​Kembara Xtra - Medicine - Hepatic Encephalopathy

​Kembara Xtra - Medicine - Hepatic Encephalopathy 
Portosystemic shunting and/or acute or chronic liver illness are associated with reversible impaired mental and motor functions.

Confusion, reduced arousability, and a "flapping tremor" (asterixis) are characteristic symptoms indicating a broad spectrum of neurologic/psychiatric disorders that range from subclinical alterations to coma.

 Hepatic, neurological, and gastrointestinal (GI) system(s) affected
Synonym(s): liver coma, portosystemic encephalopathy (PSE), and hepatic coma


Epidemiology 

(Reflects prevalence of underlying liver disease) Male = female

Incidence
Within 5 years of cirrhosis diagnosis, the risk of the first episode of overt hepatic encephalopathy (HE) is 5-25%.

The median cumulative 1-year incidence of overt HE after posttransjugular intrahepatic portosystemic shunt (TIPS) is 10- 50%.
Prevalence
Any age can develop cirrhosis, which parallels the age at which fulminant liver disease predominates and peaks in the 40s (late 50s for cirrhosis).

When there is acute liver failure (ALF) or fulminant hepatic failure, overt HE occurs in 30–40% of cirrhotic individuals.
50% of people who need liver transplants have this condition.

Pathophysiology and Etiology 

The pathophysiology underlying the emergence of HE is not known. Four different classifications have been offered (1):
- In line with the underlying illness:
Type A: brought on by abrupt liver failure
Type B: brought on by portosystemic shunting or bypass
Type C: brought on by cirrhosis
- In accordance with the degree of manifestation
West Haven categorization
 Minimal: neuropsychological or psychometric changes without adjustments to mental status
Grade I problems include inattention, nervousness, a short attention span, poor math skills, and irregular sleep patterns.
Grade III: somnolence to stupor, confusion, extreme disorientation, unusual conduct. Grade II (overt): asterixis, lethargy, disorientation to time, personality change
Coma, Grade IV
- In keeping with the chronology:
Episode-based HE
Recurrent HE is defined as occurrences within six months.
Persistent HE is defined as ongoing behavioral changes interspersed with episodes of overt HE.
- In light of the antecedents:
Precipitated and nonprecipitated

A number of metabolic parameters, such as ammonia, mercaptan, octopamine, tyramine, fatty acids, lactate, and manganese, have been linked to HE due to the liver's inability to properly metabolize these harmful CNS chemicals.
Increased levels of aromatic and reduced levels of branched chain amino acids in the blood may behave as fictitious neurotransmitters and interact with the GABA receptor to produce clinical symptoms.

Patients with long-standing cirrhosis and spontaneous intestinal blood shunting through collateral arteries or surgical portacaval shunts are most likely to develop HE.
● The inability to maintain a specific posture as a result of metabolic encephalopathy is known as asterixis. The distinctive liver flap seen when the arms and wrists are extended is caused by abnormal diencephalic function. Patients with uremia, barbiturate poisoning, and other types of pulmonary illness may also have asterixis. Therefore, asterixis is not a pathognomonic sign of HE.

Genetics Unknown Illnesses such cystic fibrosis, a lack in the enzyme 1 antitrypsin, hemochromatosis, and Wilson disease can make a person more likely to develop chronic liver disease.

Risk Elements 

Precipitating factors in patients with underlying liver disease include: Infections (overt or covert, including spontaneous bacterial peritonitis [SBP]);
GI bleeding Opiate or sedative medication use, such as benzodiazepines
Electrolyte disruption (most frequently Na+, K+, and Mg2+)
Transjugular intrahepatic portosystemic shunt (TIPS), a radiologically implanted shunt to lower portal pressure, among other fluid abnormalities:
individuals who have TIPS are more likely to develop HE than younger individuals and those with worse liver function.

Prevention 

Avoid non-essential drugs, especially opiates, benzodiazepines, and sedatives. Recognize early symptoms and seek urgent treatment.
Consider lactulose therapy as a secondary form of HE recurrence prevention.

Lactulose plus rifaximin is the best-documented medication for patients who have already gone through episodes of overt HE while using lactulose to keep their condition in remission.


