Are the criteria always right? Assessment of hepatocellular carcinoma cases in living donor liver transplantation at a high-volume center

Are the criteria always right? Assessment of hepatocellular carcinoma cases in living donor liver transplantation at a high-volume center

Background/aim: With the increased experience in living donor liver transplantation (LDLT), it has been adopted for the treatment of hepatocellular carcinoma (HCC), with emerging discussions of criteria beyond tumor size and number. In contrast to deceased donor liver transplantation (DDLT), recipient selection for LDLT is not limited by organ allocation systems. We discuss herein the assessment, criteria, and experience with liver transplantation (LT) in HCC cases at a high-volume LDLT center. Material and methods: Between August 2006 and December 2017, 191 adult LT HCC recipients with at least one-year follow-up were retrospectively analyzed. Results: In 191 patients, one-, three- and five-year survival rates were 87.2%, 81.6%, and 76.2%, respectively, including early postoperative mortality. In 174 patients with long-term follow-up, one-, three- and five-year disease-free survival rates were 91.6%, 87.7%, and 84.4%, respectively. When multivariate analysis was utilized, tumor differentiation was the only factor which statistically affected survival (p = 0.025). Conclusion: LDLT allows us to push the limits forward and the question “Are the criteria always right?” is always on the table. We can conclude that, with the advantage of LDLT, every HCC patient deserves a case-by-case basis discussion for LT under scientific literature support. In borderline cases, tumor biopsy might help determine the decision for LT.Key words : Hepatocellular carcinoma, living donor liver transplantation, criteria, outcomes

