Transcript

Lee Tetreault:

Hello and welcome to Frequently Asked Questions. We are joined today by Dr. Sanjiv Chopra. Doctor, how extensive a work-up should be done for a patient with unexplained and persistent elevated AST and ALT? 

Dr. Chopra:  

It's a very good question. The first thing to ponder is to ask yourself the question, "Is the elevated AST and ALT truly reflecting hepatic injury or disease? So it turns out that both AST and ALT can be elevated in non-hepatic disorders. For example, muscle injury or muscle disease can lead to an elevated AST. We were taught that in medical school, but also elevated ALT. The first step is to step back and say, "Does my patient really have liver disease, or there's something else possibly masquerading as liver disease? 

If there's an elevated AST, ALT, Alk Phos, Bilirubin, Albumin, Protein then we know we're dealing with hepatobillary disease. But just elevated AST and ALT, I'd like to recommend for you, to remember a simple mnemonic. It's MCAT. Could it be muscle injury or disease? Checkup his CPK. C is for celiac disease. Celiac disease can present as unexplained liver disease. A is adrenal insufficiency or Addison's Disease. And T is thyroid. So thyroid disorders are very common and can present as myopathy, and can lead to elevated AST and ALT coming from muscle. So MCAT, Muscle Celiac Adrenal Thyroid. Check the Folic test, CPK. Celiac, we test for tTG Antibody, Tissue Transglutaminase Antibody and Serum IGA level. Adrenal, check for Serum Cortisol. Thyroid, check for TSH, Thyroid Stimulating Hormone. If those are all unrevealing or negative, then we have to say we're dealing with some kind of liver disorder. And it would necessitate an appropriate serological workup, imaging work up and possibly even a liver biopsy.

Lee Tetreault:

When is jaundice an emergency? 

Dr. Chopra:  

Jaundice is an emergency in only three particular instances in adult medicine. And those are, if you suspect the patient has cholangitis. They might have a common bile duct stone or a stricture and now there's infection in the biliary tree. And this can lead to gram-negative sepsis, can lead to liver abscesses, so that's an emergency. We need to image the hepatobilliary tree, do blood cultures. If there's a stone often using an endoscopic procedure, ERCP, doing a papillotomy and extracting the stone. You have to admit the patient and do all of that.

The second situation is when the patient has Fulminant hepatic failure. Fulminant hepatic failure by definition is severe acute liver disease with any level of hepatic encephalopathy. And if that's the case, then these patients should be referred to, they are then admitted to a tertiary care center where they do liver transplants. These patients get to be number one on the liver transplant list. We don't have a treatment for Fulminant hepatic failure. There is no dialysis like we have for acute kidney failure. Fulminant hepatic failure, acute cholangitis, and the third condition in adults is massive hemolysis. They're destroying red cells that may turn out to be Babesiosis, Ehrlichiosis, Lyme disease. We actually had a patient not too long ago who had all three conditions related to a tick bite and he had massive hemolysis. That's an emergency. We need to figure out what's causing the hemolysis and treat it.

It could be malaria falciparum that is colloquially known in parts of the world where it's common as black water fever. Patients are febrile and the black water refers to the very dark urine which is related to hemoglobinuria, which is due to hemolysis. So acute cholangitis, fulminant hepatic failure, massive hemolysis are three emergencies in the setting of jaundice where the patient has to be admitted promptly to a hospital under the appropriate workup and consultation with experts has to be done.

In newborns, if they have severe unconjugated hyperbilirubinemia, that's the bilirubin that crosses the blood brain barrier. And it can stain the basal ganglia and other parts of the brain and can lead to Kernicterus and can lead to choreoathetosis, mental retardation, deafness. So that's an emergency. We see a rising unconjugated bilirubin in newborns. While we are making the diagnosis, is it Crigler-Najjar type 1? What is the cause of this severe unconjugated hyperbilirubinemia? We put the patient under bilirubin lights, that leads to photo degradation of bilirubin. And then the bilirubin levels come down as the photo-degraded products of bilirubin are excreted, and get out of the system. So only four situations, three in adults: Acute cholangitis, fulminant hepatic failure, massive hemolysis, and in newborns, severe unconjugated Hyperbilirubinemia.

