Hepatic Failure
Hepatic Failure: Excerpt from The 5-Minute Pediatric Consult
Charles Vanderpool, MDLynette A. Gillis, MD
Hepatic Failure - BASICS
Hepatic Failure - description
- Due to the difficulty in assessing for hepatic encephalopathy in younger children, a set of criteria has been proposed to diagnose acute liver failure in the pediatric population:
- Biochemical evidence of liver injury
- No previous history of chronic liver disease
- Coagulopathy not responsive to vitamin K administration
- International normalized ratio (INR) >1.5 in the presence of encephalopathy or INR >2 without encephalopathy
- In older children and adolescents where hepatic encephalopathy can be more easily assessed, acute liver failure may more simply be defined as:
- Onset of encephalopathy <8 weeks after the onset of symptoms referable to liver dysfunction (jaundice, etc.) in a patient without pre-existing liver disease of any form
Hepatic Failure - epidemiology
Prevalence of specific causes is often dependent on age and geographic region:
- In infants and children <3 years of age, indeterminate and metabolic abnormalities predominate.
- In older children and adolescents, drug-induced toxicity, especially acetaminophen, takes a more predominant role in causing acute liver failure.
- Infectious etiologies, especially hepatitis virus, vary in prevalence based on geographic region.
Hepatic Failure - pathophysiology
- Exposure to an agent that causes severe hepatocellular necrosis leads to impairment of the liver’s metabolic function. The exact mechanism of hepatocyte necrosis is often not known
- Cell necrosis leads to release of growth factors that promote hepatocyte regeneration. Hepatic failure may become terminal or permanent if the initial insult is so severe that it overcomes the liver’s regenerative capabilities, if the offending agent or derangement is not eliminated or corrected, or if secondary complications such as shock or disseminated intravascular coagulation (DIC) lead to further injury
Hepatic Failure - etiology
The major causes of acute liver failure can be grouped into the following broad categories:
- Indeterminate: Often the majority of cases
- Acetaminophen toxicity
- Nonacetaminophen drug toxicity
- Infectious
- Metabolic
- Autoimmune
- Ischemic/shock
- Vascular
Hepatic Failure - DIAGNOSIS
Hepatic Failure - signs & symptoms
Hepatic Failure - history
- Age: Helps to determine likely etiologic sub-group
- Toxin exposure
- Prodrome, especially with viral causes
- Travel history, exposure history
- Length of symptoms, acuity of onset
- Associated symptoms/ROS:
- Encephalopathy: Inconsolable crying, inattention progressing to somnolence, stupor, and eventually unresponsiveness, coma
- Bleeding, especially GI bleeding
- Weakness, fatigue
- Abdominal pain, diarrhea
- Rapid breathing secondary to acidosis
- Pruritus secondary to hyperbilirubinemia
Hepatic Failure - physical exam
- Skin: Jaundice, viral exanthem
- Eyes: Scleral icterus
- Abdominal: Hepatomegaly, ascites with dullness to percussion or fluid wave, splenomegaly
- Neurologic:
- Sequential exams are paramount to monitor for change, and should include age-appropriate mini-mental status exam.
- Questions may focus on memory, such as age or name of school teacher, tests of memorization, or simple math questions
- Assess for presence of encephalopathy, which is divided into grades based on severity:
- Grade I: Confused, altered sleep habits; reflexes normal; may have tremor or apraxia
- Grade II: Drowsy, inappropriate behavior; hyperreflexic or asterixis; dysarthria or ataxia often present
- Grade III: Stuporous but may obey simple com- mands, sleepy; hyperreflexic, Babinski positive, asterixis present; increased generalized tone
- Grade IV: Comatose, may or may not be arousable by painful stimuli; reflexes absent; often has decerebate or decorticate posturing
Hepatic Failure - tests
- Hepatocellular injury: Aminotransferases (AST, ALT) often are markedly elevated but depends on mechanism and time frame of injury
- Biliary obstruction: Elevated alkaline phosphatase, GGT (gamma glutamyl transpeptidase), total/direct bilirubin, serum or urine bile acids
- Hepatocyte synthetic function: Prolonged PT/INR, depressed factor V, VII, IX, X levels, hypoalbuminemia, hypoglycemia, depressed fibrinogen levels
- Encephalopathy: Ammonia level (has not been proven to correlate directly to presence or grade of encephalopathy)
- Tests to determine etiology:
- Toxin: Urine or serum drug screen, serum acetaminophen and aspirin level
- Infectious: Hepatitis virus serologic tests; EBV, CMV, HSV PCR or antibody tests; comprehensive viral cultures; parvovirus BMetabolic/Miscellaneous:
- Autoimmune hepatitis: Anti-LKM, anti smooth muscle, antinuclear antibodies
- Wilson disease: Decreased serum ceruloplasm (may not be reliable in setting of acute liver failure), increased serum or urinary copper, evidence of hemolysis (secondary to oxidative stress from serum copper)
- Hemochromatosis: Elevated ferritin or transferrin saturation
- Liver biopsy: Dependent on clinical stability, platelet level, presence of coagulopathy
Hepatic Failure - imaging
- Abdominal ultrasound with Doppler: Used to determine the direction of portal flow/portal hypertension, filling defects in vasculature that may indicate thrombosis
- Abdomen/Pelvic CT with or without contrast depending on renal function
- Head CT scan without IV contrast in presence of encephalopathy or neurologic signs to rule out intracranial hemorrhage
Hepatic Failure - differencial diagnosis
- The differential diagnosis of acute liver failure is extensive. It is important to note that many studies have found the cause to be indeterminate in 50% or more of cases.
