Dr. Robert Gish: PFIC now is high on my workup list. This has been a big change over the last 3 years as I've gotten more education and more experience.

So, I put the PFIC world inside unexplained chronic liver disease, atypical chronic liver disease, cholestatic liver disease with an itch pattern, cholestatic liver disease, elevated bile acids. Each of these are going to be triggers to think about genetic testing and focusing, like a laser, on that PFIC diagnosis.

So when a patient presents to me with a cholestatic liver pattern, I'm going to look for common reasons for cholestasis. I'll take an alcohol history, medication history, of course, see if they have metabolic syndrome, and fatty liver. I'll get abdominal imaging, an ultrasound to look for biliary obstruction or gallstone disease. That's the first level.

The second level is to say, "Oh, that first workup was negative," or, "Something's not typical," even though a workup may be positive or partially positive. Then I'm going to do that second-level testing that's going to include an MRCP. That's that magnetic resonance scan to look for biliary abnormalities, obstruction, PSC, IgG4. I'm going to do a liver biopsy because I may be looking for an atypical type of PBC, primary biliary cholangitis. I'm going to make sure I have bile acids. I'm going to make sure I have a direct bilirubin.

I'm going to stage their liver disease with elastography. Usually, that includes another score for how much fat's in the liver. Very important is getting a liver biopsy and helping that dissect across each of these components, and a big part of this workup is getting a genetics panel. So we have Level 1, we have Level 2. By the time Level 2 is done, in my experience, we have an explanation in 95% of patients.

Dr. Richard Thompson: We know that clinics of patients with liver disease have a huge number of underlying disease processes, and the truth is that genetic diseases are not the most prevalent. So, what we do want people to do is think about when they should be ordering genetics, what should be the triggers? And I think that is becoming clear, and I think, in simple terms, it should be a patient who doesn't fit the typical phenotype of PBC or PSC, for instance. If they're AMA negative. If they've got what looks like PSC, but they've not got IBD.

Maybe it's not the initial presentation, it's the response to treatment that makes them slightly unusual, but these are the sorts of things that we should be looking out for to try and identify patients who have got differences in presentation, differences in response to treatment, which are clues that they may have something which is different from the majority of patients with PBC, for instance.

Dr. Robert Gish: This doesn't take a lot of time, but it does take some energy to go down that pathway to make sure you have each of these tests completed to put a whole package together.