Lee Tetreault:

A patient has mild unconjugated hyperbilirubinemia, what is the appropriate workup? 

Dr. Chopra:  

Very likely that comes to light often during a physical examination for insurance purposes. A person is perfectly healthy, they get a slew of lab tests including a liver function profile. And lo and behold, the serum bilirubin total is mildly elevated, and it's predominantly unconjugated or indirect. So if the total fraction is two and more than 75% is indirect, we call it indirect hyperbilirubinemia.

In a perfectly healthy person, there are really two possibilities, either the person has low grade hemolysis, so in that case the hematocrit will be low, there will be an elevated LDH, there may be changes on peripheral smear, there may be an elevated Retic count. If we excluded hemolysis, the most common cause, and actually a very common malady is called Gilbert's syndrome. So it's pronounced Gilbert's, it's spelled G-I-L-B-E-R-T'S. And it may be present in 3-7% of adult males. So very common, comes to light, if they're stressed, if they are fasting, if they are post-operative, not being fed by mouth, or they go for the insurance exam and they have a slightly elevated total and predominantly indirect bilirubin level.

And the insurance company will often say, "We don't want to insure you, or we want to give you high premiums, you've got some liver disease", that's when they get referred to me. Once I exclude overt hemolysis, the next step is very simple, it's called caloric deprivation. So we test a total bilirubin, indirect bilirubin, let's say it's two out of which 1.7 is indirect. Over the next 24 hours the patient consumes less than 400 kilocalories. They come back, we repeat the blood test. And now the bilirubin has gone from 2 to 2.4, 2.6 and again, 75, 80, 90% is indirect. This actually proves that they have Gilbert's syndrome. We don't have to do a liver biopsy and measure the enzyme UDPGT, uridine diphosphate glucuronosyltransferase which is the enzyme responsible for conjugation of bilirubin and which is deficient in these patients with Gilbert's. That's a much more invasive test, we exclude hemolysis, do the caloric deprivation, repeat the bilirubin. And then I write them a letter, or write a letter to the insurance company and say, this patient has Gilbert's, they don't have any real liver disease. They have normal life span. In fact this person may be better off than you and me because bilirubin is a very rich anti-oxidant.

Lee Tetreault:

A common finding on ultrasound or other liver imaging studies is a small hepatic hemangioma. What is its significance and the appropriate management? 

Dr. Chopra:  

A hepatic hemangioma is a very common finding in autopsy studies, 3-7% of individuals will turn out to have a hepatic hemangioma. If the patient undergoes an ultrasound or imaging study for other reasons, for example, they're looking at the kidney or they're looking at the pancreas, and, lo and behold, when they look at the liver, they find a lesion and it's very, very characteristic on ultrasound or CT of a hemangioma, really no workup is indicated.

Important thing to remember is the size, if it's more than 10 centimeters, we call it a giant hepatic hemangioma. And if this is superficial and present in the right lobe or the left lobe I would simply caution these individuals not to partake in any kind of sports or activities where they could possibly traumatize the abdomen. So you know what, no mud wrestling and no physical fights and no bungee jumping, otherwise leave it alone. And it's only on very rare occasions in kids they can develop high output cardiac failure or in adults, there are extremely rare instances of steroid-refractory polymyalgia rheumatica. So somebody has polymyalgia rheumatica and they're not responding to steroids, we would image the liver, and if they have a hemangioma, removal of the hemangioma takes care of that condition.

Also on very rare occasions, extremely rare case reports, we're talking about patients can have severe hypothyroidism, the hemangioma tissue makes an enzyme that inactivates thyroxine, so they can develop hypothyroidism. Hypothyroidism, refractory polymyalgia rheumatica, high output failure are what we see with hemangiomas on rare occasion. Also in kids there's a rare syndrome called Kasabach-Merritt syndrome, where they have a low platelet count and it's related to the hemangioma. So most of the time, I would say 99% of the time, a hemangioma is an incidental finding, it's benign, if the radiologist is confident based on ultrasound or CT or MRI that this is a hemangioma, leave it alone.

Lee Tetreault:

Wow, this is great information doctor, thank you so much for your time today.