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Portal-Systemic Encephalopathy


Portal-Systemic Encephalopathy

Article Author:
Muhammad Khan
Article Editor:
Fatima Anjum
Updated:
8/26/2020 8:06:04 AM
For CME on this topic:
Portal-Systemic Encephalopathy CME
PubMed Link:
Portal-Systemic Encephalopathy

Introduction

Portosystemic encephalopathy, also known as hepatic encephalopathy (HE), is defined as a neuropsychiatric syndrome that can develop in patients with a portosystemic shunt. A patient with liver dysfunction having neuropsychiatric signs and symptoms should be considered as having hepatic encephalopathy until proven otherwise.[1] 

In a portosystemic shunt, blood from the splanchnic venous circulation is shunted to collateral venous drainage instead of passing through hepatic sinusoids. A portosystemic shunt can be congenital or acquired. Congenital portosystemic shunts are rare and could be extrahepatic or intrahepatic. A portosystemic shunt is called congenital when there is no history of cirrhosis, portal hypertension, or portal vein thrombosis. The acquired portosystemic shunt is usually caused by portal hypertension due to cirrhosis of the liver in end-stage liver disease. Acquired and congenital portosystemic shunt both can present with hepatic encephalopathy.[2] 

Due to the shunt, ammonia, and other neurotoxins that usually get metabolized in the liver, bypass and cross the blood-brain barrier leading to the accumulation of neurotoxins in the brain, causing cognitive and psychomotor disturbances.[3]

Etiology

Hepatic encephalopathy is common in patients with liver cirrhosis. Depending on the etiology, it can be differentiated into three types: 

  • Type A: Acute liver failure
  • Type B: Due to portosystemic shunt in patients without any liver dysfunction 
  • Type C: In patients with liver cirrhosis 

The major cause of encephalopathy in all three types is the failure of ammonia to get metabolized into a less toxic state by the urea cycle in portal hepatocytes in the liver, either due to liver dysfunction or the development of a portosystemic shunt. The astrocyte cell membrane is highly permeable to the ammonium ion. A low concentration of ammonia can cross the blood-brain barrier reaching the brain and gets deposited there. The deposition of ammonia in the brain causes a neuropsychiatric syndrome.[4]

Epidemiology

The exact incidence of hepatic encephalopathy among the general population is not known. It can affect both males and females equally and can affect individuals of any age. It is the fourth substantial cause of death among Americans between the age of 45 and 54 years with liver disease. The hepatic encephalopathy, including minimal hepatic encephalopathy, is related to 50% to 70% of all patients with liver cirrhosis. The earliest form of hepatic encephalopathy is minimal hepatic encephalopathy (MHE) and can affect up to 80% of patients with liver cirrhosis.[5] 

Roughly 23% to 53% of individuals with no liver disease but whose liver has been bypassed by a portosystemic shunt develop hepatic encephalopathy. The most common cause of hepatic encephalopathy is cirrhosis, which is estimated to affect 5.5 million people in the United States. Furthermore, hepatic encephalopathy is more common among nations with a higher occurrence of liver disease than the United States.

Pathophysiology

The most important causative factor of hepatic encephalopathy is increased ammonia level in the blood. Other known neurotoxins include short-chain fatty acids, mercaptans, tyramine, octopamine, manganese, and gamma-aminobutyric acid (GABA). Determining the blood ammonia level is complicated due to a variety of reactions taking place in multiple organs. Metabolism of ammonia takes place in the liver, gastrointestinal tract, muscles, kidney, and brain. The enormous amount of ammonia produced by amino acid metabolism is captured by the urea cycle and does not contribute to blood ammonia levels under normal conditions. The primary site of production of ammonia is the gastrointestinal tract. The three main mechanisms of production of ammonia in the gut are hydrolysis of urea by bacterial urease, bacterial protein deamination, and glutamine metabolism in the intestinal mucosa. 

