Hepatic Encephalopathy

Question 1

Definition of Hepatic Encephalopathy

Answer 1

wide spectrum of neuropsychiatric abnormalities occurs in patients with cirrhotic liver disease & portal HTN, but may also occur in acute liver failure.

Question 2

Types of hepatic encephalopathy

Answer 2

Type A: HE in acute liver failure

Type B: HE in porto-systemic shunt without cirrhosis

Type C: HE in liver cirrhosis +_ porto-systemic shunt

Question 3

Clinical types of hepatic encephalopathy

Answer 3

1. HE + Acute liver failure
2. HE in cirrhotic (end-stage) and or porto-systemic shunt:

A-Minimal HE = subclinical or covert HE
B-Episodic HE: one attack occurred within 6 months
C-Recurrent HE: more than one attack within 6 months & normal mental status in between attacks
D-Persistent HE
E-Acquired hepato-cerebral degeneration
F- Spastic paraparesis
للاسف اخر ٢ دول rare ولا ينطبق عليهم قاعدة أن hepatic encephalopathy في الاصل reversible

Question 4

Non-cirrhotic portal HTN

Answer 4

A- Pre-hepatic causes:
1. Portal vein thrombosis
2. Splenic vein thrombosis
3. Congenital abnormality of portal vein
B. Intra-hepatic causes (non-cirrhotic):
1. Idiopathic
2. Schistosomiasis
3. Nodular regenerative hyperplasia.
4. Chronic hepatitis (autoimmune, Wilson)
5. Drugs & toxins → AZA, methotrexate
C. Post-hepatic (hepatic venous outflow):

1. Budd-Chiari syndrome
2. Right-sided heart failure & constrictive pericarditis

Question 5

Stages of Hepatic Encephalopathy

Answer 5

Stage 0
→ Minimal HE, Covert HE, Subclinical HE
→ Diagnosed by psychometric hepatic encephalopathy score system

Question 6

Stages of Hepatic Encephalopathy

Answer 6

Stage 1
* Mood → Depression or euphoria, irritability
*Memory → Impaired (e.g., addition or simple math performance)
(مذكور بالعربية: “مريض ميعرفش يحسب 1+1 أو 1×1”)
* Short attention span
* Sleep → Reversed rhythm

Question 7

Stages of Hepatic Encephalopathy

Answer 7

Stage 2
* Drowsy
*Disoriented → Intermittent confusion
+ Asterixis → Flappy, hyperreflexia

Question 8

Stages of Hepatic Encephalopathy

Answer 8

*Disoriented → Totally
* Somnolent →aurausable but only with vigorous stimulus
نايم بس لو ناديت عليه يصحي

Question 9

Stages of Hepatic Encephalopathy

Answer 9

Stage 4 (Coma)

A → Coma, respond to painful stimulus

B → Coma, no response

Question 10

Management of HE

Answer 10

*Response of management confirmthe diagnosis
*3-pronged strategy for acute management:
1. Rule out other causes of encephalopathy
2. Identify & treat correctable precipitating factors of HE
3. Initiate empirical management

Question 11

Management of HE

Answer 11

2. Identify & Treat Precipitating Factors

حاجات زودت nitrogen load وبالتالي زودت الامونيا
1- Increase Protein intake
2-GIT bleeding
3-Constipation
علي BBB
Metabolic changes أثرت
1. Sepsis
2. Hypokalemia
3. Hypovolemia
4. Alkalosis
5. Azotemia or dehydration
*Miscellaneous:
1-SBP (Spontaneous bacterial peritonitis)
2-Sepsis
3-Surgery and Post surgical anastomosis
4-TIPS (Transjugular intrahepatic portosystemic shunt)
5-Tapping ascitic fluid (LVP without compensation)
*Drugs:
1-Diuretics
2-Sedatives (e.g., benzodiazepines)
3-Narcotics
4- poor compliance to Lactulose

Question 12

Management of HE

Answer 12

1. Rule out other causes of encephalopathy:
   المخ
   CNS infection
   TIA
   Cerebral edema
   Postictal state
   Intracerebral hemorrhage

الرئة
Hypoxia
Hypercapnia

الكلي
Uremia
Metabolic:
Hypoglycemia
DKA
Electrolyte disturbance
Acidosis
Drugs (alcohol, opioids)
Septic shock

Question 13

Management of HE

Answer 13

3. Initiate Empirical Management
   A-General Supportive Care:
   Appropriate nutritional support
   and void dehydration
   B-Agitation is usually resolve with treatment of HE ,but if needed, haloperidol is the drug of choice.
   C-Gut Cleansing with enema:
   250 mL of Lactulose + 750 mL warm water
   Every 2–4 hours until clinical improvement
   D-Lactulose (oral)
   Often helpful in all types of HE
   Goal: 2–3 loose bowel movements/day
   30 mL every 6 hours

Question 14

What is the role of Lactulose in HE?

