Acute hepatic failure: Difference between revisions
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*Subacute liver failure: interval of 5-12 weeks from the onset of jaundice to the onset of encephalopathy; this subset has a lower incidence of cerebral edema, but a poor prognosis | *Subacute liver failure: interval of 5-12 weeks from the onset of jaundice to the onset of encephalopathy; this subset has a lower incidence of cerebral edema, but a poor prognosis | ||
==Causes== | ===Causes=== | ||
===[[Acetaminophen Toxicity]]=== | ====[[Acetaminophen Toxicity]]==== | ||
*Now the most common cause of acute liver failure in the US<ref>Ostapowicz G, Fontana RJ, Schiodt FV, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med. 2002 Dec 17; 137(12): 947-54.</ref> | *Now the most common cause of acute liver failure in the US<ref>Ostapowicz G, Fontana RJ, Schiodt FV, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med. 2002 Dec 17; 137(12): 947-54.</ref> | ||
*Small amount of [[acetaminophen]] is metabolized by Cytochrome[[P450]] into NAPQI, which is a toxic metabolite | *Small amount of [[acetaminophen]] is metabolized by Cytochrome[[P450]] into NAPQI, which is a toxic metabolite | ||
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*See [[Acetaminophen toxicity]] | *See [[Acetaminophen toxicity]] | ||
===[[Viral Hepatitis]]=== | ====[[Viral Hepatitis]]==== | ||
*Hepatocellular pattern of injury, where AST and ALT are higher than Tbili and Alk Phos; likely to have significantly elevated ALT and AST (20x normal or higher) | *Hepatocellular pattern of injury, where AST and ALT are higher than Tbili and Alk Phos; likely to have significantly elevated ALT and AST (20x normal or higher) | ||
*Of note, transmission of [[Hepatitis B]] and [[Hepatitis C]] through donated blood, blood products, and organs is rare in the US since blood screening became available in 1992 | *Of note, transmission of [[Hepatitis B]] and [[Hepatitis C]] through donated blood, blood products, and organs is rare in the US since blood screening became available in 1992 | ||
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**Usually results in mild illness, but can cause fulminant hepatitis in pregnant women<ref>Rein DB, Stevens GA, Theaker J, Wittenborn JS, Wiersma ST. The Global Burden of Hepatitis E Virus Genotypes 1 and 2 in 2005. Hepatology, Vol. 55, No. 4, 2012: 988-997</ref> | **Usually results in mild illness, but can cause fulminant hepatitis in pregnant women<ref>Rein DB, Stevens GA, Theaker J, Wittenborn JS, Wiersma ST. The Global Burden of Hepatitis E Virus Genotypes 1 and 2 in 2005. Hepatology, Vol. 55, No. 4, 2012: 988-997</ref> | ||
===Alcohol-related Liver Disease and [[Alcoholic hepatitis]]=== | ====Alcohol-related Liver Disease and [[Alcoholic hepatitis]]==== | ||
*Presentation can range from mild abdominal pain, nausea and vomiting to acute liver failure | *Presentation can range from mild abdominal pain, nausea and vomiting to acute liver failure | ||
*May have large palpable liver from fatty infiltration, or may have small nonpalpable liver secondary to cirrhosis from chronic disease | *May have large palpable liver from fatty infiltration, or may have small nonpalpable liver secondary to cirrhosis from chronic disease | ||
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**AST:ALT ration >2 is typical | **AST:ALT ration >2 is typical | ||
*May also have electrolyte abnormalities from malnutrition or [[alcoholic ketoacidosis]] | *May also have electrolyte abnormalities from malnutrition or [[alcoholic ketoacidosis]] | ||
===Drug or Toxin Related Liver Disease=== | |||
====Drug or Toxin Related Liver Disease==== | |||
