Skip to main content
Top
Published in: Digestive Diseases and Sciences 1/2019

01-01-2019 | Original Article

Serological Risk Index Based on Alpha-Fetoprotein and C-Reactive Protein to Indicate Futile Liver Transplantation Among Patients with Advanced Hepatocellular Carcinoma

Authors: Arno Kornberg, Martina Schernhammer, Jennifer Kornberg, Helmut Friess, Katharina Thrum

Published in: Digestive Diseases and Sciences | Issue 1/2019

Login to get access

Abstract

Background

The aim of this study was to establish a preoperatively available serological risk index using alpha-fetoprotein (AFP) and C-reactive protein (CRP) for predicting oncologically futile liver transplantation (LT) in hepatocellular carcinoma (HCC) patients.

Methods

A total of 119 liver transplant patients with HCC were retrospectively analyzed. The prognostic impact of clinical and histopathologic factors including pre-LT serum AFP and CRP values was determined.

Results

Apart from microvascular tumor invasion (MVI; odds ratio [OR] 15.77), pretransplant serum levels of AFP > 100 ng/ml (OR 13.31) and CRP > 0.8 mg/dl (OR 13.97) were identified as independent predictors of HCC recurrence. The cumulative risk of HCC relapse at 5 years post-LT was 2.3% in low serological tumor activity (STA) index (AFP ≤ 100 ng/ml + CRP ≤ 0.8 mg/dl), 17.1% in intermediate STA (AFP ≤ 100 ng/ml or CRP ≤ 0.8 mg/dl), and 91.6% in high STA index (AFP > 100 ng/ml + CRP > 0.8 mg/dl; p < 0.001), respectively. High STA index was identified as most powerful pre-LT available predictor of MVI (OR 15.31) and posttransplant HCC recurrence (OR 54.44). Five-year recurrence-free survival rate in Milan Out patients with high STA was 0%, compared to 91.7% and 83.6% in those with low or intermediate STA index (p < 0.001), respectively.

