Digestive Diseases

Oct. 20, 2021

Chronic heavy alcohol consumption is the second most common cause of acute pancreatitis after gallstones. Known as alcoholic pancreatitis, this form of pancreatitis has clinical features similar to those associated with acute and chronic pancreatitis caused by other factors.

Confirming a diagnosis of alcoholic pancreatitis can be challenging. Self-reporting about alcohol use can be unreliable. And because blood alcohol levels typically peak within 1 to 2 hours after alcohol intake, by the time a patient presents with symptoms of pancreatitis, this test result may not yield useful information.

In a prospective, blinded study published in Gastroenterology in 2021, researchers from Mayo Clinic and other institutions sought to identify a biomarker for alcoholic pancreatitis. According to Vijay P. Singh, M.B.B.S, M.D., a gastroenterologist at Mayo Clinic's campus in Scottsdale, Arizona, who served as the article's corresponding author, the researchers chose to examine the role of ethanol metabolites known as fatty acid ethyl esters (FAEEs). FAEEs are elevated during intoxication and are suspected mediators of alcohol-induced organ damage.

Research methods

The research team recruited the following groups of study participants: patients seen in the emergency department presenting with acute alcoholic intoxication, hospitalized patients who were diagnosed with alcoholic pancreatitis and nonalcoholic pancreatitis, and a control group. Overall, the researchers recruited 186 patients: 25 with alcohol intoxication, 31 with alcoholic pancreatitis, 75 with nonalcoholic pancreatitis and 55 controls. They also identified 43 controls matched for sex and body mass index.

Investigators documented and compared participants' FAEE levels, nonesterified fatty acid (NEFA) levels and blood ethanol levels during the emergency department visit or within 24 hours of hospital admission. Staff members who conducted the analyses were blinded to all patient and clinical data until all analyses were complete. Investigators also performed mechanistic cell studies and animal studies to understand how FAEEs are generated and released into the circulation.

Results

Overall, Dr. Singh and co-authors note that the study findings suggest that FAEEs may be useful as biomarkers of alcoholic pancreatitis. They shared the following data and analysis related to FAEEs and NEFAs:

• Median FAEE levels were higher in patients with alcohol intoxication (205 nmol/L; 95% confidence interval, 71.8 to 515 nmol/L, P < 0.001) and in patients with alcoholic pancreatitis (103.1 nmol/L; 95% confidence interval, 53 to 689 nmol/L, P < 0.001) when compared with the control group (1.7 nmol/L; 95% confidence interval, 0.02 to 4.3 nmol/L) and when compared with patients hospitalized for nonalcoholic pancreatitis (8 nmol/L; 95% confidence interval, 1.1 to 11.5 nmol/L).
• Serum NEFAs were also elevated in patients with alcoholic pancreatitis (1024 ± 710 mmol/L) when compared with the control group (307 ± 185 mmol/L, P < 0.05).
• FAEE levels comprised 0.1% to 2% of the parent NEFA concentrations. FAEE levels also correlated strongly with NEFA levels, independent of ethanol levels, in patients with alcoholic pancreatitis. But this same association was not observed in patients with alcohol intoxication.
• Analysis of the receiver operating characteristic (ROC) curve for diagnosing alcoholic pancreatitis shows that the area under the curve for serum FAEEs was 0.87 (95% confidence interval, 0.78 to 0.95, P < 0.001).
• In mice and cells, alcohol administration transiently increased all FAEEs. Oleic acid ethyl ester was the only FAEE that demonstrated a sustained increase for up to 24 hours by intraperitoneal oleic acid plus ethanol.

"Overall, we observed that patients with alcoholic pancreatitis had a sustained, twenty- to fiftyfold increase in circulating FAEEs during alcoholic pancreatitis, even when blood alcohol levels were not elevated," explains Dr. Singh. "This increase occurred after visceral release of FAEEs and mirrored the two- to fourfold increase in NEFAs. Those increases plus the ROC curve analysis of FAEEs demonstrate that FAEEs have potential to serve as biomarkers for pancreatitis."

Dr. Singh and co-authors acknowledge that although their study has some limitations, the data support the need for additional research to continue exploring the role of FAEEs in diagnosing alcoholic pancreatitis and other alcohol-related acute diseases.

For more information

Vela S, et al. Pathophysiology and biomarker potential of fatty acid ethyl ester elevation during alcoholic pancreatitis. Gastroenterology. In press.