Korean J Transplant.  2019 Dec;33(4):65-73. 10.4285/jkstn.2019.33.4.65.

Conceptual changes in small-for-size graft and small-for-size syndrome in living donor liver transplantation

• Ikegami T
• Kim JM
• Jung DH
• Soejima Y
• Kim DS
• Joh JW
• Lee SG
• Yoshizumi
• Mori M

• KMID: 2468156
• DOI: http://doi.org/10.4285/jkstn.2019.33.4.65

Abstract

Early series in living donor liver transplantation (LDLT) in adults demonstrated a lower safe limit of graft volume standard liver volume ratio 25%-45%. A subsequent worldwide large LDLT series proposed a 0.8 graft recipient weight ratio (GRWR) to define small-for-size graft (SFSG) in adult LDLT. Thereafter, researchers identified innate and inevitable factors including changes in liver volume during imaging studies and graft shrinkage due to perfusion solution. Although the definition of small-for-size syndrome (SFSS) advocated in the 2000s was mainly based on prolonged cholestasis and ascites output, the term SFSS was inadequate to describe clinical manifestations possibly caused by multiple factors. Thus, the term "early allograft dysfunction (EAD)," characterized by total bilirubin >10 mg/dL or coagulopathy with international normalized ratio >1.6 on day 7, has become prevalent to describe graft dysfunction including SFSS after LDLT. Although various efforts have been made to overcome EAD in LDLT, graft selection to maintain an expected GRWR >0.8 and full venous drainage, as well as inflow modulation using splenic artery ligation, have become standard in recent LDLT.

Keyword

Living donor liver transplantation; Small-for-size graft; Small-for-size-syndrome; Early allograft dysfunction

MeSH Terms

Adult
Allografts
Ascites
Bilirubin
Cholestasis
Drainage
Humans
International Normalized Ratio
Ligation
Liver Transplantation*
Liver*
Living Donors*
Perfusion
Splenic Artery
Transplants*
Bilirubin

Figure

• 

  Fig. 1 Severe hepatocyte ballooning with cholestasis around the pericentral venous area (A) and the recovering phase (B), representing early allograft dysfunction (EAD) including small-for-size syndrome. The pathological findings with EAD can be distinguished from those of cholestatic lobular hepatitis C with panlobular hepatocyte ballooning (C) and acute rejection with mixed cellular infiltrations around the periportal area (D). Black arrows indicate central veins.

Reference

1. Raia S, Nery JR, Mies S. Liver transplantation from live donors. Lancet. 1989; 2:497.

2. Ozawa K, Uemoto S, Tanaka K, Kumada K, Yamaoka Y, Kobayashi N, et al. An appraisal of pediatric liver transplantation from living relatives: initial clinical experiences in 20 pediatric liver transplantations from living relatives as donors. Ann Surg. 1992; 216:547–553.

3. Kawasaki S, Makuuchi M, Matsunami H, Hashikura Y, Ikegami T, Chisuwa H, et al. Preoperative measurement of segmental liver volume of donors for living related liver transplantation. Hepatology. 1993; 18:1115–1120.

4. Hashikura Y, Makuuchi M, Kawasaki S, Matsunami H, Ikegami T, Nakazawa Y, et al. Successful living-related partial liver transplantation to an adult patient. Lancet. 1994; 343:1233–1234.

5. Lo CM, Fan ST, Chan JK, Wei W, Lo RJ, Lai CL. Minimum graft volume for successful adult-to-adult living donor liver transplantation for fulminant hepatic failure. Transplantation. 1996; 62:696–698.

6. Emond JC, Renz JF, Ferrell LD, Rosenthal P, Lim RC, Roberts JP, et al. Functional analysis of grafts from living donors: implications for the treatment of older recipients. Ann Surg. 1996; 224:544–554.

7. Lo CM, Fan ST, Liu CL, Wei WI, Lo RJ, Lai CL, et al. Adult-to-adult living donor liver transplantation using extended right lobe grafts. Ann Surg. 1997; 226:261–270.