___

  • 1. Raza A, Sood GK. Hepatocellular carcinoma review: current treatment, and evidence-based medicine. World Journal of Gastroenterology 2014; 20(15): 4115-4127. doi:10.3748/wjg. v20.i15.4115
  • 2. Kim Y, Stahl CC, Makramalla A, Olowokure OO, Ristagno RL et al. Downstaging therapy followed by liver transplantation for hepatocellular carcinoma beyond Milan criteria. Surgery 2017; 162(6): 1250-1258. doi:10.1016/j.surg.2017.08.007
  • 3. Venook AP, Papandreou C, Furuse J, de Guevara LL. The incidence and epidemiology of hepatocellular carcinoma: a global and regional perspective. The Oncologist 2010; 15(Suppl 4): 5-13. doi:10.1634/theoncologist.2010-S4-05
  • 4. Kaido T. Selection Criteria and Current Issues in Liver Transplantation for Hepatocellular Carcinoma. Liver Cancer 2016; 5(2):121-127. doi:10.1159/000367749
  • 5. Chan SC. Liver transplantation for hepatocellular carcinoma. Liver Cancer 2013; 2(3-4): 338-344. doi:10.1159/000343849
  • 6. Akamatsu N, Sugawara Y, Kokudo N. Living donor liver transplantation for patients with hepatocellular carcinoma. Liver Cancer 2014; 3(2): 108-118. doi:10.1159/000343866
  • 7. Yao FY, Ferrell L, Bass NM, Watson JJ, Bacchetti P et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology 2001; 33(6): 1394-1403. doi: 10.1053/jhep.2001.24563
  • 8. Yankol Y, Mecit N, Kanmaz T, Kalayoğlu M, Acarlı K. Complications and outcomes of 890 living liver donor hepatectomies at a single center: risks of saving loved one’s life. Turkish Journal of Surgery 2020; 36(2): 192-201. doi: 10.5578/ turkjsurg.4548
  • 9. Limkemann AJP, Abreu P, Sapisochin G. How far can we go with hepatocellular carcinoma in living donor liver transplantation? Current Opinion in Organ Transplantation 2019; 24(5): 644- 650. doi:10.1097/MOT.0000000000000692
  • 10. Goldaracena N, Gorgen A, Doyle A, Hansen BE, Tomiyama K et al. Live donor liver transplantation for patients with hepatocellular carcinoma offers increased survival vs. deceased donation. Journal of Hepatology 2019; 70(4): 666-673. doi:10.1016/j.jhep.2018.12.029
  • 11. Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. The New England Journal of Medicine 1996; 334(11): 693-699. doi:10.1056/ NEJM199603143341104
  • 12. Lee SG, Hwang S, Moon DB, Ahn CS, Kim KH et al. Expanded indication criteria of living donor liver transplantation for hepatocellular carcinoma at one large-volume center. Liver Transplantation 2008;14(7): 935-945. doi: 10.1002/lt.21445
  • 13. Kaido T, Ogawa K, Mori A, Fujimoto Y, Ito T et al. Usefulness of the Kyoto criteria as expanded selection criteria for liver transplantation for hepatocellular carcinoma. Surgery 2013; 154(5): 1053-1060. doi:10.1016/j.surg.2013.04.056
  • 14. Chen J, Xu X, Wu J, Ling Q, Wang K et al. The stratifying value of Hangzhou criteria in liver transplantation for hepatocellular carcinoma. Plos One 2014; 9(3): e93128. doi: 10.1371/journal. pone.0093128
  • 15. Kim JM, Kwon CH, Joh JW, Park JB, Lee JH et al. Expanded criteria for liver transplantation in patients with hepatocellular carcinoma. Transplantation Proceedings 2014; 46(3): 726-729. doi: 10.1016/j.transproceed.2013.11.037
  • 16. Akamatsu N, Sugawara Y, Kokudo N. Living-donor vs deceased-donor liver transplantation for patients with hepatocellular carcinoma. World Journal of Hepatology 2014; 6(9): 626-631. doi: 10.4254/wjh.v6.i9.626
  • 17. Lee SD, Lee B, Kim SH, Joo J, Kim SK et al. 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 Journal of Transplantation 2016; 6(2): 411-422. doi: 10.5500/wjt.v6.i2.411
  • 18. Azoulay D, Audureau E, Bhangui P, Belghiti J, Boillot O et al. Living or Brain-dead Donor Liver Transplantation for Hepatocellular Carcinoma: A Multicenter, Western, Intent-totreat Cohort Study. Annals of Surgery 2017; 266(6): 1035-1044. doi:10.1097/SLA.0000000000001986
  • 19. Uchiyama H, Itoh S, Yoshizumi T, Ikegami T, Harimoto N et al. Living donor liver transplantation for hepatocellular carcinoma: results of prospective patient selection by Kyushu University Criteria in 7 years. HPB (Oxford) 2017; 19(12): 1082-1090. doi:10.1016/j.hpb.2017.08.004
  • 20. Sapisochin G, Goldaracena N, Laurence JM, Dib M, Barbas A et al. The extended Toronto criteria for liver transplantation in patients with hepatocellular carcinoma: A prospective validation study. Hepatology 2016; 64(6): 2077-2088. doi:10.1002/hep.28643
