Elevated AST in Lichen Planopilaris (LPP): Is their a connection?
Elevated AST Liver Enzymes in Patients with Lichen Planopilaris
I’ve selected this question below for this week’s question of the week. It allows us to review some concepts in elevated liver enzymes in patients with autoimmune diseases.
Question
Has there been a correlation found between LPP and high AST levels before any medications? I was diagnosed with LPP a year ago and my doctor. I was prescribed hydroxychloroquine and ordered blood tests to monitor my reaction to the hydroxy and my AST was elevated to 151. The AST levels were the only elevated levels on the panel. Almost a year later my levels have increased to 210 and I have not been on any medications at all. They have run multiple liver tests and so far can find no reason for the elevated AST levels. I'm trying to find out if there has ever been any studies done linking high AST to LPP.
Thank you for your time.
Answer
Thanks for submitting this interesting question. There’s no clear or well defined relationship between elevated AST and LPP that we understand yet. However, there are a few important things to mention here. There’s little doubt in my mind that you’ll want to make sure you’ve had three things completed to figure out why your AST is elevated. Perhaps you’ve already had some of these three things done:
1) you’ll want to have a full panel of liver tests, including assessment of macro AST (see below)
2) you’ll want to have a liver ultrasound and
3) you’ll want to visit with a gastroenterologist or gastroenterologist specializing in liver issues (called a hepatologist.
Let’s go through the points that are relevant here. I’ll assume that your AST elevations are not due to hydroxychloroquine.
First, it’s important to note that there are many causes of elevated liver enzymes including medications, alcohol, viral infections, autoimmune diseases and malignancies.
The most common causes of elevated liver enzymes are nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease. Other causes that need to be considered in anyone with elevated liver enzymes medication-induced liver injury (drug induced liver injury), hepatitis B and C, hereditary hemochromatosis, alpha1-antitrypsin deficiency, autoimmune hepatitis, biliary diseases, and Wilson disease. Other diseases due to diseases outside the liver (called extrahepatic sources) include thyroid disorders, celiac disease, renal disease, muscle disorders (cardiac and skeletal), and hemolysis.
As you can see from the above list, it’s critically important for you and your doctors to realize that elevated liver enzymes don’t necessarily mean there’s an issue with just the liver itself. Elevations of the AST level may be seen in acute injury to cardiac or skeletal muscle. Elevated ALT can be seen with obesity, diseases of the biliary tract, anorexia, muscle diseases, heart diseases, and hypothyroidism.
The key point with your story is to confirm that your AST is elevated all on its own and everything else is perfectly. Elevated AST (with normal ALT levels) is not a common phenomenon. If any other tests are abnormal like ALT, ALP or bilirubin it changes the list of possibilities quite dramatically. So I’ll assume here that largely your AST is high and everything else is normal.
Do patients with LPP have an increased risk of Liver disease?
Liver disease is not that uncommon in the population. According to the CDC, at least 2 % of the US population has some kind of liver disease. It has been estimated that 1 in 10 people in the US have elevated liver enzymes. So it’s not that uncommon that someone comes into the hair clinic with abnormal liver enzymes. About 5 % of those with elevated liver enzymes will have some sort of underlying serious disease. Most do not.
Patients with LPP don’t seem to be at all that much of an increased risk of developing liver disease - at least how we understand it now. it would seem that 1 in 10 patient with LPP should have elevated liver enzymes just like the risk in the general population.
Whether patient with LPP truly are at increased risk of non alcoholic fatty liver disease (NAFLD) is not clear, but it’s something that needs more research study. We know that patients with LPP are at increased risk for metabolic syndrome (see prior article) and patients with metabolic syndrome are at increased risk for NAFLD. Therefore, it’s at least conceivable that patients with LPP are at increased with for NAFLD. NAFLD is commonly seen in those with metabolic syndrome.
However, non alcoholic fatty liver disease does not typically give an elevated AST and a completely normal ALT. Rather, the typical findings in NAFLD are raised ALT and AST. The levels are not elevated equally - and the ALT is generally elevated more than AST with an ALT: AST ratio of around 1.5. Patients with NAFLD may have a raised gamma glutamyl transferase (GGT) and, occasionally, raised alkaline phosphatase (ALP). During progression of NAFLD to cirrhosis this ratio of AST:ALT can change.
We don’t have any reason to suspect that patients with LPP are at increased risk to be diagnosed with underlying hepatitis C. This has been described in some countries with lichen planus - but not with lichen planopilaris. Still, as you’ll see below, most physicians will screen for hepatitis C in someone with LPP and elevated liver enzymes.
Blood tests for those with Elevated Liver Enzymes
There are a series of liver and non-liver related tests that your doctor will consider. The exact tests you’ll need will depend on your complete story since birth and what is found on physical examination so I can’t say for sure which tests you should have (because I don’t know your full story and haven’t examined you).
The following blood tests, however, should at least be considered in anyone with your story:
CBC, reticulocyte count, urinalysis, AST, ALT, GGT, CK, LDH, amylase, albumin, PTT, INR, ferritin, total protein, bilirubin, ALP, TSH, anti-tissue transglutaminase, serum zinc and copper. Fasting cholesterol, HDL, LDL, triglycerides, glucose and hemoglobin A1C are generally ordered. Hepatitis C screening (anti HCV), hepatitis B screening (anti - HBSAb, anti HBSAg), CMV and EBV. ANA is often appropriate in these cases to order as well. I generally order a serum protein electrophoresis - especially in those with elevated AST.
