Acute Hepatitis with Enzymes > 1000

Today's case involved a middle-aged man with not much past medical history besides hypertension.  He presented secondary to abnormal laboratory values including a bilirubin of nearly 400, and elevated transaminases into the 1000’s.  He had ascites and imaging evidence of chronic cirrhosis, as well as a portal vein thrombus.  He did, however, have normal liver enzymes only a few weeks prior to his presentation suggesting this to be an acute process.

There were multiple valuable learning points today:

-Acute transaminase elevation into the range of thousands has a limited differential diagnosis which is worth remembering.  This includes viral hepatitis, autoimmune hepatitis, acute cholangitis/gallstone obstruction, acute fatty liver of pregnancy, drug-induced heptatitis (acetaminophen, not alcohol), portal vein thrombosis, and ischemic hepatitis (shock liver as it is so lovingly called).

-We spoke briefly about the physical examination for ascites.  It is worth remembering that ankle edema has a 93% sensitivity for ascites, meaning that ascites presence is extremely unlikely if there is no ankle edema.  That said, if there is ankle edema, you need a specific test to rule in ascites.  The combination of flank dullness, a positive shifting dullness, and a positive fluid wave can be helpful in this case.  Most of your patients will receive abdominal ultrasounds anyways.

-We briefly discussed hemolysis (the other cause of hyperbilirubinemia).  The hemolytic workup includes a CBC, blood film, LDH, haptoglobin, and bilirubin.  To this I sometimes add a DAT or Coomb’s test for autoimmune hemolytic anemia, and sometimes a fibrinogen level and/or D-Dimer for consumptive coagulopathies like disseminated intravascular coagulation.

-We talked about liver function which is frequently and erroneously misinterpreted as transaminase levels.  The two are completely different and occasionally unrelated.  The liver’s function is to produce albumin, coagulation factors (check INR/PTT), eliminate nitrogenous waste (asterixis/encephalopathy), clear portal blood of toxins/nutrients (ascites and thrombocytopenia from portal hypertension), and produce glucose in states of starvation (hypoglycemia is a feature of advanced liver failure).  Transaminase elevation can occur without impairing these functions, and these functions can be quite impaired with mild or no transaminase elevation.

For further reading, I’m including a review of an approach to abnormal liver enzymes, and a review and approach to thrombotic microangiopathy, as well as the JAMA Rational Clinical Exam series article about ascites.

Further Reading:

Kaplowitz, N. (2004). Drug-induced liver injury. Clinical Infectious Diseases, 38(Supplement 2), S44-S48.

Moake, J. L. (2002). Thrombotic microangiopathies. New England Journal of Medicine, 347(8), 589-600.

Limdi, J. K., & Hyde, G. M. (2003). Evaluation of abnormal liver function tests. Postgraduate medical journal, 79(932), 307-312.
Chicago

Williams, J. W., & Simel, D. L. (1992). Does This Patient Have Ascites?: How to Divine Fluid in the Abdomen. Jama, 267(19), 2645-2648.