- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Mult-Organ Transplantation of Ministry of Public Health， Hangzhou 310003, China;
Objective To introduce the mechanisms of graft injuries after small-for-size liver transplantation and protective measures.
Methods Recently relevant literatures were reviewed and summarized.
Results Portal hypertension after small-for-size liver transplantation induces mechanical injuries as well as hepatic sinusoidal microcirculation disturbance and cytokines release, which worsened the injuries. Decrease portal pressure by surgery or drug could improve grafts function.
ConclusionComprehending the mechanisms of graft injuries will contribute a lot for the living donor liver transplantation.
Citation： LIANG Liang,LIANG Tingbo. Achievements of Basic Research in Small-for-Size Liver Transplantation. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(5): 428-432. doi: Copy
| 1. | Bismuth H, Houssin D. Reduced-sized orthotopic liver graft in hepatic transplantation in children [J]. Surgery， 1984; 95(3): 367-370. |
| 2. | Strong RW, Lynch SV, Ong TH, et al. Successful liver transplantation from a living donor to her son [J]. N Engl J Med, 1990; 322(21): 1505-1507. |
| 3. | Heaton N. Small-for-size liver syndrome after auxiliary and split liver transplantation: donor selection [J]. Liver Transpl, 2003; 9(9): S26-S28. |
| 4. | Urata K, Hashikura Y, Ikegami T, et al. Standard liver volume in adults [J]. Transplant Proc, 2000; 32(7): 2093-2094. |
| 5. | Kiuchi T, Kasahara M, Uryuhara K, et al. Impact of graft size mismatching on graft prognosis in liver transplantation from living donors[J]. Transplantation, 1999; 67(2): 321-327. |
| 6. | Emond JC, Renz JF, Ferrell LD, et al. Functional analysis of grafts from living donors. Implications for the treatment of older recipients [J]. Ann Surg, 1996; 224(4): 544-552. |
| 7. | Nishizaki T, Ikegami T, Hiroshige S, et al. Small graft for living donor liver transplantation [J]. Ann Surg, 2001; 233(4): 575-580. |
| 8. | Ohkohchi N, Shibuya H, Tsukamoto S, et al. Kupffer’s cells modulate neutrophile activity by superoxide anion and tumor necrosis factor-delta in reperfusion injury of liver transplantation-mechanisms of radical generation and reperfusion injury after cold ischemia [J]. Transplant Proc, 1999; 31(1-2): 1055-1058. |
| 9. | Ku Y, Fukumoto T, Nishida T, et al. Evidence that portal vein decompression improves survival of canine quarter orthotopic liver transplantation [J]. Transplantation, 1995; 59(10): 1388-1392. |
| 10. | Man K, Lo CM, Ng IO, et al. Liver transplantation in rats using small-for-size grafts: a study of hemodynamic and morphological changes [J]. Arch Surg, 2001; 136(3): 280-285. |
| 11. | García-Valdecasas JC, Fuster J, Charco R, et al. Changes in portal vein flow after adult living-donor liver transplantation: does it influence postoperative liver function? [J]. Liver Transpl, 2003; 9(6): 564-569. |
| 12. | Troisi R, de Hemptinne B. Clinical relevance of adapting portal vein flow in living donor liver transplantation in adult patients [J]. Liver Transpl, 2003; 9(9): S36-S41. |
| 13. | Man K, Fan ST, Lo CM, et al. Graft injury in relation to graft size in right lobe live donor liver transplantation: a study of hepatic sinusoidal injury in correlation with portal hemodynamics and intragraft gene expression [J]. Ann Surg, 2003; 237(2): 256-264. |
| 14. | Smyrniotis V, Kostopanagiotou G, Kondi A, et al. Hemodynamic interaction between portal vein and hepatic artery flow in small-for-size split liver transplantation [J]. Transpl Int, 2002; 15(7): 355-360. |
