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 : Defined as interval between onset of the illness and appearance of encephalopathy < 8 weeks
Etiology: Western countries: heterogenous, drugs (acetaminophen, NSAID), viruses Developing countries: viruses, regional Difference (endemic area ?)
Journal of Gastroenterology and Hepatology(2002)17, S268–S273
Acetaminophen toxicity • Idiosyncratic drug toxicity • Hepatotropic viruses • Miscellaneous causes • Indeterminate acute liver failure (viruses can not be demonstrated ? )
Uncommon causes: Wilson’s disease, other infections (CMV, HSV, EBV), vascular abnormality, toxin, acute fatty liver of pregnancy, antoimmune hepatitis, ischemia, malignant infiltration
Symptoms and signs: Jaundice, altered mental status, nausea/ vomiting, anorexia, fatigue, malaise, myalgia/arthralgia Most of them present hepatoencephalopathy and icteric appearance.
Non-specific Management Hypoglycemia Encephalopathy Infections Hemorrhage Coagulopathy Hypotension(hypovolemia, vascular resistance ↓) Respiratory failure Renal failure Pancreatitis
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
Respiratory failure (ARDS): mechanical ventilation. • Renal failure (hypovolemia, hepatorenal syndrome, ATN): hemodynamic monitor, central pressure, volume repletion, avoid nephrotoxic agent
Encephalopathy • major complication • precise mechanism remains unclear • Hypothesis: Ammonia production • Treatment toward reducing ammonia production • Watch out airway, prevent aspiration
Encephalopathy • Stage 1: day-night reversal, mild confusion, somnolence • Stage 2: confusion, drowsiness • Stage 3: stupor • Stage 4: coma
Encephalopathy Predisposing factor of hepatic encephalopathy: GI bleeding, increased protein intake, hypokalemic alkalosis, hyponatremia, infection, constipation, hypoxia, infection, sedatives and tranquilizers
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
Encephalopathy • Oral antibiotics: neomycin lack of evidence nephrotoxicity limited use.
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
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
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.
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
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
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
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 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.
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.
Encephalopathy • Coagulopathy (PT)
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.
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
Advanced age and HIV disease: relative contra-indication (site-specific management)
Liver support system • Non-cell-based: plasmapheresis and charcoal-based hemoabsorption • Cell-based systems: known as bioartificial liver support systems
Liver support system • Non-cell-based: not improved survival. Available systems: molecular adsorbents recirculation system (MARS) • Cell-based systems: undergoing trial.
