Acute hepatic failure

Background

Liver vascular anatomy.

Definitions

  • 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[1]
  • 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[2]
  • 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[3]

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.
  • 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

  • Hepatic dysfunction
  • Biliary disease (e.g. CBD obstruction)
  • Hemolysis
  • Pregnancy
  • Congenital diseases (e.g. inborn errors of metabolism; (more likely to present in early childhood)

Hepatic Dysfunction

Infectious

Neoplastic

Metabolic

Biliary

  • Biliary cirrhosis

Drugs

Miscellaneous

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
    • 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[7]
    • 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
    • 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

Calculators

MELD Score

MELD Score (Model for End-Stage Liver Disease)
Parameter Value
Creatinine (mg/dL) — capped at 4.0
Bilirubin (mg/dL)
INR
On Dialysis (2× in past week or CVVHD) 1 No   Yes (Cr set to 4.0)
MELD Score
Interpretation — 3-Month Mortality
<10 ~2% mortality.
10–19 ~6% mortality.
20–29 ~20% mortality.
30–39 ~53% mortality.
≥40 ~71% mortality. Consider transplant evaluation.
References
  • Kamath PS, Wiesner RH, Malinchoc M, et al. A model to predict survival in patients with end-stage liver disease. Hepatology. 2001;33(2):464-470. PMID 11172350.
  • Wiesner R, Edwards E, Freeman R, et al. Model for end-stage liver disease (MELD) and allocation of donor livers. Gastroenterology. 2003;124(1):91-96. PMID 12512033.
  • Formula: MELD = 10 × [0.957 × ln(Cr) + 0.378 × ln(Bilirubin) + 1.120 × ln(INR) + 0.643]. Minimum lab values set to 1.0. Cr capped at 4.0.


Child-Pugh Score

Child-Pugh Score
Factor 1 Point 2 Points 3 Points
Bilirubin (mg/dL) 1 <2 2–3 >3
Albumin (g/dL) 1 >3.5 2.8–3.5 <2.8
INR 1 <1.7 1.7–2.3 >2.3
Ascites 1 None Mild/controlled Moderate-severe
Encephalopathy 1 None Grade I–II Grade III–IV
Child-Pugh Score / 15
Interpretation
Class Score 1-Year Survival
A | 5–6 | ~100%
B | 7–9 | ~80%
C | 10–15 | ~45%
References
  • Pugh RN, Murray-Lyon IM, Dawson JL, et al. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973;60(8):646-649. PMID 4541913.
  • Durand F, Valla D. Assessment of the prognosis of cirrhosis: Child-Pugh versus MELD. J Hepatol. 2005;42(Suppl 1):S100-107. PMID 15777564.

See Also

  • Jaundice
  • Cirrhosis
  • Acute hepatitis
  • Hepatic encephalopathy

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