| 15. | Palmes D, Minin E, Budny T, et al. The endothelin/nitric oxide balance determines small-for-size liver injury after reduced-size rat liver transplantation [J]. Virchows Arch, 2005; 447(4): 731-741. |
| 16. | Li J, Liang L, Ma T, et al. Sinusoidal microcirculatory changes after small-for-size liver transplantation in rats [J]. Transpl Int, 2010 Feb 19. [Epub ahead of print]. |
| 17. | 徐世国， 郑树森， 梁廷波, 等. 大鼠不同体积肝移植早期肺组织内诱导性一氧化氮合成酶的表达 [J]. 中华肝胆外科杂志, 2005; 11(1): 273-275. |
| 18. | Liang TB, Man K, Kin-Wah Lee T, et al. Distinct intragraft response pattern in relation to graft size in liver transplantation [J]. Transplantation, 2003; 75(5): 673-678. |
| 19. | Liang T, Xu S, Yu J, et al. Activation pattern of mitogen-activated protein kinases in early phase of different size liver isografts in rats [J]. Liver Transpl, 2005; 11(12): 1527-1532. |
| 20. | Mao L, Qiu YD, Fang S, et al. Liver progenitor cells activated after 30% small-for-size liver transplantation in rats: a preliminary study [J]. Transplant Proc, 2008; 40(5): 1635-1640. |
| 21. | Huda KA, Guo L, Haga S, et al. Ex vivo adenoviral gene transfer of constitutively activated STAT3 reduces post-transplant liver injury and promotes regeneration in a 20% rat partial liver transplant model [J]. Transpl Int, 2006; 19(5): 415-423. |
| 22. | Debonera F, Wang G, Xie J, et al. Severe preservation injury induces Il-6/STAT3 activation with lack of cell cycle progression after partial liver graft transplantation [J]. Am J Transplant, 2004; 4(12): 1964-1971. |
| 23. | Zhong Z, Schwabe RF, Kai Y, et al. Liver regeneration is suppressed in small-for-size liver grafts after transplantation: involvement of c-Jun N-terminal kinase, cyclin D1, and defective energy supply [J]. Transplantation, 2006; 82(2): 241-250. |
| 24. | Mabuchi A, Mullaney I, Sheard PW, et al. Role of hepatic stellate cell/hepatocyte interaction and activation of hepatic stellate cells in the early phase of liver regeneration in the rat [J]. J Hepatol, 2004; 40(6): 910-916. |
| 25. | Yoshizumi T, Taketomi A, Soejima Y, et al. The beneficial role of simultaneous splenectomy in living donor liver transplantation in patients with small-for-size graft [J]. Transpl Int, 2008; 21(9): 833-842. |
| 26. | Ito T, Kiuchi T, Yamamoto H, et al. Changes in portal venous pressure in the early phase after living donor liver transplantation: pathogenesis and clinical implications [J]. Transplantation, 2003; 75(8): 1313-1317. |
| 27. | Yagi S, Iida T, Hori T, et al. Optimal portal venous circulation for liver graft function after living-donor liver transplantation [J]. Transplantation, 2006; 81(3): 373-378. |
| 28. | Troisi R, de Hemptinne B. Clinical relevance of adapting portal vein flow in living donor liver transplantation in adult patients [J]. Liver Transpl, 2003; 9(9): S36-S41. |
| 29. | Reynaert H, Vaeyens F, Qin H, et al. Somatostatin suppresses endothelin-1-induced rat hepatic stellate cell contraction via somatostatin receptor subtype 1 [J]. Gastroenterology, 2001; 121(4): 915-930. |
| 30. | Xu X, Man K, Zheng SS, et al. Attenuation of acute phase shear stress by somatostatin improves small-for-size liver graft survival [J]. Liver Transpl, 2006; 12(4): 621-627. |
| 31. | Man K, Lee TK, Liang TB, et al. FK 409 ameliorates small-for-size liver graft injury by attenuation of portal hypertension and down-regulation of Egr-1 pathway [J]. Ann Surg, 2004; 240(1): 159-168. |