8. Kiuchi T, Kasahara M, Uryuhara K, Inomata Y, Uemoto S, Asonuma K, et al. Impact of graft size mismatching on graft prognosis in liver transplantation from living donors. Transplantation. 1999; 67:321–327.

9. Inomata Y, Uemoto S, Asonuma K, Egawa H. Right lobe graft in living donor liver transplantation. Transplantation. 2000; 69:258–264.

10. Uemura T, Wada S, Kaido T, Mori A, Ogura Y, Yagi S, et al. How far can we lower graft-to-recipient weight ratio for living donor liver transplantation under modulation of portal venous pressure? Surgery. 2016; 159:1623–1630.

11. Nishizaki T, Ikegami T, Hiroshige S, Hashimoto K, Uchiyama H, Yoshizumi T, et al. Small graft for living donor liver transplantation. Ann Surg. 2001; 233:575–580.

12. Soejima Y, Taketomi A, Yoshizumi T, Uchiyama H, Harada N, Ijichi H, et al. Feasibility of left lobe living donor liver transplantation between adults: an 8-year, single-center experience of 107 cases. Am J Transplant. 2006; 6(5 Pt 1):1004–1011.

13. Sugawara Y, Makuuchi M, Takayama T, Imamura H, Dowaki S, Mizuta K, et al. Small-for-size grafts in living-related liver transplantation. J Am Coll Surg. 2001; 192:510–513.

14. Hwang S, Lee SG, Lee YJ, Sung KB, Park KM, Kim KH, et al. Lessons learned from 1,000 living donor liver transplantations in a single center: how to make living donations safe. Liver Transpl. 2006; 12:920–927.

15. Suh KS, Suh SW, Lee JM, Choi Y, Yi NJ, Lee KW. Recent advancements in and views on the donor operation in living donor liver transplantation: a single-center study of 886 patients over 13 years. Liver Transpl. 2015; 21:329–338.

16. Chan SC, Lo CM, Ng KK, Fan ST. Alleviating the burden of small-for-size graft in right liver living donor liver transplantation through accumulation of experience. Am J Transplant. 2010; 10:859–867.

17. Goldaracena N, Sapisochin G, Spetzler V, Echeverri J, Kaths M, Cattral MS, et al. Live donor liver transplantation with older (≥50 years) versus younger (<50 years) donors: does age matter? Ann Surg. 2016; 263:979–985.

18. Botha JF, Langnas AN, Campos BD, Grant WJ, Freise CE, Ascher NL, et al. Left lobe adult-to-adult living donor liver transplantation: small grafts and hemiportocaval shunts in the prevention of small-for-size syndrome. Liver Transpl. 2010; 16:649–657.

19. Ogura Y, Hori T, El Moghazy WM, Yoshizawa A, Oike F, Mori A, et al. Portal pressure <15 mm Hg is a key for successful adult living donor liver transplantation utilizing smaller grafts than before. Liver Transpl. 2010; 16:718–728.

20. Ikegami T, Yoshizumi T, Sakata K, Uchiyama H, Harimoto N, Harada N, et al. Left lobe living donor liver transplantation in adults: what is the safety limit? Liver Transpl. 2016; 22:1666–1675.

21. Macshut M, Kaido T, Yao S, Yagi S, Ito T, Kamo N, et al. Older donor age is a risk factor for negative outcomes after adult living donor liver transplantation using small-for-size grafts. Liver Transpl. 2019; 25:1524–1532.

22. Kaido T, Ogawa K, Fujimoto Y, Ogura Y, Hata K, Ito T, et al. Impact of sarcopenia on survival in patients undergoing living donor liver transplantation. Am J Transplant. 2013; 13:1549–1556.

23. Kelly DM, Miller C. Understanding the splenic contribution to portal flow: the role of splenic artery ligation as inflow modification in living donor liver transplantation. Liver Transpl. 2006; 12:1186–1188.

24. Urata K, Kawasaki S, Matsunami H, Hashikura Y, Ikegami T, Ishizone S, et al. Calculation of child and adult standard liver volume for liver transplantation. Hepatology. 1995; 21:1317–1321.

