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Hidden away under the ribs. It is a

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non-complaining organ. The bowel complains

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a lot. The liver doesn't. My patients

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who come in with their chronic

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Hepatitis C, and they say, Oh my liver is

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giving me all this horrible pain right

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here. Okay, a little lesson here, the

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liver is over here. (laugh) The liver

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doesn't cause much pain.

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

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What tools do we have for trying to

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identify disease in the liver?

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There are nonspecific things. If you

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look at that list, lots of diseases cause

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these things. So, they're really

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nonspecific. They tell you there's nothing

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really wrong, but they don't necessarily

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tell you what the disease is. Something

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that's a little more specific is if

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patients are jaundiced. If they have

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yellow sclerae. If their urine looks like

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coca-cola color, although acute tubular

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necrosis that you probably learned of in

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kidney can do that also, or hematuria can.

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Patients with chronic liver disease can

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develop ascites, swelling in the abdomen,

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Rich Mose will tell you about that. They

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can develop peripheral edema, but you

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already know that peripheral edema can

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be caused by many things. What would be

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another common cause of peripheral edema?

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- Heart failure. -Heart failure. And

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renal failure requiring dialysis can do

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it. So, some of these are also not very

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specific. And they really mean the liver

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is very, very badly damaged. You are at

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an end stage. It doesn't help you with

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early stage. We're gonna talk about

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several categories of tests that you can

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use to screen for liver disease. And

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that's what most of this talk will be

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about. How can we identify ongoing liver

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cell injury, problems with bile flow,

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which is called cholestasis. Then we'll

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talk a little bit about do we have any

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ways of calculating liver function or

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quantitative? Then you actually use

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pattern of liver tests abnormalities to

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start sorting liver diseases into groups.

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This is a lot easier than diarrhea,

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I promise. Finally, there is diagnosis

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of specific liver diseases. The other

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lectures you're gonna hear in the next

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couple of days, we'll talk mostly about

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those. So, how can you tell the liver

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cells died or were injured?

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Transaminases, which many people call

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liver function tests, even though they're

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not, or liver enzymes, are two enzymes:

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alanine aminotransferase,

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aspartate aminotransferase. Now, what

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are these? Well they have a normal

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function in the liver. They're used for

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transferring amino group from one amino

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acid to another and to make amino acids.

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That has nothing to do with their role as

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liver injury tests. They just happen to be

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there in very large amounts. They're

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easily measured. An ALT is very specific

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for liver. AST is also in muscle.

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Just to make life confusing. Again, ALT is

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

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in other tissues, although the liver has

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

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mitochondrial fraction. Now depending

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on the method your laboratory uses, it

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is a normal range. The old normal ranges

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

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they're down to about 30 or 35 because

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the methods were changed a little bit.

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And we realize that some of our normal

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population wasn't all that normal.

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There's always some in your blood because

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liver cells turn over! They don't survive

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

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So there's always some. Another fact that

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we will talk about later is that they

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require a B vitamin pyridoxal 5 phosphate

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as an essential cofactor. And that works

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into a few little interesting clues you

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can use to look at alcoholic liver

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disease. So these are usually measured

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in our automated systems in the lab. You

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throw the serum with the substrate into

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a little tube, and it runs through,

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and a colored product is developed,

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and you can measure that with a photo

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detector, and then you could change the

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absorbance or light to enzyme activity.

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So what the lab measures is the enzymatic

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activity of these, not the protein.

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And there's no DNA here, so molecular

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biology's out. So this is my crude

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drawing of a liver cell that gets injured,

105
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and here's the bile canaliculi. You got

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mitochondria. You got a nucleus. You've

107
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got AST in several places. You got ALT

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in the cytosol. When the liver cell

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finally ruptures, these things can get

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directly into blood because you've got

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that nice fenestrated endothelial. So

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they're easily detectable in blood. There

113
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convenient, there's a lot of it in liver.

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It directly gets released into blood.

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So, you can really- this is a very

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sensitive and relatively specific measure

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of ongoing cell injury. So, I kind of

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joke that it's telling you how many

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liver cells died in the last 24 hours.

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Because these enzymes have been cleared

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by the reticuloendothelial system or

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other things. They don't tell you how

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many liver cells died two weeks ago.

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They don't tell you how many are going to

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die tomorrow. They told you what injury

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is going on right now.

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And so you can look at patterns in

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different diseases. Diseases that kill

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a lot of hepatocytes in a fairly short

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period of time are going to have much

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higher levels of this in blood at any

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given time. Then people who have a disease

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where there's only a little bit of damage

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occurring. Doesn't tell you about duration

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of disease. It tells you how much injury.

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So, if I give you a severe attack of

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acute viral hepatitis, and you're really

138
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sick, and a lot of liver cells are dying

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everyday, you're going to have values

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

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If you have a much milder disease

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clinically, that usually means a lot less

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cells are being killed at any one time,

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going to have a lower level. Hepatitis C,

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which you'll hear about tomorrow and

146
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next week, is a virus that causes a

147
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low-grade chronic injury. So on a

148
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day-to-day basis, you have a very low

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level of these enzymes. [06:51]