title: Combinations of biomarkers and Milan criteria for predicting hepatocellular carcinoma recurrence after liver transplantation.
abstract: Growing evidence suggests that pretransplant alpha-fetoprotein (AFP) predicts outcomes of hepatocellular carcinoma (HCC) patients treated with liver transplantation. We aimed to determine whether pretransplant AFP, Lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3), and des-gamma-carboxyprothrombin (DCP) predicted HCC recurrence after transplantation. A retrospective cohort study of 313 HCC patients undergoing transplantation between 2000 and 2008 was conducted, and 48 (15.3%) developed recurrence during a median follow-up of 90.8 months. The 127 patients with available serum drawn before transplantation were included; they included 86 without recurrence and 41 with recurrence. Serum was tested for AFP, AFP-L3%, and DCP in a blinded fashion with the μTASWako i30 immunoanalyzer. All biomarkers were significantly associated with HCC recurrence. The hazard ratios (HRs) were 3.5 [95% confidence interval (CI), 1.9-6.7; P < 0.0001] for DCP ≥ 7.5 ng/mL and 2.8 (95% CI, 1.4-5.4; P = 0.002) for AFP ≥ 250 ng/mL. The HR increased to 5.2 (95% CI, 2.3-12.0; P < 0.0001) when AFP ≥ 250 ng/mL and DCP ≥7.5 ng/mL were considered together. When they were combined with the Milan criteria, the HR increased from 2.6 (95% CI, 1.4-4.7; P = 0.003) for outside the Milan criteria to 8.6 (95% CI, 3.0-24.6; P < 0.0001) for outside the Milan criteria and AFP ≥ 250 ng/mL and to 7.2 (95% CI, 2.8-18.1; P < 0.0001) for outside the Milan criteria and DCP ≥7.5 ng/mL. Our findings suggest that biomarkers are useful for predicting the risk of HCC recurrence after transplantation. Using both biomarkers and the Milan criteria may be better than using the Milan criteria alone in optimizing the decision of liver transplantation eligibility.
authors: Division of Gastroenterology and Hepatology, Mayo Clinic Cancer Center, Rochester, MN; Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
authors: Roongruedee
authors: R
authors: Chaiteerakij
authors: Xiaodan
authors: X
authors: Zhang
authors: Benyam D
authors: BD
authors: Addissie
authors: Essa A
authors: EA
authors: Mohamed
authors: William S
authors: WS
authors: Harmsen
authors: Paul J
authors: PJ
authors: Theobald
authors: Brian E
authors: BE
authors: Peters
authors: Joseph G
authors: JG
authors: Balsanek
authors: Melissa M
authors: MM
authors: Ward
authors: Nasra H
authors: NH
authors: Giama
authors: Catherine D
authors: CD
authors: Moser
authors: Abdul M
authors: AM
authors: Oseini
authors: Naoki
authors: N
authors: Umeda
authors: Sudhakar
authors: S
authors: Venkatesh
authors: Denise M
authors: DM
authors: Harnois
authors: Michael R
authors: MR
authors: Charlton
authors: Hiroyuki
authors: H
authors: Yamada
authors: Shinji
authors: S
authors: Satomura
authors: Alicia
authors: A
authors: Algeciras-Schimnich
authors: Melissa R
authors: MR
authors: Snyder
authors: Terry M
authors: TM
authors: Therneau
authors: Lewis R
authors: LR
authors: Roberts
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery*; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000473:pathology; D037121:Plant Lectins / Q000737:chemistry; D016016:Proportional Hazards Models; D011498:Protein Precursors / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D012189:Retrospective Studies; D012720:Severity of Illness Index; D015398:Signal Transduction; D014057:Tomography, X-Ray Computed / Q000379:methods; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D015415:Biomarkers; D037121:Plant Lectins; D011498:Protein Precursors; D000509:alpha-Fetoproteins; C033619:lentil lectin; C008208:acarboxyprothrombin; D011516:Prothrombin