学位論文内容の要旨
博士の専攻分野の名称

博士（医 学）氏 名

小林 健太郎

学 位 論 文 題 名
Postoperative assessment of donor’s hepatic asialoglycoprotein receptor function using
Tc-99m GSA scintigraphy in living donor liver transplantation（Tc-99m GSA シンチグラフィを用いた生体肝移植ドナーにおける術後のアシアロ糖タンパク受容体機能評価に関する研究）【Background】
Living donor liver transplantation is an established surgical approach to treat patients withsevere hepatic disorders. Despite technical advances and accumulated experience with liver resection,living liver donation is associated with size-dependent complications. Scintigraphy using
technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (Tc-99mGSA) is a widely used for in-vivo imaging to quantify liver function.
The purpose of Chapter 1 was to determine if the current partial hepatectomy procedures arecompleted under the safety margin of the resectable size, by measuring asialoglycoprotein receptor(ASGPR) function of donor’s remnant liver. In chapter 2, I will show the chronological data of liver
volume and GSA scintigraphy, and propose a hypothesis regarding liver regeneration potential.
Chapter1【Methods】
Seventy-four living donors (35 ± 11 yrs old, ranging from 18 to 62) underwent Tc-99m
GSA scintigraphy at 1 postoperative week (1POW). There were 3 types of hepatectomy: left lobe
hepatectomy (n=46), lateral lobe hepatectomy (n=11), and right lobe hepatectomy (n=17). We
evaluated the scintigraphic results using established parameters of GSA clearance from the blood
pool (HH15). Based on the literature, we consider HH15 < 0.55 to indicate normal ASGPR function,and 0.55 ≤ HH15 < 0.65 to mild impairment. We analyzed the sizes of the resected livers calculatedusing computed tomography in relation to ASGPR function and the regeneration volume of thedonors’ residual liver.
【Results】
The average resected size was 337±170 mL, corresponding to 28±12% of the original
donor’s whole liver volume. No donors showed 0.65 ≤ HH15, suggesting moderate or severely
impaired ASGPR function. However, larger resection size (35–53%) was positively associated withhigher HH15 values (R=0.53, p<0.001). In the range of HH15 (0.35–0.64) among present donors,
higher HH15 values did not affect the regeneration volume (R=0.03, p=NS).
【Discussions】
Although the present results confirmed the safety of the partial hepatectomy of less than
54% of donors’ original liver volume, it demonstrated mildly impaired ASGPR function in donors
who underwent larger resection (≥35% of the original liver volume). This may indicate the need for
careful postoperative attention to prevent significant life-threatening complications.

【Conclusion of chapter 1】
Liver dysfunction defined by GSA clearance was observed in 7/19 (37%) of larger
resection group (≥35%) and in only 2/55 (4%) of smaller resection group. Thus, we suggest that 35%
may be the cut-off of safe hepatectomy.
Chapter 2【Methods】
Forty-five donors (left lobe hepatectomy; n=28, lateral lobe hepatectomy; n=8, right lobehepatectomy; n=9) underwent GSA scintigraphy four times after hepatectomy, including 1, 2, 4, and
12 POW. From 99mTc-GSA scintigraphy, Receptor density index (RDI) was calculated by liver
uptake at 15 minutes (LU15) divided by remnant liver volume. The abdominal CT images were used
to measure the liver volume.
【Results】
At 1-POW, RDI was significantly higher in right lobectomy group (0.00058 ± 0.00014ml-1) than in left lobectomy group (0.00027 ± 0.00007 ml-1, P<0.0001) and lateral lobectomy group(0.00033 ± 0.00009 ml-1, P<0.0001), indicating that right lobectomy group had the highest liverfunction per unit volume among three groups at 1-POW. Right lobectomy group then started todecrease in RDI until 2-POW and remained stable after 2-POW. Similar but less-steep trends wereobserved in the other groups (left lobectomy and lateral lobectomy groups. Correlation analysis wasdone between each time-point RDI vs. regenerated fraction. RDI at 1-POW was found to be moststrongly associated with regenerated fraction (R=0.71, P<0.0001)【Discussions】
We found that donors who underwent larger resection had a larger RDI. In addition, alarger RDI was associated with larger regenerated fraction of the liver. Since RDI is considered torepresent ASGPR function per unit volume, these results suggested that the ASGPR function per unit
volume is upregulated after hepatectomy. Also, the liver that has greater potential of proliferation has
more active ASGRP receptor function per unit volume.
Because the current investigation was just a correlation analysis, the causal relationship isstill unknown. In the orchestrated process of liver regeneration, little is known about the role ofASGRP. Many molecules, including interleukin (IL)-1, -6, tumor necrosis factor(TNF)-α, andhepatocyte growth factor (HGF), and many cells, including Kupffer cells, hepatic stellate cells andhepatic endothelial cells (HEC), are known to be involved in liver regeneration process.
It is known that HGF increases hepatic 99mTc-GSA uptake in a rodent model and thatIL-1 and 6 promote ASGPR synthesis. Thus, it is reasonable that liver regeneration can be visualizedindirectly and non-invasively by measuring ASGPR function using Tc-99m GSA scintigraphy.
We demonstrated that RDI is the parameter that can predict liver regeneration potential
after hepatectomy of healthy donors. In clinical settings, however, it would be more useful if RDI
can provide the information for patients.
【Conclusions of chapter 2】
Donors who underwent larger resection had a larger RDI, which was associated with larger
regenerated fraction of the liver. Estimating ASGPR function using Tc-99m-GSA and RDI may
predict the liver regeneration potential.