- The differential diagnosis is best categorized under various sub-groups:
- Drug induced/Toxin:
- Acetaminophen: Most common, especially in older children and adolescents
- Salicylates
- Iron compounds
- Anti-convulsants
- Isoniazid
- Ethanol
- Antineoplastic agents: Methotrexate, 6MP
- Ketoconazole
- Allopurinol
- Antibiotics: Erythromycin, tetracycline
- Amanita species (mushrooms)
- Metabolic/Miscellaneous:
- Early infancy
- Galactosemia
- Tyrosinemia
- Neonatal hemochromatosis
- Storage diseases
- Hereditary fructose intolerance
- Fatty acid oxidation disorders
- Mitochondrial disorders
- Childhood/Adolescence:
- Autoimmune hepatitis
- Wilson disease
- Pregnancy (acute fatty liver of pregnancy, HELLP syndrome)
- Reye syndrome: Associated with influenza, varicella with or without salicylate exposure
- Infectious:
- Hepatitis virus: A, B, E; less commonly C
- Herpes virus: HSV, EBV, CMV, VZV, HHV6
- Can be more common in neonates or immunocompromised:
- Echovirus, especially in neonates
- Parvovirus
- Adenovirus
- Vascular/Ischemic:
- CHF
- Shock
- Budd Chiari: Hepatic venous outflow obstruction syndrome
- Veno-occulsive disease: Nonthrombotic occlusion of hepatic venule, most common after stem cell transplantation
- Heat stroke/Hyperthermia
- Rhabdomyolysis
- Malignancy:
- Primary: Hepatoblastoma, hepatocellular carcinoma
- Leukemia, lymphoma
- HLH: Hemophagocytic lymphohistiocytosis
Hepatic Failure - TREATMENT
Hepatic Failure - initial stabilization
- Initial evaluation should include assessment of neurologic status:
- Elective intubation should be considered in grades III or IV encephalopathy with somnolence.
- Hemodynamic status should quickly be determined by vital signs and examination:
- Aggressive initial fluid resuscitation should be avoided unless evidence of severe hemodynamic compromise.
Hepatic Failure - general measures
- Patients with acute liver failure should be closely monitored, preferably in an ICU setting at a tertiary care center with a liver transplantation program.
- Therapy should be directed at the underlying cause if a cause can be determined. Specific supportive care for the patient with liver failure is as follows:
- Fluid/Electrolytes:
- Fluid restriction: Total fluids should remain at or just below maintenance requirements—this must include all drips, medications, blood product infusions
- Sodium restriction: Patient typically should not receive >0.25 NS as maintenance fluids. Hyponatremia should not be corrected with hypertonic saline as this can worsen fluid overload and encephalopathy.
Hepatic Failure - medication
- Medications should be mixed in fluids without sodium, such as D
- Hypoglycemia: Often requires a high dextrose infusion rate of 10–20% or more
- Diuresis: Potassium-sparing diuretics, such as spironolactone, are useful in cases of volume overload or ascites. Use of loop diuretics is controversial and should be used sparingly due to possible intravascular depletion.
GI:- Maintain aggressive acid suppression with an H
- Hematologic:
- Hemoglobin levels should be corrected to a goal minimum of 10–12 g/dL to ensure adequate tissue perfusion.
- Coagulopathy: Coagulopathy should be corrected conservatively in the absence of active bleeding.
- Vitamin K should be administered IV for prolonged INR.
- FFP and cryoprecipitate should be reserved for acute severe bleeding, as their administration subsequently eliminates the ability to monitor response of PT and factor levels as prognostic indicators.
- Recombinant factor VIIa can also be used in cases of acute severe bleeding, or when there are concerns of fluid overload:
- Infectious disease:
- Minimize invasive catheterization when possible due to risk of infection.
- Monitor closely for fever and consider prophylactic antibiotics if febrile, especially in the setting of central venous access catheters.
- Renal:
- Nephrotoxic drugs should be avoided when possible.
- Renal dose medications when renal compromise is evident.