| 32. | Tenhunen R, Marver HS, Schmid R. The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase [J]. Proc Natl Acad Sci USA, 1968; 61(2): 748-755. |
| 33. | Yang ZF, Tsui TY, Ho DW, et al. Heme oxygenase-1 potentiates the survival of small-for-size liver graft [J]. Liver Transpl, 2004; 10(6): 784-793. |
| 34. | Tang LM, Wang YP, Wang K, et al. Exogenous biliverdin ameliorates ischemia-reperfusion injury in small-for-size rat liver grafts [J]. Transplant Proc, 2007; 39(5): 1338-1344. |
| 35. | Morioka D, Kubota T, Sekido H, et al. Prostaglandin E1 improved the function of transplanted fatty liver in a rat reduced-size-liver transplantation model under conditions of permissible cold preservation [J]. Liver Transpl, 2003; 9(1): 79-86. |
| 36. | Tang LM, Wang YP, Wang K, et al. Protective effect of adenosine A2A receptor activation in small-for-size liver transplantation [J]. Transpl Int, 2007; 20(1): 93-101. |
| 37. | Zhao Y, Man K, Lo CM, et al. Attenuation of small-for-size liver graft injury by FTY720: significance of cell-survival Akt signaling pathway [J]. Am J Transplant, 2004; 4(9): 1399-1407. |
| 38. | Yu Y, Yao AH, Chen N, et al. Mesenchymal stem cells over-expressing hepatocyte growth factor improve small-for-size liver grafts regeneration [J]. Mol Ther, 2007; 15(7): 1382-1389. |
| 39. | Song J, Zhang YW, Yao AH, et al. Adenoviral cardiotrophin-1 transfer improves survival and early graft function after ischemia and reperfusion in rat small-for-size liver transplantation model [J]. Transpl Int, 2008; 21(4): 372-383. |
| 40. | Ricciardi R, Schaffer BK, Shah SA, et al. Bosentan, an endothelin antagonist, augments hepatic graft function by reducing graft circulatory impairment following ischemia/reperfusion injury [J]. J Gastrointest Surg, 2001; 5(3): 322-329. |
| 41. | Palmes D, Budny TB, Stratmann U, et al. Endothelin-A receptor antagonist reduces microcirculatory disturbances and transplant dysfunction after partial liver transplantation [J]. Liver Transpl, 2003; 9(9): 929-939. |
| 42. | Liang L, Ma T, Chen W, et al. Therapeutic potential and related signal pathway of adipose-derived stem cell transplantation for rat liver injury [J]. Hepatol Res, 2009; 39(8): 822-832. |
- 1. Bismuth H, Houssin D. Reduced-sized orthotopic liver graft in hepatic transplantation in children [J]. Surgery， 1984; 95(3): 367-370.
- 2. Strong RW, Lynch SV, Ong TH, et al. Successful liver transplantation from a living donor to her son [J]. N Engl J Med, 1990; 322(21): 1505-1507.
- 3. Heaton N. Small-for-size liver syndrome after auxiliary and split liver transplantation: donor selection [J]. Liver Transpl, 2003; 9(9): S26-S28.
- 4. Urata K, Hashikura Y, Ikegami T, et al. Standard liver volume in adults [J]. Transplant Proc, 2000; 32(7): 2093-2094.
- 5. Kiuchi T, Kasahara M, Uryuhara K, et al. Impact of graft size mismatching on graft prognosis in liver transplantation from living donors[J]. Transplantation, 1999; 67(2): 321-327.
- 6. Emond JC, Renz JF, Ferrell LD, et al. Functional analysis of grafts from living donors. Implications for the treatment of older recipients [J]. Ann Surg, 1996; 224(4): 544-552.
- 7. Nishizaki T, Ikegami T, Hiroshige S, et al. Small graft for living donor liver transplantation [J]. Ann Surg, 2001; 233(4): 575-580.
- 8. Ohkohchi N, Shibuya H, Tsukamoto S, et al. Kupffer’s cells modulate neutrophile activity by superoxide anion and tumor necrosis factor-delta in reperfusion injury of liver transplantation-mechanisms of radical generation and reperfusion injury after cold ischemia [J]. Transplant Proc, 1999; 31(1-2): 1055-1058.
