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.
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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).
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).
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.
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).
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.
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).
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Williams PN, Watto MF. “#302 LFTs Triple Distilled”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list Final publishing date October 27, 2021.
The Curbsiders are partnering with VCU Health Continuing Education to offer FREE continuing education credits for physicians and other healthcare professionals. Visit curbsiders.vcuhealth.org and search for this episode to claim credit.
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