25. Marcos A, Orloff M, Mieles L, Olzinski AT, Renz JF, Sitzmann JV. Functional venous anatomy for right-lobe grafting and techniques to optimize outflow. Liver Transpl. 2001; 7:845–852.

26. Hiroshige S, Shimada M, Harada N, Shiotani S, Ninomiya M, Minagawa R, et al. Accurate preoperative estimation of liver-graft volumetry using three-dimensional computed tomography. Transplantation. 2003; 75:1561–1564.

27. Radtke A, Sotiropoulos GC, Nadalin S, Molmenti EP, Schroeder T, Lang H, et al. Preoperative volume prediction in adult living donor liver transplantation: how much can we rely on it? Am J Transplant. 2007; 7:672–679.

28. Yoneyama T, Asonuma K, Okajima H, Lee KJ, Yamamoto H, Takeichi T, et al. Coefficient factor for graft weight estimation from preoperative computed tomography volumetry in living donor liver transplantation. Liver Transpl. 2011; 17:369–372.

29. Kayashima H, Taketomi A, Yonemura Y, Ijichi H, Harada N, Yoshizumi T, et al. Accuracy of an age-adjusted formula in assessing the graft volume in living donor liver transplantation. Liver Transpl. 2008; 14:1366–1371.

30. Ben-Haim M, Emre S, Fishbein TM, Sheiner PA, Bodian CA, Kim-Schluger L, et al. Critical graft size in adult-to-adult living donor liver transplantation: impact of the recipient’s disease. Liver Transpl. 2001; 7:948–953.

31. Soejima Y, Shimada M, Suehiro T, Hiroshige S, Ninomiya M, Shiotani S, et al. Outcome analysis in adult-to-adult living donor liver transplantation using the left lobe. Liver Transpl. 2003; 9:581–586.

32. Dahm F, Georgiev P, Clavien PA. Small-for-size syndrome after partial liver transplantation: definition, mechanisms of disease and clinical implications. Am J Transplant. 2005; 5:2605–2610.

33. Kulik U, Lehner F, Klempnauer J, Borlak J. Primary non-function is frequently associated with fatty liver allografts and high mortality after re-transplantation. Liver Int. 2017; 37:1219–1228.

34. Hill MJ, Hughes M, Jie T, Cohen M, Lake J, Payne WD, et al. Graft weight/recipient weight ratio: how well does it predict outcome after partial liver transplants? Liver Transpl. 2009; 15:1056–1062.

35. Ikegami T, Shirabe K, Yoshizumi T, Aishima S, Taketomi YA, Soejima Y, et al. Primary graft dysfunction after living donor liver transplantation is characterized by delayed functional hyperbilirubinemia. Am J Transplant. 2012; 12:1886–1897.

36. Hoyer DP, Paul A, Gallinat A, Molmenti EP, Reinhardt R, Minor T, et al. Donor information based prediction of early allograft dysfunction and outcome in liver transplantation. Liver Int. 2015; 35:156–163.

37. Lee DD, Singh A, Burns JM, Perry DK, Nguyen JH, Taner CB. Early allograft dysfunction in liver transplantation with donation after cardiac death donors results in inferior survival. Liver Transpl. 2014; 20:1447–1453.

38. Wadei HM, Lee DD, Croome KP, Mai ML, Golan E, Brotman R, et al. Early allograft dysfunction after liver transplantation is associated with short- and long-term kidney function impairment. Am J Transplant. 2016; 16:850–859.

39. Olthoff KM, Emond JC, Shearon TH, Everson G, Baker TB, Fisher RA, et al. Liver regeneration after living donor transplantation: adult-to-adult living donor liver transplantation cohort study. Liver Transpl. 2015; 21:79–88.

40. Pomposelli JJ, Goodrich NP, Emond JC, Humar A, Baker TB, Grant DR, et al. Patterns of early allograft dysfunction in adult live donor liver transplantation: the A2ALL experience. Transplantation. 2016; 100:1490–1499.

41. Okamura Y, Yagi S, Sato T, Hata K, Ogawa E, Yoshizawa A, et al. Coexistence of bilirubin ≥10 mg/dL and prothrombin time-international normalized ratio ≥1.6 on day 7: a strong predictor of early graft loss after living donor liver transplantation. Transplantation. 2018; 102:440–447.

