liver failure mackay memorial hospital department of internal medicine division of gastroenterology...
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Liver FailureLiver Failure
Mackay Memorial Hospital Department of Internal Medicine
Division of GastroenterologyR4 陳泓達
97/6/22
Liver failure:Liver failure:
Clinical syndrome: sudden loss of Clinical syndrome: sudden loss of liver liver
parenchymal and metabolic parenchymal and metabolic functionfunction
Manifest as coagulopathy and Manifest as coagulopathy and
encephalopathyencephalopathy
Acute liver failure :Acute liver failure :
Defined as interval between onset of Defined as interval between onset of the illness and appearance of the illness and appearance of encephalopathy < 8 weeks encephalopathy < 8 weeks
Etiology:Etiology:
Western countries: heterogenous, Western countries: heterogenous, drugs drugs
(acetaminophen, NSAID), viruses(acetaminophen, NSAID), viruses
Developing countries: viruses, Developing countries: viruses, regional regional
Difference (endemic area ?)Difference (endemic area ?)
Acetaminophen toxicityAcetaminophen toxicity Idiosyncratic drug toxicityIdiosyncratic drug toxicity Hepatotropic virusesHepatotropic viruses Miscellaneous causesMiscellaneous causes Indeterminate acute liver failure Indeterminate acute liver failure
(viruses can not be demonstrated ? )(viruses can not be demonstrated ? )
Uncommon causes:Uncommon causes:
Wilson’s disease, other infections Wilson’s disease, other infections (CMV, HSV, (CMV, HSV,
EBV), vascular abnormality, toxin, EBV), vascular abnormality, toxin, acute fatty liver acute fatty liver
of pregnancy, antoimmune hepatitis, of pregnancy, antoimmune hepatitis, ischemia, ischemia,
malignant infiltrationmalignant infiltration
Symptoms and signs:Symptoms and signs:
Jaundice, altered mental status, Jaundice, altered mental status, nausea/ nausea/
vomiting, anorexia, fatigue, malaise,vomiting, anorexia, fatigue, malaise,
myalgia/arthralgiamyalgia/arthralgia
Most of them present Most of them present hepatoencephalopathy hepatoencephalopathy
and icteric appearance. and icteric appearance.
Non-specific Non-specific ManagementManagement
HypoglycemiaHypoglycemiaEncephalopathyEncephalopathyInfectionsInfectionsHemorrhageHemorrhageCoagulopathyCoagulopathyHypotension(hypovolemia, vascular Hypotension(hypovolemia, vascular
resistance ↓)resistance ↓)Respiratory failureRespiratory failureRenal failureRenal failurePancreatitisPancreatitis
Hypoglycemia: monitoring blood Hypoglycemia: monitoring blood glucose, IV glucose supplement.glucose, IV glucose supplement.
Infection: aseptic care, high index of Infection: aseptic care, high index of suspicion, preemptive antibiotic.suspicion, preemptive antibiotic.
Hemorrhage (i.e. GI): NG placement, Hemorrhage (i.e. GI): NG placement, H2 blocker or PPI.H2 blocker or PPI.
Hypotension: hemodynamic Hypotension: hemodynamic monitoring or central pressures, monitoring or central pressures, volume repletion volume repletion
Respiratory failure (ARDS): Respiratory failure (ARDS): mechanical ventilation.mechanical ventilation.
Renal failure (hypovolemia, Renal failure (hypovolemia, hepatorenal syndrome, ATN): hepatorenal syndrome, ATN): hemodynamic monitor, central hemodynamic monitor, central pressure, volume repletion, avoid pressure, volume repletion, avoid nephrotoxic agentnephrotoxic agent
EncephalopathyEncephalopathy
major complication major complication precise mechanism remains unclearprecise mechanism remains unclear Hypothesis: Ammonia productionHypothesis: Ammonia production Treatment toward reducing Treatment toward reducing
ammonia productionammonia production Watch out airway, prevent aspirationWatch out airway, prevent aspiration
EncephalopathyEncephalopathy
Stage 1: day-night reversal, mild Stage 1: day-night reversal, mild confusion, somnolenceconfusion, somnolence
Stage 2: confusion, drowsinessStage 2: confusion, drowsiness Stage 3: stuporStage 3: stupor Stage 4: comaStage 4: coma
EncephalopathyEncephalopathy
Predisposing factorPredisposing factor of hepatic of hepatic encephalopathy:encephalopathy:
GI bleeding, increased protein intake, GI bleeding, increased protein intake, hypokalemic hypokalemic
alkalosis, hyponatremia, infection, alkalosis, hyponatremia, infection, constipation, constipation,
hypoxia, infection, sedatives and hypoxia, infection, sedatives and tranquilizerstranquilizers
EncephalopathyEncephalopathy
TX upon ammonia hypothesisTX upon ammonia hypothesis Correction of hypokalemiaCorrection of hypokalemia Reduction in ammoniagenic Reduction in ammoniagenic
substrates: cleansing enemas and substrates: cleansing enemas and dietary protein restriction.dietary protein restriction.
