Acute hepatic failure: Difference between revisions

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==Definitions<ref>O’Grady, JG, Schalm SW, Williams R. Acute liver failure: redefining the syndromes. Lancet. July 1993, Volume 342, Issue 8866, Page 273-275</ref>==
==Background==
===Definitions<ref>O’Grady, JG, Schalm SW, Williams R. Acute liver failure: redefining the syndromes. Lancet. July 1993, Volume 342, Issue 8866, Page 273-275</ref>===
*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
*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
*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
*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==
{{Acute hepatitis causes}}
===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>
*Small amount of Acetaminophen is metabolized by Cytochrome P450 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===
====Drug or Toxin Related Liver Disease====
*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 <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>
**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<ref> www.cdc.gov/hepatitis </ref>
{| {{table}}
| align="center" style="background:#f0f0f0;"|'''Clinical Scenario'''
| align="center" style="background:#f0f0f0;"|'''HBsAg'''
| align="center" style="background:#f0f0f0;"|'''anti-HBc'''
| align="center" style="background:#f0f0f0;"|'''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
**Transmitted through IV drug use (most common) and infrequently through sexual contact
**90% of HCV infections progress to chronic hepatitis<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>
*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<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===
*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/starvation 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<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
**Acetaminophen
**[[Acetaminophen]]
**Amiodarone
**[[Amiodarone]]
**Amphotericin
**[[Amphotericin]]
**Anabolic steroids
**Anabolic steroids
**Azathioprine
**[[Azathioprine]]
**Carbamazepine
**[[Carbamazepine]]
**Chlorpromazine
**[[Chlorpromazine]]
**Cisplatin
**Cisplatin
**Contraceptives
**Contraceptives
**Cyclophosphamide
**[[Cyclophosphamide]]
**Erythromycin
**[[Erythromycin]]
**Gold salts
**Gold salts
**Haloperidol
**[[Haloperidol]]
**Isoniazid
**[[Isoniazid]]
**Ketoconazole
**[[Ketoconazole]]
**Lovastatin
**Lovastatin
**Methotrexate
**[[Methotrexate]]
**Methoxyflurane
**Methoxyflurane
**Methyldopa
**Methyldopa
**Phenobarbital
**[[Phenobarbital]]
**Phenytoin
**[[Phenytoin]]
**Quinidine
**[[Quinidine]]
**Salicylates
**[[Salicylates]]
**Tetracycline
**[[Tetracycline]]
**Valproic acid
**[[Valproic acid]]
**Verapamil
**[[Verapamil]]
 
===Other Rare Causes of Acute Liver Failure===
===Other Rare Causes of Acute Liver Failure===
*'''Wilson’s disease''': unexplained elevations in LFTs, neuro-psychiatric symptoms, Kayser-Fleischer rings on eye exam
*'''[[Wilson's disease]]''': unexplained elevations in LFTs, neuro-psychiatric symptoms, Kayser-Fleischer rings on eye exam
*'''Auto-immune hepatitis''': more common in women, liver disease without explanation, may have family history of other autoimmune disorders
*'''[[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
*'''[[Hemochromatosis]]''': family history of liver disease and cardiac disease
*'''Budd-Chiari''': history of hypercoagulable disorder, abdominal pain, and ascites
*'''[[Budd-Chiari]]''': history of hypercoagulable disorder, abdominal pain, and ascites
*'''Viral infections''': HSV, Epstein-Barr, varicella-zoster, toxoplasmosis
 
==Clinical Features==
==Clinical Features==
[[File:Jaundice08.jpg|thumb|Jaundice of the skin]]
[[File:SpiderAngioma.jpg|thumb|Spider angioma]]
[[File:Hepaticfailure.jpg|thumb||Ascites secondary to [[cirrhosis]].]]
[[File:Jaundice.jpg|thumb|Pediatric jaundice with icterus of sclera.]]
*Common findings in acute liver failure
*Common findings in acute liver failure
**Tender hepatomegaly
**Tender [[hepatomegaly]]
**Jaundice
**[[Jaundice]]
**Encephalopathy
**[[Hepatic encephalopathy]]
**Asterixis
**Asterixis
*Common findings in chronic liver failure
*Common findings in chronic liver failure
**Ascites
**[[Ascites]]
**Caput medusae
**Caput medusae
**Palmar erythema
**Palmar erythema
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**Parotid gland enlargement
**Parotid gland enlargement
**Muscular atrophy
**Muscular atrophy
**May also have jaundice, encephalopathy, and asterixis as in acute liver failure
**May also have [[jaundice]], [[hepatic encephalopathy|encephalopathy]], and asterixis as in acute liver failure
 
