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Liver Failure

Liver Failure. Mackay Memorial Hospital Department of Internal Medicine Division of Gastroenterology R4 陳泓達. 97/6/22. Liver failure: Clinical syndrome: sudden loss of liver parenchymal and metabolic function Manifest as coagulopathy and encephalopathy. Acute liver failure :

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Liver Failure

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  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 ? )

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

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

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

  10. 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

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

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

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

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

  15. 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

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

  17. 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

  18. 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

  19. 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.

  20. 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

  21. 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

  22. 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

  23. 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

  24. 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.

  25. 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.

  26. Encephalopathy • Coagulopathy (PT)

  27. 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.

  28. 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

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

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

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

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