ALT;

Test your knowledge by answering the following questions based on some of the most frequently viewed pearls on Pearls4Peers during the last quarter!

FA Manian MD, MPH, , , , , , , , , , Leave a comment

Please answer each question first then click on the link provided for pearls!

The urine culture of my female patient with urgency is growing Lactobacillus spp.  Should I treat it? – Pearls4Peers 

What is the significance of teardrop cells (dacrocytes) on the peripheral smear of my patient with newly-discovered pancytopenia? – Pearls4Peers

What does an “indeterminate” result in QuantiFERON Gold in-Tube test for latent tuberculosis really mean? – Pearls4Peers

Why is serum AST levels generally higher than ALT in alcohol-induced liver injury? – Pearls4Peers

What’s causing an isolated GGT elevation in my patient with an abnormal alkaline phosphatase on her routine admission lab? – Pearls4Peers

How should I interpret the growth of “normal respiratory flora” from sputum of my patient with community-acquired pneumonia (CAP)? – Pearls4Peers

Is meropenem a good choice of antibiotic for treatment of my patient’s intraabdominal infection involving enterococci? – Pearls4Peers

Is iron therapy contraindicated in my patient with active infection? – Pearls4Peers

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

Test your knowledge by answering the following questions based on some of the most frequently viewed pearls on Pearls4Peers during the last quarter!

My patient with choledocholithiasis presents with acute abdominal pain, bile duct dilatation and markedly elevated serum aminotransferases (AST and ALT).  Can her markedly elevated AST and ALT levels be caused by cholelithiasis with bile duct obstruction?  

FA Manian MD, MPH, , , , , , , , , , , , , Leave a comment

Although markedly increased serum alanine transaminase (ALT) and aspartate transaminase (AST) are often considered a marker for severe hepatocellular injury or necrosis (particularly when levels exceed 1000 IU/L), occasionally such elevations may also be due to isolated acute biliary duct obstruction caused by choledocholithiasis.1  

In one case series, patients  diagnosed with choledocholithiasis were found to have transient elevations in their AST/ALT (>1000 units/L) directly proportional to the degree of common bile duct dilation in the absence of any hepatocellular disease on imaging. These levels were found to rapidly fall following intervention with endoscopic retrograde cholangiopancreatography (ERCP). 2   Intriguingly, the authors of this study suggest that patients who present with severe abdominal pain associated with an acute and markedly elevated serum aminotransferase levels, are more likely to have acute biliary obstruction than hepatocellular disease.3  Several other case series have also shown similar elevations of serum aminotransferases in choledocholithiasis, with some levels reaching >2000 IU/L.4   

Several hypotheses have been proposed to explain this phenomenon, including pressure-induced damage of hepatocytes and bile salt-induced hepatocyte injury in the setting of acute biliary duct obstruction.2 Of interest, some have proposed that the gallbladder may minimize elevations in serum aminotransferases by protecting the liver from rapid increases in biliary duct pressure.  In fact, more robust elevations in aminotransferases in choledocholithiasis have been observed in those who have had cholecystectomy.4   

So even though choledocholithiasis is traditionally associated with a “cholestatic” pattern of enzyme elevations—with elevated alkaline-phosphatase, and gamma-glutamyl transferase (GGT) levels 1,3—when associated with bile duct obstruction, it  can also be associated with markedly elevated ALT and AST.  

Bonus Pearl: Did you know that when assessing for choledocholithiasis, magnetic resonance cholangiopancreatography (MRCP) is more sensitive than ultrasound (81% vs 18-74 %).4,5,6  

Contributed by Connor S. Shaw, D.O., Mercy Hospital, St. Louis, Missouri

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

 

 

