Ischemic Hepatitis (DDX Acute Hepatitis)

• Ischemic Hepatitis refers to diffuse hepatic injury secondary to acute hypoperfusion.  This is somewhat different than Hepatic Infarction which refers to focal ischemic injury of the liver (i.e. from hepatic artery chemoembolization, thrombosis, etc.). 
• Ischemic Hepatitis can occur from anything causing hypotension or hemodynamic instability, such as cardiogenic shock, sepsis etc. 
• Importantly, however, shock liver can also occur in the absence of clinically overt hypotension (up to 50% of cases in one series)!!! - as in our patient's case.  This tends to occur in predisposed patients, likely those with preexisting passive congestion, or portal hypertension.
• Besides hypotension, other etiologies have been reported:
  1. Severe Respiratory Failure
  2. Systemic Hypoxemia
  3. Severe anemia
  4. Focal interruption of the hepatic blood supply – i.e. hepatic artery thrombosis in a patient with preexisting portal vein thrombosis (hepatic artery thrombosis alone wouldn’t do it, due to the liver’s dual blood supply)
• Many times, ischemic hepatitis overlaps with congestive hepatopathy, since both are related to decreased cardiac output states.
• Symptoms and clinical presentation tend to reflect the underlying state of shock, but can sometimes also include nausea, vomiting, anorexia, malaise, and RUQ pain.
• Ischemic Hepatitis has a characteristic pattern of LFTs:  AST/ALT rise rapidly, peaking in the 1000s within 1-3 days, with an early massive rise in LDH.  If the circulatory disturbance is corrected, LFTs decline steadily to normal values in 7-10 days.  The bilirubin and alk phos are usually only mildly elevated, although the bilirubin tends to be slower to return to normal. 
• The liver’s synthetic function is generally preserved or only mildly impaired, as evidenced by the INR being normal or only mildly elevated. 
• Management: There is no specific treatment for shock liver, only to address the underlying etiology and optimize hemodynamics.
• Ischemic hepatitis is generally benign and self-limited, and prognosis is more related to the underlying etiology of shock. That being said, it occasionally leads to fulminant hepatic failure when superimposed on chronic CHF or preexisting cirrhosis.

Differential Diagnosis for Severe Transaminitis in the 1000s
While LFTs in the 100s range is fairly common, the the DDx of AST/ALT > 1000 is narrow.  The 3 most common causes are:
1)  Ischemic Hepatitis
2)  Acute Viral Hepatitis (HAV, HBV, NOT HCV)
3)  Drug/Toxin Induced Liver Injury – by far the most common being Tylenol
**Of note, alcoholic hepatitis does not cause AST/ALT rises > 500!! **
Clues that favor ischemic hepatitis over the other viral or drug-injury:

• Markedly elevated LDH – fairly specific for ischemic hepatitis
• Rapid fall in AST/ALT after initial insult (in viral or drug-induced liver injury, LFTs take weeks to months to normalize)
• Other signs of shock or end-organ perfusion, especially renal failure

Other, less common causes of LFTs in the 1000s include:

• Exacerbation of Autoimmune Hepatitis
• Acute Budd Chiari, especially with concomitant portal vein thrombosis
• HELLP, Acute Fatty Liver of Pregnancy
• Hepatic Infarction
• Reactivation of chronic Hep B, or Hepatitis D superimposed on chronic Hep B
• Wilsonian Crisis – presents with acute liver failure in young adults/children, with concomitant hemolytic anemia.

(Chanu Rhee MD, 5/23/11)