1. Acute (fulminant) hepatic failure
It is a rare syndrome in which hepatic encephalopathy results from a sudden severe impairment of hepatic function.
It must occur within 8 weeks of onset of the precipitating illness
In the absence of evidence of pre-existing liver disease

3. Clinical grading of hepatic encephalopathy
Hepatic encephalopathy is the cardinal manifestation of acute hepatic failure.
Clinical grading of hepatic encephalopathy
Clinical grade
Clinical signs
Grade 1
Poor concentration, slurred speech, slow mentation, disordered sleep rhythm
Grade 2
Drowsy but easily rousable, occasional aggressive behavior, lethargic
Grade 3
Marked confusion, drowsy, sleepy but responds to pain & voice, gross disorientation
Grade 4
Unresponsive to voice, may or may not respond to painful stimuli, unconscious

4. Fulminant hepatic failure
Hepatic encephalopathy include the following:
Reduced alertness & poor concentration
Behavioral abnormalities e.g. restlessness, aggressive outbursts & mania
Confusion
Disorientation
Inversion of sleep rhythm
Slurred speech
Yawning
Hiccup
Convulsions

5. Fulminant hepatic failure
Flapping tremor (asterixis) is characteristic for cases of acute hepatic failure but may be absent.
Cerebral edema:
Produce increased intracranial pressure
This results in:
Unequal or abnormally reacting pupils
Fixed pupils
Hypertensive episodes
Bradycardia
Hyperventilation
Profuse sweating
Local or general myoclonus
Focal fits
Decerebrate posturing
Papiledema
Right hypochondrial pain (occasionally)

6. Fulminant hepatic failure
Examination can reveal:
Jaundice
Fetor hepaticus
Initially the liver is enlarged (later may become impalpable)
Splenomegaly (uncommon)
Ascites & edema (late features)

7. Fulminant hepatic failure
Investigations to determine the cause of acute hepatic failure:
Toxicology screen of blood & urine
IgM anti-HBc
IgM anti-HAV.
Anti-HEV, HCV, CMV, herpes simplex, EBV
Ceruloplasmin, serum copper, urinary copper
Autoantibodies: ANF, AMA, ASMA, LKM.
Ultrasound of liver & Doppler of hepatic veins

8. Adverse prognostic criteria in acute hepatic failure
Paracetamol overdose:
pH < 7.3 at or beyond 24 hours following the overdose OR
Serum creatinine >300 μmol/l, prothrombin time >100 seconds and encephalopathy grade 3 or 4
Non-paracetamol cases:
Prothrombin time >100 seconds
Any THREE of the following:
Jaundice to encephalopathy time > 7 days
Age < 10 yrs or > 40 yrs
Indeterminate or drug-induced causes
Bilirubin > 300 μmol/l
Prothrombin time > 50 seconds
These adverse prognosis criteria predict a mortality rate of ≥ 90%

9. Observations in fulminant hepatic failure
Neurological:
Conscious level
Pupils
Size
Equality
Reactivity
Fundi: Papiledema
Plantar responses
Cardiorespiratory:
Pulse
Blood pressure
Central venous pressure
Respiratory rate
Fluid balance:
Input:
Oral
Intravenous
Output:
Hourly urine output
24 hours sodium output
Vomiting
Diarrhea

10. Observations in fulminant hepatic failure
Blood analysis:
Arterial blood gases
Peripheral blood count (including platelets)
Creatinine, urea
Na, K, HCO3, Ca, Mg
Glucose (2-hourly in acute phase).
Prothrombin time
Infection surveillance:
Cultures:
Blood
Urine
Throat
Sputum
Canula sites
Chest radiograph
Temperature

11. Complications of acute hepatic failure
Encephalopathy
Cerebral edema
Respiratory failure
Hypotension
Hypothermia
Infection
Bleeding
Pancreatitis
Renal failure
Metabolic:
Hypoglycemia
Hypokalemia
Hypocalcemia
Hypomagnesemia
Acid-base disturbance

12. Management Conservative treatment Intensive care unit
Role of N-acetylecystein therapy
Liver transplantation

13. Chronic liver failure
Chronic liver failure is a syndrome complex that can occur as a consequence of insidious destruction of the hepatocytes.
It is more commonly precipitated by a number of events such as variceal hemorrhage or infection.
Liver cirrhosis results from progressive and widespread death of liver cells associated with inflammation and fibrosis.

14. Causes of cirrhosis Any cause of chronic hepatitis Alcohol
Primary biliary cirrhosis
Primary sclerosing cholangitis
Secondary biliary cirrhosis (stones, strictures)
Hemochromatosis
Wilson’s disease
α-1 antitrypsin deficiency
Cystic fibrosis

15. Pathophysiology Recurrent or persistent hepatocyte death:
Viral hepatitis
Alcohol
Prolonged biliary damage or obstruction:
Primary biliary cirrhosis
Sclerosing cholangitis
Post-surgical biliary stricture
Stone
Persistent blockage to the venous return:
Veno-occlusive disease
Budd Chiari syndrome

16. World wide the most common causes of cirrhosis are:
Viral hepatitis
Prolonged, excessive alcohol consumption

17. Clinical features of hepatic cirrhosis
Hepatomegaly (although the liver may be small)
Jaundice
Ascites
Circulatory changes:
Spider telangiectasia
Palmar erythema
Cyanosis
Endocrine changes:
Loss of libido
Loss of hair
Men: gynecomastia, testicular atrophy, impotence
Women: breast atrophy, irregular menses, amenorrhea
Hemorhagic tendency:
Bruises, purpura, epistaxis, menprrhagia
Portal hypertension:
Splenomegaly
Collateral vessels
Variceal bleeding
Fetor hepaticus
Hepatic (portasystemic) encephalopathy
Other features:
Pigmentation
Digital clubbing
Low grade fever

18. Stigmata of chronic liver disease

19. Gynecomastia in male patient with liver cirrhosis

20. Ascites with dilated blood vessels

21. Ascites with everted umbilicus

22. Spontaneous bruises in patient with cirrohsis

23. Hepato-splenomegaly

24. Spider naevi (telangeicatasia) in patient with alcoholic cirrhosis

25. Spider nevi Spider nevi
Notice fading of peripheral capillaries after pressing the central arteriole
Spider nevi

26. Palmar erythema

27. Duputyrine contracture

28. Management This includes:
Treatment of any cause
The maintenance of nutrition
Treatment of the complications of liver cirrhosis.
Chronic liver failure due to liver cirrhosis can also be treated by orthotopic liver transplantation.

29. Indications for orthoptopic liver transplantation
Cholestatic form of cirrhosis especially that is due to primary biliary cirrhosis
Alcoholic cirrhosis (the patient must has capacity for abstinence)
Cirrhosis due to hepatitis C virus
Rarer indications include:
α -1 antitrypsin deficiency
Hemachromatosis

30. Signs of liver failure pointing to transplantation
Sustained or increased jaundice
Bilirubin > 100 mmol/l in cholestatic diseases like primary biliary cirrhosis
Ascites or hepatic encephalopathy not responding readily to medical therapy
Hypoalbuminemia
Albumin < 30g/l
Additional indications:
Fatigue & lethargy affecting the quality of life.
Intractable itching in cholestatic disease
Recurrent variceal bleeding

31. Main contraindications for liver transplantation
Sepsis
AIDS
Extrahepatic malignancy
Active alcohol or other substance misuse
Marked cardiorespiratory dysfunction
Survival at 1 year after transplantation is about 80% and the prognosis thereafter is good