hepatic encephalopathy: a case study in patient management

Hepa%c Encephalopathy: A Case Study in Pa%ent Management

2

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

3

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

3

•  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

4

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

5

Natural History of Chronic Liver Disease

5

Chronic liver disease

Cirrhosis

Hepatocellular carcinoma

(liver cancer)

Decompensated cirrhosis Portal hypertension

Hepatic encephalopathy

Ascites Varices

6

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

7

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

8

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

9

Overt vs. Minimal HE •  Overt HE

–  Clinical presentation with neuropsychiatric signs and symptoms of HE

–  Consider HE if any of the following:

9

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

10

•  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

10

11

Pathogenesis of HE

11

12

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

12

Moroni F. Lancet 1998 James JH. Science 1998

Mans AM. J Neurochem 1983 Bode C. J Hepatol 1987

13

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

13

Moroni F. Lancet 1998

14

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

15

Clinical Features of Portal Hypertension

15

•  Clinical features –  Ascites, spontaneous

bacterial peritonitis (SBP) –  Hepatic hydrothorax –  Bleeding gastric or

esophageal varices –  Portal gastropathy

16

Precipitants of HE: Overview

16

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

17

Precipitant of HE: Drugs

•  Drugs –  Alcohol –  Benzodiazepines –  Narcotics –  Anything mood altering if advanced disease…

17

18

Precipitant of HE: Infections

•  Infection –  Any infection –  Ascites infection = SPB

•  Spontaneous bacterial peritonitis

–  Pneumonia •  Pneumococcal vaccine

recommended –  Influenza

•  Vaccine recommended

18

19

Precipitant of HE: TIPS

•  TIPS –  Transjugular intrahepatic

portosystemic shunt –  Indications

•  Uncontrolled variceal bleeding

•  Refractory ascites –  Risk of HE

•  10%-44%

19

20

Diagnosis of HE

20

21

Spectrum of HE

21

Normal Minimal HE I II III IV

Overt HE Stages

Conn HO. Gastroenterology 1978 Bajaj, J.S. Hepatology 2009

22

Stages of HE: West Haven or Conn Criteria

22

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

23

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

24

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

25

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

26

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)

26

Conn, HO. Am J Dig Dis 1977 Edwin, D. Hepatology 1999

Weissenborn, K. J Hepatol 2001

Number connection test

27

Management of the Patient with HE

27

28

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

29

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

30

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

31

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

32

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

32

Vilstrup H. et al. Hepatology 2014; 60 (2): 715-735.

33

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

34

Prognosis with HE

34

Bustamante J. J Hepatol 1999

Transplant free survival aQer 1st HE episode

35

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

36

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

36

Plauth M. ESPEN Guidelines on Enteral Nutrition: Liver Disease. Clin Nutr. 2006

37

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

38

Liver Wellness for Patients with Cirrhosis

•  Vaccinations recommended –  Hepatitis A and B series –  Influenza vaccine –  Pneumococcal vaccination

MMWR Vol 62, Feb 2013

39


•  Alcohol abstinence –  No safe amount determined

•  Avoid fatty liver disease –  Goals

•  BMI < 25 kg/m2 •  Normal hemoglobin A1C

Ghany MC. Hepatology 2009

40


•  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

41


•  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

42

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

43

Resources for Your Pa%ents

44

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

45

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

46

For More Information Visit www.HE123.org

46

hepatic encephalopathy: a case study in patient management

Documents