- 9. Ku Y, Fukumoto T, Nishida T, et al. Evidence that portal vein decompression improves survival of canine quarter orthotopic liver transplantation [J]. Transplantation, 1995; 59(10): 1388-1392.
- 10. Man K, Lo CM, Ng IO, et al. Liver transplantation in rats using small-for-size grafts: a study of hemodynamic and morphological changes [J]. Arch Surg, 2001; 136(3): 280-285.
- 11. García-Valdecasas JC, Fuster J, Charco R, et al. Changes in portal vein flow after adult living-donor liver transplantation: does it influence postoperative liver function? [J]. Liver Transpl, 2003; 9(6): 564-569.
- 12. Troisi R, de Hemptinne B. Clinical relevance of adapting portal vein flow in living donor liver transplantation in adult patients [J]. Liver Transpl, 2003; 9(9): S36-S41.
- 13. Man K, Fan ST, Lo CM, et al. Graft injury in relation to graft size in right lobe live donor liver transplantation: a study of hepatic sinusoidal injury in correlation with portal hemodynamics and intragraft gene expression [J]. Ann Surg, 2003; 237(2): 256-264.
- 14. Smyrniotis V, Kostopanagiotou G, Kondi A, et al. Hemodynamic interaction between portal vein and hepatic artery flow in small-for-size split liver transplantation [J]. Transpl Int, 2002; 15(7): 355-360.
- 15. Palmes D, Minin E, Budny T, et al. The endothelin/nitric oxide balance determines small-for-size liver injury after reduced-size rat liver transplantation [J]. Virchows Arch, 2005; 447(4): 731-741.
- 16. Li J, Liang L, Ma T, et al. Sinusoidal microcirculatory changes after small-for-size liver transplantation in rats [J]. Transpl Int, 2010 Feb 19. [Epub ahead of print].
- 17. 徐世国， 郑树森， 梁廷波, 等. 大鼠不同体积肝移植早期肺组织内诱导性一氧化氮合成酶的表达 [J]. 中华肝胆外科杂志, 2005; 11(1): 273-275.
- 18. Liang TB, Man K, Kin-Wah Lee T, et al. Distinct intragraft response pattern in relation to graft size in liver transplantation [J]. Transplantation, 2003; 75(5): 673-678.
- 19. Liang T, Xu S, Yu J, et al. Activation pattern of mitogen-activated protein kinases in early phase of different size liver isografts in rats [J]. Liver Transpl, 2005; 11(12): 1527-1532.
- 20. Mao L, Qiu YD, Fang S, et al. Liver progenitor cells activated after 30% small-for-size liver transplantation in rats: a preliminary study [J]. Transplant Proc, 2008; 40(5): 1635-1640.
- 21. Huda KA, Guo L, Haga S, et al. Ex vivo adenoviral gene transfer of constitutively activated STAT3 reduces post-transplant liver injury and promotes regeneration in a 20% rat partial liver transplant model [J]. Transpl Int, 2006; 19(5): 415-423.
- 22. Debonera F, Wang G, Xie J, et al. Severe preservation injury induces Il-6/STAT3 activation with lack of cell cycle progression after partial liver graft transplantation [J]. Am J Transplant, 2004; 4(12): 1964-1971.
- 23. Zhong Z, Schwabe RF, Kai Y, et al. Liver regeneration is suppressed in small-for-size liver grafts after transplantation: involvement of c-Jun N-terminal kinase, cyclin D1, and defective energy supply [J]. Transplantation, 2006; 82(2): 241-250.
- 24. Mabuchi A, Mullaney I, Sheard PW, et al. Role of hepatic stellate cell/hepatocyte interaction and activation of hepatic stellate cells in the early phase of liver regeneration in the rat [J]. J Hepatol, 2004; 40(6): 910-916.
