HISTORY OF HEPATIC ENCPHALOPATHY

2. Introduction
• HE is viewed as a broad range of negative alterations to behavioral, cognitive, or motor
system functions that are caused by hepatic insufficiencies, perihepatic shunting, or both
• It has a broad spectrum of neuro-psychiatric manifestations ranging in severity from
subclinical alterations to coma.

3. History
Hippocrates
(460–371 B.C.)
The association between liver disease and mood disturbances was
recognized.
Celsus and
Galen (Rome)
Hippocratic Corpus, observed that “those who are mad from phlegm are quiet
and do not cry or make a noise; but those from bile [presumably yellow bile, the
“choleric humor,” are vociferous, malignant and will not be quiet.
GB. Morgagni
(1682–1771)
Case of hepatic encephalopathy first recording of the progression of the disorder
through a series of worsening stages.
F.T. Frerichs
(1860)
The existence of episodes of delirium, somnolence and coma in liver disease is
reported in the famous “treatise on liver diseases”
Hann et al Dogs undergoing experimental portalcaval shunt develop behavioral changes
within 10-40 days after surgery.
William
Saunders
Originally termed “hepatic coma”, inferred a relationship between the brain and
the liver
Gabuzda et al They used resins to treat ascites associated with chronic liver disease ,noticed
neurological changes and confirmed the role of ammonia in the pathogenesis of
hepatic encephalopathy.

4. • A definite improvement in the description of the clinical findings, the pathophysiology and
treatment of hepatic encephalopathy was given by S. Sherlock and her disciples in
London,(1952)
• She also coined the term ‘portal-systemic encephalopathy’ that was exceptionally
appropriate to underline that:
1) The symptoms are not only limited to coma, but to a wide spectrum of manifestations
both behavioral and neurological.
2) The symptoms are ascribable to an underlying dysfunction of the brain and consequently,
this dysfunction is relevant for clinical investigation.

5. 3) Portal-systemic shunt, and substances of gut origin with high hepatic extraction, are key
element in the pathophysiology of the disorder.
• In addition, she confirmed the relevant role of hyperammonaemia in the pathophysiology
of the disorder and the role of gut microbiota that could be modulated by antibiotics to
revert coma.

6. • The definition of hepatic encephalopathy-related syndromes was first made in 1998 by the
World Congress of Gastroenterology meeting in Vienna.
• The first main change that the meeting established was to do away with the term
“portosystemic encephalopathy,” as not all hepatic encephalopathy requires the presence
of portosystemic shunts.
• They also incorporated the classification of hepatic encephalopathy based on four main
factors or axes:

7. 4 Axes :

8. The Underlying Cause
• Type A is HE that develops as a result of ALF.
• HE caused by ALF is associated with osmotic disturbances in the brain, systemic
inflammations, and elevated intracranial pressure that can cause cerebral herniation.
• Type B is HE associated with portal-systemic bypass or shunting in the absence of
intrinsic liver dysfunction.
• Type C, describes HE caused by cirrhosis, which is the most common risk factor for HE.

9. The Severity of the Disease Manifestation

10. • The range of neurocognitive abnormalities in patients with cirrhosis forms a continuous
spectrum that ranges from normal to abnormalities only on specialized testing, known as
covert HE (CHE), and clinical signs of HE, called overt HE (OHE).
• CHE consists of minimal HE (MHE) and West Haven grade 1 HE.
• Overt HE, large percentage of patients who are normal by clinical examination but have
significant abnormalities on specialized neuropsychometric or neurophysiologic tests.

11. According to Disease Time
Course
• The time course of HE is divided into 3 intervals:
1) Episodic
2) Recurrent
3) Persistent
• In the episodic interval, patients experience HE bouts more than 6 months apart.
• Patients with recurrent HE suffer from bouts that take place within 6 months or less.
• In the case of persistent HE, patients tend to experience unremitted behavioral
modifications that are combined with relapses of overt HE bouts

12. The Existence of
Precipitating Factors
Infections- spontaneous bacterial
peritonitis, urinary tract infections,
respiratory infections, skin infections, and
sepsis.
In cirrhosis: Include MHE, prior history of
overt HE, sarcopenia, hyponatremia,
epilepsy, type 2 diabetes mellitus , higher
creatinine levels, higher bilirubin levels,
lower levels of albumin, PPI use,
nonselective beta-blockers use, and statin
use.

13. Epidemiology and burden

15. Epidemiology and burden in India
• In developing countries like India, liver diseases continue to pose a significant health
problem.
• The rise in the burden of chronic liver diseases and its complications has a huge impact
on the economy.
• In the recently reported WHO (World Health Organization) data, 2.95% of total deaths in
India were caused by liver diseases deaths.
• It is associated with poor survival and a high risk of recurrence and even in its mildest
form, health-related quality of life is reduced drastically.
• Subtle signs of HE are observed in nearly 70% of patients and overt hepatic
encephalopathy occurs in about 30-45% of patients with cirrhosis.
• Despite appropriate treatment, patients with a previous history of overt HE have a 42%
risk of recurrence within one year.

16. • Thank you

17. History
• The association between liver disease and mood disturbances was recognized, in the western world,
by the father of medicine, Hippocrates (460–371 B.C.).
• Celsus and Galen in Rome both noted in the Hippocratic Corpus, observed that “those who are mad
from phlegm are quiet and do not cry or make a noise; but those from bile [presumably yellow bile,
the “choleric humor,” are vociferous, malignant and will not be quiet.
• The description was done by GB. Morgagni (1682–1771) Professor of Theoretical Medicine in
Padua, Italy who described a case of hepatic encephalopathy,
• Wrote about the fate of an alcoholic Venetian nobleman, subsequently shown at postmortem to have
cirrhosis of the liver, whose death was preceded by ascites, agitation, somnolence, violent delirium,
and coma, thus providing the first recording of the progression of the disorder through a series of
worsening stages.

18. • The existence of episodes of delirium, somnolence and coma in liver disease is
reported in the famous “treatise on liver diseases” by F.T. Frerichs1860.
• Experimental studies by Hann et al who showed that dogs undergoing
experimental portalcaval shunt develop behavioral changes within 10-40 days
after surgery.
• The authors called this disorder an ‘encephalitis’ related to a ‘meat intoxication
syndrome’.
• After this experiment achieved to understand the relationship between the liver
and the brain.

19. • At the beginning of the 19th century, the stage was actually set for understanding the
pathophysiological basis of what was originally termed “hepatic coma,” when Scottish
physician William Saunders , inferred a relationship between the brain and the liver.
• The first significant intervention study relating to liver disease and hepatic encephalopathy
was done in 1947 by Gabuzda et al.
• They used resins to treat ascites associated with chronic liver disease (which exchanged
sodium for ammonia) and noticed neurological changes and confirmed the role of
ammonia in the pathogenesis of hepatic encephalopathy.
• This was a novel finding as up until that time only acute liver failure was known to be
associated with cerebral edema.

20. • Subclinical hepatic encephalopathy (SHE) was first highlighted by Rikkers et al. via EEG
studies where neurophysiological and psychometric alterations were noted in cognitive
abilities of patients with cirrhosis who otherwise appeared normal on exam .
• The terminology of SHE has subsequently evolved to covert hepatic encephalopathy.
• The new term ‘hepatic encephalopathy’ (HE) was coined, by Fazekas, et al.