Combinations of biomarkers and Milan criteria for predicting hepatocellular carcinoma recurrence after liver transplantation

Roongruedee Chaiteerakij, Xiaodan Zhang, Benyam D. Addissie, Essa A. Mohamed, William S. Harmsen, Paul J. Theobald, Brian E. Peters, Joseph G. Balsanek, Melissa M. Ward, Nasra H. Giama, Catherine D. Moser, Abdul M. Oseini, Naoki Umeda, Sudhakar K Venkatesh, Denise Harnois, Michael R. Charlton, Hiroyuki Yamada, Shinji Satomura, Alicia Algeciras-Schimnich, Melissa R. SnyderTerry M Therneau, Lewis Rowland Roberts

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)599-606
Number of pages8
JournalLiver Transplantation
Volume21
Issue number5
DOIs
StatePublished - May 1 2015

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alpha-Fetoproteins
Liver Transplantation
Hepatocellular Carcinoma
Biomarkers
Recurrence
Confidence Intervals
Transplantation
Serum
Cohort Studies
Retrospective Studies
acarboxyprothrombin

ASJC Scopus subject areas

  • Surgery
  • Transplantation
  • Hepatology

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Combinations of biomarkers and Milan criteria for predicting hepatocellular carcinoma recurrence after liver transplantation. / Chaiteerakij, Roongruedee; Zhang, Xiaodan; Addissie, Benyam D.; Mohamed, Essa A.; Harmsen, William S.; Theobald, Paul J.; Peters, Brian E.; Balsanek, Joseph G.; Ward, Melissa M.; Giama, Nasra H.; Moser, Catherine D.; Oseini, Abdul M.; Umeda, Naoki; Venkatesh, Sudhakar K; Harnois, Denise; Charlton, Michael R.; Yamada, Hiroyuki; Satomura, Shinji; Algeciras-Schimnich, Alicia; Snyder, Melissa R.; Therneau, Terry M; Roberts, Lewis Rowland.

In: Liver Transplantation, Vol. 21, No. 5, 01.05.2015, p. 599-606.

Research output: Contribution to journalArticle

Chaiteerakij, R, Zhang, X, Addissie, BD, Mohamed, EA, Harmsen, WS, Theobald, PJ, Peters, BE, Balsanek, JG, Ward, MM, Giama, NH, Moser, CD, Oseini, AM, Umeda, N, Venkatesh, SK, Harnois, D, Charlton, MR, Yamada, H, Satomura, S, Algeciras-Schimnich, A, Snyder, MR, Therneau, TM & Roberts, LR 2015, 'Combinations of biomarkers and Milan criteria for predicting hepatocellular carcinoma recurrence after liver transplantation', Liver Transplantation, vol. 21, no. 5, pp. 599-606. https://doi.org/10.1002/lt.24117
Chaiteerakij, Roongruedee ; Zhang, Xiaodan ; Addissie, Benyam D. ; Mohamed, Essa A. ; Harmsen, William S. ; Theobald, Paul J. ; Peters, Brian E. ; Balsanek, Joseph G. ; Ward, Melissa M. ; Giama, Nasra H. ; Moser, Catherine D. ; Oseini, Abdul M. ; Umeda, Naoki ; Venkatesh, Sudhakar K ; Harnois, Denise ; Charlton, Michael R. ; Yamada, Hiroyuki ; Satomura, Shinji ; Algeciras-Schimnich, Alicia ; Snyder, Melissa R. ; Therneau, Terry M ; Roberts, Lewis Rowland. / Combinations of biomarkers and Milan criteria for predicting hepatocellular carcinoma recurrence after liver transplantation. In: Liver Transplantation. 2015 ; Vol. 21, No. 5. pp. 599-606.
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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.",
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T1 - Combinations of biomarkers and Milan criteria for predicting hepatocellular carcinoma recurrence after liver transplantation

AU - Chaiteerakij, Roongruedee

AU - Zhang, Xiaodan

AU - Addissie, Benyam D.

AU - Mohamed, Essa A.

AU - Harmsen, William S.

AU - Theobald, Paul J.

AU - Peters, Brian E.

AU - Balsanek, Joseph G.

AU - Ward, Melissa M.

AU - Giama, Nasra H.

AU - Moser, Catherine D.

AU - Oseini, Abdul M.

AU - Umeda, Naoki

AU - Venkatesh, Sudhakar K

AU - Harnois, Denise

AU - Charlton, Michael R.

AU - Yamada, Hiroyuki

AU - Satomura, Shinji

AU - Algeciras-Schimnich, Alicia

AU - Snyder, Melissa R.

AU - Therneau, Terry M

AU - Roberts, Lewis Rowland

PY - 2015/5/1

Y1 - 2015/5/1

N2 - 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.

AB - 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.

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