Conclusion

Our proposed serological risk index based on pretransplant serum AFP and CRP values is able to predict oncologically futile LT among advanced HCC patients.
Literature
1.
go back to reference Sapisochin G, Bruix J. Liver transplantation for hepatocellular carcinoma: outcomes and novel surgical approaches. Nat Rev Gastroenterol Hepatol. 2017;14:203–217.CrossRef Sapisochin G, Bruix J. Liver transplantation for hepatocellular carcinoma: outcomes and novel surgical approaches. Nat Rev Gastroenterol Hepatol. 2017;14:203–217.CrossRef
2.
go back to reference Aravinthan AD, Bruni SG, Doyle AC, et al. Liver transplantation is a preferable alternative to palliative therapy for selected patients with advanced hepatocellular carcinoma. Ann Surg Oncol. 2017;24:1843–1851.CrossRef Aravinthan AD, Bruni SG, Doyle AC, et al. Liver transplantation is a preferable alternative to palliative therapy for selected patients with advanced hepatocellular carcinoma. Ann Surg Oncol. 2017;24:1843–1851.CrossRef
3.
go back to reference Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334:693–699.CrossRef Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334:693–699.CrossRef
4.
go back to reference Mazzaferro V, Chun YS, Poon RT, et al. Liver transplantation for hepatocellular carcinoma. Ann Surg Oncol. 2008;15:1001–1007.CrossRef Mazzaferro V, Chun YS, Poon RT, et al. Liver transplantation for hepatocellular carcinoma. Ann Surg Oncol. 2008;15:1001–1007.CrossRef
5.
go back to reference Taniguchi M. Liver transplantation in the MELD era—analysis of the OPTN/UNOS registry. Clin Transpl. 2012:41–65. Taniguchi M. Liver transplantation in the MELD era—analysis of the OPTN/UNOS registry. Clin Transpl. 2012:41–65.
6.
go back to reference Adler M, De Pauw F, Vereerstraeten P, et al. Outcome of patients with hepatocellular carcinoma listed for liver transplantation within the Eurotransplant allocation system. Liver Transplant. 2008;14:526–533.CrossRef Adler M, De Pauw F, Vereerstraeten P, et al. Outcome of patients with hepatocellular carcinoma listed for liver transplantation within the Eurotransplant allocation system. Liver Transplant. 2008;14:526–533.CrossRef
7.
go back to reference Ecker BL, Hoteit MA, Forde KA, et al. Patterns of discordance between pretransplant imaging stage of hepatocellular carcinoma and posttransplant pathologic stage: a contemporary appraisal of the Milan criteria. Transplantation. 2018;102:648–655.CrossRef Ecker BL, Hoteit MA, Forde KA, et al. Patterns of discordance between pretransplant imaging stage of hepatocellular carcinoma and posttransplant pathologic stage: a contemporary appraisal of the Milan criteria. Transplantation. 2018;102:648–655.CrossRef
8.
go back to reference Shah SA, Tan JC, McGilvray ID, et al. Accuracy of staging as a predictor for recurrence after liver transplantation for hepatocellular carcinoma. Transplantation. 2006;81:1633–1639.CrossRef Shah SA, Tan JC, McGilvray ID, et al. Accuracy of staging as a predictor for recurrence after liver transplantation for hepatocellular carcinoma. Transplantation. 2006;81:1633–1639.CrossRef
9.
go back to reference Yao FY, Xiao L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: validation of the UCSF-expanded criteria based on preoperative imaging. Am J Transplant. 2007;7:2587–2596.CrossRef Yao FY, Xiao L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: validation of the UCSF-expanded criteria based on preoperative imaging. Am J Transplant. 2007;7:2587–2596.CrossRef
10.
go back to reference Duffy JP, Vardanian A, Benjamin E, et al. Liver transplantation criteria for hepatocellular carcinoma should be expanded: a 22-year experience with 467 patients at UCLA. Ann Surg. 2007;246:502–509.CrossRef Duffy JP, Vardanian A, Benjamin E, et al. Liver transplantation criteria for hepatocellular carcinoma should be expanded: a 22-year experience with 467 patients at UCLA. Ann Surg. 2007;246:502–509.CrossRef
11.
go back to reference Silva M, Moya A, Berenguer M, et al. Expanded criteria for liver transplantation in patients with cirrhosis and hepatocellular carcinoma. Liver Transplant. 2008;14:1449–1460.CrossRef Silva M, Moya A, Berenguer M, et al. Expanded criteria for liver transplantation in patients with cirrhosis and hepatocellular carcinoma. Liver Transplant. 2008;14:1449–1460.CrossRef
12.
go back to reference Mazzaferro V, Llovet JM, Miceli R, et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol. 2009;10:35–43.CrossRef Mazzaferro V, Llovet JM, Miceli R, et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol. 2009;10:35–43.CrossRef
13.
