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 | ||
{{Acute hepatitis causes}} | |||
= | ====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 | ||
**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 | ||
*''' | *'''[[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 | ||
==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]] | ||
** | **[[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 | *[[Biliary disease]] (e.g. [[Choledocholithiasis|CBD obstruction]]) | ||
*[[Pregnancy]] | *[[Pregnancy]] | ||
*[[ | *Congenital diseases (e.g. [[inborn errors of metabolism]]; (more likely to present in early childhood) | ||
==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]] | ||
* | *[[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 | **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
- Acetaminophen toxicity (most common cause of acute liver failure in the US[2])
- Viral hepatitis
- Toxoplasmosis
- Acute alcoholic hepatitis
- Toxins
- Ischemic hepatitis
- Autoimmune hepatitis
- Wilson's 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[3]
- 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
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[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).^
- High SAAG > 1.1 g/dL – Indicative of portal hypertension[5]
- Cirrhosis
- Heart failure
- Ascites total protein > 2.5 g/dL suggests cardiac ascites[6]
- 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
- ↑ 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.