*Liver damage from drugs or toxins may be cytotoxic from the primary drug or its metabolites, or may be caused by veno-occlusive disease or hypersensitivity disease<ref>Oyama, LC: Disorders of the Liver and Biliary Tractin Marx JA, Hockberger RS, Walls RM, et al (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, ed 8. St. Louis, Mosby, Inc., 2014, (Ch) 107: p 1186-1204</ref> | *Liver damage from drugs or toxins may be cytotoxic from the primary drug or its metabolites, or may be caused by veno-occlusive disease or hypersensitivity disease<ref>Oyama, LC: Disorders of the Liver and Biliary Tractin Marx JA, Hockberger RS, Walls RM, et al (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, ed 8. St. Louis, Mosby, Inc., 2014, (Ch) 107: p 1186-1204</ref> | ||
*Common Drugs and Toxins | *Common Drugs and Toxins |
Revision as of 17:59, 4 June 2020
Background
Definitions[1]
- Hyperacute liver failure: encephalopathy occurs within 7 days of the onset of jaundice; this subset is likely to survive with medical management despite the high incidence of cerebral edema
- Acute liver failure: interval of 8-28 days from jaundice to encephalopathy; this subset has a high incidence of cerebral edema and a poorer prognosis without liver transplant
- Subacute liver failure: interval of 5-12 weeks from the onset of jaundice to the onset of encephalopathy; this subset has a lower incidence of cerebral edema, but a poor prognosis
Causes
Acetaminophen Toxicity
- Now the most common cause of acute liver failure in the US[2]
- Small amount of acetaminophen is metabolized by CytochromeP450 into NAPQI, which is a toxic metabolite
- In therapeutic doses, NAPQI combines rapidly with glutathione to form nontoxic metabolites that are excreted in the urine
- In overdose, glutathione stores are used up and NAPQI binds to cell proteins in the liver which leads to cell death
- See Acetaminophen toxicity
Viral Hepatitis
- Hepatocellular pattern of injury, where AST and ALT are higher than Tbili and Alk Phos; likely to have significantly elevated ALT and AST (20x normal or higher)
- Of note, transmission of Hepatitis B and Hepatitis C through donated blood, blood products, and organs is rare in the US since blood screening became available in 1992
- Hepatitis A
- Fecal-oral transmission
- Associated with epidemics linked to a common source (water)
- Most common risk factor is travel outside of the US [3]
- Not associated with chronic carrier state; incubation period is approximately 30 days, and infectivity usually resolved prior to symptom onset
- Hepatitis B
- Transmitted parenterally, blood contact, and unprotected sex
- 90% of exposed infants progress to chronic hepatitis; 10% of exposed adults progress to chronic hepatitis
- Serology[4]
Clinical Scenario | HBsAg | anti-HBc | anti-HBs |
Susceptible to infection | negative | negative | negative |
Immune due to natural infection | negative | positive | positive |
Immune due to Hep B infection | negative | negative | positive |
Acutely infected | positive | anti-HBc- positive; IgM anti-HBc- positive | negative |
Chronically infected | positive | anti-HBc- positive; IgM anti-HBc- negative | negative |
- Hepatitis C
- Blood-borne, in US, most commonly transmitted through IV drug use. Infrequently transmitted through sexual contact
- 90% of HCV infections progress to chronic hepatitis[5]
- Hepatitis D
- Transmission similar to Hepatitis B
- Can only co-infect patients with Hepatitis B (actively producing HBsAg)
- Presentation can range from acute self-limited disease to fulminant hepatitis or chronic infection
- Hepatitis E
- Fecal-oral transmission
- Usually results in mild illness, but can cause fulminant hepatitis in pregnant women[6]
- Presentation can range from mild abdominal pain, nausea and vomiting to acute liver failure
- May have large palpable liver from fatty infiltration, or may have small nonpalpable liver secondary to cirrhosis from chronic disease
- Will have moderate elevations in AST and ALT (levels >10x normal are unusual)
