Criteria
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Conn HO. Gastroenterology 1978
Stage Consciousness Intellect and behavior Neurological findings
0 Normal Normal Normal examina%on
I Mild lack of awareness
Shortened aKen%on span; impaired addi%on or subtrac%on
Mild asterixis or tremor
II Lethargic Disoriented; inappropriate behaviour
Obvious asterixis; slurred speech
III Somnolent but arousable
Gross disorienta%on; bizarre behaviour
Muscular rigidity and clonus; Hyper-‐reflexia
IV Coma Coma Decerebrate posturing
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Diagnosis of HE
• Most patients have signs of cirrhosis, portal hypertension – Splenomegaly – Ascites – Edema – Gynecomastia – Spider angiomata – Palmar erythema
• Low platelet count – likelihood of cirrhosis ↑
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Diagnosis of HE
• Asterixis – Asterixis caused by sudden loss of motor tone – Arms fully extended, wrists dorsiflexed – Look for rhythmic flapping, not shaking/tremor
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Diagnosis of HE: What About Ammonia?
• Ammonia – Limited value
• Samples need to be evaluated quickly – Clinic samples to off-site lab will have á ammonia
• Venous samples inconsistent • Arterial samples more reliable
– Not needed to make the diagnosis • Liver disease and AMS = HE until proven otherwise
– Can be helpful if diagnosis is unclear – Do NOT use to follow response to therapy
• Treat the patient - not the lab test
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Diagnosis of HE: Neuropsychometric Testing
• Neuropsychometric testing – Number connection test – Reaction time to auditory
and visual stimuli – Psychometric Hepatic
Encephalopathy Score (PHES)
These are helpful if diagnosis is unclear (chronic HE vs. dementia)
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Conn, HO. Am J Dig Dis 1977 Edwin, D. Hepatology 1999
Weissenborn, K. J Hepatol 2001
Number connection test
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Management of the Patient with HE
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Initial Triage of Patient with HE
• Grade I – Consider outpatient management if good caregiver support
• Grade II – Consider inpatient admission
• Grade III-IV – Inpatient admission required – Consider ICU admission unless quick response – May need to intubate for airway protection
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Management: Identify Precipitating Factor
• Treat precipitating disorder – Infection, bleeding, dehydration, stop meds, etc.
• Correction of hypokalemia – Hypokalemia á renal ammonia production – Often also metabolic alkalosis
• Promotes ammonium (NH4+) à ammonia (NH3)
– NH3 can cross the blood-brain barrier
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Management: Lactulose MOA
• Lactulose: Nonabsorbable disaccharide – Mechanism: In colon, lactulose metabolized by colonic
bacteria so pH lowered • Acidification of bowel contributes to cathartic effect • Ammonia drawn from blood stream into colon to be
excreted • â ammonia
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Management: Lactulose • Indications
– First choice treatment for episodic overt HE – Prevention of recurrent HE episodes
• Management – Rx: 30-45 mL (2-3 tbsp) 2-4 times per day
• Goal of 2-3 BMs/day – Urgency, incontinence
• Tips to patients – Give with other liquids to improve taste – Gas-forming so consider not taking with meals
• Progressive HE – á lactulose frequency until improves – Lactulose enemas if unable to take PO
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Management: Rifaximin
• Rifaximin: Antibiotic â colonic deaminating bacteria that produce ammonia
• Indications – FDA: “Reduction in risk of overt HE recurrence” – Recommendations
• Effective add-on therapy to lactulose for prevention of overt HE recurrence
• Recommended for prevention of recurrent episodes of HE after the second episode
• Dose: 550 mg bid
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Vilstrup H. et al. Hepatology 2014; 60 (2): 715-735.
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Back to Case: Mr. C
Mr. C, 67 year-old man with new diagnosis of HE and cirrhosis during admission for pneumonia
• Pneumonia responds to antibiotics • Encephalopathy responds to lactulose + rifaximin • Ready for discharge. What is plan to manage HE post-d/
c? – Early post-discharge visit is key – Does he need long-term HE treatment? – Is treating the precipitant (pneumonia) enough?
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Prognosis with HE
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Bustamante J. J Hepatol 1999
Transplant free survival aQer 1st HE episode
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Back to Case: Mr. C
Mr. C, 67 year-old man with new diagnosis of HE and cirrhosis during admission for pneumonia
• Liver disease has progressed • Patient now has decompensated cirrhosis • Risk of death or need for transplant á
• He needs lactulose and/or rifaximin long-term to prevent further episodes and readmissions.
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Other Recommendations for Patients with HE
• Diet – Historical recommendation to restrict protein
• Protein restriction rarely recommended – Patients are malnourished
• Dietary recommendations in patients with cirrhosis – Energy intake: 35-40 kcal/kg/day – Protein intake: 1.2-1.5 g/kg/day
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Plauth M. ESPEN Guidelines on Enteral Nutrition: Liver Disease. Clin Nutr. 2006
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Other Recommendations for Patients with HE
• Driving – Impairment reported with overt and minimal HE – Physician reporting requirements relative to patients
with impaired driving vary state by state
• Caregiver – Key to monitoring and early intervention – Need to monitor or administer meds – Risk of fatigue
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Liver Wellness for Patients with Cirrhosis
• Vaccinations recommended – Hepatitis A and B series – Influenza vaccine – Pneumococcal vaccination
MMWR Vol 62, Feb 2013
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Liver Wellness for Patients with Cirrhosis
• Alcohol abstinence – No safe amount determined
• Avoid fatty liver disease – Goals
• BMI < 25 kg/m2 • Normal hemoglobin A1C
Ghany MC. Hepatology 2009
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Liver Wellness for Patients with Cirrhosis
• Coffee encouraged – Lower disease progression in the
HALT-C trial
• Milk thistle? – No benefit in recent NIH HCV
randomized trial
Ghany M. Hepatology 2009 Freedman ND. Hepatology 2009
Fried MW JAMA 2012
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Liver Wellness for Patients with Cirrhosis
• Pain management – Avoid NSAIDs if cirrhosis
• Renal, GI risks – Narcotics
• Risk of precipitating HE depending on dose, stage of liver disease
– Acetaminophen • Safe up to 2000 mg per day if cirrhosis • Monitor multiple sources (pain meds, allergy or cold
meds, sleep aids) for accidental overdose
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Key Points
• Low threshold to evaluate for chronic liver disease – Identify patients at risk for cirrhosis, HE
• Development of HE is a sign of advanced disease with increased risk of mortality
• HE is a clinical diagnosis: Confusion and asterixis in the presence of advanced liver disease – Ammonia level usually not helpful
• Most patients will have relapsing course – Watch for precipitants and intervene quickly – Long-term treatment needed
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Resources for Your Pa%ents
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American Liver Foundation Resources • Online HE Information Center, HE 123 (www.HE123.org)
• National Helpline: 1-800-GO-LIVER (800-465-4837)
• Education Materials: www.liverfoundation.org/education
• Drug Discount Card for uninsured and underinsured patients: www.liverfoundation.org/support/needymeds
• Online Patient/Caregiver Support Community – Inspire:
https://www.inspire.com/groups/american-liver-foundation
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General Resources
• Financial – Partnership for Prescription Assistance (PPARx) for
uninsured patients: Call 888-477-2669 or visit https://www.pparx.org
– NeedyMeds provides list of financial assistance programs: Visit http://www.needymeds.org
• Caregiver Support/Information – AARP at www.aarp.org/home-family/caregiving – Caregiver.com at www.caregiver.com – Family Caregiver Alliance at www.caregiver.org
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For More Information Visit www.HE123.org
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