{"doi":"10.1007/s10620-021-07299-2","title":"Duodenal Microbiome and Serum Metabolites Predict Hepatocellular Carcinoma in a Multicenter Cohort of Patients with Cirrhosis","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.","journal":"Digestive Diseases and Sciences","year":2021,"id":174941,"datarank":0.8061870860404021,"base_score":3.2188758248682006,"endowment":3.2188758248682006,"self_citation_contribution":0.48283137373023016,"citation_network_contribution":0.3233557123101719,"self_endowment_contribution":0.48283137373023016,"citer_contribution":0.3233557123101719,"corpus_percentile":null,"corpus_rank":null,"citation_count":24,"citer_count":24,"citers_with_citation_signal":16,"citers_with_endowment":16,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9299,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":36336,"name":"Jonathan P. Jacobs","orcid":"0000-0003-4698-0254","position":1,"is_corresponding":false},{"id":241819,"name":"Vatche G. Agopian","orcid":"0000-0003-0130-9838","position":2,"is_corresponding":false},{"id":278349,"name":"Joseph R. Pisegna","orcid":"0000-0002-5442-2474","position":3,"is_corresponding":false},{"id":490943,"name":"Walid S. Ayoub","orcid":"0000-0002-9123-5918","position":4,"is_corresponding":false},{"id":286136,"name":"Francisco Durazo","orcid":"0000-0001-7495-389X","position":5,"is_corresponding":false},{"id":491526,"name":"Pedram Enayati","orcid":null,"position":6,"is_corresponding":false},{"id":490942,"name":"Vinay Sundaram","orcid":"0000-0002-1450-7756","position":7,"is_corresponding":false},{"id":278348,"name":"Jihane N. Benhammou","orcid":"0000-0003-2442-5145","position":8,"is_corresponding":false},{"id":291021,"name":"Mazen Noureddin","orcid":"0000-0003-2127-2040","position":9,"is_corresponding":false},{"id":491527,"name":"Gina Choi","orcid":null,"position":10,"is_corresponding":false},{"id":301054,"name":"Venu Lagishetty","orcid":"0000-0001-6500-8255","position":11,"is_corresponding":false},{"id":6363,"name":"Oliver Fiehn","orcid":"0000-0002-6261-8928","position":12,"is_corresponding":false},{"id":33585,"name":"Marc T. Goodman","orcid":"0000-0002-4839-3021","position":13,"is_corresponding":false},{"id":58606,"name":"David Elashoff","orcid":"0000-0002-5865-8580","position":14,"is_corresponding":false},{"id":369565,"name":"Shehnaz K. Hussain","orcid":"0000-0002-2015-0546","position":15,"is_corresponding":false},{"id":301052,"name":"Tien S. Dong","orcid":"0000-0003-0105-8063","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:47:11.249697Z","pmid":"34799768","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}