Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.
Hepatic Encephalopathy
Nick Harper
“A neuropsychiatric syndrome
caused by hepatic insufficiency due
to acute or chronic liver disease”
– personality changes
...
Classification
(World congress of gastroenterology 1998)
• Type A “Acute liver failure”
• Type B “portal systemic Bypass a...
Epidemiology
• Prevalence 1.4 per 100,000 population (UK
2008)
• 70% of patients with cirrhosis
• 1 year survival 42%
• 3 ...
GABA
Osm
Serum ammonia raised in 90% of cases.
Not all hyperammonaemia is associated with encephalopathy
EEG
• Stage I – III triphasic
waves (5Hz) over
frontal lobes
• Stage IV slow delta
wave
PSE index (Conn 1977)
• Mental state
• Arterial ammonia
levels
• Degree of asterixis
• EEG scoring
• Number connection
tes...
West Haven criteria
(Conn score)
Grade 1: sleep reversal, mild lack of awareness,
shortened attention span
Grade 2: lethar...
Reduce production
and absorption of
ammonia in the gut
Non absorbable disaccharides
(Lactulose)
• Increase bowel transit
• Ammonia to ammonium (not absorbed)
• GI effects, dehyd...
Neomycin
• Aminoglycoside
• Reduce
encephalopathy
inducing bacterial
waste products
• Ototoxicity
• Nephrotoxicity
Rifaximin
• Antibiotic – Rifamycin class
• Wide spectrum
• Inhibits bacterial DNA dependent
RNA polymerase
• Very poorly a...
Mas et al 2003 (Journal Hepatology)
• Prospective, randomised, double blind, double
dummy, controlled trial
• Grade I-III ...
Ammonia
EEG
PSE score
Bass et al 2012 NEJM
• Phase 3 multicentre, randomised, double blind,
placebo controlled trial
• Rifaximin Vs Placebo
• n=...
Placebo Rifaximin
encephalopathy 46% 22%
Hospitilisation 22.6% 13.6%
Mortality 7% 6%
• FDA approval 2010
– “reduction in risk of overt hepatic encephalopathy
recurrence” 550mg PO BD
• Mostly Child-Pugh A/B c...
Current treatment
• Lactulose
– lack of good evidence but used since 70s
• Rifaximin
– More effective at reducing recurren...
Hepatic Encephalopathy
Hepatic Encephalopathy
Hepatic Encephalopathy
Upcoming SlideShare
Loading in …5
×

Hepatic Encephalopathy

3,174 views

Published on

  • ⇒ www.HelpWriting.net ⇐ This service will write as best as they can. So you do not need to waste the time on rewritings.
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here

Hepatic Encephalopathy

  1. 1. Hepatic Encephalopathy Nick Harper
  2. 2. “A neuropsychiatric syndrome caused by hepatic insufficiency due to acute or chronic liver disease” – personality changes – Intellectual impairment – reduced level of consciousness – altered neuromuscular activity
  3. 3. Classification (World congress of gastroenterology 1998) • Type A “Acute liver failure” • Type B “portal systemic Bypass and no intrinsic hepatocellular disease” • Type C “Cirrhosis and portal hypertension” Episodic, persistent, minimal
  4. 4. Epidemiology • Prevalence 1.4 per 100,000 population (UK 2008) • 70% of patients with cirrhosis • 1 year survival 42% • 3 year survival 23%
  5. 5. GABA Osm
  6. 6. Serum ammonia raised in 90% of cases. Not all hyperammonaemia is associated with encephalopathy
  7. 7. EEG • Stage I – III triphasic waves (5Hz) over frontal lobes • Stage IV slow delta wave
  8. 8. PSE index (Conn 1977) • Mental state • Arterial ammonia levels • Degree of asterixis • EEG scoring • Number connection test result •Mental state, EEG and NCT not independent variables •Arbitrary multplicator used for mental state •NCT and EEG are given arbitrary units •No age correction used for NCT
  9. 9. West Haven criteria (Conn score) Grade 1: sleep reversal, mild lack of awareness, shortened attention span Grade 2: lethargy, poor memory, personality change, asterixis Grade 3: Somnolence, confusion, disorientation, hyper-reflexia, nystagmus, clonus, rigidity Grade 4: Stupor and coma
  10. 10. Reduce production and absorption of ammonia in the gut
  11. 11. Non absorbable disaccharides (Lactulose) • Increase bowel transit • Ammonia to ammonium (not absorbed) • GI effects, dehydration, non compliance • Recurrence of hepatic encephalopathy over 14 months (Sharma et al 2009) – Placebo 46.8% – Lactulose 19.6%
  12. 12. Neomycin • Aminoglycoside • Reduce encephalopathy inducing bacterial waste products • Ototoxicity • Nephrotoxicity
  13. 13. Rifaximin • Antibiotic – Rifamycin class • Wide spectrum • Inhibits bacterial DNA dependent RNA polymerase • Very poorly absorbed (<0.4%) • Maintain high concentrations inside the gut
  14. 14. Mas et al 2003 (Journal Hepatology) • Prospective, randomised, double blind, double dummy, controlled trial • Grade I-III HE • n=103 • Rifaximin Vs Lactitol
  15. 15. Ammonia
  16. 16. EEG
  17. 17. PSE score
  18. 18. Bass et al 2012 NEJM • Phase 3 multicentre, randomised, double blind, placebo controlled trial • Rifaximin Vs Placebo • n=299 • 2 episodes of hepatic encephalopathy in last 6 months • Time to first breakthrough of encephalopathy (grade 2 or above) • 6 month follow up
  19. 19. Placebo Rifaximin encephalopathy 46% 22% Hospitilisation 22.6% 13.6% Mortality 7% 6%
  20. 20. • FDA approval 2010 – “reduction in risk of overt hepatic encephalopathy recurrence” 550mg PO BD • Mostly Child-Pugh A/B cirrhosis • Dual therapy – 90% also had lactulose • Not currently approved by MHRA
  21. 21. Current treatment • Lactulose – lack of good evidence but used since 70s • Rifaximin – More effective at reducing recurrence (FDA) – More effective in initial treatment – No change in overall mortality – Not licensed for encephalopathy in UK – £9.20 per day (BNF cost)

×