Cirrhosis and portal hypertension are associated conditions that may develop as a result of acute fatty liver during pregnancy. These conditions are rare in patients who have a portacaval shunt and normal liver function.

Confusion; changed mental status; impaired arousability; prior hepatic illness; present history; constipation;


clinical assessment 

Age 10 to 60 - West Haven classification, five levels of confusion and obtundation:
 Minimal: neuropsychological or psychometric changes without adjustments to mental status
Grade I symptoms include lack of awareness, anxiety, diminished attention span, difficulty with math, and irregular sleep patterns. Grade II symptoms include asterixis, lethargy, changes in personality, and disorientation to time. Grade III symptoms include somnolence to stupor, bewilderment, and extreme disorientation.
Coma, Grade IV
- Prominent symptoms of underlying liver illness (50%); jaundice is the most prevalent symptom, followed by ascites.
- Hematemesis or melena along with GI bleeding (20%)
- Pulmonary infection (20%), urinary tract infection (20%), or systemic infection (20%)

Age >60 years: Decreased liver disease symptoms (25%).
More evident confusion; less frequent identification of GI bleeding or infection that is progressing.
- Advancement is slower.
Age 10 years - Prominent signs of underlying liver disease, such as severe cirrhosis or fulminant hepatic failure
- The rate of progression is often hours.
Wilson illness is able to mimic HE.
Vital indicators:
- Bradycardia - Blood pressure that is higher than normal and may indicate higher intracranial pressure
CNS exam: Evaluate short-term memory and the existence of asterixis (also known as "liver flap," which is the flapping of the wrist when the arms and wrists are stretched). Jaundice, ascites, and other correlates of liver illness (such as spider telangiectasias, muscle wasting).

Pupillary reaction declines with worsening HE, going from normal to slow to nil.

Head trauma, concussion, subdural hematoma, transient ischemic attack (TIA), and ischemic stroke are among the differential diagnoses for metabolic encephalopathy caused by anoxia, hypoglycemia, hypokalemia, hypo- or hypercalcemia, or uremia.
Meningitis and encephalitis, as well as increased intracranial pressure (ICP), intracranial hemorrhage (ICH), alcohol intoxication, alcohol withdrawal syndrome, meningitis, and encephalitis, as well as Wilson disease without cirrhosis, Reye syndrome, and Wernicke-Korsakoff syndrome.

Clinical findings are diagnostic in 80% of instances based on laboratory results.
Response to therapy frequently validates the diagnosis
Basic rhythm is symmetrically slowed in EEG (limited utility); this is similarly seen in other metabolic encephalopathies.
Number connection test, line drawing test, critical flicker frequency test, digit symbol test, continuous reaction time test, inhibitory control test, repeatable battery for the assessment of neuropsychological status (RBANS), and other psychometric tests may be used to evaluate minimal HE. Visual evoked potential: specific in grades II to IV.
Initial examinations (lab, imaging)
90% of patients with HE have increased serum ammonia levels, although these levels are neither diagnostic nor correlated with the severity of the disease; instead, they are influenced by infusions of amino acid solutions, opiate use (which causes constipation), uremia, tissue disintegration, burns, trauma, or infection.

A normal ammonia level necessitates a diagnostic recheck.
Prothrombin time (PT) and international normalized ratio (INR) frequently elevated; CBC: anemia and leukocytosis; complete metabolic profile to identify hypokalemia, hyperbilirubinemia, altered calcium concentration, hypomagnesemia, and hypoglycemia; and liver function tests, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and serum albumin. BUN: Creatinine >20 indicates either GI hemorrhage or dehydration.
Paracentesis diagnostic to rule out SBP
As clinically indicated, blood, urine, sputum, and ascitic fluid cultures to detect infection.
Consider measuring arterial blood gas, getting a toxicology check, using a head CT to look for frontal cortical atrophy or edema, or using an MRI to check for elevated T1 signal in the globus pallidus.
Tests in the Future & Special Considerations
When assessing the severity of HE, clinicians shouldn't rely solely on serial monitoring of serum ammonia levels.
Interpretation of Tests
Brain edema is present in all fatal cases. Chronic encephalopathy causes glial hypertrophy.

