The Best Liver Tests in Primary Care

Matthew F. Watto, MD; Paul N. Williams, MD


November 30, 2021

This transcript has been edited for clarity.

Matthew F. Watto, MD: Welcome back to The Curbsiders. I'm Dr Matthew Watto, here with my great friend, Dr Paul Nelson Williams. Paul, what are we going to talk about today?

Paul N. Williams, MD: In these short videos, we recap podcast episodes that we've done, and the one we will be talking about tonight is our podcast episode 293, which was all about liver testing with the great Dr Elliott Tapper, an amazing hepatologist who talked us through how to evaluate common lab abnormalities that we may see in clinical practice.

Liver Tests and R Scores

Watto: One of the main teaching pearls was to please avoid using "LFTs" to refer to liver tests. In general, the hepatologists don't like that abbreviation, although you can use it in your notes.

If you have a patient with acute liver injury and acutely abnormal liver tests, then we talked about using the R score, which I hadn't used before. But I think it's helpful in the differential diagnosis, if it's a purely hepatocellular injury pattern (AST/ALT very high) vs a cholestatic pattern where you have predominantly an alkaline phosphatase (ALP) elevation. Unfortunately for me, most patients seem to be a mixed picture, so I end up having to test for everything. But it is helpful to know this.

For the R score, you plug in the ALT and the ALP. If the score is > 5, it tells you that it is probably hepatocellular. If it’s between 2 and 5, it might be more of a mixed picture; and if the R score is < 2, it is more consistent with a cholestatic injury.

The hepatocellular and cholestatic workups are a little bit different, but there's some overlap. With hepatocellular, you don't have to get super-fancy. The main thing that you might think about ordering for acute liver injury are autoimmune hepatitis labs. Autoimmune hepatitis is probably the condition that's most unfamiliar to generalists. You're looking for really high antinuclear antibodies (ANA) — definitely more than 1:80. You're looking for serum immunoglobulins, such as a high IgG level, and for anti–smooth muscle antibodies. So if you see a mixed or a hepatocellular pattern, think about autoimmune hepatitis. It’s less likely to present with just an isolated cholestatic picture.

For either a mixed or hepatocellular picture, test for hepatitis C, B, and A, and it’s never wrong to get an ultrasound. What additional testing do people need to think about if it's more of a cholestatic picture?

Williams: There isn’t much, because as you’ve said, there is a significant amount of overlap. With an obstructive process, you can see elevations in transaminases. It can manifest that way. Imaging is almost always the right way to go. An ultrasound is a great place to start if you have a cholestatic injury pattern, typically characterized by an elevated ALP with some elevation in the transaminases. You would also consider antimitochondrial antibody, which is specifically looking for primary biliary cholangitis. You are looking for things that cause obstruction and infiltrative diseases, such as sarcoidosis. We talked about what a hero you would be if you actually managed to diagnose common variable immunodeficiency (CVID) syndrome, which can cause this type of cholestatic injury pattern.

This pattern can also be seen with drug-induced liver injury depending on what toxin we're talking about. Metabolic-associated fatty liver disease can also sometimes manifest with a slightly obstructive pattern where you have this elevation of ALP and maybe mild transaminase elevation, which I found helpful because I have a number of patients who fit into this category. So if someone has the right phenotype with insulin resistance and central adiposity, that might be a reasonable explanation for it as well, after you've ruled out some of the scarier stuff.

Watto: The antimitochondrial antibodies go along with the cholestatic picture. This test is less familiar, but it's one we should think about ordering in the first round of testing for acute liver injury. When patients have AST and ALT > 1000, Dr Tapper said not to worry about the AST:ALT ratio, thinking that it could be alcohol related. Some of the most common causes of really high transaminase levels are ischemia, stone disease, and drug-induced liver injury (especially acetaminophen) and viral hepatitis. Those are four things most likely to cause very high transaminase levels. He made the point that alcoholic hepatitis doesn't cause elevations into the thousands like that. So if you're seeing them that high, maybe something else is going on besides alcohol.

Williams: He made the very specific point that if the ALT plus the AST is > 500, then alcohol-related hepatitis is less likely, and the drug of interest is usually acetaminophen.

Watto: What about acute liver failure, Paul? What exactly is that? It’s a vague definition. How does it differ from acute liver injury?

Williams: Dr Tapper provided some reassurance. It’s often talked about, but it turns out that fulminant hepatic failure is actually pretty uncommon. You have to have the biochemical markers of liver damage, but then also a coagulopathy and hepatic encephalopathy. He made the point that encephalopathy has to be present for this process to be considered fulminant hepatic failure. So it's actually fairly uncommon for us to see this in clinical practice.

Watto: I've seen it with acetaminophen overdose, and that is the only time I remember seeing it. As Dr Tapper said, if you see someone with acute liver injury, it’s unlikely that they have acute liver failure. What you should think about as a barometer for disease is the bilirubin level. He said that the heart rate is tied to how high the bilirubin is, which is really a useful pearl.

Moving away from the acute picture, we talked about some of the banes of primary care, which are these very mild, maybe even isolated elevations in things like ALP. What pearls can you give about this?

Williams: I don't want to leave our audience with the impression that these things should be ignored, but I think sometimes these mild elevations, especially a high ALP in isolation, are found almost incidentally. Dr Tapper said that sometimes you can let time be the arbiter of truth. So if you have a patient with an elevated ALP who has symptoms of cholestasis (and pruritus is one of the most worrisome symptoms) and they just feel kind of crummy, that should prompt a little bit more of an aggressive workup that might involve looking for antimitochondrial antibodies and primary biliary cholangitis. But if it's just a slight elevation that you found incidentally and the patient is asymptomatic, you can just keep an eye on it and just follow it. Not infrequently, the ALP level will dip back into normal or remain just slightly elevated in some cases, such as metabolic-associated fatty liver disease. In addition to watching the ALP, you do the things you normally would do for the patient: counseling about weight loss and glycemic control. You can see an improvement in the ALP with those measures.

Watto: This was a great conversation with a fantastic guest. Click on The Best of Liver Tests to listen to the full podcast episode. You can subscribe to The Curbsiders mailing list, where you can get our really extensive show notes that we make to go along with each episode. Until next time, I’m Dr Matthew Frank Watto.

Williams: And I remain Dr Paul Nelson Williams. Thank you and goodbye.

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