42. Kiuchi T, Tanaka K, Ito T, Oike F, Ogura Y, Fujimoto Y, et al. Small-for-size graft in living donor liver transplantation: how far should we go? Liver Transpl. 2003; 9:S29–S35.

43. Ikegami T, Shimada M, Imura S, Arakawa Y, Nii A, Morine Y, et al. Current concept of small-for-size grafts in living donor liver transplantation. Surg Today. 2008; 38:971–982.

44. Yagi S, Uemoto S. Small-for-size syndrome in living donor liver transplantation. Hepatobiliary Pancreat Dis Int. 2012; 11:570–576.

45. Lo CM, Liu CL, Fan ST. Portal hyperperfusion injury as the cause of primary nonfunction in a small-for-size liver graft-successful treatment with splenic artery ligation. Liver Transpl. 2003; 9:626–628.

46. Cheng YF, Huang TL, Chen TY, Concejero A, Tsang LL, Wang CC, et al. Liver graft-to-recipient spleen size ratio as a novel predictor of portal hyperperfusion syndrome in living donor liver transplantation. Am J Transplant. 2006; 6:2994–2999.

47. Humar A, Beissel J, Crotteau S, Cohen M, Lake J, Payne WD. Delayed splenic artery occlusion for treatment of established small-for-size syndrome after partial liver transplantation. Liver Transpl. 2009; 15:163–168.

48. Ikegami T, Shirabe K, Soejima Y, Yoshizumi T, Uchiyama H, Yamashita Y, et al. Strategies for successful left-lobe living donor liver transplantation in 250 consecutive adult cases in a single center. J Am Coll Surg. 2013; 216:353–362.

49. Yoshizumi T, Taketomi A, Soejima Y, Ikegami T, Uchiyama H, Kayashima H, et al. The beneficial role of simultaneous splenectomy in living donor liver transplantation in patients with small-for-size graft. Transpl Int. 2008; 21:833–842.

50. Ikegami T, Toshima T, Takeishi K, Soejima Y, Kawanaka H, Yoshizumi T, et al. Bloodless splenectomy during liver transplantation for terminal liver diseases with portal hypertension. J Am Coll Surg. 2009; 208:e1–e4.

51. Uehara H, Akahoshi T, Kawanaka H, Hashimoto N, Nagao Y, Tomikawa M, et al. Endothelin-1 derived from spleen-activated Rho-kinase pathway in rats with secondary biliary cirrhosis. Hepatol Res. 2012; 42:1039–1047.

52. Kawanaka H, Akahoshi T, Kinjo N, Iguchi T, Ninomiya M, Yamashita YI, et al. Effect of laparoscopic splenectomy on portal haemodynamics in patients with liver cirrhosis and portal hypertension. Br J Surg. 2014; 101:1585–1593.

53. Moon DB, Lee SG, Hwang S, Ahn CS, Kim KH, Ha TY, et al. Splenic devascularization can replace splenectomy during adult living donor liver transplantation: a historical cohort study. Transpl Int. 2019; 32:535–545.

54. Boillot O, Delafosse B, Méchet I, Boucaud C, Pouyet M. Small-for-size partial liver graft in an adult recipient: a new transplant technique. Lancet. 2002; 359:406–407.

55. Troisi R, Ricciardi S, Smeets P, Petrovic M, Van Maele G, Colle I, et al. Effects of hemi-portocaval shunts for inflow modulation on the outcome of small-for-size grafts in living donor liver transplantation. Am J Transplant. 2005; 5:1397–1404.

56. Yamada T, Tanaka K, Uryuhara K, Ito K, Takada Y, Uemoto S. Selective hemi-portocaval shunt based on portal vein pressure for small-for-size graft in adult living donor liver transplantation. Am J Transplant. 2008; 8:847–853.

57. Ikegami T, Soejima Y, Taketomi A, Sanefuji K, Kayashima H, Harada N, et al. Living donor liver transplantation with extra-small graft: inflow modulation using splenectomy and temporary portocaval shunt. Hepatogastroenterology. 2008; 55:670–672.