{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T10:34:00Z","timestamp":1780050840510,"version":"3.53.1"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T00:00:00Z","timestamp":1737590400000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background and Aim<\/jats:title><jats:p>In recent years, there has been a rise in cryptogenic hepatocellular carcinoma (c\u2010HCC) cases in Japan, posing a detection challenge due to an unknown etiology. This study aims to enhance diagnostic strategies for c\u2010HCC by analyzing its characteristics and exploring current opportunities for detection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective study was conducted from April 2012 to March 2022, enrolling 372 newly diagnosed hepatocellular carcinoma (HCC) patients. Excluding cases associated with hepatitis viral infection, alcoholic liver disease, non\u2010alcoholic fatty liver disease\/steatohepatitis, autoimmune hepatitis, primary biliary cholangitis, and congestive hepatopathy, the study specifically focused on genuine c\u2010HCC. The analysis delved into the characteristics, detection opportunities, and survival outcomes associated with c\u2010HCC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the non\u2010viral HCC cases, 55 patients (29.3%) (34 men and 21 women) were diagnosed with c\u2010HCC, making it the second\u2010highest etiology. Notably, individuals with c\u2010HCC, typically aged 60 and above (median age 76.0), exhibited a women predominance and presented with larger tumors (4.5\u2009cm vs. 2.5\u2009cm), correlating with a poorer prognosis. Cirrhosis was notably absent in most c\u2010HCC cases (72.7%), and more than half (56.4%) did not have diabetes mellitus (DM). Diagnostic pathways for c\u2010HCC primarily involved incidental imaging (47%) and symptoms (24%). Within the cohort of c\u2010HCC, the prognosis for symptomatic cases is notably unfavorable compared to other cases [median survival time 19.0 (7.0\u201345.0) months vs. 47.0 (29.0\u201376.0) months, <jats:italic>p<\/jats:italic>\u2009=\u20090.029]. In the multivariate regression analysis, age and women emerged as independent factors associated with c\u2010HCC. Rather than a significant increase in women, there is a narrowing gender gap.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Patients with c\u2010HCC were predominantly elderly, without cirrhosis or diabetes, and exhibited minimal gender differences. Detection often occurred incidentally through abdominal imaging. Considering the limitations of conventional surveillance, it seems reasonable to propose that abdominal imaging be included in cancer screening, particularly for individuals aged 60 and older.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p>1610A127<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.70490","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T10:49:25Z","timestamp":1737629365000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Characterization and Detection Strategy Exploration in Cryptogenic Hepatocellular Carcinoma: Insights From a Super\u2010Aged Region in Japan"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0522-1884","authenticated-orcid":false,"given":"Takaaki","family":"Sugihara","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Nephrology, Department of 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