In people with a normal healthy liver, most of this ammonia produced by the gastrointestinal tract is removed by the liver. Patients who develop a portosystemic shunt due to any reason like cirrhosis of the liver or, in the case of a trans-jugular portosystemic shunt, lose the first-pass metabolism of ammonia leading to hyperammonemia usually observed in patients with chronic liver disease. As this high level of ammonia crosses the blood-brain barrier, it starts depositing in brain cells leading to the neuropsychiatric syndrome.[6][7]

History and Physical

Hepatic encephalopathy can present with a wide range of signs and symptoms. Initial signs of hepatic encephalopathy can be hyperreflexia, rigidity, tremors, positive Babinski's sign, or asterixis (jerky movements of hands-on outstretched arms at wrists). Severe hepatic encephalopathy presents with agitation, disorientation in time-space and person, somnolence, rapidly developing confusion, and ultimately coma.[7][8] The physical exam may demonstrate signs of chronic liver disease.

Evaluation

The diagnosis of hepatic encephalopathy needs a thorough physical examination of the patient, followed by the categorization of signs and symptoms according to the West Haven criteria. It is important to rule out other causes of encephalopathy such as viral encephalopathy, intracranial lesions, masses, hemorrhage or stroke, post-seizure encephalopathy, intracranial infections, or toxic encephalopathy. The diagnosis of hepatic encephalopathy is based on four main factors: 

  • Peculiar clinical pattern 
  • Diagnosis of liver dysfunction or portosystemic shunt along with hyperammonemia
  • Alternative diagnoses ruled out
  • Response of the patient to ammonia lowering therapy

An electroencephalogram (EEG), computed tomography (CT) scan, and magnetic resonance imaging (MRI) of the head can be used to rule out other causes of encephalopathy.[8]

Treatment / Management

Hepatic encephalopathy is a relevant cause of hospitalization. The management of hepatic encephalopathy involves primary and secondary prophylaxis, dietary changes, and potentially a liver transplant.

  • Primary prophylaxis: Patients with an upper GI bleed are at considerable risk of hepatic encephalopathy. Gastrointestinal lavage by mannitol or non-absorbable disaccharides reduces the risk for overt HE. Treatment of cirrhosis that reduces or reverts the progression of the disease may be considered primary prophylaxis for HE, for instance, alcohol abstinence in alcohol misusers, antiviral drugs in virus-related cirrhosis, proper nutrition in malnourished patients (both excess and deficiency), and iron overload, among others.  
  • Secondary prophylaxis: It is for the patients who have suffered from episodes of hepatic encephalopathy and have a higher risk of more episodes. The use of lactulose following an episode decreases the risk of another episode by 50%. For those who cannot tolerate lactulose well can use rifaximin (a non-absorbable antibiotic). For patients with recurrent episodes of hepatic encephalopathy, a combination of lactulose and rifaximin can further decrease the risk of another episode. In patients who are severely debilitated due to disease, the goal is to find the shunt and obliterate it.
  • Dietary changes: For a patient with hepatic encephalopathy, the following dietary changes are advised: 
    • The addition of snacks in between meals and before going to bed in order to reduce gluconeogenesis and catabolism of proteins. 
    • Decrease consumption of meat proteins. 
    • Try replacing meat protein with milk protein. 
    • Increase the use of fiber.
    • Compensate for micronutrients by taking prescribed vitamins and minerals.  
    • Add probiotics to the diet.[9]

Patients with increased risk for aspiration or respiratory compromise should be prophylactically intubated and monitored in the ICU.  

  • Liver Transplant: Patients with hepatic encephalopathy are usually poor candidates for a liver transplant due to poor prognosis and quality of life.[10]

Differential Diagnosis

  • Intracranial lesions such as intracranial hemorrhage, abscess, tumor, stroke, subdural hematoma
  • Meningitis 
  • Hypoglycemia 
  • Anoxia 
  • Wernicke encephalopathy 
  • Post-seizure encephalopathy 
  • Drugs such as antipsychotics, sedatives, antidepressants[11]

Prognosis

Hepatic encephalopathy is associated with a poor prognosis in terms of survival and subsequent relapses of overt hepatic encephalopathy. The quality of life for patients is poor, and there is an increased burden for caregivers. Moreover, patients have a higher risk for falls and poor driving ability, and it is associated with a lower income.

