Biomarkers for living donor liver transplants in hepatocellular carcinoma

Abstract

Liver transplantation is one of the more definitive treatments for hepatocellular carcinoma (HCC). In the United States, liver transplantation has historically been focused on deceased donor organs, and tumor burden is used for risk-stratifying patients on the transplant waitlist. Living donor liver transplantation (LDLT) is gaining popularity in the United States and has long been practiced in Asian countries. To improve outcomes of overall survival and disease-free survival post-living donor liver transplantation, surrogates of tumor biology are now being regarded to be as important as tumor burden. This article reviews the different surrogates of tumor biology and discusses their role in the application of LDLT for advanced HCC.

Keywords

LDLT / HCC / tumor biology

References

[1] Mazzaferro V,Doci R.Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis.N Engl J Med1996;334:693-9

[2] Yao FY,Bass NM.Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival.Hepatology2001;33:1394-403

[3] Lee SG,Moon DB.Expanded indication criteria of living donor liver transplantation for hepatocellular carcinoma at one large-volume center.Liver Transpl2008;14:935-45

[4] Sugawara Y,Makuuchi M.Living donor liver transplantation for hepatocellular carcinoma: Tokyo University series.Dig Dis2007;25:310-2

[5] Trotter JF,Lo CM.Documented deaths of hepatic lobe donors for living donor liver transplantation.Liver Transpl2006;12:1485-8

[6] Cho JY,Kwon CH.Outcome of donors with a remnant liver volume of less than 35% after right hepatectomy.Liver Transpl2006;12:201-6

[7] Hwang S,Lee YJ.Lessons learned from 1,000 living donor liver transplantations in a single center: how to make living donations safe.Liver Transpl2006;12:920-7

[8] Lo CM,Liu CL.Lessons learned from one hundred right lobe living donor liver transplants.Ann Surg2004;240:151-8 PMCID:PMC1356387

[9] Marsh JW,Ness R.Complications of right lobe living donor liver transplantation.J Hepatol2009;51:715-24 PMCID:PMC2955892

[10] Yi NJ,Cho JY.Three-quarters of right liver donors experienced postoperative complications.Liver Transpl2007;13:797-806

[11] Mehta N,Yao FY.Liver Transplantation for hepatocellular carcinoma. working group report from the ILTS transplant oncology consensus conference.Transplantation2020;104:1136-42

[12] Grant RC,Dixon PR,Grant DR.Living vs. deceased donor liver transplantation for hepatocellular carcinoma: a systematic review and meta-analysis.Clin Transplant2013;27:140-7

[13] Liang W,Ling X.Living donor liver transplantation versus deceased donor liver transplantation for hepatocellular carcinoma: a meta-analysis.Liver Transpl2012;18:1226-36

[14] Ito T,Ueda M.Expansion of selection criteria for patients with hepatocellular carcinoma in living donor liver transplantation.Liver Transpl2007;13:1637-44

[15] Kwon CH,Han YS.HCC in living donor liver transplantation: can we expand the Milan criteria?.Dig Dis2007;25:313-9

[16] Soejima Y,Yoshizumi T.Extended indication for living donor liver transplantation in patients with hepatocellular carcinoma.Transplantation2007;83:893-9

[17] Kaido T,Mori A.Usefulness of the Kyoto criteria as expanded selection criteria for liver transplantation for hepatocellular carcinoma.Surgery2013;154:1053-60

[18] Lee SD,Kim SH.Proposal of new expanded selection criteria using total tumor size and (18)F-fluorodeoxyglucose - positron emission tomography/computed tomography for living donor liver transplantation in patients with hepatocellular carcinoma: The national cancer center Korea criteria.World J Transplant2016;6:411-22 PMCID:PMC4919746

[19] Pawlik TM,Anders RA,Maley W.Preoperative assessment of hepatocellular carcinoma tumor grade using needle biopsy: implications for transplant eligibility.Ann Surg2007;245:435-42 PMCID:PMC1877015

[20] Rodríguez-Pérez C,Verardo V.Changes in dietary behaviours during the COVID-19 outbreak confinement in the Spanish COVIDiet study.Nutrients2020;12:1730 PMCID:PMC7353108

[21] Lin CC.Living donor liver transplantation for hepatocellular carcinoma achieves better outcomes.Hepatobiliary Surg Nutr2016;5:415-21 PMCID:PMC5075822

[22] Torizuka T,Inokuma T.In vivo assessment of glucose metabolism in hepatocellular carcinoma with FDG-PET.J Nucl Med1995;36:1811-7

[23] Ahn SY,Joo I.Prediction of microvascular invasion of hepatocellular carcinoma using gadoxetic acid-enhanced MR and (18)F-FDG PET/CT.Abdominal imaging2014;40:843-51

[24] Lin CY,Chu LY.Predictive value of 18F-FDG PET/CT for vascular invasion in patients with hepatocellular carcinoma before liver transplantation.Clin Nucl Med2017;42:e183-7