- AST:ALT ration >2 is typical
- May also have electrolyte abnormalities from malnutrition or alcoholic ketoacidosis
Drug or Toxin Related Liver Disease
- Liver damage from drugs or toxins may be cytotoxic from the primary drug or its metabolites, or may be caused by veno-occlusive disease or hypersensitivity disease[7]
- Common Drugs and Toxins
- Acetaminophen
- Amiodarone
- Amphotericin
- Anabolic steroids
- Azathioprine
- Carbamazepine
- Chlorpromazine
- Cisplatin
- Contraceptives
- Cyclophosphamide
- Erythromycin
- Gold salts
- Haloperidol
- Isoniazid
- Ketoconazole
- Lovastatin
- Methotrexate
- Methoxyflurane
- Methyldopa
- Phenobarbital
- Phenytoin
- Quinidine
- Salicylates
- Tetracycline
- Valproic acid
- Verapamil
Other Rare Causes of Acute Liver Failure
- Wilson's disease: unexplained elevations in LFTs, neuro-psychiatric symptoms, Kayser-Fleischer rings on eye exam
- Autoimmune hepatitis: more common in women, liver disease without explanation, may have family history of other autoimmune disorders
- Hemochromatosis: family history of liver disease and cardiac disease
- Budd-Chiari: history of hypercoagulable disorder, abdominal pain, and ascites
- Infections: HSV, Epstein-Barr virus, varicella zoster virus, toxoplasmosis
Clinical Features
- Common findings in acute liver failure
- Tender hepatomegaly
- Jaundice
- Hepatic encephalopathy
- Asterixis
- Common findings in chronic liver failure
- Ascites
- Caput medusae
- Palmar erythema
- Spider angiomata
- Gynecomastia
- Testicular atrophy
- Parotid gland enlargement
- Muscular atrophy
- May also have jaundice, encephalopathy, and asterixis as in acute liver failure
Differential Diagnosis
Encephalopathy (altered mental status)
- Hypoglycemia
- Hypoxia
- Intracerebral hemorrhage or mass
- Meningitis/encephalitis
- CVA
- Alcohol intoxication
- Myxedema coma
- Wernicke encephalopathy
- Sepsis
- Seizure/post-ictal state
- Uremia
- Electrolyte abnormality
- Acute hepatic failure
Jaundice
- Hepatitis
- Hemolysis
- Biliary disease (e.g. CBD obstruction)
- Pregnancy
- Congenital diseases (e.g. inborn errors of metabolism; (more likely to present in early childhood)
Evaluation
Labs
- LFTs
- AST and ALT
- Enzymes found mainly in hepatic cells, though ALT is more specific to the liver than AST
- Extreme elevation in AST (>3000U/L, or >40x upper limit of normal) is consistent with acetaminophen toxicity or ischemic injury
- Moderate elevations (10-40x upper limit of normal) is consistent with viral hepatitis
- Mild elevations (<10x upper limit of normal) is consistent with alcoholic hepatitis
- Alkaline Phosphatase
- Found in bile canaliculi (but also in placenta, ileal mucosa, bone, and kidney)
- Elevated in diseases of cholestasis
- Rare for levels to be >3x normal limit in acute liver failure
- Bilirubin
- Elevated in diseases of cholestasis
- In obstructive diseases, the direct bilirubin will usually be about 50% of the total bilirubin; if indirect bilirubin is higher, more suggestive of hemolysis or problem with conjugation
- AST and ALT
- Coagulation Studies
- Reflects the liver’s ability to synthesize clotting factors
- INR >6.5 or PT >20 seconds indicates patients at high risk for death
- Albumin
- Reflects synthetic function of the liver
- Has a long half-life (20 days) and may not be decreased early in disease
- Ammonia
- Elevated as a result of impaired clearance
- Poor correlation between degree of elevation and severity of encephalopathy symptoms
- Chemistry Panel
- Electrolyte abnormalities may indicate malnutrition or dehydration
- Creatinine is used as a prognostic indicator
- Need to check a glucose because patients with liver failure are prone to hypoglycemia
- CBC
- Not useful in diagnosing the cause of liver failure, but helpful in determining coexisting infection, anemia, thrombocytopenia
- Viral hepatitis Serologies