Identify and address any precipitating reasons, such as electrolyte imbalance, GI hemorrhage, or infection.
Sedatives, benzodiazepines, opiates, diphenoxylate, and atropine should be avoided.
Grade I or above: Consider lactulose enema for patients without diarrhea; provide appropriate fluid and calorie intake; prevent hypoglycemia; and, if clumsiness and poor judgment are noticeable, put fall precautions in place.

First Line of Medicine
Lactulose syrup: 30 to 45 mL PO up to every hour for a target of 3 to 6 bowel movements per day. This non-absorbable disaccharide has laxative action that shortens colonic transit time and bacterial digestion that acidifies the colon to promote conversion of ammonia [NH3] to ammonium [NH4+]. Reduce to 15 to 30 mL BID when there are fewer than 3 bowel motions per day.

Lactulose enema: 300 mL lactulose plus 700 mL tap water, kept for an hour (for individuals who cannot tolerate lactulose or who have a suspected ileus).

 Add antibiotics if acute deterioration develops or if there is no improvement after 2 days:
- Rifaximin, a nonabsorbable antibiotic with potent anti-HE properties, 400 mg PO TID or 550 mg PO BID

Contraindications include total ileus and an allergic response.
Safety measures:
- Dehydration, hypokalemia, other electrolyte imbalances, and renal failure

Next Line

If renal function is within normal ranges, administer 1 to 2 g of neomycin orally every 6 to 8 hours.

Lactulose may not be as successful in treating acute HE as polyethylene glycol.

Metronidazole and vancomycin are substitute antibiotics, but their use is constrained by their unfavorable side effects and potential for the development of antimicrobial resistance.
Flumazenil might be helpful for certain patients.

Although it is not accessible in the United States, the medicine oral L-ornithine-L-aspartate (LOLA), which is made up of two amino acid substrates, is widely used in Europe to encourage the urea cycle and subsequent loss of ammonia.


Referral 

Refer early to a reputable transplant center, especially if the patient is not responding to medication.

Surgical Techniques 

As a stopgap measure before transplantation, artificial liver perfusion devices are helpful in fulminant hepatic failure.
A liver transplant is indicated in cases of liver failure accompanied by recurring, untreatable overt HE.
Consider a liver transplant if your HE is grade II to IV.

Alternative Therapies 
Through altering gut flora, probiotics and prebiotics have been linked to an improvement in HE.


Admissions 
When the diagnosis is clear, closely monitor clinical status in grades I and II and keep an eye out for advancement.
Assess candidates for liver transplantation who have fulminant hepatic failure and HE grades II to IV.

as tolerated once the issue has been rectified

patient observation
Asterixis and the trail-making test, which involves asking the patient to connect the dots based on numbers, both aid in the monitoring of HE patients. Determined by periodic examination are the diet and maintenance regimen. Test frequently at first, then at each visit when dietary and pharmacological modifications are made.
If the trailmaking test results change, consult with patients every two weeks. Patients that are stable should be seen every month.
Patient monitoring can also be aided by administering an NCT or line drawing test at each office visit.
In cases of cirrhosis, consider liver transplantation and routinely check the MELD score. Uncontrolled hyperglycemia and malnutrition are linked to the emergence of overt HE in cirrhotic patients.

Diet 
Sarcopenia and weight loss may make HE worse.
A regular protein diet (1.2 to 1.5 g/kg/day); patients are generally undernourished, hence protein-limited diets are avoided.
In patients with severe cirrhosis, vegetable protein diets are more tolerable than animal protein diets; specialized IV/enteral formulations with enhanced branched chain amino acids are also available.
Patients in Grades III to IV require jejunal feeds or parenteral nutrition.

Prognosis: Acute HE frequently gets better with the right care.
Chronic liver disease: HE recurs; HE is harder to treat with each recurrence; the rate of recovery after treatment is lower; and the mortality rate is close to 80%.


Hepatorenal syndrome, persistent basal ganglia injury (non-Wilsonian hepatolenticular degeneration), and recurrence are complications.