Duodenal Microbiome and Serum Metabolites Predict Hepatocellular Carcinoma in a Multicenter Cohort of Patients with Cirrhosis

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

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)3831-3841
Number of pages11
JournalDigestive Diseases and Sciences
Issue number8
StatePublished - Aug 2022


  • Alloprevotella
  • Bile acids
  • Biogenic amines
  • Methionine
  • Small intestine
  • Taurocholic acid
  • Time-to-event

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology


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