  • 21. Wong TCL, Ng KKC, Fung JYY, Chan AAC, Cheung TT et al. Long-Term Survival Outcome Between Living Donor and Deceased Donor Liver Transplant for Hepatocellular Carcinoma: Intention-to-Treat and Propensity Score Matching Analyses. Annals of Surgical Oncology 2019; 26(5): 1454-1462. doi:10.1245/s10434-019-07206-0
  • 22. Kayaalp C, Ince V, Ersan V, Karakas S, Kahraman et al. Liver Transplantation for Hepatocellular Carcinoma at Inonu University. Journal of Gastrointestinal Cancer 2017; 48(3): 268-271. doi: 10.1007/s12029-017-9965-2
  • 23. Karakayali H, Sevmis S, Moray G, Yilmaz U, Ozcay F et al. Liver transplantation in patients with hepatocellular carcinoma: one center’s experience. Transplantation Proceedings 2008; 40(1): 213-218. doi:10.1016 /j.transproceed.2007.11.006
  • 24. Gunay Y, Guler N, Yaprak O, Dayangac M, Akyildiz M et al. Living Donor Liver Transplantation Outcomes for Hepatocellular Carcinoma Beyond Milan or UCSF Criteria. The Indian Journal of Surgery 2015; 77(Suppl 3): 950-956. doi: 10.1007 /s12262-014-1078-6
  • 25. Yilmaz C, Karaca CA, Iakobadze Z, Farajov R, Kilic K et al. Factors Affecting Recurrence and Survival After Liver Transplantation for Hepatocellular Carcinoma. Transplantation Proceedings 2018; 50(10): 3571-3576. doi:10.1016/j.transproceed.2018.05.027
  • 26. Todo S, Furukawa H, Tada M, Japanese Liver Transplantation Study G. Extending indication: role of living donor liver transplantation for hepatocellular carcinoma. Liver Transplantation 2007; 13(11 Suppl 2): S48-54. doi: 10.1002/ lt.21334
  • 27. Sugawara Y, Tamura S, Makuuchi M. Living donor liver transplantation for hepatocellular carcinoma: Tokyo University series. Digestive Diseases and Sciences 2007; 25(4) :310-312. doi:10.1159/000106910
  • 28. Mazzaferro V, Llovet JM, Miceli R, Bhoori S, Schiavo M et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. The Lancet Oncology 2009; 10(1): 35-43. doi: 10.1016/S1470-2045(08)70284-5
  • 29. Lee SD, Kim SH, Kim SK, Kim YK, Park SJ. Clinical Impact of 18F-Fluorodeoxyglucose Positron Emission Tomography/ Computed Tomography in Living Donor Liver Transplantation for Advanced Hepatocellular Carcinoma. Transplantation 2015 ; 99(10): 2142-2149. doi: 10.1097/TP.0000000000000719
  • 30. Yoon YI, Lee SG. Living Donor Liver Transplantation for Hepatocellular Carcinoma: An Asian Perspective. Digestive Diseases and Sciences 2019 ; 64(4): 993-1000. doi:10.1007/ s10620-019-05551-4
  • 31. Piardi T, Gheza F, Ellero B, Woehl-Jaegle ML, Ntourakis D et al. Number and tumor size are not sufficient criteria to select patients for liver transplantation for hepatocellular carcinoma. Annals of Surgical Oncology 2012; 19(6): 2020-2026. doi:10.1245/s10434-011-2170-9
  • 32. Pommergaard HC, Rostved AA, Adam R, Thygesen LC, Salizzoni M et al. Vascular invasion and survival after liver transplantation for hepatocellular carcinoma: a study from the European Liver Transplant Registry. HPB (Oxford) 2018; 20(8): 768-775. doi:10.1016/j.hpb.2018.03.002
  • 33. Banerjee S, Wang DS, Kim HJ, Sirlin CB, Chan MG et al. A computed tomography radiogenomic biomarker predicts microvascular invasion and clinical outcomes in hepatocellular carcinoma. Hepatology 2015; 62(3): 792-800. doi:10.1002/ hep.27877
  • 34. DuBay D, Sandroussi C, Sandhu L, Cleary S, Guba M et al. Liver transplantation for advanced hepatocellular carcinoma using poor tumor differentiation on biopsy as an exclusion criterion. Annals of Surgery 2011; 253(1): 166-172. doi:10.1097/ sla.0b013e31820508f1
  • 35. Acarli K. Liver Transplantation for Hepatocellular Carcinoma: “Experience of Memorial Sisli Hospital”. Journal of Gastrointestinal Cancer. 2017; 48(3): 272-273. doi:10.1007/ s12029-017-9966-1
  • 36. Chapman WC, Majella Doyle MB, Stuart JE, Vachharajani N, Crippin JS et al. Outcomes of neoadjuvant transarterial chemoembolization to downstage hepatocellular carcinoma before liver transplantation. Annals of Surgery 2008; 248(4): 617-625. doi:10.1097/SLA.0b013e31818a07d4
  • 37. Server S, Sabet S, Yaghouti K, Namal E, Inan N et al.Value of Imaging Findings in the Prediction of Microvascular Invasion in Hepatocellular Carcinoma. Transplantation Proceedings 2019; 51(7): 2403-2407. doi: 10.1016/j.transproceed.2019.01.178
  • 38. Yamamoto K, Imamura H, Matsuyama Y, Hasegawa K, Beck Y et al. Significance of alpha-fetoprotein and des-gamma-carboxy prothrombin in patients with hepatocellular carcinoma undergoing hepatectomy. Annals of Surgical Oncology 2009; 16(10): 2795-2804. doi: 10.1245/s10434-009-0618-y