go back to reference El-Fattah MA. Hepatocellular carcinoma biology predicts survival outcome after liver transplantation in the USA. Indian J Gastroenterol. 2017;36:117–125.CrossRef El-Fattah MA. Hepatocellular carcinoma biology predicts survival outcome after liver transplantation in the USA. Indian J Gastroenterol. 2017;36:117–125.CrossRef
15.
go back to reference Mehta N, Heimbach J, Harnois DM, et al. Validation of a Risk Estimation of Tumor Recurrence After Transplant (RETREAT) Score for hepatocellular carcinoma recurrence after liver transplant. JAMA Oncol. 2017;3:493–500.CrossRef Mehta N, Heimbach J, Harnois DM, et al. Validation of a Risk Estimation of Tumor Recurrence After Transplant (RETREAT) Score for hepatocellular carcinoma recurrence after liver transplant. JAMA Oncol. 2017;3:493–500.CrossRef
17.
go back to reference Pawlik TM, Gleisner AL, Anders RA, Assumpcao L, Maley W, Choti MA. Preoperative assessment of hepatocellular carcinoma tumor grade using needle biopsy: implications for transplant eligibility. Ann Surg. 2007;245:435–442.CrossRef Pawlik TM, Gleisner AL, Anders RA, Assumpcao L, Maley W, Choti MA. Preoperative assessment of hepatocellular carcinoma tumor grade using needle biopsy: implications for transplant eligibility. Ann Surg. 2007;245:435–442.CrossRef
18.
go back to reference Lai Q, Inostroza M, Rico Juri JM, Goffette P, Lerut J. Delta-slope of alpha-fetoprotein improves the ability to select liver transplant patients with hepatocellular cancer. HPB (Oxford). 2015;17:1085–1095.CrossRef Lai Q, Inostroza M, Rico Juri JM, Goffette P, Lerut J. Delta-slope of alpha-fetoprotein improves the ability to select liver transplant patients with hepatocellular cancer. HPB (Oxford). 2015;17:1085–1095.CrossRef
19.
go back to reference She WH, Chan ACY, Cheung TT, Lo CM, Chok KSH. Survival outcomes of liver transplantation for hepatocellular carcinoma in patients with normal, high and very high preoperative alpha-fetoprotein levels. World J Hepatol. 2018;10:308–318.CrossRef She WH, Chan ACY, Cheung TT, Lo CM, Chok KSH. Survival outcomes of liver transplantation for hepatocellular carcinoma in patients with normal, high and very high preoperative alpha-fetoprotein levels. World J Hepatol. 2018;10:308–318.CrossRef
20.
go back to reference Notarpaolo A, Layese R, Magistri P, et al. Validation of the AFP model as a predictor of HCC recurrence in patients with viral hepatitis-related cirrhosis who had received a liver transplant for HCC. J Hepatol. 2017;66:552–559.CrossRef Notarpaolo A, Layese R, Magistri P, et al. Validation of the AFP model as a predictor of HCC recurrence in patients with viral hepatitis-related cirrhosis who had received a liver transplant for HCC. J Hepatol. 2017;66:552–559.CrossRef
21.
go back to reference Clavien PA, Lesurtel M, Bossuyt PM, Gores GJ, Langer B, Perrier A. OLT for HCC Consensus Group: recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report. Lancet Oncol. 2012;13:e11–e22.CrossRef Clavien PA, Lesurtel M, Bossuyt PM, Gores GJ, Langer B, Perrier A. OLT for HCC Consensus Group: recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report. Lancet Oncol. 2012;13:e11–e22.CrossRef
22.
go back to reference Mazzaferro V, Sposito C, Zhou J, et al. Metroticket 2.0 model for analysis of competing risks of death after liver transplantation for hepatocellular carcinoma. Gastroenterology. 2018;154:128–139.CrossRef Mazzaferro V, Sposito C, Zhou J, et al. Metroticket 2.0 model for analysis of competing risks of death after liver transplantation for hepatocellular carcinoma. Gastroenterology. 2018;154:128–139.CrossRef
23.
go back to reference Lai Q, Avolio AW, Manzia TM, et al. Role of alpha-fetoprotein in selection of patients with hepatocellular carcinoma waiting for liver transplantation: must we reconsider it? Int J Biol Markers. 2011;26:153–159.CrossRef Lai Q, Avolio AW, Manzia TM, et al. Role of alpha-fetoprotein in selection of patients with hepatocellular carcinoma waiting for liver transplantation: must we reconsider it? Int J Biol Markers. 2011;26:153–159.CrossRef
24.
go back to reference Hameed B, Mehta N, Sapisochin G, Roberts JP, Yao FY. Alpha-fetoprotein level > 1000 ng/mL as an exclusion criterion for liver transplantation in patients with hepatocellular carcinoma meeting the Milan criteria. Liver Transplant. 2014;20:945–951.CrossRef Hameed B, Mehta N, Sapisochin G, Roberts JP, Yao FY. Alpha-fetoprotein level > 1000 ng/mL as an exclusion criterion for liver transplantation in patients with hepatocellular carcinoma meeting the Milan criteria. Liver Transplant. 2014;20:945–951.CrossRef
25.
go back to reference Agopian VG, Harlander-Locke MP, Markovic D, et al. Evaluation of patients with hepatocellular carcinomas that do not produce α-fetoprotein. JAMA Surg. 2017;152:55–64.CrossRef Agopian VG, Harlander-Locke MP, Markovic D, et al. Evaluation of patients with hepatocellular carcinomas that do not produce α-fetoprotein. JAMA Surg. 2017;152:55–64.CrossRef