The above tests are the tests I typically order myself in patients with liver enzyme issues. There are more tests yet that can be ordered- but I typically leave these for the gastroenterologist (or liver specialist) to order or advise me on ordering.
For example, your gastroenterologist or liver doctors will decide whether any of the autoimmune hepatitis panels are appropriate but generally those should be left for the internists or liver doctors. These include the anti-liver-kidney microsomal antibodies (so called anti LMK test ) and anti smooth muscle (anti SMA) antibody. I also generally leave screening for Wilson’s disease to the liver doctor (these are tests called ceruloplasmin, copper). Tests for alpha-1-antitrypsin deficiency are also best left for the liver doctor.
Blood tests for those with Elevated AST
ALT is said to be a more liver ‘specific’ enzyme. AST can be elevated in many conditions including thyroid disorders, muscle disorder, celiac disease and blood problems causing hemolysis. Alcohol consumption can injure the liver and raise AST. Generally the ratio of AST to ALT is above 2:1 in alcoholic liver disease (often 3:1 or more) It’s not common for AST to be elevated and ALT to be normal in alcoholic liver disease.
AST is rich in heart tissue, liver, muscle, kidney, pancreas, brain and red blood cells. You can quickly see that elevated AST can come from many sources - not only the liver. For this reason, it is often said that ALT is more specific test for liver injury. A work up by a liver doctor is reasonable to help sort all this out (see below).
If AST is the only test that’s really elevated (and ALT, bilirubin and the other tests are normal), you’ll want to consider the possibility of something known as “macro‐AST” as a possible cause for this increase in AST. Using a special lab test involving precipitation with polyethylene glycol (PEG), ultracentrifugation and gel filtration chromatography (GFC) the lab can determine a person’s true AST level.
Macro AST is generally thought to be increased in those with various autoimmune issues and tends to occur when AST forms complexes each other or with immunoglobulins (like IgG and IgA) in the blood stream. Because these complexes are so big, they can’t be cleared by the kidneys very easily so they just accumulate in the blood.
In 2011, Lee and colleagues suggested that about 13% to 60 % of those being evaluated for elevated AST levels had macro AST.
It’s difficult sometimes to find a lab that knows how to deal with macro AST testing and perform the necessarily testing to evaluate true AST from macro AST levels. However, a liver doctor will know how to access these tests.
The AST and ALT Ratio: DeRetis Ratio
A lot of attention is often paid to the ratio of AST and ALT in liver disease. It’s not very specific. But AST to ALT levels well above 3:1 are often seen in alcoholic liver disease. As mentioned above, one needs to consider macro AST when there is no good history of alcohol use and the rest of the blood tests come back normal.
AST to ALT level are often above 2:1 in alcoholic hepatitis, non alcoholic steatohepatitis, myocardial infarction, drug, and some viral hepatitis infections. Liver cirrhosis and liver metastases often have AST to ALT above 2:1
Levels of AST to ALT are less than 1 (ie ALT is the bigger number) with various liver toxins, hepatocellular injury, viruses (viral hepatitis), and intrahepatitic cholestasis and extrahepatic biliary obstruction
Liver Ultrasound
You’ll want to discuss with your doctors the possibility of having a liver ultrasound scan to further evaluation for any liver issues. This can be a very useful test to evaluate for possible liver disease or disease in the biliary tree.
Referral to a Gastroenterologist or Subspecialty Liver Doctor
Referral to a liver doctor may be advised in some cases. Generally speaking, levels of AST or ALT above 5 time the upper limit of normal make if all the more important to consider referral. With levels of 210, referral to a liver doctor makes good sense. The liver doctor will review the story, perform an examination and review the blood tests (see above) and liver ultrasound findings. The liver doctor will determine if any other tests are needed (liver MRI) and whether a liver biopsy is likely to help.
Certainly a liver doctor will know how to access tests to evaluate for macro AST.
The liver doctor will help formulate the exact reason for the elevated AST and can always refer to other specialists (rheumatologist etc) if this is thought to be helpful. Referral to a rheumatologist is helpful if there is any joint stiffness, fevers or unusual fatigue (and if any of the tests for ANA or autoimmune panels come back positive).
Conclusion and Summary
Thanks for submitting this question. I think it’s important to make sure you’ve had a proper work up and evaluation via all the blood tests. An internist or general practitioner can help get these ordered and can perform a good history and good head to toe examination looking for any concerns. Some of the more autoimmune based tests (ANA, anti SMA, anti LMK) are relevant to anyone with autoimmune disease like LPP but these are often left to the liver doctor to decide how best to order.
A liver ultrasound may be needed to rule out any pathology.
In the setting of completely normal tests, and good health, it may be really important to consider the MACRO-AST phenomenon. Your liver doctor can help you with that.
REFERENCE
Lee M, Vajro P, Keeffe EB. Isolated aspartate aminotransferase elevation: think macro-AST. Dig Dis Sci. 2011;56:311-313.
Giannini EG, Testa R, Savarino V. Liver enzyme alteration: a guide for clinicians.CMAJ. 2005 Feb 1;172(3):367-79. doi: 10.1503/cmaj.1040752
Oh RC et al. Mildly Elevated Liver Transaminase Levels: Causes and Evaluation., Hustead TR, Ali SM, Pantsari MW.Am Fam Physician. 2017 Dec 1;96(11):709-715.