Liver Damage

 BY DEREK LOWE

In that post about the longitudinal study looking for long Covid effects I mentioned that the authors searched for liver damage signs in the blood work, and I realized while writing it that I'd also written that look at hepatitis, for which that's also an important sign. Those prompt me to follow up with a look at how you see liver damage in blood tests, and what the various signs might be telling you.

The two key enzymes that you'll look at first are ALT and AST. ALT is alanine transaminase (also called alanine aminotransferase, especially by old-timers). It catalyzes the shift from alanine and alpha-ketoglutarate to pyruvate and L-glutamate, and it's an enzyme that's normally found in plasma and a number of other tissues. But it's particularly abundant in the liver, and elevated levels of it in the blood are very suggestive of liver trouble, although they aren't quite definitive. Damaged hepatocytes can leak excess ALT into the blood, but it fluctuates under normal conditions, so mildly elevated ALT may not be a sign of anything at all. AST is aspartate transaminase, (or aspartate aminotransferase), which similarly catalyzes the shift from aspartate and alpha-ketoglutarate to oxaloacetate and L-glutamate, using vitamin B6 (which our bodies can't make) as an essential cofactor. So if you're wondering where vitamins come into play, there's a key example! That reaction is important in both the degradation and the synthesis of amino acids, and the amino group that ends up on glutamate is the source of most of the urea that is excreted in the urine as the body sheds nitrogen. AST is found in larger amounts in more types of tissue than ALT, so elevated levels of it are (by themselves) somewhat less specifically diagnostic of liver damage, but you absolutely still need to track it down if it shows up in a blood screen. A third enzyme that is measured for liver diagnostic purposes is ALP, alkaline phosphatase, which dephosphorylates a whole list of proteins. It's found in many tissues as well, and its levels can fluctuate for a number of reasons, but elevated levels can indicate liver damage as well as several other conditions (including pregnancy!) Various forms of ALP can be distinguished with further tests (bone ALP versus liver ALP, especially), and if you've zeroed in on the latter, then you're likely to be looking at various forms of liver damage (incuding drug-induced), or bile duct/pancreatic problems.

In general, elevated transaminases are a warning sign no matter what. The first thing to suspect is liver damage, but that can be a surprisingly hard diagnosis to nail down, given the other reasons for these enzymes to go up. That goes for all the possible causes. Drug-induced liver damage, for example, can be difficult to diagnose unless the patient has taken (or especially taken too much of) one of the drugs that is most associated with trouble. Acetominophen/paracetaol leads that list, unfortunately, but there are a lot of idiosyncratic reactions that make this a tough call for a diagnostician.

Most types of liver damage will indeed elevate ALT and AST, for example, but so will plenty of other things. The ratio of the two can be a useful marker. High AST/ALT is a sign of alcoholic liver damage, but it can also occur in nonalcoholic fatty liver disease. Most other types of liver damage tend to cause higher ALT/AST, by contrast., But you still have to be careful with these - for example, AST and ALT can also leak from damaged muscle cells, especially the former, and someone who's had a strenuous workout can show an AST/ALT that could lead you to the wrong conclusions entirely. Some muscle diseases will show the same pattern. Things get easier to pin down when the levels are way off the normal range. It takes really severe liver damage to produce levels of these enzymes that are (for example) twenty times or more than normal baselines, and you're probably looking at acute viral hepatitis or perhaps an ischemic injury. Very bad news, in either case.

So what this should do is make you glad that you're not diagnosing liver disease for a living - unless of course you are diagnosing liver disease for a living, in which case you have recourse to several other less common blood markers, to imaging, and even to liver biopsy samples if it comes to that (there is no such thing as a casual liver biopsy). One should expect nothing less from such a complex and multifunctional organ, one that the body's entire blood supply is constantly sluicing through, and one which is responsible for processing the immediate contents of a digested meal in the bloodstream, for clearing metabolites (known and unknown) from the bloodstream, and several other can't-survive-without-'em functions. Respect the liver!

https://www.science.org/content/blog-post/liver-damage