  • 39. Miyaaki H, Nakashima O, Kurogi M, Eguchi K, Kojiro M. Lens culinaris agglutinin-reactive alpha-fetoprotein and protein induced by vitamin K absence II are potential indicators of a poor prognosis: a histopathological study of surgically resected hepatocellular carcinoma. Journal of Gastroenterology 2007; 42(12): 962-968. doi:10.1007/s00535-007-2117-x
  • 40. Mahmud N, John B, Taddei TH, Goldberg DS. Pre-transplant alpha-fetoprotein is associated with post-transplant hepatocellular carcinoma recurrence mortality. Clinical Transplantation 2019; 33(7): e13634. doi: 10.1111/ctr.13634
  • 41. O’Rourke JM, Shetty S, Shah T, Perera M. Liver transplantation for hepatocellular carcinoma: pushing the boundaries. Translational Gastroenterology and Hepatology 2019; 4:1. doi:10.21037/tgh.2018.12.07
  • 42. Mehta N, Dodge JL, Roberts JP, Hirose R, Yao FY. AlphaFetoprotein Decrease from > 1,000 to < 500 ng/mL in Patients with Hepatocellular Carcinoma Leads to Improved Posttransplant Outcomes. Hepatology 2019; 69(3): 1193-1205. doi:10.1002/hep.30413
  • 43. Hong G, Suh KS, Suh SW, Yoo T, Kim H et al. Alpha-fetoprotein and (18)F-FDG positron emission tomography predict tumor recurrence better than Milan criteria in living donor liver transplantation. Journal of Hepatology 2016; 64(4): 852-859. doi:10.1016/j.jhep.2015.11.033
  • 44. Yaprak O, Acar S, Ertugrul G, Dayangac M. Role of pretransplant 18F-FDG PET/CT in predicting hepatocellular carcinoma recurrence after liver transplantation. World Journal of Gastrointestinal Oncology 2018; 10(10): 336-343. doi:10.4251/wjgo.v10.i10.336
  • 45. Lorente L. New prognostic biomarkers of mortality in patients undergoing liver transplantation for hepatocellular carcinoma. World Journal of Gastroenterology 2018; 24(37): 4230-4242. doi: 10.3748/wjg.v24.i37.4230
  • 46. Toso C, Meeberg GA, Bigam DL, Oberholzer J, Shapiro AM et al. De novo sirolimus-based immunosuppression after liver transplantation for hepatocellular carcinoma: long-term outcomes and side effects. Transplantation 2007; 83(9): 1162- 1168. doi: 10.1097/01.tp.0000262607.95372.e0
  • 47. Mehta N, Yao FY. What Are the Optimal Liver Transplantation Criteria for Hepatocellular Carcinoma? Clinical Liver Disease 2019; 13(1): 20-25. doi:10.1002/cld.793
  • 48. Choi JY, Yu JI, Park HC, David Kwon CH, Kim JM et al. The possibility of radiotherapy as downstaging to living donor liver transplantation for hepatocellular carcinoma with portal vein tumor thrombus. Liver Transplantation 2017; 23(4): 545-551. doi: 10.1002/lt.24729
  • 49. Choi HJ, Kim DG, Na GH, Hong TH, Bae SH et al. The clinical outcomes of patients with portal vein tumor thrombi after living donor liver transplantation. Liver Transplantation 2017; 23(8): 1023-1031. doi: 10.1002/lt.24782
  • 50. Han DH, Joo DJ, Kim MS, Choi GH, Choi JS et al. Living Donor Liver Transplantation for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis after Concurrent Chemoradiation Therapy. Yonsei Medical Journal 2016 ; 57(5): 1276-1281. doi: 10.3349/ymj.2016.57.5.1276
  • 51. Sevmis S, Karakayali H, Karakayali F, Savas NA, Akkoc H et al. Postsurgical complications in living-related liver donors. Transplantation Proceedings 2008; 40(1): 245-247. doi: 10.1016/j.transproceed.2007.11.009
  • 52. Guler N, Yaprak O, Gunay Y, Dayangac M, Akyildiz M et al. Major complications of adult right lobe living liver donors. Hepatobiliary and Pancreatic Diseases International 2015;14(2):150-156. doi: 10.1016/s1499-3872(15)60346-0
  • 53. Onur A, Akbulut S, Dirican A, Isik B, Yilmaz S. Life-threatening or nearly life-threatening complications in living liver donors. Clinical Transplantation 2018 ; 32(6): e13262. doi: 10.1111/ ctr.13262
  • 54. Ozsoy M, Unalp OV, Sozbilen M, Alper M, Kilic M et al. Results of surgery-related complications in donors of right lobe liver graft: analysis of 272 cases. Transplantation Proceedings 2014; 46(5): 1377-1383. doi: 10.1016/j.transproceed.2013.12.065
  • 55. European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. Journal of Hepatology 2018; 69(1): 182-236. doi:10.1016/j.jhep.2018.03.019
  • 56. Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 2018 ; 67(1): 358-380. doi: 10.1002/ hep.29086
  • 57. Costentin CE, Bababekov YJ, Zhu AX, Yeh H. Is It Time to Reconsider the Milan Criteria for Selecting Patients With Hepatocellular Carcinoma for Deceased-Donor Liver Transplantation? Hepatology 2019; 69(3): 1324-1336. doi:10.1002/hep.30278
Turkish Journal of Medical Sciences-Cover
  • ISSN: 1300-0144
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: TÜBİTAK
Sayıdaki Diğer Makaleler

