This document summarizes liver failure, including its etiology, symptoms, management, and treatment options. Acute liver failure is defined as the development of encephalopathy within 8 weeks of illness onset and can be caused by drugs, viruses, and other factors. Management involves treating complications like encephalopathy, coagulopathy, and cerebral edema. Liver transplantation remains the primary treatment for fulminant hepatic failure when criteria like prolonged prothrombin time or age are met. Liver support systems are also discussed as potential therapies.

1. Liver Failure
Mackay Memorial Hospital
Department of Internal Medicine
Division of Gastroenterology
R4 陳泓達
97/6/22

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 75 - 80 % 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)] + 11.2[Ln INR]
+ 9.6[Ln serum creatinine (mg/dL)] + 6.4
Ln: natural logarithm.

29. Liver transplant
 CONTRAINDICATIONS:
1. Cardiopulmonary disease can not be corrected,
or preclude surgery.
2. Malignancy outside of the liver within 5 years
of evaluation, or can not be cured.
3. 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.