References  

  1. Feldman, Mark, et al. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management. Elsevier, 2021.  
  2. Tetangco, Eula Plana, et al. “Markedly Elevated Liver Enzymes in Choledocholithiasis in the Absence of Hepatocellular Disease.” Journal of Investigative Medicine High Impact Case Reports, vol. 4, no. 2, 2016, p. 232470961665109., https://doi.org/10.1177/2324709616651092. 
  3. De Angelis C, Marietti M, Bruno M, Pellicano R, Rizzetto M. Endoscopic ultrasound in common bile duct dilatation with normal liver enzymes. World J Gastrointest Endosc. 2015 Jul 10;7(8):799-805. doi: 10.4253/v7.i8.799. PMID: 26191344; PMCID: PMC4501970.
  4. Agahi, A., and A. McNair. “Choledocholithiasis Presenting with Very High Transaminase Level.” Case Reports, vol. 2012, no. nov22 2, 2012, https://doi.org/10.1136/bcr-2012-007268.
  5. Makmun, Dadang, et al. “Sensitivity and Specificity of Magnetic Resonance Cholangiopancreatography versus Endoscopic Ultrasonography against Endoscopic Retrograde Cholangiopancreatography in Diagnosing Choledocholithiasis: The Indonesian Experience.” Clinical Endoscopy, vol. 50, no. 5, 2017, pp. 486–490., https://doi.org/10.5946/ce.2016.159.
  6. Ferri, João Victor, et al. “Níveis Elevados De Transaminases Em Um Caso De Coledocolitíase: A Importância Do Reconhecimento Deste Padrão.” Revista De Medicina, vol. 96, no. 2, 2017, p. 131., https://doi.org/10.11606/issn.1679-9836.v96i2p131-133.   

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

My patient with choledocholithiasis presents with acute abdominal pain, bile duct dilatation and markedly elevated serum aminotransferases (AST and ALT).  Can her markedly elevated AST and ALT levels be caused by cholelithiasis with bile duct obstruction?  

How would you answer these 7 most popular clinical questions of 2022 on Pearls4Peers??

FA Manian MD, MPH, , , , , , , , , , , , , , Leave a comment

Peers,

www.Pearls4Peers.com just turned 7 with 2022 poised to become its best year ever in viewership  (>30,000 views so far)!  To mark this “momentous” occasion, I thought I would share with you, loyal viewers and subscribers, the 7 most viewed posts  of 2022 at its midway point.  Imagine rounding on the wards with your team and someone asks you one or more of these questions.  Take a crack at answering them and compare your answers with those of P4P (Ctrl+Click)! Have fun!

  1. What is the significance of teardrop cells(dacrocytes) on the peripheral smear of my patient with newly-discovered pancytopenia?
  2.  My elderly patient developed a flare-up of her gout few days after receiving covid-19 vaccine. Is there a connection between immunization and gout flare? 
  3. What is the clinical relevance of the “SPICE” organisms? 
  4. What does an “indeterminate” result in QuantiFERON Gold in-Tube Test for latent tuberculosis really mean? 
  5. What is the difference between “moderate” and “high complexity” medical decision making under the Centers for Medicare and Medicaid Services (CMS) rule? 
  6. The urine culture of my female patient with urgency is growing Lactobacillus. Should I treat it?
  7. Why is serum AST levels generally higher than ALT in alcohol-induced liver injury?

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

How would you answer these 7 most popular clinical questions of 2022 on Pearls4Peers??

How often is the liver affected by Covid-19?

FA Manian MD, MPH, , , , , , , , , , , , , Leave a comment

Abnormal liver enzymes in patients with Covid-19 are common, particularly in those with severe disease.

 
Elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) have been reported in 14-53% of patients in several case series. More severe cases appear to have a higher prevalence of AST elevation (1). As some cases also have elevated creatine kinase (CK), the relative contribution of muscles to these enzyme abnormalities is unclear (2).

 
A small study involving ICU patients with Covid-19 reported a prevalence of elevated AST of 62% compared to 25% in non-ICU patients (3). Other studies have confirmed lower incidence of AST abnormality among patients with mild or subclinical disease (4,5).

 
Although much of the published reports of liver injury in Covid-19 have revolved around AST and ALT abnormalities, gamma-glutamyl transferase (GGT) may also be elevated. GGT was abnormal in 54% of patients with Covid-19 during their hospitalization with alkaline phosphatase elevation reported in ~2.0% (1, unpublished reports). Elevation of total bilirubin has also been reported occasionally (1).