What is the restorative effect of VEGF inhibitor bevacuzimab against subarachnoid hemorrhage in an experimental model?

Ersin ÖZEREN, Yahya GÜVENÇ, Adnan Yalçın DEMİRC, Çetin AKYOL, Pınar BAYRAM, Deniz BİLLUR, Sevim AYDIN, Hakan SEÇKİN, Kazım YİĞİTKANLI

The role of gold weight implants in the management of paralytic lagophthalmos

Recep KARAMERT, Mehmet DÜZLÜ, Alper CEYLAN, Hakan TUTAR, Süleyman CEBECİ, Muammer Melih ŞAHİN, Eray UZUNOĞLU, Mücahit YALÇIN, Gökçen CESUR, Mehmet Birol UĞUR

Central nervous system involvement in patients with acute myeloid leukemia

Yahya BÜYÜKAŞIK, Hakan GÖKER, Hatime Arzu YAŞAR, Olgu Erkin ÇINAR, Nur YAZDALI KÖYLÜ, İbrahim BARIŞTA

Allergic diseases in the elderly population: a single-center experience

Gökhan AYTEKİN, Fatih ÇÖLKESEN, Eray YILDIZ, Şevket ARSLAN, Recep EVCEN, Filiz SADİ AYKAN, Mehmet KILINÇ

Assessment of fragmented QRS formation and its relationship with left ventricular hypertrophy in nonhypertensive acromegaly patients

Kadir Uğur MERT, Göknur YORULMAZ, Selda MURAT, Muhammet DURAL, Elif Sevil ALAGÜNEY, Ahmet Serdar YILMAZ, Nur KEBAPÇI, Ezgi CAMLI, Belgin EFE, Aysen AKALIN, Ahmet Toygar KALKAN

A single center survey study of systemic vasculitis and COVID-19 during the first months of pandemic

Lale ÖCAL, Mehmet Salih SEVDİ, Sibel ZARALI, Murat İNANÇ, Murat BEKTAŞ, Ahmet GÜL, Burak İNCE, Nevzat KOCA, Besim Fazıl AĞARGÜN, Damla Yenersu GÜZEY, Ayşe İNCE, Yasemin YALÇINKAYA, Bahar ARTIM ESEN

The visceral adiposity index, lipid accumulation product, and plasma atherogenic index are associated with subclinical atherosclerosis in patients with newly diagnosed acromegaly

Mustafa ÖZBEK, Erman ÇAKAL, Murat ÇALAPKULU, Hayri BOSTAN, İlknur ÖZTÜRK ÜNSAL, Sema HEPŞEN, Muhammed Erkam SENCAR

Fatty acid-binding protein-4 as a biomarker predicting acromegaly-associated diabetes mellitus

Mustafa ÖZBEK, Erman ÇAKAL, Muhammed Erkam SENCAR, Murat ÇALAPKULU, Davut SAKIZ, İlknur ÖZTÜRK ÜNSAL, Sema HEPŞEN, Pınar AKHANLI, Hakan DÜĞER, Bekir UÇAN, Seyit Murat BAYRAM

Assessment of erythrocyte morphology in patients with type 2 diabetes mellitus: a pilot study of electron microscopy-based analysis in relation to healthy controls

Şenay ARIKAN DURMAZ, Tülay MORTAŞ, Şaban Cem SEZEN, Yasemin SAVRANLAR

Clinical characteristics and risk factors for 28-day mortality in critically ill patients with COVID-19: a retrospective cohort study

Naciye Sinem GEZER, Begüm ERGAN, Ali Necati GÖKMEN, Ali CANTÜRK, Bilgin CÖMERT, Mehmet Nuri YAKAR, Erdem YAKA, Murat KÜÇÜK, Bişar ERGÜN, Mahmut Cem ERGON