26.
go back to reference Endig J, Buitrago-Molina LE, Marhenke S, et al. Dual role of the adaptive immune system in liver injury and hepatocellular carcinoma development. Cancer Cell. 2016;30:308–323.CrossRef Endig J, Buitrago-Molina LE, Marhenke S, et al. Dual role of the adaptive immune system in liver injury and hepatocellular carcinoma development. Cancer Cell. 2016;30:308–323.CrossRef
27.
go back to reference Cescon M, Bertuzzo VR, Ercolani G, Ravaioli M, Odaldi F, Pinna AD. Liver transplantation for hepatocellular carcinoma: role of inflammatory and immunological state on recurrence and prognosis. World J Gastroenterol. 2013;19:9174–9182.CrossRef Cescon M, Bertuzzo VR, Ercolani G, Ravaioli M, Odaldi F, Pinna AD. Liver transplantation for hepatocellular carcinoma: role of inflammatory and immunological state on recurrence and prognosis. World J Gastroenterol. 2013;19:9174–9182.CrossRef
28.
go back to reference Aravalli RN. Role of innate immunity in the development of hepatocellular carcinoma. World J Gastroenterol. 2013;19:7500–7514.CrossRef Aravalli RN. Role of innate immunity in the development of hepatocellular carcinoma. World J Gastroenterol. 2013;19:7500–7514.CrossRef
29.
go back to reference Guo J, Chen S, Chen Y, Li S, Xu D. Combination of CRP and NLR: a better predictor of postoperative survival in patients with gastric cancer. Cancer Manag Res. 2018;10:315–321.CrossRef Guo J, Chen S, Chen Y, Li S, Xu D. Combination of CRP and NLR: a better predictor of postoperative survival in patients with gastric cancer. Cancer Manag Res. 2018;10:315–321.CrossRef
31.
go back to reference Dolan RD, McSorley ST, Horgan PG, Laird B, McMillan DC. The role of the systemic inflammatory response in predicting outcomes in patients with advanced inoperable cancer: systematic review and meta-analysis. Crit Rev Oncol Hematol. 2017;116:134–146.CrossRef Dolan RD, McSorley ST, Horgan PG, Laird B, McMillan DC. The role of the systemic inflammatory response in predicting outcomes in patients with advanced inoperable cancer: systematic review and meta-analysis. Crit Rev Oncol Hematol. 2017;116:134–146.CrossRef
32.
go back to reference Nakanishi H, Kurosaki M, Tsuchiya K, et al. Novel pretreatment scoring incorporating C-reactive protein to predict overall survival in advanced hepatocellular carcinoma with sorafenib treatment. Liver Cancer.. 2016;5:257–268.CrossRef Nakanishi H, Kurosaki M, Tsuchiya K, et al. Novel pretreatment scoring incorporating C-reactive protein to predict overall survival in advanced hepatocellular carcinoma with sorafenib treatment. Liver Cancer.. 2016;5:257–268.CrossRef
33.
go back to reference Li Z, Xue TQ, Chen XY. Predictive values of serum VEGF and CRP levels combined with contrast enhanced MRI in hepatocellular carcinoma patients after TACE. Am J Cancer Res. 2016;6:2375–2385.PubMedPubMedCentral Li Z, Xue TQ, Chen XY. Predictive values of serum VEGF and CRP levels combined with contrast enhanced MRI in hepatocellular carcinoma patients after TACE. Am J Cancer Res. 2016;6:2375–2385.PubMedPubMedCentral
34.
go back to reference Zheng Z, Zhou L, Gao S, Yang Z, Yao J, Zheng S. Prognostic role of C-reactive protein in hepatocellular carcinoma: a systematic review and meta-analysis. Int J Med Sci. 2013;10:653–664.CrossRef Zheng Z, Zhou L, Gao S, Yang Z, Yao J, Zheng S. Prognostic role of C-reactive protein in hepatocellular carcinoma: a systematic review and meta-analysis. Int J Med Sci. 2013;10:653–664.CrossRef
36.
go back to reference Kim YK, Kim SH, Lee SD, Hong SK, Park SJ. Pretransplant serum levels of C-reactive protein predict prognoses in patients undergoing liver transplantation for hepatocellular carcinoma. Transplant Proc. 2015;47:686–693.CrossRef Kim YK, Kim SH, Lee SD, Hong SK, Park SJ. Pretransplant serum levels of C-reactive protein predict prognoses in patients undergoing liver transplantation for hepatocellular carcinoma. Transplant Proc. 2015;47:686–693.CrossRef
37.
go back to reference Na GH, Kim DG, Han JH, et al. Inflammatory markers as selection criteria of hepatocellular carcinoma in living-donor liver transplantation. World J Gastroenterol. 2014;20:6594–6601.CrossRef Na GH, Kim DG, Han JH, et al. Inflammatory markers as selection criteria of hepatocellular carcinoma in living-donor liver transplantation. World J Gastroenterol. 2014;20:6594–6601.CrossRef
38.
go back to reference An HJ, Jang JW, Bae SH, et al. Serum C-reactive protein is a useful biomarker for predicting outcomes after liver transplantation in patients with hepatocellular carcinoma. Liver Transplant. 2012;18:1406–1414.CrossRef An HJ, Jang JW, Bae SH, et al. Serum C-reactive protein is a useful biomarker for predicting outcomes after liver transplantation in patients with hepatocellular carcinoma. Liver Transplant. 2012;18:1406–1414.CrossRef