[25] Bailly M,Orain I,Ribeiro MJ.18F-FDG PET in liver transplantation setting of hepatocellular carcinoma: predicting histology?.Clin Nucl Med2016;41:e126-9

[26] Kornberg A,Bärthel E.18F-FDG-uptake of hepatocellular carcinoma on PET predicts microvascular tumor invasion in liver transplant patients.Am J Transplant2009;9:592-600

[27] Kornberg A,Tannapfel A.Patients with non-[18 F]fludeoxyglucose-avid advanced hepatocellular carcinoma on clinical staging may achieve long-term recurrence-free survival after liver transplantation.Liver Transpl2012;18:53-61

[28] Lee SD,Kim SK,Park SJ.Clinical impact of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in living donor liver transplantation for advanced hepatocellular carcinoma.Transplantation2015;99:2142-9

[29] Lee SD,Kim YK.(18)F-FDG-PET/CT predicts early tumor recurrence in living donor liver transplantation for hepatocellular carcinoma.Transpl Int2013;26:50-60

[30] Yang SH,Lee HW.The role of (18)F-FDG-PET imaging for the selection of liver transplantation candidates among hepatocellular carcinoma patients.Liver Transpl2006;12:1655-60

[31] Bhangui P,Gautam D.Incorporating tumor biology to predict hepatocellular carcinoma recurrence in patients undergoing living donor liver transplantation using expanded selection criteria.Liver Transpl2021;27:209-21

[32] Hsu CC,Wang CC.Combination of FDG-PET and UCSF criteria for predicting HCC recurrence after living donor liver transplantation.Transplantation2016;100:1925-32

[33] Lee JW,Kang KW.Prediction of tumor recurrence by 18F-FDG PET in liver transplantation for hepatocellular carcinoma.J Nucl Med2009;50:682-7

[34] Lu RC,Gao WT.Positron-emission tomography for hepatocellular carcinoma: Current status and future prospects.World J Gastroenterol2019;25:4682-95 PMCID:PMC6718031

[35] Gao FJ,Chen MH.Des-gamma-carboxy prothrombin increases the expression of angiogenic factors in human hepatocellular carcinoma cells.Life Sci2008;83:815-20

[36] Poté N,Albuquerque M.Performance of PIVKA-II for early hepatocellular carcinoma diagnosis and prediction of microvascular invasion.J Hepatol2015;62:848-54

[37] Shirabe K,Yoshizumi T.The predictors of microvascular invasion in candidates for liver transplantation with hepatocellular carcinoma-with special reference to the serum levels of des-gamma-carboxy prothrombin.J Surg Oncol2007;95:235-40

[38] Wang SB,Cui SX.Des-gamma-carboxy prothrombin stimulates human vascular endothelial cell growth and migration.Clin Exp Metastasis2009;26:469-77

[39] Takada Y,Ueda M.Living donor liver transplantation for patients with HCC exceeding the Milan criteria: a proposal of expanded criteria.Dig Dis2007;25:299-302

[40] Todo S,Tada M.Japanese Liver Transplantation Study GroupExtending indication: role of living donor liver transplantation for hepatocellular carcinoma.Liver Transpl2007;13:S48-54

[41] Chaiteerakij R,Addissie BD.Combinations of biomarkers and Milan criteria for predicting hepatocellular carcinoma recurrence after liver transplantation.Liver Transpl2015;21:599-606 PMCID:PMC4490162

[42] Motomura T,Mano Y.Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment.J Hepatol2013;58:58-64

[43] Shindoh J,Nagata R.Evaluation methods for pretransplant oncologic markers and their prognostic impacts in patient undergoing living donor liver transplantation for hepatocellular carcinoma.Transpl Int2014;27:391-8

[44] Harimoto N,Shimagaki T.Inflammation-based prognostic score in patients with living donor liver transplantation for hepatocellular carcinoma.Anticancer Res2016;36:5537-42

[45] Lai Q,Rico Juri JM,Lerut J.Neutrophil and platelet-to-lymphocyte ratio as new predictors of dropout and recurrence after liver transplantation for hepatocellular cancer.Transpl Int2014;27:32-41

[46] Na GH,Han JH.Inflammatory markers as selection criteria of hepatocellular carcinoma in living-donor liver transplantation.World J Gastroenterol2014;20:6594-601 PMCID:PMC4047346

[47] Wang W,Wang T.Prognostic prediction of male recipients selected for liver transplantation: with special attention to neutrophil to lymphocyte ratio.Hepatol Res2016;46:899-907

[48] Yoshizumi T,Yoshiya S.Impact of tumor size, number of tumors and neutrophil-to-lymphocyte ratio in liver transplantation for recurrent hepatocellular carcinoma.Hepatol Res2013;43:709-16

[49] Halazun KJ,Rana AA.Negative impact of neutrophil-lymphocyte ratio on outcome after liver transplantation for hepatocellular carcinoma.Ann Surg2009;250:141-51

[50] Xu ZG,Liu LX.The pretransplant neutrophil-lymphocyte ratio as a new prognostic predictor after liver transplantation for hepatocellular cancer: a systematic review and meta-analysis.Biomark Med2018;12:189-99