- Consider for all patients with undifferentiated liver failure
- IgM anti-HBc may be the only positive marker in acute Hepatitis B infection
- Anti-HCV and HCV RNA are present in both chronic and acute Hepatitis C infections, so it is difficult to differentiate based on serologies, but presence of HCV RNA in the absence of anti-HCV is more suggestive of acute infection[8]
- Only need to test for IgM anti-HEV in patients who are symptomatic and have just travelled from areas where Hepatitis E is endemic
Imaging
- Consider RUQ US or CT in patients with jaundice to evaluate for a mechanical obstruction
- Otherwise, tailor imaging towards specific complaints
Ascites Diagnosis
The differential diagnosis of ascites is often clarified by the calculation of the serum albumin to ascites gradient (SAAG).^
- High SAAG > 1.1 g/dL – Indicative of portal hypertension[9]
- Cirrhosis
- Heart failure
- Ascites total protein > 2.5 g/dL suggests cardiac ascites[10]
- Alcoholic hepatitis
- Budd-Chiari syndrome
- Portal vein thrombosis
- Low SAAG < 1.1 g/dL
- Malignancy / peritoneal carcinomatosis
- Nephrotic syndrome
- Pancreatitis
- Peritoneal tuberculosis
- Serositis
- Bowel infarction
- Chylous
- ^SAAG = (serum albumin in g/dL) − (ascitic albumin in g/dL)
Management
- Treatment is mostly supportive and tailored towards the specific etiology
- Early consideration regarding transporting patient to a transplant center given potential for rapid deterioration
- Symptom specific supportive treatment options
- Encephalopathy: consider lactulose of neomycin
- Seizures: consider phenytoin over benzodiazepines (prevent benzodiazepine oversedation secondary to decreased hepatic clearance)
- Intracranial Hypertension: elevated head of bed, mannitol, short-term hyperventilation; hypothermia may be a bridge to transplant; no benefit from steroids
- Coagulopathy
- Prophylactic normalization of the INR is not necessary unless procedure (such as paracentesis) is planned; then can give Vitamin K
- Recommend platelet transfusion to 10K for asymptomatic patients, and to 50-70K for patients undergoing invasive procedures
- See Acetaminophen toxicity for specifics regarding treatment of acetaminophen toxicity
- See Spontaneous Bacterial Peritonitis for specifics regarding diagnosis and treatment of SBP
Disposition
- Admission to ICU with early consideration for transportation to transplant center
See Also
References
- ↑ O’Grady, JG, Schalm SW, Williams R. Acute liver failure: redefining the syndromes. Lancet. July 1993, Volume 342, Issue 8866, Page 273-275
- ↑ Ostapowicz G, Fontana RJ, Schiodt FV, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med. 2002 Dec 17; 137(12): 947-54.
- ↑ Oyama, LC: Disorders of the Liver and Biliary Tractin Marx JA, Hockberger RS, Walls RM, et al (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, ed 8. St. Louis, Mosby, Inc., 2014, (Ch) 107: p 1186-1204.
- ↑ www.cdc.gov/hepatitis
- ↑ Oyama, LC: Disorders of the Liver and Biliary Tractin Marx JA, Hockberger RS, Walls RM, et al (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, ed 8. St. Louis, Mosby, Inc., 2014, (Ch) 107: p 1186-1204
- ↑ Rein DB, Stevens GA, Theaker J, Wittenborn JS, Wiersma ST. The Global Burden of Hepatitis E Virus Genotypes 1 and 2 in 2005. Hepatology, Vol. 55, No. 4, 2012: 988-997
- ↑ Oyama, LC: Disorders of the Liver and Biliary Tractin Marx JA, Hockberger RS, Walls RM, et al (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, ed 8. St. Louis, Mosby, Inc., 2014, (Ch) 107: p 1186-1204
- ↑ Bailey, C, Hern HG. Hepatic Failure: An Evidence-Based Approach In The Emergency Department. Emergency Medicine Practice. Vol. 12, No. 4, 2014.
- ↑ Runyon BA. Management of adult patients with ascites due to cirrhosis: update 2012. Amer Assoc Study Liv Dis. 2012; 1-96.
- ↑ Runyon BA. Cardiac ascites: a characterization. J Clin Gastro. 1998; 10(4): 410-412.