 
Although the exact mechanism(s) of Covid-19-related is unclear, direct viral infection of liver cells is one possibility as viremia has been documented in some cases (1). Of interest, a related coronavirus, SARS-CoV-1 has been shown to infect liver tissue and cholangiocytes may express ACE2 receptors, a prime target for Covid-19 virus (1,6,7, unpublished reports).

 

Despite these observations, to date, viral inclusions have not been demonstrated in the liver. Other possible causes of liver injury in Covid-19 include innate immune dysregulation, cytokine storm, hypoxia and drugs (1,2).

 

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

 

References
1. Zhang C, Shi L, Wang FS. Liver injury in COVID-19:management and challenges. Lancet Gastroenterol Hepatol 2020; March 4. https://doi.org/10.1016/S2468-1253(20)30057-1
2. Bangash MN, Patel J, Parekh D. COVID-19 and the liver: little cause for concern. Lancet Gastroenterol Hepatol 2020;March 20. https://doi.org/10.1016/52468-1253(20)30084-4
3. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506. https://pubmed.ncbi.nlm.nih.gov/31986264/
4. Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of 2019 novel coronavirus infection in China. N Engl J Med 2020;published online Feb 28. DOI:10.1056/NEJMoa2003032
5. Shi H, Han X, Jiang N, et al. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis 2020; published onlineFeb 24. DOI:10.1016/S1473-3099(20)30086-4 (lancet 8)
6. Chai X, Hu L, Zhang Y, et al. Specific ACE2 expression in cholangiocytes may cause liver damage after 209-nCoV infection. bioRxiv 2020;published online Feb 4. https://doi.org/10.1101/2020.02.03.931766.
7. Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 2020; published online Feb 18. DOI:10.1016/S2213-2600(20)30076-X

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

How often is the liver affected by Covid-19?

Can the elevation of AST and ALT in my patient with rhabdomyolysis be related to the muscle injury itself?

FA Manian MD, MPH, , , , , , , , , , , , , , , , , , , , , Leave a comment

Yes! Elevated serum AST and ALT in the setting of rhabdomyolysis is not uncommon and, at least in some cases, appears to be related to the skeletal muscle injury itself.1,2

In a study of 16 patients considered to have significant muscle necrosis due to extreme exercise, polymyositis or seizures without evidence of liver disease (eg, viral hepatitis, exposure to hepatotoxic drugs, heart failure, biliary tract disease, recent hypotension) AST and, to lesser degree, ALT was elevated. For extreme exercise, the median AST and ALT concentrations were 2,466 IU/L and 497 U/L, respectively, while for seizures these levels were 1,448 U/L and 383 U/L respectively.1  

Another study reported AST elevation (>40 U/L) in 93.1% of patients with rhabdomyolysis and ALT elevation (>40 U/L) in 75.0% of patients with serum creatine kinase ≥1000 U/L. 2  Further supporting a skeletal muscle origin for AST elevation was the finding that AST concentrations fell in parallel with CK drop during the first 6 days of hospitalization for rhabdomyolysis. It was posited that ALT concentrations dropped slower because of its longer serum half-life (47 hours vs 17 hours for AST).2 Despite these findings, concurrent liver injury as an additional source of AST or ALT elevation cannot be excluded.

Elevation of AST and ALT with muscle injury should not come as a surprise. AST is found in heart and skeletal muscle among many other organs. Even ALT which is considered more specific to liver is found in organs such as skeletal muscle, heart and kidney, though at lower concentrations.3

Bonus Pearl: Did you know that the first description of rhabdomyolysis in the literature involved English victims of crush injuries during World War II?2

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

 

References

  1. Nathwani RA, Pais S, Reynolds TB, et al. Serum alanine aminotransferase in skeletal muscle diseases. Hepatology 2005;41:380-82. https://www.ncbi.nlm.nih.gov/pubmed/15660433
  2. Weibrecht K, Dayno M, Darling C, et al. Liver aminotransferases are elevated with rhabdomyolysis in the absence of significant liver injury. J Med Toxicol 2010;6:294-300. https://link.springer.com/article/10.1007%2Fs13181-010-0075-9
  3. Giannini EG, Testa R, Savarino V. Liver enzyme alteration: a guidance for clinicians. CMAJ2005;172:367-79. Giannini EG, Testa R, Savarino V. Liver enzyme alteration: a guidance for clinicians. CMAJ 2005;172:367-79. https://www.ncbi.nlm.nih.gov/pubmed/15684121
Can the elevation of AST and ALT in my patient with rhabdomyolysis be related to the muscle injury itself?