- 25. Yoshizumi T, Taketomi A, Soejima Y, et al. The beneficial role of simultaneous splenectomy in living donor liver transplantation in patients with small-for-size graft [J]. Transpl Int, 2008; 21(9): 833-842.
- 26. Ito T, Kiuchi T, Yamamoto H, et al. Changes in portal venous pressure in the early phase after living donor liver transplantation: pathogenesis and clinical implications [J]. Transplantation, 2003; 75(8): 1313-1317.
- 27. Yagi S, Iida T, Hori T, et al. Optimal portal venous circulation for liver graft function after living-donor liver transplantation [J]. Transplantation, 2006; 81(3): 373-378.
- 28. Troisi R, de Hemptinne B. Clinical relevance of adapting portal vein flow in living donor liver transplantation in adult patients [J]. Liver Transpl, 2003; 9(9): S36-S41.
- 29. Reynaert H, Vaeyens F, Qin H, et al. Somatostatin suppresses endothelin-1-induced rat hepatic stellate cell contraction via somatostatin receptor subtype 1 [J]. Gastroenterology, 2001; 121(4): 915-930.
- 30. Xu X, Man K, Zheng SS, et al. Attenuation of acute phase shear stress by somatostatin improves small-for-size liver graft survival [J]. Liver Transpl, 2006; 12(4): 621-627.
- 31. Man K, Lee TK, Liang TB, et al. FK 409 ameliorates small-for-size liver graft injury by attenuation of portal hypertension and down-regulation of Egr-1 pathway [J]. Ann Surg, 2004; 240(1): 159-168.
- 32. Tenhunen R, Marver HS, Schmid R. The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase [J]. Proc Natl Acad Sci USA, 1968; 61(2): 748-755.
- 33. Yang ZF, Tsui TY, Ho DW, et al. Heme oxygenase-1 potentiates the survival of small-for-size liver graft [J]. Liver Transpl, 2004; 10(6): 784-793.
- 34. Tang LM, Wang YP, Wang K, et al. Exogenous biliverdin ameliorates ischemia-reperfusion injury in small-for-size rat liver grafts [J]. Transplant Proc, 2007; 39(5): 1338-1344.
- 35. Morioka D, Kubota T, Sekido H, et al. Prostaglandin E1 improved the function of transplanted fatty liver in a rat reduced-size-liver transplantation model under conditions of permissible cold preservation [J]. Liver Transpl, 2003; 9(1): 79-86.
- 36. Tang LM, Wang YP, Wang K, et al. Protective effect of adenosine A2A receptor activation in small-for-size liver transplantation [J]. Transpl Int, 2007; 20(1): 93-101.
- 37. Zhao Y, Man K, Lo CM, et al. Attenuation of small-for-size liver graft injury by FTY720: significance of cell-survival Akt signaling pathway [J]. Am J Transplant, 2004; 4(9): 1399-1407.
- 38. Yu Y, Yao AH, Chen N, et al. Mesenchymal stem cells over-expressing hepatocyte growth factor improve small-for-size liver grafts regeneration [J]. Mol Ther, 2007; 15(7): 1382-1389.
- 39. Song J, Zhang YW, Yao AH, et al. Adenoviral cardiotrophin-1 transfer improves survival and early graft function after ischemia and reperfusion in rat small-for-size liver transplantation model [J]. Transpl Int, 2008; 21(4): 372-383.
- 40. Ricciardi R, Schaffer BK, Shah SA, et al. Bosentan, an endothelin antagonist, augments hepatic graft function by reducing graft circulatory impairment following ischemia/reperfusion injury [J]. J Gastrointest Surg, 2001; 5(3): 322-329.
- 41. Palmes D, Budny TB, Stratmann U, et al. Endothelin-A receptor antagonist reduces microcirculatory disturbances and transplant dysfunction after partial liver transplantation [J]. Liver Transpl, 2003; 9(9): 929-939.
- 42. Liang L, Ma T, Chen W, et al. Therapeutic potential and related signal pathway of adipose-derived stem cell transplantation for rat liver injury [J]. Hepatol Res, 2009; 39(8): 822-832.