1. Liver Failure
By Dr.Manoj Sida

2. Liver failure:
Clinical syndrome: sudden loss of liver
parenchymal and metabolic function
Manifest as coagulopathy and
encephalopathy

3. Acute liver failure :
Defined as interval between onset of the illness and appearance of encephalopathy < 8 weeks

4. Etiology:
Western countries: heterogenous, drugs
(acetaminophen, NSAID), viruses
Developing countries: viruses, regional
Difference (endemic area ?)

5. Journal of Gastroenterology and Hepatology(2002)17,
S268–S273

6. Acetaminophen toxicity
Idiosyncratic drug toxicity
Hepatotropic viruses
Miscellaneous causes
Indeterminate acute liver failure (viruses can not be demonstrated ? )

8. Uncommon causes:
Wilson’s disease, other infections (CMV, HSV,
EBV), vascular abnormality, toxin, acute fatty liver
of pregnancy, antoimmune hepatitis, ischemia,
malignant infiltration

9. Symptoms and signs:
Jaundice, altered mental status, nausea/
vomiting, anorexia, fatigue, malaise,
myalgia/arthralgia
Most of them present hepatoencephalopathy
and icteric appearance.

10. Non-specific Management
Hypoglycemia
Encephalopathy
Infections
Hemorrhage
Coagulopathy
Hypotension(hypovolemia, vascular resistance ↓)
Respiratory failure
Renal failure
Pancreatitis

11. Hypoglycemia: monitoring blood glucose, IV glucose supplement.
Infection: aseptic care, high index of suspicion, preemptive antibiotic.
Hemorrhage (i.e. GI): NG placement, H2 blocker or PPI.
Hypotension: hemodynamic monitoring or central pressures, volume repletion

12. Respiratory failure (ARDS): mechanical ventilation.
Renal failure (hypovolemia, hepatorenal syndrome, ATN): hemodynamic monitor, central pressure, volume repletion, avoid nephrotoxic agent

13. Encephalopathy major complication precise mechanism remains unclear
Hypothesis: Ammonia production
Treatment toward reducing ammonia production
Watch out airway, prevent aspiration

14. Encephalopathy Stage 1: day-night reversal, mild confusion, somnolence
Stage 2: confusion, drowsiness
Stage 3: stupor
Stage 4: coma

15. Encephalopathy Predisposing factor of hepatic encephalopathy:
GI bleeding, increased protein intake, hypokalemic
alkalosis, hyponatremia, infection, constipation,
hypoxia, infection, sedatives and tranquilizers

16. Encephalopathy TX upon ammonia hypothesis Correction of hypokalemia
Reduction in ammoniagenic substrates: cleansing enemas and dietary protein restriction.
Lactulose: improved encephalopathy, but not improved outcome.
Dose 2-3 soft stools per day

17. Encephalopathy Oral antibiotics: neomycin  lack of evidence
nephrotoxicity  limited use.

18. Cerebral Edema
Cerebral edema develops in % of patients with grade IV encephalopathy.
precise mechanism : not completely understood
Possible contributing factor:
osmotic derangement in astrocytes
changes in cellular metabolism
alterations in cerebral blood flow

19. Cerebral Edema Clinical manifestations:
↑intracranial pressure (ICP) and brainstem
Herniation  the most common causes of death
in fulminant hepatic failure
ischemic and hypoxic injury to the brain
hypertension, bradycardia, and irregular
respirations, ↑ muscle tone, hyperreflexia

20. Cerebral Edema Monitoring of ICP:
routinely used by more than one-half of liver
transplantation programs in the United States
Tx: to maintain ICP below 20 mmHg and the CPP above 50 mmHg.

21. Coagulopathy
diminished capacity of the failing liver to synthesize coagulation factors.
The most common bleeding site: GI tract.
Prophylactic administration of FFP: not recommended.
 performed before transplant or invasive procedure

22. Specific Treatment ACT intoxication: charcol followed by NAC
Drug induced hepatotoxicity: discontinue drugs
supportive treatment
Viral hepatitis:
HBV: anti-HBV treatment, lamivudine
HSV/varicella zoster: acyclovir
others: supportive care

23. Wilson’s disease: early diagnosis  liver transplant
autoimmune hepatitis: confirm diagnosis (liver biopsy), corticosteroid liver transplant
acute fatty liver of pregnancy or the HELLP syndrome: obstetrical services, and expeditious delivery are recommended

24. Acute ischemic injury (shock liver): cardiovascular support
Malignant infiltration: liver biopsy for diagnosis
treat underlying disease.
Indeterminate etiology: consider biopsy for diagnosis and further guide of treatment 

25. Liver transplant
Liver transplant: remain backbone of treatment of fulminant hepatic failure
reliable criteria to identify these patients who really need transplant.
 remain unresolved in fulminant hepatic failure.

26. At King’s College hospital in London (not due to ACT)
either PT>100 second
or the presence of any three of the following variables:
1. age < 10 or > 40 years ;
2. an etiology of non-A, non-B hepatitis, halothane, drug induced liver failure;
3. duration of jaundice before onset of encephalopathy > 7 days, prothrombin time >50 s, and serum bilirubin > 300 mmol/L.

27. Encephalopathy
Coagulopathy (PT)

28. Liver transplant Criteria: In chronic liver disease
most commonly used prognostic model
MELD score (Model for End-stage Liver
Disease )
3.8[Ln serum bilirubin (mg/dL)] [Ln INR]
+ 9.6[Ln serum creatinine (mg/dL)] + 6.4
Ln: natural logarithm.

29. Liver transplant CONTRAINDICATIONS:
Cardiopulmonary disease can not be corrected, or preclude surgery.
Malignancy outside of the liver within 5 years of evaluation, or can not be cured.
Active alcohol and drug use

30. Advanced age and HIV disease: relative contra-indication (site-specific management)

31. Liver support system
Non-cell-based: plasmapheresis and charcoal-based hemoabsorption
Cell-based systems : known as bioartificial liver support systems

32. Liver support system Non-cell-based: not improved survival.
Available systems:
molecular adsorbents recirculation system (MARS)
Cell-based systems: undergoing trial.