title: 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.
abstract: OBJECTIVE
  To investigate the degree and mechanism of hepatic sinusoidal injury in different graft sizes in right lobe live donor liver transplantation (LDLT).
  
  
  BACKGROUND
  Liver grafts from living donors are likely to be small-for-size for adult recipients. Graft injury after reperfusion is common, but the mechanism and degree of injury remain unclear. The hepatic sinusoidal injury in different graft sizes and its relationship with portal hemodynamics and intragraft gene response at the early phase after reperfusion have not been studied in right lobe LDLT.
  
  
  METHODS
  From May 2000 to November 2001, 40 adults receiving right lobe LDLT had portal pressure measured continuously before and after reperfusion. Liver biopsies were taken before and after reperfusion for detection of vasoregulatory genes (endothelin-1 and endothelial nitric oxide synthase) and heat shock genes (heat shock protein 70 and heme oxygenase-1), and electron microscope examination. Blood samples from the portal vein and suprahepatic inferior vena cava were taken for the measurement of plasma nitric oxide level.
  
  
  RESULTS
  The recipients were grouped according to the ratio of graft weight to estimated standard liver weight: group 1 (n = 10), less than 40%; group 2 (n = 21), 40% to 60%; and group 3 (n = 9), more than 60%. The portal pressures recorded after reperfusion in group 1 were significantly higher within 30 minutes of reperfusion than those in groups 2 and 3. After reperfusion, the intragraft endothelin-1 mRNA level in group 1 increased by 161% of the basal level but decreased by 31.5% and 62% of the basal level in groups 2 and 3, respectively. The intragraft mRNA level of heme oxygenase-1 in groups 1 and 2 decreased by 75.5% and 25.3% of the basal level respectively but increased by 41% of basal level in group 3. The intragraft protein level of heat shock protein 70 decreased by 50 ng/mL after reperfusion in group 1 but increased by 12.4 ng/mL and 0.6 ng/mL in groups 2 and 3, respectively. The portal vein plasma nitric oxide level decreased more significantly after reperfusion in group 1 than in group 2. Electron microscope examination of liver biopsies in group 1 showed tremendous mitochondrial swelling as well as irregular large gaps between the sinusoidal lining cells. There were two hospital deaths in group 1 and none in the other two groups.
  
  
  CONCLUSIONS
  Patients implanted with grafts less than 40% of standard liver weight suffered from transient portal hypertension early after reperfusion. The phenomenon was accompanied by intragraft upregulation of endothelin-1 and ultrastructural evidence of sinusoidal damage. The transient portal hypertension after reperfusion, subsequent endothelin-1 overexpression, and plasma nitric oxide level reduction, together with downregulation of heme oxygenase-1 and heat shock protein 70, may account for the small-for-size graft injury.
authors.affiliation: Centre for the Study of Liver Disease and Department of Surgery, University of Hong Kong Medical Centre, Queen Mary Hospital, Hong Kong SAR, China.
authors.forename: Kwan
authors.initials: K
authors.lastname: Man
authors.forename: Sheung-Tat
authors.initials: ST
authors.lastname: Fan
authors.forename: Chung-Mau
authors.initials: CM
authors.lastname: Lo
authors.forename: Chi-Leung
authors.initials: CL
authors.lastname: Liu
authors.forename: Peter Chin-Wan
authors.initials: PC
authors.lastname: Fung
authors.forename: Ting-Bo
authors.initials: TB
authors.lastname: Liang
authors.forename: Terence Kin-Wah
authors.initials: TK
authors.lastname: Lee
authors.forename: Steven Hung-Teng
authors.initials: SH
authors.lastname: Tsui
authors.forename: Irene Oi-Lin
authors.initials: IO
authors.lastname: Ng
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Zhang
authors.forename: John
authors.initials: J
authors.lastname: Wong
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019332:Endothelin-1 / Q000032:analysis / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis / Q000235:genetics; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis / Q000235:genetics; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D006975:Hypertension, Portal / Q000209:etiology / Q000503:physiopathology*; D008099:Liver / Q000098:blood supply* / Q000293:injuries / Q000648:ultrastructure; D008102:Liver Circulation / Q000502:physiology*; D016031:Liver Transplantation / Q000009:adverse effects / Q000473:pathology* / Q000502:physiology*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D009929:Organ Size / Q000502:physiology; D011168:Portal System / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis; D015427:Reperfusion Injury / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019737:Transplants / Q000009:adverse effects*
chemical_list: D019332:Endothelin-1; D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D006419:Heme Oxygenase (Decyclizing)