==Differential Diagnosis==
==Differential Diagnosis==
===[[Encephalopathy]] (altered mental status)===
===[[Encephalopathy]] (altered mental status)===
*[[Hypoglycemia]]
*[[Hypoglycemia]]
*[[Hypoxia]]
*[[Hypoxia]]
*Intracerebral hemorrhage or mass
*[[Intracerebral hemorrhage]] or mass
*[[Meningitis]]/[[encephalitis]]
*[[Meningitis]]/[[encephalitis]]
*[[CVA]]
*[[CVA]]
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*[[Uremia]]
*[[Uremia]]
*[[Electrolyte abnormality]]
*[[Electrolyte abnormality]]
*[[Acute hepatic failure]]


===[[Jaundice]]===
===[[Jaundice]]===
*[[Hepatitis]]
*[[Hepatitis]]
*Hemolysis
*[[hemolytic anemia|Hemolysis]]
*Biliary pathology (CBD obstruction)
*[[Biliary disease]] (e.g. [[Choledocholithiasis|CBD obstruction]])
*[[Pregnancy]]
*[[Pregnancy]]
*[[Congenital diseases]] (more likely to present in early childhood)
*Congenital diseases (e.g. [[inborn errors of metabolism]]; (more likely to present in early childhood)
 
{{Ascites DDX}}


==Evaluation==
==Evaluation==
===Labs===
===Labs===
*AST and ALT
*[[LFTs]]
**Enzymes found mainly in hepatic cells, though ALT is more specific to the liver than AST
**AST and ALT
**Extreme elevation in AST (>3000U/L, or >40x upper limit of normal) is consistent with acetaminophen toxicity or ischemic injury
***Enzymes found mainly in hepatic cells, though ALT is more specific to the liver than AST
**Moderate elevations (10-40x upper limit of normal) is consistent with viral hepatitis
***Extreme elevation in AST (>3000U/L, or >40x upper limit of normal) is consistent with acetaminophen toxicity or ischemic injury
**Mild elevations (<10x upper limit of normal) is consistent with alcoholic hepatitis
***Moderate elevations (10-40x upper limit of normal) is consistent with viral hepatitis
*Alkaline Phosphatase
***Mild elevations (<10x upper limit of normal) is consistent with alcoholic hepatitis
**Found in bile canaliculi (but also in placenta, ileal mucosa, bone, and kidney)
**Alkaline Phosphatase
**Elevated in diseases of cholestasis
***Found in bile canaliculi (but also in placenta, ileal mucosa, bone, and kidney)
**Rare for levels to be >3x normal limit in acute liver failure
***Elevated in diseases of cholestasis
*Bilirubin
***Rare for levels to be >3x normal limit in acute liver failure
**Elevated in diseases of cholestasis
**Bilirubin
**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
***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
*Coagulation Studies
*Coagulation Studies
**Reflects the liver’s ability to synthesize clotting factors
**Reflects the liver’s ability to synthesize clotting factors
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**Need to check a glucose because patients with liver failure are prone to hypoglycemia
**Need to check a glucose because patients with liver failure are prone to hypoglycemia
*CBC
*CBC
**Not useful in diagnosing the cause of liver failure, but helpful in determining coexisting infection, anemia, thrombocytopenia
**Not useful in diagnosing the cause of liver failure, but helpful in determining coexisting [[infection]], [[anemia]], [[thrombocytopenia]]
*Hepatic Viral Serologies
*[[Viral hepatitis]] Serologies
**Consider for all patients with undifferentiated liver failure
**Consider for all patients with undifferentiated liver failure
**IgM anti-HBc may be the only positive marker in acute Hepatitis B infection
**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<ref>Bailey, C, Hern HG. Hepatic Failure: An Evidence-Based Approach In The Emergency Department. Emergency Medicine Practice. Vol. 12, No. 4, 2014.</ref>
**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<ref>Bailey, C, Hern HG. Hepatic Failure: An Evidence-Based Approach In The Emergency Department. Emergency Medicine Practice. Vol. 12, No. 4, 2014.</ref>
**Only need to test for IgM anti-HEV in patients who are symptomatic and have just travelled from areas where Hepatitis E is endemic
**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===
===Imaging===
