Differential diagnosis of elevated LFTs

I'm sorry to go all medicalese but this blog in part serves as a repository for stuff I learn in the hospital. I'm on my medicine subI this month (hooray and oh my gosh I'm already a fourth year?!), and we got a fine chalk talk by a liver fellow about how to think about elevated liver function tests (LFTs).

The case is as follows: A 30M, previously healthy, arrives at the hospital with these abnormal findings on LFTs: ALT 1500, AST 750, AP 120, and TB 30. What pattern of liver disease does he have and what's the differential and workup?

The LFT panel consists of the ALT, AST, Alk phos, and total bili.

Surprisingly, this patient does NOT have a mixed pattern, for the definition of cholestatic disease is an elevated AP (ULM is ~100, but with ALTs and ASTs that high, 120 isn't considered cholestatic).

Here's the way to categorize:
The patterns of liver disease are:
1. Hepatocellular (> 5)
2. Cholestatic (< 2) 3. Mixed (2-5) Calculate this ratio: (# x ALT > ULN)/(# x AP > ULN)

*ULN = upper limit of normal

If it's > 5 then, it's hepatocellular, if < 2, then cholestatic, and mixed is somewhere in between. Kind of a simplified rule of thumb. Of course, there are measures of liver FUNCTION, namely: 1) INR: an indirect measure of the vitamin K dependent clotting factors (II, VII, IX, X, Protein C, S) in the extrinsic pathway 2) Albumin 3) Platelets: liver produces thrombopoeitin which stimulates platelet production in the bone marrow The differential diagnosis for ALT > 1000 is actually quite limited:
1) Toxins: Tylenol, Tylenol, Tylenol. If you suspect this, order a 5 panel tox screen and give N-acetylcysteine right away

2) Ischemia
- shock liver
- portal vein thrombosis
- hepatic artery thrombosis
Get a lactate, a ultrasound WITH doppler and/or a CTA/V

3) Viral
- HepA (test the IgM for acute infection)
- HepB (core IgM for acute infection)
- HebC (Ab or RNA)
- HepD and E
- EBV
- CMV
- HSV

4) Autoimmune
- test anti-smooth muscle Ab
- we'll often get an ANA and see elevated IgG from increased circulating immunoglobulins

5) Other (i.e Metabolic)
- Reye's syndrome, which is why you shouldn't give aspirin to kids!
- Acute fatty liver disease
- Wilson's acute crisis

Make sure you ask about a history of drugs, including IV drug use, tattoos, sexual history, travel, and history of autoimmune diseases.

Call the liver team when you suspect fulminant hepatic failure, as may be evidenced by encephalopathy. Test for asterixis and use tests of concentration. The "A cross-out test" is supposed to be a great way to track progress in encephalopathy. It's basically having the patient cross out every "A" she sees on a page with a few sentences of text. We actually used in a woman with alcoholic hepatic encephalopathy: on day 1, she missed nearly every 5th A. After several days of treatment, she got most of them. If the patient is encephalopathic, do NOT give agents that will alter mental status - benzos, opiates, Benadryl, NSAIDS - the drugs will muddy the etiology of the encephalopathy.