title: Serum Tumor Markers Provide Refined Prognostication in Selecting Liver Transplantation Candidate for Hepatocellular Carcinoma Patients Beyond the Milan Criteria.
abstract: OBJECTIVE
  To develop and validate a model to predict tumor recurrence after living donor liver transplantation (LDLT) (MoRAL) for hepatocellular carcinoma (HCC) beyond the Milan criteria (MC).
  
  
  BACKGROUND
  Some subgroups of HCC exceeding the MC experience substantial benefit from LDLT.
  
  
  METHODS
  This multicenter study included a total of 566 consecutive patients who underwent LDLT in Korea: the beyond-MC cohort (n = 205, the derivation [n = 92] and validation [n = 113] sets) and the within-MC cohort (n = 361). The primary endpoint was time-to-recurrence.
  
  
  RESULTS
  Using multivariate Cox proportional hazard model, we derived the MoRAL score using serum levels of protein induced by vitamin K absence-II and alpha-fetoprotein, which provided a good discriminant function on time-to-recurrence (concordance index = 0.88). Concordance index was maintained similarly on both internal and external validations (mean 0.87 and 0.84, respectively). At cut off of 314.8 (75th percentile value), a low MoRAL score (≤314.8) was associated with significantly longer recurrence-free (versus > 314.8, HR = 5.29, P < 0.001) and overall survivals (HR = 2.59, P = 0.001) in the beyond-MC cohort. The 5-year recurrence-free and overall survival rates of beyond-MC patients with a low MoRAL score were as high as 66.3% and 82.6%, respectively. The within-MC patients with a high MoRAL score showed a higher risk of recurrence than beyond-MC patients with a low MoRAL score (HR = 2.56, P = 0.035). The MoRAL score was significantly correlated with explant histology.
  
  
  CONCLUSIONS
  This new model using protein induced by vitamin K absence-II and alpha-fetoprotein provides refined prognostication. Among beyond-MC HCC patients, those with a MoRAL score ≤314.8 and without extrahepatic metastasis might be potential candidates for LDLT.
authors.affiliation: *Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea †Department of Internal Medicine, CHA Gangnam Medical Center, CHA University, Seoul, Republic of Korea ‡Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea ¶Department of Surgery, Seoul National University College of Medicine, Seoul, Korea §Center for Liver Cancer, National Cancer Center, Goyang-Si, Gyeonggi-Do, Korea ||Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea **Mary Lea Johnson Richards Organ Transplantation Center, New York University Langone Medical Center, New York, NY.
authors.forename: Jeong-Hoon
authors.initials: JH
authors.lastname: Lee
authors.forename: Yuri
authors.initials: Y
authors.lastname: Cho
authors.forename: Hwi Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Cho
authors.forename: Dong Hyeon
authors.initials: DH
authors.lastname: Lee
authors.forename: Su Jong
authors.initials: SJ
authors.lastname: Yu
authors.forename: Jae Woo
authors.initials: JW
authors.lastname: Lee
authors.forename: Nam-Joon
authors.initials: NJ
authors.lastname: Yi
authors.forename: Kwang-Woong
authors.initials: KW
authors.lastname: Lee
authors.forename: Seoung Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Jong Man
authors.initials: JM
authors.lastname: Kim
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Joh
authors.forename: Lewis W
authors.initials: LW
authors.lastname: Teperman
authors.forename: James S
authors.initials: JS
authors.lastname: Park
authors.forename: Yoon Jun
authors.initials: YJ
authors.lastname: Kim
authors.forename: Kyung-Suk
authors.initials: KS
authors.lastname: Suh
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Yoon
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000175:diagnosis / Q000473:pathology / Q000601:surgery*; D003952:Diagnostic Imaging; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000175:diagnosis / Q000473:pathology / Q000601:surgery*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D018579:Patient Selection; D011237:Predictive Value of Tests; D011379:Prognosis; D056910:Republic of Korea; D018570:Risk Assessment; D016019:Survival Analysis
chemical_list: D015415:Biomarkers