*Consider US or CT in patients with jaundice to evaluate for a mechanical obstruction
*Consider [[RUQ US]] or CT in patients with jaundice to evaluate for a mechanical obstruction
*Otherwise, tailor imaging towards specific complaints
*Otherwise, tailor imaging towards specific complaints
{{Ascites Evaluation}}
==Management==
==Management==
*Treatment is mostly supportive and tailored towards the specific etiology
*Treatment is mostly supportive and tailored towards the specific etiology
*Early consideration regarding transporting patient to a transplant center given potential for rapid deterioration
*Early consideration regarding transporting patient to a transplant center given potential for rapid deterioration
*Symptom specific supportive treatment options
*Symptom specific supportive treatment options
**Encephalopathy: consider lactulose of neomycin
**[[Hepatic encephalopathy|Encephalopathy]]: consider [[lactulose]] of [[neomycin]]
**Seizures: consider [[phenytoin]] over benzodiazepines (prevent benzodiazepine oversedation secondary to decreased hepatic clearance)
**[[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
**[[Increased ICP|Intracranial Hypertension]]: elevated head of bed, [[mannitol]], short-term hyperventilation; hypothermia may be a bridge to transplant; no benefit from steroids
**Coagulopathy
**[[liver disease induced coagulopathy|Coagulopathy]]
***Prophylactic normalization of the INR is not necessary unless procedure (such as paracentesis) is planned; then can give Vitamin K
***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
***Recommend [[platelet transfusion]] to 10K for asymptomatic patients, and to 50-70K for patients undergoing invasive procedures
**See [[Acetaminophen (Tylenol) toxicity]] for specifics regarding treatment of acetaminophen toxicity
**See [[Acetaminophen toxicity]] for specifics regarding treatment of acetaminophen toxicity
**See [[Spontaneous Bacterial Peritonitis]] for specifics regarding diagnosis and treatment of SBP
**See [[Spontaneous Bacterial Peritonitis]] for specifics regarding diagnosis and treatment of SBP
==Disposition==
==Disposition==
*Admission to ICU with early consideration for transportation to transplant center
*Admission to ICU with early consideration for transportation to transplant center
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*[[Jaundice]]
*[[Jaundice]]
*[[Cirrhosis]]
*[[Cirrhosis]]
*[[Acute hepatitis]]
*[[Hepatic encephalopathy]]


==References==
==References==

Revision as of 18:47, 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 of acute hepatitis

Drug or Toxin Related Liver Disease

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

Clinical Features

Jaundice of the skin
Spider angioma
Ascites secondary to cirrhosis.
Pediatric jaundice with icterus of sclera.

Differential Diagnosis

Encephalopathy (altered mental status)

Jaundice

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
  • 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
  • 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[4]
    • 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).^

^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

Disposition

  • Admission to ICU with early consideration for transportation to transplant center

See Also

References

  1. O’Grady, JG, Schalm SW, Williams R. Acute liver failure: redefining the syndromes. Lancet. July 1993, Volume 342, Issue 8866, Page 273-275
  2. 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.
  3. 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
  4. Bailey, C, Hern HG. Hepatic Failure: An Evidence-Based Approach In The Emergency Department. Emergency Medicine Practice. Vol. 12, No. 4, 2014.
  5. Runyon BA. Management of adult patients with ascites due to cirrhosis: update 2012. Amer Assoc Study Liv Dis. 2012; 1-96.
  6. Runyon BA. Cardiac ascites: a characterization. J Clin Gastro. 1998; 10(4): 410-412.