Liver Failure By Dr.Manoj Sida

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.