title: Decrypting cryptogenic hepatocellular carcinoma: clinical manifestations, prognostic factors and long-term survival by propensity score model.
abstract: OBJECTIVE
  The clinical aspects of cryptogenic hepatocellular carcinoma (HCC), defined as HCC in patients without hepatitis B, C or alcoholism, are not clear. We investigated its clinical presentations, long-term survival and prognostic predictors.
  
  
  METHODS
  A total of 2645 HCC patients were studied. One-to-one matched pairs between viral/alcoholic and cryptogenic HCC patients were generated by using the propensity model. The survival analysis was performed with the Kaplan-Meier method and log-rank test, and hazard ratios were calculated with Cox proportional hazards model.
  
  
  RESULTS
  Among 366 (14%) patients with cryptogenic HCC, 34% of patients were presented with abdominal discomfort, and 31% of patients were identified incidentally. Compared to patients with viral/alcoholic HCC, cryptogenic HCC patients were significantly older (p<0.0001), with poorer performance status (p = 0.0031) and less often underwent curative treatment (p = 0.0041). They also had larger tumor burden (p<0.0001), poorer renal function (p<0.0001), lower α-fetoprotein level (p<0.0001), and more advanced Barcelona Clinic Liver Cancer stages (p<0.0001). With propensity score model, 366 pairs of similar HCC patients were selected and similar long-term survival between the two groups of patients was found (p = 0.1038). For cryptogenic HCC patients, α-fetoprotein ≧49 ng/mL (hazard ratio [HR]: 1.955, p = 0.0002), Child-Turcotte-Pugh class B/C (HR: 2.798, p<0.0001), performance status ≧1 (HR: 2.463, p<0.0001) and vascular invasion (HR: 1.608, p = 0.0257) were independent predictors of poor prognosis.
  
  
  CONCLUSIONS
  Patients with cryptogenic HCC are usually diagnosed with poor general condition at late stages. However, cryptogenic HCC patients have similar prognostic predictors and long-term survival compared with viral/alcoholic HCC patients. Diagnosis at an early stage may improve their clinical outcomes.
authors.affiliation: Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan ; Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan ; Department of Biostatistics, UCLA, Los Angeles, California, United States of America.
authors.forename: Chia-Yang
authors.initials: CY
authors.lastname: Hsu
authors.affiliation: Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan ; Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Yun-Hsuan
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan ; Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Po-Hong
authors.initials: PH
authors.lastname: Liu
authors.affiliation: Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan ; Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Cheng-Yuan
authors.initials: CY
authors.lastname: Hsia
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan ; Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Yi-Hsiang
authors.initials: YH
authors.lastname: Huang
authors.affiliation: Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan ; Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Han-Chieh
authors.initials: HC
authors.lastname: Lin
authors.affiliation: Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan ; Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Yi-You
authors.initials: YY
authors.lastname: Chiou
authors.affiliation: Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan ; Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Fa-Yauh
authors.initials: FY
authors.lastname: Lee
authors.affiliation: Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan ; Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Teh-Ia
authors.initials: TI
authors.lastname: Huo
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000401:mortality* / Q000473:pathology*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000401:mortality* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D057216:Propensity Score; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016019:Survival Analysis