Hepa%c Encephalopathy: A Case Study in Pa%ent Management
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
2
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
• 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
3
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
4
Natural History of Chronic Liver Disease Chronic liver disease
Cirrhosis
Hepatocellular carcinoma (liver cancer)
Decompensated cirrhosis Portal hypertension
Ascites
Varices
Hepatic encephalopathy 5
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
6
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
7
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
8
Overt vs. Minimal HE • Overt HE – Clinical presentation with neuropsychiatric signs and symptoms of HE – Consider HE if any of the following: 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
9
Conditions Associated with HE • Portal hypertension – Majority will have cirrhosis – Less common: Portal hypertension but no liver disease • Acute liver failure – Acetaminophen toxicity most common cause
10
Pathogenesis of HE
11
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 Moroni F. Lancet 1998 James JH. Science 1998 Mans AM. J Neurochem 1983 Bode C. J Hepatol 1987 12
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 Moroni F. Lancet 1998 13
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
14
Clinical Features of Portal Hypertension • Clinical features – Ascites, spontaneous bacterial peritonitis (SBP) – Hepatic hydrothorax – Bleeding gastric or esophageal varices – Portal gastropathy
15
Precipitants of HE: Overview Drugs Alcohol
ammonia Dehydra0on
Shunts
Vascular occlusion
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
Hepatocellular carcinoma
16
Precipitant of HE: Drugs • Drugs – Alcohol – Benzodiazepines – Narcotics – Anything mood altering if advanced disease…
17
Precipitant of HE: Infections • Infection – Any infection – Ascites infection = SPB • Spontaneous bacterial peritonitis – Pneumonia • Pneumococcal vaccine recommended – Influenza • Vaccine recommended
18
Precipitant of HE: TIPS • TIPS – Transjugular intrahepatic portosystemic shunt – Indications • Uncontrolled variceal bleeding • Refractory ascites – Risk of HE • 10%-44%
19
Diagnosis of HE
20
Spectrum of HE Overt HE Stages
Normal
Minimal HE
I
II
III
IV
Conn HO. Gastroenterology 1978 Bajaj, J.S. Hepatology 2009
21
Stages of HE: West Haven or Conn Criteria 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 Mild asterixis or tremor subtrac%on
II
Lethargic
Disoriented; inappropriate Obvious asterixis; slurred behaviour speech
III
Somnolent but arousable
Gross disorienta%on; bizarre behaviour
Muscular rigidity and clonus; Hyper-‐reflexia
IV
Coma
Coma
Decerebrate posturing
Conn HO. Gastroenterology 1978 22
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 ↑
23
Diagnosis of HE • Asterixis – Asterixis caused by sudden loss of motor tone – Arms fully extended, wrists dorsiflexed – Look for rhythmic flapping, not shaking/tremor
24
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 25
Diagnosis of HE: Neuropsychometric Testing • Neuropsychometric testing – Number connection test – Reaction time to auditory and visual stimuli – Psychometric Hepatic Encephalopathy Score (PHES)
Number connection test
These are helpful if diagnosis is unclear (chronic HE vs. dementia) Conn, HO. Am J Dig Dis 1977 Edwin, D. Hepatology 1999 Weissenborn, K. J Hepatol 2001 26
Management of the Patient with HE
27
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
28
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
29
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
30
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 31
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 Vilstrup H. et al. Hepatology 2014; 60 (2): 715-735. 32
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?
33
Prognosis with HE Transplant free survival aQer 1st HE episode
Bustamante J. J Hepatol 1999 34
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.
35
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 Plauth M. ESPEN Guidelines on Enteral Nutrition: Liver Disease. Clin Nutr. 2006
36
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
37
Liver Wellness for Patients with Cirrhosis • Vaccinations recommended – Hepatitis A and B series – Influenza vaccine – Pneumococcal vaccination
MMWR Vol 62, Feb 2013 38
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 39
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 40
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
41
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
42
Resources for Your Pa%ents
43
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
44
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
45
For More Information Visit www.HE123.org
46