Answer 14

↓ Ammonia absorption

↑ Ammonia excretion
*****بيقلل absorption bازاي؟
> Lactulose is a non-absorbable disaccharide that reaches the colon unchanged and is metabolized in presence of colon bacteria into acetic acid and lactic acid, which:
Convert NH₃ → NH₄⁺ (less absorbable)and passed in stool.
**بيزود execration ازاي؟
Lactulose acts as an osmotic laxative which draws water into the colon → promotes bowel movements → helps in rapid elimination of ammonia and other toxins from the gut.
**Alters gut microbiota:
Promotes growth of non-urease producing bacteria (e.g. Lactobacilli) &Inhibits growth of ammonia-producing bacteria (e.g. Proteus, Klebsiella)

Question 15

Response of Management

Answer 15

Response of Management (فشل العلاج):
Failure of response to HE therapy after 72h of treatment may indicate:
1. Missed another cause of encephalopathy or it’s not HE
2. Missed or not well-treated precipitating factor
3. Lack of reach of Lactulose into small intestine or right colon → (مثلاً في وجود إمساك شديد)

Question 16

2nd Line Therapy:

Answer 16

1-Oral antibiotics:
Rifaximin 550 mg PO 1*2 (for 3–6 months)
↓ risk of recurrence of HE Especially in chronic HE
Metronidazole 250 mg PO 14
Vancomycin 250 mg PO 14
2-LOLA – L-ornithine L-aspartate
*↓ Ammonia level because it converts ammonia → glutamine
Oral form is less effective than parenteral
Dose: 1 gm IV 12
3-Branched chain A.A
4-plyethyline glycol أي كلام
5-Na benzoate.
6–Flumazenil: only in benzodiazepine toxicity

Question 17

Long term treatment of HE

Answer 17

2L+2B
*Lacteluse syrup
*Lola
*Branched chain amino acids
*Bromocreptine : used in extra pyramidal symptoms .
Rifaximin 550 12 (3-6months)
*Vegetable based protein
*Zinc
*Na benzoate

Question 18

Intractable or recurrent hepatic encephalopathy

Answer 18

1-Liver transplantation
In cases of
*Intractable HE
* recurrent HE.
*HE respond only to low protein diet.
2-if the patient not fit for liver transplant or MELD score <15:
Radiological or surgical modification as TIPS or chemoembolization
3-liver supportive system

Question 19

Pathophysiology of HE*

Answer 19

1-↓ Hepatic metabolism & clearance of compounds which maintain normal CNS function.
2- Failure of hepatic detoxification of neurotoxins. due to:
* Loss of function or mass of hepatocytes.
* Intra & extra hepatic splanchnic blood shunting

Question 20

Possible mechanisms of HE

Answer 20

1-Ammonia neurotoxicity
2-Allelic mutations of glutaminase:
خلي بالك…
الجلوتامينيز يحول الجلوتانين لامونيا
وجلوتامينات
3-Astrocyte hypersensitivity
4- Alteration of CNS tryptophan metabolism
5-Synthesis of neuro-active neurotransmitters as octopamine.
5-synergistic neurotoxins act on ammonia, mercaptopurine

Question 21

Covert hepatic encephalopathy

Answer 21

Mild neurocognitive changes in hepatic patient with no clinical signs of H.E.
*About 60-70% of cirrhotic patient have subclinical HE even they are compensated.
* about of those patient & minimal HE will develop overt HE within 2 years

Question 22

Diagnosis of covert hepatic encephalopathy

Answer 22

Diagnosis is made by psychometric encephalopathy score system
1-Number connection test a,b
2-Digit symbol test.
3-serial dotting test
4- line drawing test.