39.
go back to reference Kornberg A, Witt U, Kornberg J, Müller K, Friess H, Thrum K. Postoperative peak serum C-reactive protein is a predictor of outcome following liver transplantation for hepatocellular carcinoma. Biomarkers. 2016;21:152–159.CrossRef Kornberg A, Witt U, Kornberg J, Müller K, Friess H, Thrum K. Postoperative peak serum C-reactive protein is a predictor of outcome following liver transplantation for hepatocellular carcinoma. Biomarkers. 2016;21:152–159.CrossRef
40.
go back to reference Roberts LR, Sirlin CB, Zaiem F, et al. Imaging for the diagnosis of hepatocellular carcinoma: a systematic review and meta-analysis. Hepatology. 2018;67:401–421.CrossRef Roberts LR, Sirlin CB, Zaiem F, et al. Imaging for the diagnosis of hepatocellular carcinoma: a systematic review and meta-analysis. Hepatology. 2018;67:401–421.CrossRef
41.
go back to reference Cillo U, Giuliani T, Polacco M, et al. Prediction of hepatocellular carcinoma biological behavior in patient selection for liver transplantation. World J Gastroenterol. 2016;22:232–252.CrossRef Cillo U, Giuliani T, Polacco M, et al. Prediction of hepatocellular carcinoma biological behavior in patient selection for liver transplantation. World J Gastroenterol. 2016;22:232–252.CrossRef
42.
go back to reference Jonas S, Bechstein WO, Steinmüller T, et al. Vascular invasion and histopathologic grading determine outcome after liver transplantation for hepatocellular carcinoma in cirrhosis. Hepatology. 2001;33:1080–1086.CrossRef Jonas S, Bechstein WO, Steinmüller T, et al. Vascular invasion and histopathologic grading determine outcome after liver transplantation for hepatocellular carcinoma in cirrhosis. Hepatology. 2001;33:1080–1086.CrossRef
43.
go back to reference Lauerer M, Kaiser K, Nagel E. Organ transplantation in the face of donor shortage—ethical implications with a focus on liver allocation. Visc Med. 2016;32:278–285.CrossRef Lauerer M, Kaiser K, Nagel E. Organ transplantation in the face of donor shortage—ethical implications with a focus on liver allocation. Visc Med. 2016;32:278–285.CrossRef
44.
go back to reference Lai Q, Vitale A, Iesari S, et al. Intention-to-treat survival benefit of liver transplantation in patients with hepatocellular cancer. Hepatology. 2017;66:1910–1919.CrossRef Lai Q, Vitale A, Iesari S, et al. Intention-to-treat survival benefit of liver transplantation in patients with hepatocellular cancer. Hepatology. 2017;66:1910–1919.CrossRef
46.
go back to reference Grąt M, Krasnodębski M, Patkowski W, et al. Relevance of pre-transplant α-fetoprotein dynamics in liver transplantation for hepatocellular cancer. Ann Transplant. 2016;21:115–124.CrossRef Grąt M, Krasnodębski M, Patkowski W, et al. Relevance of pre-transplant α-fetoprotein dynamics in liver transplantation for hepatocellular cancer. Ann Transplant. 2016;21:115–124.CrossRef
50.
go back to reference Toso C, Meeberg G, Hernandez-Alejandro R, et al. Total tumor volume and alpha-fetoprotein for selection of transplant candidates with hepatocellular carcinoma: a prospective validation. Hepatology. 2015;62:158–165.CrossRef Toso C, Meeberg G, Hernandez-Alejandro R, et al. Total tumor volume and alpha-fetoprotein for selection of transplant candidates with hepatocellular carcinoma: a prospective validation. Hepatology. 2015;62:158–165.CrossRef
51.
go back to reference Lai Q, Avolio AW, Manzia TM, et al. Combination of biological and morphological parameters for the selection of patients with hepatocellular carcinoma for liver transplantation. Clin Transplant. 2012;26:125–131.CrossRef Lai Q, Avolio AW, Manzia TM, et al. Combination of biological and morphological parameters for the selection of patients with hepatocellular carcinoma for liver transplantation. Clin Transplant. 2012;26:125–131.CrossRef
52.
go back to reference Zheng SS, Xu X, Wu J, et al. Liver transplantation for hepatocellular carcinoma: Hangzhou experience. Transplantation. 2008;12:1726–1732.CrossRef Zheng SS, Xu X, Wu J, et al. Liver transplantation for hepatocellular carcinoma: Hangzhou experience. Transplantation. 2008;12:1726–1732.CrossRef
Metadata
Title
Serological Risk Index Based on Alpha-Fetoprotein and C-Reactive Protein to Indicate Futile Liver Transplantation Among Patients with Advanced Hepatocellular Carcinoma
Authors
Arno Kornberg
Martina Schernhammer
Jennifer Kornberg
Helmut Friess
Katharina Thrum
Publication date
01-01-2019
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 1/2019
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-018-5296-9

Other articles of this Issue 1/2019

Digestive Diseases and Sciences 1/2019 Go to the issue