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?  

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

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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?  

My patient with history of gastric bypass surgery now presents with right upper quadrant pain and gallstones. Is there a connection between gastric bypass surgery and gallstones?

An increased risk of new gallstones following gastric bypass surgery (GBS) has been reported by several studies (1-5).  More specifically, a study involving patients with baseline normal gallbladder ultrasound found that at 6 months following GBS 36% of patients developed gallstones and 13% developed sludge (4).  Similarly, a gallstone formation rate of 32% has been reported after GBS among patients who did not receive prophylactic treatment (5). 

New cholelithiasis following GBS may be largely attributed to rapid weight loss following this procedure, not the surgery itself or its related anatomical changes. Of interest, rapid weight loss, even by dieting, has been shown to increase the risk of gallstones (6).

However, overweight patients also have an increased risk of developing cholelithiasis at baseline, in part related to increased cholesterol secretion resulting in bile supersaturation with cholesterol (1).  Though weight loss may be expected to decrease this risk, rapid weight loss is thought to change the bile composition towards higher concentrations of calcium and cholesterol and increased production of gallbladder mucin, contributing to the pathogenicity of gallstone formation (5). 

In light of these findings, some have recommended routine prophylactic cholecystectomy as part of the GBS (7,8),  while others have argued against it (9,10), largely due to different observed rates of post-GBS symptomatic gallstones requiring cholecystectomies in various studies. Of note, post-operative ursodiol (ursodeoxycholic acid) may also reduce the incidence of post-GBS cholelithiasis (5,11). 

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References

1. Everhart JE. Contributions of obesity and weight loss to gallstone disease. Ann Intern Med 1993;119(10):1029–35. https://www.ncbi.nlm.nih.gov/pubmed/8214980
2. Wudel LJ, Wright JK, Debelak JP, Allos TM, Shyr Y, Chapman WC. Prevention of gallstone formation in morbidly obese patients undergoing rapid weight loss: Results of a randomized controlled pilot study. J Surg Res 2002;102(1):50–6. https://www.ncbi.nlm.nih.gov/pubmed/11792152
3. Manatsathit W, Leelasincharoen P, Al-Hamid H, Szpunar S, Hawasli A. The incidence of cholelithiasis after sleeve gastrectomy and its association with weight loss: A two-centre retrospective cohort study. Int J Surg [Internet] 2016;30:13–8. Available from: http://dx.doi.org/10.1016/j.ijsu.2016.03.060 https://www.ncbi.nlm.nih.gov/pubmed/27063855
4. Shiffman M, Sugerman H, Kellum J, Brewer W, Moore E. Gallstone formation after rapid weight loss: a prospective study in patients undergoing gastric bypass surgery for treatment of morbid obesity. Am J Gastroenterol 1991;(86):1000–5. https://www.ncbi.nlm.nih.gov/pubmed/1858735
5. Sugerman H, Brewer W, Shiffman M, et al. A Multicenter, Placebo-Controlled, Randomized, Double-Blind, Prospective Trial of Prophylactic Ursodiol for the Prevention of Gallstone Formation Rapid Weight Loss. Am Jourmal Surg 1995;169(January):91–7. https://www.ncbi.nlm.nih.gov/pubmed/7818005

6. de Oliverira CIB, Chaim EA, da Silva BB. Impact of rapid weight reduction on risk of cholelithiasis after bariatric surgery. Obesity Surgery 2003;13:625-8.
7. Tarantino I, Warschkow R, Steffen T, Bisang P, Schultes B, Thurnheer M. Is routine cholecystectomy justified in severely obese patients undergoing a laparoscopic Roux-en-Y gastric bypass procedure? A comparative cohort study. Obes Surg 2011;21(12):1870–8. https://reference.medscape.com/medline/abstract/21863228
8. Amstutz S, Michel JM, Kopp S, Egger B. Potential Benefits of Prophylactic Cholecystectomy in Patients Undergoing Bariatric Bypass Surgery. Obes Surg 2015;25(11):2054–60. https://link.springer.com/article/10.1007%2Fs11695-015-1650-6
9. Karadeniz M, Gorgun M, Kara C. The evaluation of gallstone formation in patients undergoing Roux-en -Y gastric bypass due to morbid obesity. Turkish J Surg 2014;30(2):76–9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4379817/
10. D’Hondt M, Sergeant G, Deylgat B, Devriendt D, Van Rooy F, Vansteenkiste F. Prophylactic Cholecystectomy, a Mandatory Step in Morbidly Obese Patients Undergoing Laparoscopic Roux-en-Y Gastric Bypass? J Gastrointest Surg 2011;15(9):1532–6. https://www.ncbi.nlm.nih.gov/pubmed/21751078
11. Miller K, Hell E, Lang B, Lengauer E. Gallstone Formation Prophylaxis after Gastric Restrictive Procedures for Weight Loss: A Randomized Double-Blind Placebo-Controlled Trial. Ann Surg 2003;238(5):697–702. https://www.ncbi.nlm.nih.gov/pubmed/14578732

Contributed by Kim Schaefer, Harvard medical student, Boston, MA. 

 

My patient with history of gastric bypass surgery now presents with right upper quadrant pain and gallstones. Is there a connection between gastric bypass surgery and gallstones?

What is the clinical significance of “white bile” from my patient’s gallbladder drain?

“White bile” (WB) (Figure) is a clear sero-mucous secretion of gallbladder that is largely devoid of bilirubin and bile salts. It arises from glycoproteins that are normally secreted by the mucosal glands of the gallbladder infundibulum and neck, and is thought to shield the gallbladder wall from the lytic action of bile.

WB is observed in “hydrops” of gallbladder and is caused by absorption of bile by the gallbladder wall in the setting of persistent cystic duct obstruction1. It is commonly held that in persistent cystic duct obstruction, bile in the gallbladder is eventually absorbed into the lymphatics and blood vessels but that the gallbladder epithelium continues to produce clear sero-mucous secretions. In this setting, dilatation, perforation, and atrophy of the gallbladder lumen may also occur1-3.  Early cholecystostomy tube placement or cholecystectomy is often indicated1,3.

Common etiologies of persistent cystic duct blockage in adults include, stone impaction, cystic duct stenosis, tumors/polyps, and parasites (eg, ascariasis).

Figure: “White bile” drainage from a cholecystostomy drain of a patient with cholecystitis and persistent cystic duct blockage due to stones. The drainage was completely clear with mucous characteristics. 

whitebile

Reference:

  1. Schwartz, Seymour I, Brunicardi, F. Charles., eds. Schwartz’s Principles Of Surgery. New York : McGraw-Hill Medical, 2011.
  2. Ahmed A, Cheung RC, Keeffe EB. Management of gallstones and their complications. Am Fam Physician 2000; 61, 1673-1680.
  3. Lawrence S. Friedman, Mark Feldman. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease 10th Edition. Philadelphia, PA: Elsevier, 2015.

Contributed by Alireza Sameie, Medical Student, Harvard Medical School

What is the clinical significance of “white bile” from my patient’s gallbladder drain?