What’s causing an isolated GGT elevation in my patient with an abnormal alkaline phosphatase on her routine admission lab?

FA Manian MD, MPH, , , , , , , , , , , , , , , , , , , Leave a comment

Although serum gamma-glutamyl transpeptidase or GGT is a very sensitive test for liver disease, especially of biliary origin, it’s by no means a very specific test. Besides the liver, GGT is found in the kidneys, pancreas, prostate, heart, brain, and seminal vesicles but not in bone (1-4).

 
Obesity, alcohol consumption and drugs are common causes of GGT elevation (2). As early as 1960s, elevated GGT was reported in such seemingly disparate conditions as diabetes mellitus, congestive heart failure, myocardial infarction, nephrotic syndrome and renal neoplasm (3). Nonalcoholic steatohepatitis, viral hepatitis, biliary obstruction, COPD, liver metastasis, drug-induced liver injury can all cause GGT elevation (1-4).

 
An isolated GGT does not necessarily indicate serious or progressive liver disease. That’s one reason it’s often not included in routine “liver panel” lab tests (1).

What to do when GGT is high but other liver panel tests such as ALT, AST, albumin, and bilirubin are normal? If your patient is at risk of acquired liver disease, then further workup may be necessary (eg, hepatitis B and C screening tests). Alcohol consumption should be queried. Don’t forget conditions associated with iron overload. If your patient is obese, diabetic or has elevated both lipids, an ultrasound of the liver to look for fatty liver should be considered. In the absence of risk factors, symptoms, or physical exam suggestive of liver disease, isolated GGT elevation should not require further investigation (1).

 
One good thing that may come out of finding an isolated elevated GGT is to encourage your patient to curb alcohol consumption or lose weight when indicated. But don’t rely on a normal GGT to rule out heavy alcohol consumption as it may miss 70% to 80% of cases (6)! 

 
Bonus Pearl: Did you know that GGT activity is thought to increase in alcohol use due to its role in maintaining intracellular glutathione, an anti-oxidant, at adequate levels to protect cells from oxidative stress caused by alcohol?

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

References

1. Carey WD. How should a patient with an isolated GGT elevation be evaluated? Clev Clin J Med 2000;67:315-16. https://www.ncbi.nlm.nih.gov/pubmed/10832186
2. Newsome PN, Cramb R, Davison SM, et al. Guidelines on the management of abnormal liver blood tests. Gut 2018;67:6-19. https://gut.bmj.com/content/gutjnl/67/1/6.full.pdf
3. Whitfield JB, Pounder RE, Neale G, et al. Serum gamma-glutamyl transpeptidase activity in liver disease. Gut 1972;13:702-8. https://www.ncbi.nlm.nih.gov/pubmed/4404786
4. Tekin O, Uraldi C, Isik B, et al. Clinical importance of gamma glutamyltransferase in the Ankara-Pursaklar region of Turkey. Medscape General Medicine 2004;6(1):e16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1140713/
5. Van Beek JHDA, de Moor MHM, Geels LM, et al. The association of alcohol intake with gamma-glutamyl transferase (GGT) levels:evidence for correlated genetic effects. Drug Alcohol Depend 2014;134:99-105. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909645/

6. Bertholet N, Winter MR, Cheng DM, et al. How accurate are blood (or breath) tests for identifying self-reported heavy drinking among people with alcohol dependence? Alcohol and Alcoholism 2014;49:423-29. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4060735/pdf/agu016.pdf

What’s causing an isolated GGT elevation in my patient with an abnormal alkaline phosphatase on her routine admission lab?