Lactulose: improved encephalopathy, Lactulose: improved encephalopathy, but not improved outcome. but not improved outcome.
DoseDose 2-3 soft stools per day 2-3 soft stools per day
EncephalopathyEncephalopathy
Oral antibiotics: neomycin Oral antibiotics: neomycin lack of lack of evidenceevidence
nephrotoxicity nephrotoxicity limited use. limited use.
Cerebral EdemaCerebral Edema
Cerebral edema develops in 75 - 80 % Cerebral edema develops in 75 - 80 % of patients with grade IV of patients with grade IV encephalopathy.encephalopathy.
precise mechanism : not completely precise mechanism : not completely understoodunderstood
Possible contributing factor: Possible contributing factor:
osmotic derangement in astrocytesosmotic derangement in astrocytes
changes in cellular metabolismchanges in cellular metabolism
alterations in cerebral blood flow alterations in cerebral blood flow
Cerebral EdemaCerebral Edema
Clinical manifestations::
↑↑intracranial pressure (ICP) and intracranial pressure (ICP) and brainstem brainstem
Herniation Herniation the most common causes the most common causes of death of death
in fulminant hepatic failurein fulminant hepatic failure
ischemic and hypoxic injury to the brainischemic and hypoxic injury to the brain
hypertension, bradycardia, and irregularhypertension, bradycardia, and irregular
respirations, ↑ muscle tone, hyperreflexia respirations, ↑ muscle tone, hyperreflexia
Cerebral EdemaCerebral Edema
Monitoring of ICP:Monitoring of ICP:
routinely used by more than one-half routinely used by more than one-half of liver of liver
transplantation programs in the transplantation programs in the United States United States
Tx: to maintain ICP below 20 mmHg Tx: to maintain ICP below 20 mmHg and the CPP above 50 mmHg. and the CPP above 50 mmHg.
CoagulopathyCoagulopathy
diminished capacity of the failing liver diminished capacity of the failing liver to synthesize coagulation factors.to synthesize coagulation factors.
The most common bleeding site: GI The most common bleeding site: GI tract.tract.
Prophylactic administration of FFP: Prophylactic administration of FFP: not recommended.not recommended.
performed before transplant or performed before transplant or invasive procedureinvasive procedure
Specific TreatmentSpecific 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
Wilson’s disease: early diagnosis Wilson’s disease: early diagnosis liver transplantliver transplant
autoimmune hepatitis: confirm autoimmune hepatitis: confirm diagnosis (liver biopsy), diagnosis (liver biopsy), corticosteroid corticosteroid liver transplantliver transplant
acute fatty liver of pregnancy or the acute fatty liver of pregnancy or the HELLP syndrome: obstetrical HELLP syndrome: obstetrical services, and expeditious delivery services, and expeditious delivery are recommendedare recommended
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
Liver transplantLiver transplant
Liver transplant: remain backbone of Liver transplant: remain backbone of treatment of fulminant hepatic treatment of fulminant hepatic failurefailure
reliable criteria to identify these reliable criteria to identify these patients who really need transplant.patients who really need transplant.
remain unresolved in fulminant remain unresolved in fulminant hepatic failure.hepatic failure.
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.
Liver transplantLiver transplant Criteria: Criteria: In chronic liver diseaseIn chronic liver diseasemost commonly used prognostic model most commonly used prognostic model MELD score (MELD score (Model for End-stage LiverModel for End-stage LiverDiseaseDisease ) )3.8[Ln serum bilirubin (mg/dL)] + 11.2[Ln 3.8[Ln serum bilirubin (mg/dL)] + 11.2[Ln
INR] INR] + 9.6[Ln serum creatinine (mg/dL)] + 6.4+ 9.6[Ln serum creatinine (mg/dL)] + 6.4 Ln: natural logarithm.Ln: natural logarithm.
Liver transplantLiver transplant
CONTRAINDICATIONSCONTRAINDICATIONS: :
1.1. Cardiopulmonary disease can not Cardiopulmonary disease can not be corrected, or preclude surgery.be corrected, or preclude surgery.
2.2. Malignancy outside of the liver Malignancy outside of the liver within 5 years of evaluation, or can within 5 years of evaluation, or can not be cured.not be cured.
3.3. Active alcohol and drug use Active alcohol and drug use
Advanced age and HIV disease: Advanced age and HIV disease: relative contra-indication (site-relative contra-indication (site-specific management)specific management)
Liver support systemLiver support system
Non-cell-based: plasmapheresis and Non-cell-based: plasmapheresis and charcoal-based hemoabsorption charcoal-based hemoabsorption
Cell-based systems : known as Cell-based systems : known as bioartificial liver support systems bioartificial liver support systems
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