[51] Halazun KJ,Abdelmessih RM.Recurrence after liver transplantation for hepatocellular carcinoma: a new moral to the story.Ann Surg2017;265:557-64

[52] Bambace NM.The platelet contribution to cancer progression.J Thromb Haemost2011;9:237-49

[53] Kusumanto YH,Hospers GA,Mulder NH.Platelets and granulocytes, in particular the neutrophils, form important compartments for circulating vascular endothelial growth factor.Angiogenesis2003;6:283-7

[54] Lu Y,Li W.Alpha fetoprotein plays a critical role in promoting metastasis of hepatocellular carcinoma cells.J Cell Mol Med2016;20:549-58 PMCID:PMC4759472

[55] Wang X.Alpha-fetoprotein and hepatocellular carcinoma immunity.Can J Gastroenterol Hepatol2018;2018:9049252 PMCID:PMC5899840

[56] Bhatti ABH,Tahir R.When to call it off: defining transplant candidacy limits in liver donor liver transplantation for hepatocellular carcinoma.BMC Cancer2020;20:754 PMCID:PMC7425141

[57] Crocetti L,Scalise P.Locoregional treatments for bridging and downstaging hcc to liver transplantation.Cancers2021;13:5558 PMCID:PMC8583584

[58] Mehta N,Roberts JP,Yao FY.Alpha-fetoprotein decrease from > 1,000 to < 500 ng/ml in patients with hepatocellular carcinoma leads to improved posttransplant outcomes.Hepatology2019;69:1193-205 PMCID:PMC7087461

[59] Halazun KJ,Najjar M.Is it time to abandon the milan criteria?: results of a bicoastal US collaboration to redefine hepatocellular carcinoma liver transplantation selection policies.Ann Surg2018;268:690-9

[60] DuBay D,Sandhu L.Liver transplantation for advanced hepatocellular carcinoma using poor tumor differentiation on biopsy as an exclusion criterion.Ann Surg2011;253:166-72

[61] Hameed B,Sapisochin G,Yao FY.Alpha-fetoprotein level > 1,000 ng/mL as an exclusion criterion for liver transplantation in patients with hepatocellular carcinoma meeting the Milan criteria.Liver Transpl2014;20:945-51 PMCID:PMC4807739

[62] Assalino M,Grat M.Liver transplantation for hepatocellular carcinoma after successful treatment of macrovascular invasion - a multi-center retrospective cohort study.Transpl Int2020;33:567-75

[63] Lee KW,Choi Y.Macrovascular invasion is not an absolute contraindication for living donor liver transplantation.Liver Transpl2017;23:19-27

[64] Mehta N,Harnois DM.Validation of a risk estimation of tumor recurrence after transplant (RETREAT) score for hepatocellular carcinoma recurrence after liver transplant.JAMA Oncol2017;3:493-500 PMCID:PMC5395317

[65] Prasad KR,Burra P.Summary of candidate selection and expanded criteria for liver transplantation for hepatocellular carcinoma: a review and consensus statement.Liver Transpl2011;17 Suppl 2:S81-9

[66] Son JA,You D.Novel gene signatures as prognostic biomarkers for predicting the recurrence of hepatocellular carcinoma.Cancers2022;14:865 PMCID:PMC8870597

[67] Zhou T,Ma N.A novel ten-gene signature predicting prognosis in hepatocellular carcinoma.Front Cell Dev Biol2020;8:629 PMCID:PMC7372135

[68] Wang J,Shi F.A seven-gene signature to predict prognosis of patients with hepatocellular carcinoma.Front Genet2021;12:728476 PMCID:PMC8481951

[69] Pinto-Marques H,Silva S.A gene expression signature to select hepatocellular carcinoma patients for liver transplantation.Ann Surg2022;276:868-74 PMCID:PMC9534058

[70] Suh KS,Lee HW,Yi NJ.Liver transplantation for hepatocellular carcinoma in patients who do not meet the Milan criteria.Dig Dis2007;25:329-33

[71] Suh KS.Liver transplantation for advanced hepatocellular carcinoma: how far can we go?.Hepat Oncol2015;2:19-28 PMCID:PMC6095306

[72] Bhatti ABH,Khan NA.Living Donor Liver Transplantation for hepatocellular carcinoma: appraisal of the united network for organ sharing modified TNM staging.Front Surg2020;7:622170 PMCID:PMC7859519

[73] Bhatti ABH,Khan NY.Living donor liver transplantation for advanced hepatocellular carcinoma including macrovascular invasion.J Cancer Res Clin Oncol2022;148:245-53 PMCID:PMC8752562

[74] Sherman CB,Dodge JL,Yao FY.Distinguishing tumor from bland portal vein thrombus in liver transplant candidates with hepatocellular carcinoma: the A-VENA criteria.Liver Transpl2019;25:207-16 PMCID:PMC7103424

[75] Muhammad H,Ting PS.Long-term outcomes of living donor versus deceased donor liver transplant for hepatocellular carcinoma in the United States.Exp Clin Transplant2022;20:279-84