- Neurologic/Hepatic encephalopathy:
- Sedatives, especially benzodiazepines, should be avoided in grade I or II encephalopathy as they may make neurologic deficits worse.
- In grades III or IV encephalopathy, efforts to minimize increased intracranial pressure should include head elevation, mannitol, or barbiturates.
- Intracranial pressure monitoring should be instituted, especially in those progressing to need for liver transplantation:
- Other:
- Experimental therapies whose relative benefit has not been determined include antioxidant therapy, prostaglandin E, and plasmapheresis
- N-acetylcysteine is the cornerstone of treatment for acetaminophen-induced hepatic toxicity, but is also being investigated as a treatment for nonacetaminophen-induced acute liver failure due to its ability to scavenge free radicals, replenish glutathione, and act as a vasodilator to improve splanchnic blood flow
Hepatic Failure - surgery
Liver transplantation:
- Those likely to require liver transplantation include: Children with acute liver failure secondary to indeterminate cause, idiosyncratic drug reaction (such as to anticonvulsants), or Wilson disease
- Those likely to have spontaneous recovery include: Children with acute liver failure secondary to autoimmune hepatitis, acetaminophen toxicity without severe acidosis, or ischemic shock
- 5-year graft survival in pediatric patients with acute liver failure has improved to 60–70% at most centers.
Hepatic Failure - FOLLOW UP
Hepatic Failure - prognosis
- King’s College Criteria has been used to predict outcome for patients with acetaminophen-induced acute liver failure. Factors predicting a poor outcome include:
- pH <7.3 regardless of grade of encephalopathy OR
- All of: PT >100 sec (INR >6.5), serum creatinine >3.4 g/dL, stage III or IV encephalopathy
- In patients with nonacetaminophen-induced acute liver failure, there is no consensus regarding a prognostic set of criteria. Factors that have been associated with a poor prognosis include:
- Factor V levels <10%
- PT >50 sec (INR >3.5), especially when not responsive to vitamin K
- Grade III or grade IV encephalopathy
- Duration of jaundice to encephalopathy >7 days
- Ratio of total to direct bilirubin of >2
Hepatic Failure - complications
- Complications are a direct consequence of loss of hepatic metabolic function:
- Encephalopathy: Due to an inability to eliminate neurotoxins (such as ammonia) or depressants (such as benzodiazepines)
- Cerebral edema: Incompletely understood, but may be secondary to increased blood brain barrier permeability (from endotoxins or inflammatory response), hyperammonemia causing increase glutamine levels in astrocytes, or iatrogenic causes with fluid resuscitation
- Coagulopathy: Failure of the hepatic synthesis of clotting and fibrinolytic factors
- Hypoglycemia: Secondary to impaired hepatic glucose synthesis and release, as well as decreased hepatic degradation of insulin
- Acidosis: Failure of the liver to eliminate lactic acid or free fatty acids
- In cases of hepatic encephalopathy, remember to consider other etiologies of neurologic change: Hypoglycemia, intracranial hemorrhage, and acute infection or sepsis
- One must have a high index of suspicion for encephalopathy, as it is often difficult to detect on a clinical basis in young children:
- There is often rapid progression through the stages of encephalopathy.
- Increased intracranial pressure can develop quickly and can lead to irreversible neurologic sequelae.
Hepatic Failure - bibliography
- Bucuvalas J, Yazigin N, Squeres RH, et al. Acute liver failure in children. Clin Liver Dis. 2006;10:149–168.
- Futagawa Y, Terasaki PI. An analysis of the OPTN/UNOS liver transplant registry. Clin Transpl. 2004:315–329.
Kay M, McDiarmid S. Liver failure and transplantation. Wyllie/Hyams Pediatric Gastrointestinal Disease, 2nd ed. WB Saunders Co, 1999.- Miyake Y, Sakaguchi K, Iwasaki Y, et al. New prognostic scoring model for liver transplantation in patients with non-acetaminophen-related fulminant hepatic failure. Transplantation. 2005;80:930–936.
- Sklar, GE, Subramaniam M. Acetylcysteine treatment for non-acetaminophen-induced acute liver failure. Ann Pharmacother. 2004;38:498–501.
- Squires RH, Shneider BL, Bucmvalas J, et al. Acute liver failure in children: The first 348 patients in the pediatric acute liver failure study group. J Pediatr. 2006;148:652–658.
Hepatic Failure - CODES
Hepatic Failure - icd9
572.2 Hepatic encephalopathy
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Book Source Details
- Book Title: The 5-Minute Pediatric Consult
- Author(s): M. William Schwartz MD; et al.
- Year of Publication: 2008
- Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.
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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.
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More About This Book:
Title: The 5-Minute Pediatric Consult
Authors: M. William Schwartz MD; et al.
Publisher: Lippincott Williams & Wilkins
Copyright: 2008
ISBN: 0-7817-7577-9
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