{"doi":"10.1111/liv.14835","title":"Pathological predictive factors for late recurrence of hepatocellular carcinoma in chronic liver disease","abstract":"BACKGROUND & AIMS: Late recurrence of hepatocellular carcinoma (HCC) is regarded as de novo HCC from chronic hepatitis. This study investigated clinicopathological and molecular factors to develop a nomogram for predicting late HCC recurrence (>2 years after curative resection). METHODS: The training and validation cohorts included HCC patients with a major aetiology of hepatitis B who underwent curative resection. Clinicopathological features including lobular and porto-periportal inflammatory activity, fibrosis and liver cell change were evaluated. Proteins encoded by genes related to late recurrence were identified using a reverse phase protein array of 95 non-tumourous liver tissues. Immunoexpression of phosphorylated signal transducer and activator of transcription 3 (pSTAT3), plasminogen activator inhibitor-1, phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) and spleen tyrosine kinase (SYK) was measured. RESULTS: Late recurrence occurred in 74/402 (18%) and 47/243 (19%) in the training and validation cohorts respectively. Cirrhosis, moderate/severe lobular inflammatory activity, and expression of pSTAT3, pERK1/2, and SYK proteins correlated to the gene signature of hepatocyte injury and regeneration were independently associated with late recurrence, with odds ratios (95% confidence intervals) of 2.0 (1.2-3.3), 21.1 (4.3-102.7) and 6.0 (2.1-17.7) respectively (P < .05 for all). A nomogram based on these variables (histological parameters and immunohistochemical marker combinations) showed high reliability in both the training and validation cohorts (Harrell's C index: 0.701 and 0.716; 95% confidence intervals: 0.64-0.76 and 0.64-0.79 respectively). CONCLUSIONS: The combination of pSTAT3, pERK1/2 and SYK immunoexpression with high lobular inflammatory activity and cirrhosis (fibrosis) predicts late HCC recurrence.","journal":"Liver International","year":2021,"id":199801,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9526,"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":776393,"name":"Hye Sun Lee","orcid":"0000-0001-6328-6948","position":1,"is_corresponding":false},{"id":404990,"name":"Haeryoung Kim","orcid":"0000-0002-4205-9081","position":2,"is_corresponding":false},{"id":776394,"name":"Sun Young Yim","orcid":"0000-0001-7346-5974","position":3,"is_corresponding":false},{"id":402112,"name":"Ji‐Hyun Shin","orcid":"0000-0002-0887-1180","position":4,"is_corresponding":false},{"id":776395,"name":"Jeong Eun Yoo","orcid":"0000-0001-9990-279X","position":5,"is_corresponding":false},{"id":776396,"name":"Sang Hoon Ahn","orcid":"0000-0002-3629-4624","position":6,"is_corresponding":false},{"id":776397,"name":"Jin Sub Choi","orcid":"0000-0002-6467-6494","position":7,"is_corresponding":false},{"id":278888,"name":"Ju‐Seog Lee","orcid":"0000-0002-5666-9753","position":8,"is_corresponding":false},{"id":571100,"name":"Young Nyun Park","orcid":"0000-0003-0357-7967","position":9,"is_corresponding":false},{"id":776392,"name":"Ji Hae Nahm","orcid":"0000-0003-0902-866X","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-18T23:50:40.558460Z","pmid":"33638929","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":[]}