The Curbsiders podcast

#302 LFTs Triple Distilled

October 27, 2021 | By

Fine-tune your approach to liver tests!  It’s LFTs Triple Distilled! Paul and Matt channel the wisdom of hepatologist, Dr. Elliot Tapper (@ebtapper) to cover hepatocellular vs cholestatic vs mixed patterns, which tests to order, which ones to skip, how to handle isolated alkaline phosphatase elevation, mild, chronic ALT elevation, and even how to interpret liver test abnormalities in pregnancy. 

Note: No CME for this mini-episode but visit to claim credit for shows #293 at!

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  • Written, Produced, and Hosted by: Matthew Watto MD, FACP; Paul Williams MD, FACP  
  • Infographic by: Elena Gibson MD
  • Cover Art: Matthew Watto MD, FACP
  • Editor: Matthew Watto MD, FACP (written materials); Clair Morgan of

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CME Partner: VCU Health CE

The Curbsiders are partnering with VCU Health Continuing Education to offer FREE continuing education credits for physicians and other healthcare professionals. Visit and search for this episode to claim credit. 

Show Segments

  • Intro, disclaimer, guest bio
  • Hepatocellular pattern
  • Cholestatic pattern
  • Chronic ALT elevation
  • Isolated Alkaline phosphatase elevation
  • Liver test abnormalities in pregnancy
  • Outro

Episode #293 The Best of Liver Tests

Featuring Elliot Tapper with production and graphics by Elena Gibson

Matt’s Pearl – For acute liver injury, first identify the pattern. You can use the R score (ratio of ALT to ALP elevation) to determine if hepatocellular (>5), mixed (2-5), or cholestatic (<2). 

Hepatocellular injury pattern: 

Common acute causes include viral hepatitis, acetaminophen, DILI, ischemia, autoimmune hepatitis. Dr. Tapper recommends checking HAV, HBV, HCV, acetaminophen levels, ANA, IgG, ASMA, and review all medications (LiverTox). Consider imaging because stone disease can cause elevation in the 100s or 1000s (expert opinion).

Kashlak Pearl: The bilirubin is intimately linked to Dr. Tapper’s heart!

Kashlak Pearl: Dr. Tapper rarely starts immunosuppression for AI hepatitis without a liver biopsy to confirm (expert opinion). 

Kashlak Pearl: Hemochromatosis and Alpha-1 antitrypsin do not cause acute liver injury. Wilson’s can cause acute injury (and failure), but it is rare, especially in older adults. Ceruloplasmin has poor sensitivity and specificity (Korman, 2008).

Kashlak Pearls: Avoid these tests for most patients with acute liver injury (expert opinion). 

  • Don’t order HSV, EBV, and CMV unless the patient is receiving chemotherapy, or on immunosuppression for organ transplant (expert opinion).
  • Non-hepatologists don’t need to order anti-LMK (liver-kidney microsome) or SLA antibodies (solube liver antigen) for all-comers with liver disease (expert opinion).

Cholestatic injury pattern

He pays special attention to symptoms of fatigue or itching, which suggest primary biliary cholangitis (an uncommon condition). The differential diagnosis for cholestatic disease includes biliary obstruction (e.g. PBC, PSC, choledocholithiasis), infiltrative diseases (e.g. sarcoidosis), DILI, CVID, and even NAFLD. Typically, Dr. Tapper starts with RUQ ultrasound and antimitochondrial antibody (AMA). He usually sends ASMA, and ANA whenever testing for PBC (expert opinion). An MRCP can be a second round test depending on the findings. 

Chronic ALT elevation 

We had a lot of questions after the show about the patient with chronic, mild ALT elevation. Dr. Tapper published a paper in 2017 that he shared on Twitter (Tapper, 2017). In general, focused testing (HCV Ab, HBV sAg, ETOH screen, hepatic US) can provide a diagnosis for many patients. The FIB-4 score, and/or transient elastography can provide a barometer for NAFLD disease. More extensive serologic testing can lead to false positives, but paradoxically may cost less and require fewer office visits (Tapper, 2017). Both Matt and Paul typically perform focused testing for most patients suspected of having NAFLD (aka MAFLD). They’re more likely to perform extensive testing (e.g Wilson’s, hemochromatosis, alpha-1 antitrypsin, autoimmune hepatitis, PBC) if the story doesn’t fit typical patterns or if symptoms suggest an alternative diagnosis (Curbsiders opinion). 

Isolated Hyperbilirubinemia 

We discussed how mild isolated bilirubin elevation (usually <4) should be fractionated. Indirect hyperbilirubinemia without evidence of hemolysis (LDH, haptoglobin, or negative peripheral smear) is diagnostic of Gilbert’s.

Isolated Alkaline Phosphatase Elevation

Dr. Tapper notes that these people generally need an imaging test. Patients with mild (<2 times normal) elevation, and without worrisome symptoms (e.g. fatigue or itching) can be followed with serial measurements. We can “let time be the arbiter of truth” –Dr. Elliot Tapper

The differential diagnosis and workup for isolated alkaline phosphatase elevation is the same as for cholestatic liver disease (see above). 

Note: Dr. Tapper is not a fan of GGT as it is not specific to cholestatic liver disease (Twitter thread by @ebtapper). 

Liver diseases of pregnancy

  1. Preeclampsia
  2. Intrahepatic cholestasis of pregnancy –cholestatic liver injury with elevated serum bile salts. Treatments: First line = ursodeoxycholic acid and 2nd line cholestyramine to lower serum bile salts! Higher levels are associated with poor fetal outcomes.
  3. Remember! A pregnant patient can have any other cause of liver disease discussed above!


Listeners will review tops pearls from recent curbsiders episodes

Learning objectives

After listening to this episode listeners will…

  1. Build a framework to interpret liver test abnormalities
  2. Order the appropriate testing based on the pattern of liver tests


The Curbsiders report no relevant financial disclosures. 


Williams PN, Watto MF. “#302 LFTs Triple Distilled”. The Curbsiders Internal Medicine Podcast. Final publishing date October 27, 2021.

CME Partner


The Curbsiders are partnering with VCU Health Continuing Education to offer FREE continuing education credits for physicians and other healthcare professionals. Visit and search for this episode to claim credit.

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