Complications

  • Severe confusion 
  • Psychomotor changes
  • Disorientation 
  • Somnolence 
  • Cognitive changes 
  • Coma 
  • Death

Consultations

  • Gastroenterologist
  • Radiologist 
  • Hepatologist 
  • Transplant surgeon 
  • Hospice

Deterrence and Patient Education

Patients with hepatic encephalopathy can present with different signs and symptoms. The patient could present with hyperreflexia, rigidity, tremors, positive Babinski's sign, or asterixis in initial stages. Severe hepatic encephalopathy can present with agitation, disorientation in time-space and person, somnolence, rapidly developing confusion, and ultimately coma. The newly diagnosed patient should be given emotional support and detailed information about the condition, its treatment, prognosis, and effects on everyday life.

The patient should be provided with educational material about the disease. Flow charts, diagrams, and videos should be used to explain every aspect of the disease, treatment, and lifestyle changes. Patient education should be continued until the patient fully understands everything and is satisfied with the provision of care.

Pearls and Other Issues

  • Hepatic encephalopathy is a liver dysfunction presenting with psycho-motor signs and symptoms.  
  • Hepatic encephalopathy is caused by acute liver failure, portosystemic shunt in patients without any liver dysfunction or in patients with liver cirrhosis due to failure of metabolism of ammonia by the liver. 
  • Males and females are equally affected by hepatic encephalopathy. 
  • Hepatic encephalopathy could present with agitation, disorientation in time-space and person, somnolence, rapidly developing confusion, and ultimately coma. 
  • Diagnosis is made by the categorization of signs and symptoms according to the West-Haven criteria. 
  • Treatment usually consists of primary and secondary prophylaxis with lactulose, rifaximin, and dietary changes. 
  • Hepatic encephalopathy has a poor prognosis, and patients have a poor quality of life.

Enhancing Healthcare Team Outcomes

It is the responsibility of healthcare professionals that the patient has a good understanding of the disease and the appropriate treatment available for the disease. Diagnosis of hepatic encephalopathy can cause significant anxiety among patients. It is vital for healthcare providers to provide emotional support to the newly diagnosed patient. The approach to hepatic encephalopathy should be with an interprofessional team, including a primary clinician, pharmacist, radiologist, pathologist, gastroenterologist, and transplant surgeon in order to provide the best care.

After the diagnosis of hepatic encephalopathy is made, the prognosis is poor, and most of the patients die within a year. Most patients have little knowledge about their disease, and hepatic encephalopathy can be debilitating. Thus, a consult with a home care nurse, social worker, and physical therapist is recommended to ensure the patient is receiving adequate care.


References

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[3] Philips CA,Rajesh S,Augustine P,Padsalgi G,Ahamed R, Portosystemic shunts and refractory hepatic encephalopathy: patient selection and current options. Hepatic medicine : evidence and research. 2019;     [PubMed PMID: 30774483]
[4] Fiati Kenston SS,Song X,Li Z,Zhao J, Mechanistic insight, diagnosis, and treatment of ammonia-induced hepatic encephalopathy. Journal of gastroenterology and hepatology. 2019 Jan;     [PubMed PMID: 30070387]
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[8] Amodio P, Hepatic encephalopathy: Diagnosis and management. Liver international : official journal of the International Association for the Study of the Liver. 2018 Jun;     [PubMed PMID: 29624860]
[9] Vilstrup H,Amodio P,Bajaj J,Cordoba J,Ferenci P,Mullen KD,Weissenborn K,Wong P, Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology (Baltimore, Md.). 2014 Aug;     [PubMed PMID: 25042402]
[10] Patidar KR,Bajaj JS, Covert and Overt Hepatic Encephalopathy: Diagnosis and Management. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2015 Nov;     [PubMed PMID: 26164219]
[11] Marois C,Quirins M,Hermann B,Mouri S,Bouzbib C,Rudler M,Thabut D,Weiss N, [Metabolic encephalopathies]. La Revue de medecine interne. 2019 Feb;     [PubMed PMID: 30638703]