Title Page

Contents

Abstract 9

Ⅰ. Background Knowledge 11

1. Venous Congestion and Ischemia-Reperfusion Injury 11

1) Hypoxia and angiogenesis as drivers of tumor recurrence 12

2) Ischemia-reperfusion injury: mechanisms and outcomes 12

3) Interplay between venous congestion, ischemia-reperfusion injury, and liver regeneration 12

2. Role of Cytokines in Immune Response 13

1) Cytokines and post-transplant complications 13

2) Clinical importance of early post-transplant cytokine profiles 14

Ⅱ. Introduction 15

Ⅲ. Materials and Methods 17

1. Study population 17

2. Data collection 17

3. Measurement of plasma 18

4. Venous congestion volume measurement 18

5. Statistical analysis 19

Ⅳ. Results 20

1. Basic Characteristics 20

2. Venous reconstruction 20

3. Major ischemic events in the postoperative course 21

4. Follow up data regarding HCC 21

5. Postoperative course 22

(1) Liver chemistry 22

(2) Cytokines 22

6. Ischemic Events (N＝8) 23

(1) Comparison of liver chemistry 23

(2) Comparison of plasma cytokines 23

7. Congestion ≥ 15% (N＝9) 24

(1) Comparison of liver chemistry 24

(2) Comparison of plasma cytokines 24

8. Ischemic events or congestion ≥ 15% (N＝13) 25

(1) Comparison of liver chemistry 25

(2) Comparison of plasma cytokines 25

9. Different four groups 26

(1) Comparison of liver chemistry 27

(2) Comparison of plasma cytokines 27

10. Degree of congestion (ischemic event excluded) 28

(1) Comparison of liver chemistry 28

(2) Comparison of plasma cytokines 28

11. Tumor Recurrence (N＝4) 29

12. Tumor Recurrence, among beyond Milan (N＝12) 30

Ⅴ. Discussion 33

Ⅵ. Conclusion 39

References 40

논문요약 76

Table 1. Baseline characteristics of the patients included to the study. 47

Table 2. Venous reconstruction of the patients included to the study. 49

Table 3. Major ischemic event in the postoperative course of the patients included to the study. 50

Table 4. Follow up data regarding HCC of the patients included to the study. 51

Table 5. Comparison of baseline characteristics between tumor recurrence group and no recurrence group. 52

Table 6. Comparison of venous reconstruction between tumor recurrence group and no recurrence group. 53

Table 7. Comparison of postoperative course between tumor recurrence group and no recurrence group. 54

Table 8. Comparison of follow up data regarding HCC between tumor recurrence group and no recurrence group. 55

Table 9. Comparison of pre-transplant predictors and post-transplant outcomes between recurrence group and no recurrence group, among beyond Milan 56

Figure 1. Study protocol for post-LT monitoring and assessment 57

Figure 2. (a) 3D model of the liver graft at two-weeks post-transplantation demonstrating greater than 15% congestion in the anterior section and portal vein stenosis. The graft... 58

Figure 3. Liver chemistry of the study from pre-LT up to POD 14. 59

Figure 4. Plasma cytokines levels of the study on POD 1, 3, 7 and 14 61

Figure 5. Comparison of liver chemistry between groups with observed major ischemic events and no ischemic event in the postoperative course 62

Figure 6. Comparison of plasma cytokines between groups with observed major ischemic events and no ischemic event in the postoperative course 63

Figure 7. Comparison of liver chemistry post-liver transplantation between groups with ≥ 15% congestion and 〈15% congestion 64

Figure 8. Comparison of plasma cytokines post-liver transplantation between groups with ≥ 15% congestion and 〈15% congestion 65

Figure 9. Comparison of liver chemistry post-liver transplantation between groups with Ischemic events or congestion ≥ 15% and 〈15% congestion without ischemic events 66

Figure 10. Comparison of plasma cytokines post-liver transplantation between groups with Ischemic events or congestion ≥ 15% and 〈15% congestion without ischemic events 67

Figure 11. Dynamic changes in liver chemistry post-liver transplantation across groups with varying degrees of congestion and ischemic events 68

Figure 12. Dynamic changes in plasma cytokines post-liver transplantation across groups with varying degrees of congestion and ischemic events 69

Figure 13. Post-transplant liver chemistry outcomes across groups with varying degrees of congestion 70

Figure 14. Post-transplant plasma cytokine levels across groups with varying degrees of congestion 71

Figure 15. Comparison of liver chemistry between tumor recurrence group and no recurrence group 72

Figure 16. Comparison of plasma cytokines between tumor recurrence group and no recurrence group 73

Figure 17. Comparison of liver chemistry between recurrence group and no recurrence group, among beyond Milan 74

Figure 18. Comparison of plasma cytokines between recurrence group and no recurrence group, among beyond Milan 75