{"doi":"10.1016/j.ajpath.2025.04.016","title":"Alcohol-Associated Hepatocarcinogenesis","abstract":"Long-term alcohol consumption is a leading global health concern, primarily due to its deleterious effects on liver function and its well-established association with hepatocellular carcinoma. Alcohol-related liver disease (ALD) encompasses a continuum-from reversible hepatic steatosis and steatohepatitis through progressive fibrosis and cirrhosis to overt hepatocellular carcinoma. Accumulating studies have revealed that the Wnt/β-catenin signaling pathway is an essential regulator in ALD pathogenesis, orchestrating diverse molecular, immunologic, and epigenetic processes. Aberrant β-catenin activity disrupts redox homeostasis, promotes chronic inflammation, drives extracellular matrix remodeling, and alters hepatocyte cell fate, thereby creating a microenvironment that is highly conducive to carcinogenesis. This article provides a systematic review of the significant function of Wnt/β-catenin signaling in ALD, emphasizing its regulatory impact on liver fat accumulation, its inflammatory role in steatohepatitis, its involvement in fibrogenesis, and its tumor-promoting effects in alcohol-related hepatocellular carcinoma. In addition, emerging therapeutic strategies that offer potential for early identification and tailored therapy of ALD are explored-including direct Wnt modulators, combinatory therapeutics, and precision medicine approaches.","journal":"American Journal Of Pathology","year":2025,"id":532351,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9557,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":891580,"name":"Tian Tian","orcid":"0000-0002-0340-230X","position":1,"is_corresponding":false},{"id":1413923,"name":"Melak Ottallah","orcid":null,"position":2,"is_corresponding":false},{"id":1413924,"name":"Mahfuza Mannan","orcid":null,"position":3,"is_corresponding":false},{"id":1074169,"name":"Joshua Barkin","orcid":null,"position":4,"is_corresponding":false},{"id":1041888,"name":"Brady Jin-Smith","orcid":"0009-0003-0653-7693","position":5,"is_corresponding":false},{"id":415529,"name":"Liya Pi","orcid":"0000-0002-9868-7677","position":6,"is_corresponding":false},{"id":406265,"name":"Yuhua Xue","orcid":"0000-0001-5804-5162","position":0,"is_corresponding":true}],"reference_count":88,"raw_metadata":null,"created_at":"2026-07-19T02:51:23.237536Z","pmid":"40350059","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":[]}