Published in:
Open Access
20-11-2021 | Hepatic Encephalopathy | Original Article
Duodenal Microbiome and Serum Metabolites Predict Hepatocellular Carcinoma in a Multicenter Cohort of Patients with Cirrhosis
Authors:
Tien S. Dong, Jonathan P. Jacobs, Vatche Agopian, Joseph R. Pisegna, Walid Ayoub, Francisco Durazo, Pedram Enayati, Vinay Sundaram, Jihane N. Benhammou, Mazen Noureddin, Gina Choi, Venu Lagishetty, Oliver Fiehn, Marc T. Goodman, David Elashoff, Shehnaz K. Hussain
Published in:
Digestive Diseases and Sciences
|
Issue 8/2022
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Abstract
Background
Hepatocellular carcinoma (HCC) is rapidly increasing in the U.S. and is a leading cause of mortality for patients with cirrhosis. Discovering novel biomarkers for risk stratification of HCC is paramount. We examined biomarkers of the gut-liver axis in a prospective multicenter cohort.
Methods
Patients with cirrhosis without a history of HCC were recruited between May 2015 and March 2020 and prospectively followed at 3 tertiary care hospitals in Los Angeles. Microbiome analysis was performed on duodenal biopsies and metabolomic analysis was performed on serum samples, collected at the time of enrollment. Optimal microbiome-based survival analysis and Cox proportional hazards regression analysis were used to determine microbiota and metabolite associations with HCC development, respectively.
Results
A total of 227 participants with liver cirrhosis contributed a total of 459.58 person-years of follow-up, with 14 incident HCC diagnoses. Male sex (HR = 7.06, 95% CI = 1.02–54.86) and baseline hepatic encephalopathy (HE, HR = 4.65, 95% CI = 1.60–13.52) were associated with developing HCC over follow-up. Adjusting for age, sex, baseline HE, and alkaline phosphatase, an increased risk of HCC were observed for participants with the highest versus lowest three quartiles for duodenal Alloprevotella (HR = 3.22, 95% CI = 1.06–9.73) and serum taurocholic acid (HR = 6.87, 95% CI = 2.32–20.27), methionine (HR = 9.97, 95% CI = 3.02–32.94), and methioninesulfoxide (HR = 5.60, 95% CI = 1.84–17.10). Being in the highest quartile for Alloprevotella or methionine had a sensitivity and specificity for developing HCC of 85.71% and 60.56%, respectively, with an odds ratio of 10.92 (95% CI = 2.23–53.48).
Conclusion
Alloprevotella and methionine, methioninesulfoxide, and taurocholic acid predicted future HCC development in a high-risk population of participants with liver cirrhosis.