Liver Tests: Use and Interpretation

Hidden away under the ribs. It is a

non-complaining organ. The bowel complains

a lot. The liver doesn't. My patients

who come in with their chronic

Hepatitis C, and they say, Oh my liver is

giving me all this horrible pain right

here. Okay, a little lesson here, the

liver is over here. (laugh) The liver

doesn't cause much pain.

Okay, so what we're gonna try to do is say

What tools do we have for trying to

identify disease in the liver?

There are nonspecific things. If you

look at that list, lots of diseases cause

these things. So, they're really

nonspecific. They tell you there's nothing

really wrong, but they don't necessarily

tell you what the disease is. Something

that's a little more specific is if

patients are jaundiced. If they have

yellow sclerae. If their urine looks like

coca-cola color, although acute tubular

necrosis that you probably learned of in

kidney can do that also, or hematuria can.

Patients with chronic liver disease can

develop ascites, swelling in the abdomen,

Rich Mose will tell you about that. They

can develop peripheral edema, but you

already know that peripheral edema can

be caused by many things. What would be

another common cause of peripheral edema?

- Heart failure. -Heart failure. And

renal failure requiring dialysis can do

it. So, some of these are also not very

specific. And they really mean the liver

is very, very badly damaged. You are at

an end stage. It doesn't help you with

early stage. We're gonna talk about

several categories of tests that you can

use to screen for liver disease. And

that's what most of this talk will be

about. How can we identify ongoing liver

cell injury, problems with bile flow,

which is called cholestasis. Then we'll

talk a little bit about do we have any

ways of calculating liver function or

quantitative? Then you actually use

pattern of liver tests abnormalities to

start sorting liver diseases into groups.

This is a lot easier than diarrhea,

I promise. Finally, there is diagnosis

of specific liver diseases. The other

lectures you're gonna hear in the next

couple of days, we'll talk mostly about

those. So, how can you tell the liver

cells died or were injured?

Transaminases, which many people call

liver function tests, even though they're

not, or liver enzymes, are two enzymes:

alanine aminotransferase,

aspartate aminotransferase. Now, what

are these? Well they have a normal

function in the liver. They're used for

transferring amino group from one amino

acid to another and to make amino acids.

That has nothing to do with their role as

liver injury tests. They just happen to be

there in very large amounts. They're

easily measured. An ALT is very specific

for liver. AST is also in muscle.

Just to make life confusing. Again, ALT is

liver only. It's in the cytosol. AST is

in other tissues, although the liver has

a huge amount. In the cytosol, there's a

mitochondrial fraction. Now depending

on the method your laboratory uses, it

is a normal range. The old normal ranges

use to go up to 70. Now, in most labs,

they're down to about 30 or 35 because

the methods were changed a little bit.

And we realize that some of our normal

population wasn't all that normal.

There's always some in your blood because

liver cells turn over! They don't survive

forever. They're long-lived, but they die.

So there's always some. Another fact that

we will talk about later is that they

require a B vitamin pyridoxal 5 phosphate

as an essential cofactor. And that works

into a few little interesting clues you

can use to look at alcoholic liver

disease. So these are usually measured

in our automated systems in the lab. You

throw the serum with the substrate into

a little tube, and it runs through,

and a colored product is developed,

and you can measure that with a photo

detector, and then you could change the

absorbance or light to enzyme activity.

So what the lab measures is the enzymatic

activity of these, not the protein.

And there's no DNA here, so molecular

biology's out. So this is my crude

drawing of a liver cell that gets injured,

and here's the bile canaliculi. You got

mitochondria. You got a nucleus. You've

got AST in several places. You got ALT

in the cytosol. When the liver cell

finally ruptures, these things can get

directly into blood because you've got

that nice fenestrated endothelial. So

they're easily detectable in blood. There

convenient, there's a lot of it in liver.

It directly gets released into blood.

So, you can really- this is a very

sensitive and relatively specific measure

of ongoing cell injury. So, I kind of

joke that it's telling you how many

liver cells died in the last 24 hours.

Because these enzymes have been cleared

by the reticuloendothelial system or

other things. They don't tell you how

many liver cells died two weeks ago.

They don't tell you how many are going to

die tomorrow. They told you what injury

is going on right now.

And so you can look at patterns in

different diseases. Diseases that kill

a lot of hepatocytes in a fairly short

period of time are going to have much

higher levels of this in blood at any

given time. Then people who have a disease

where there's only a little bit of damage

occurring. Doesn't tell you about duration

of disease. It tells you how much injury.

So, if I give you a severe attack of

acute viral hepatitis, and you're really

sick, and a lot of liver cells are dying

everyday, you're going to have values

in the thousands. It could even be 5,000.

If you have a much milder disease

clinically, that usually means a lot less

cells are being killed at any one time,

going to have a lower level. Hepatitis C,

which you'll hear about tomorrow and

next week, is a virus that causes a

low-grade chronic injury. So on a

day-to-day basis, you have a very low

level of these enzymes. [06:51]