- Email: [email protected]
Impact of Graft Type in Living Donor Liver Transplantation: Remnant Liver Regeneration and Outcome in Donors
Impact of Graft Type in Living Donor Liver Transplantation: Remnant Liver Regeneration and Outcome in Donors L.L.-C. Tsanga, Y.-C. Tunga, H.-W. Hsua, H.-Y. Oua, C.-Y. Yua, T.-L. Huanga, C.-L. Chenb, and Y.-F. Chenga,* a
Departments of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; and bDepartments of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
ABSTRACT Objectives. Liver regeneration and donor safety in right-lobe (RL) and left-lobe (LL) grafts are essential for donors in living donor liver transplantation (LDLT). Our aim was to compare the liver regeneration rate and postoperative outcome between different donor graft types in LDLT. Materials and Methods. A total of 95 donors were divided into 2 groups: RL (n ¼ 42) and LL (n ¼ 53). The remnant liver of LL donors were subdivided into 3 subgroups according to the different hepatic venous drainage pattern that dominates from right hepatic vein (dominant RHV; n ¼ 34), middle hepatic vein (dominant MHV; n ¼ 10), and include MHV for left lateral segment (LLS) graft (n ¼ 9). The demographic data, postoperative laboratory data, complications, remnant liver volume (RLV), and remnant liver regeneration rate (RLRR) 6 months after surgery were compared. Results. The postoperative total bilirubin (TB), prothrombin time (PT), and intensive care unit (ICU) stays of the LL group were lower than the RL group (P < .05). The LL group has no significant better regeneration rate 6 months after surgery than the RL group. However, dominant RHV and LLS groups have significantly better RLRR than the RL group (89.2% vs 86% and 95.1% vs 86%, respectively, P < .05), but no significance in the dominant MHV group. Conclusion. In conclusion, different hepatic venous drainage patterns of remnant liver grafts may affect the regeneration rate in LL LDLT, especially with dominant RHV donors, may have more comparable outcomes with that of RL, and should be a favorable option during donor selection.
L
IVER transplantation has been considered to be a main therapy for patients with end-stage liver disease. Living donor liver transplantation (LDLT) has become a popular treatment option. The safety of donors is the first priority during the whole procedure in LDLT. Remnant liver volume (RLV) is known to be a major concern in donor surgery, especially for donors undergoing right hepatectomy in LDLT [1]. Some studies reported that RLV is correlated with liver dysfunction, postoperative adverse event, and longer hospital stays [2]. Some studies showed that left-lobe (LL) donor operations potentially carry a lower complication rate than those using RL graft donations [3] and
This work was supported by grants from Health and welfare surcharge of tobacco products, Ministry of Health and Welfare, Taiwan (MOHW103-TD-B-111-07, MOHW104-TDU-B-212-124004, MOHW105-TDU-B-212-134006 to Chen CL). and Chang Gung Medical Foundation Institutional Review Board, Taiwan approval has been obtained (104-8523B and 101-3673B). *Address correspondence to Yu-Fan Cheng, MD, Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao-Sung, Kaosiung 833, Taiwan. E-mail: [email protected]
ª 2016 Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/16 http://dx.doi.org/10.1016/j.transproceed.2015.12.123
Transplantation Proceedings, 48, 1015e1017 (2016)
1015
1016
suggest that LL donation is thought to be a favorable option in LDLT for donor safety [2]. However, the influence of different dominate hepatic vein patterns in regeneration of remnant liver of LL donors after operation compared with the right-lobe (RL) groups has not been discussed clearly. In general, the remnant liver of LL groups after LDLT could be subdivided into 3 subgroups according to the drainage patterns of hepatic veins, dominates from right hepatic vein (dominant RHV), dominates from middle hepatic vein (dominant MHV), and remnant liver includes MHV for left lateral segment (LLS). The purpose of this study was to compare the liver regeneration rates and postoperative outcomes between different types of donor grafts, which include RL and LL liver grafts with different territories of venous drainage in LDLT. MATERIALS AND METHODS From January 2013 to November 2013, 95 donors underwent hepatectomy for LDLT in Kaohsiung Chang Gung Memorial Hospital. Right hepatectomy (without MHV), left hepatectomy (with MHV), and left lateral segmentectomy were performed in 42, 44, and 9 donors, respectively. The remnant liver of LL donors were subdivided into 3 subgroups according to the territories of venous drainage, including dominant RHV (n ¼ 34), dominant MHV (n ¼ 10), and LLS (n ¼ 9). The demographic data, postoperative laboratory data, complications, RLV, and remnant liver regeneration rate (RLRR) 6 months after surgery were compared.
Computed Tomography Volumetry of the Donor Spleen and Remnant Liver The total liver and spleen volumes of donors were measured using multislice-computed tomography (CT) and semiautomatic volumetry (AZE liver manual, VirtualPlace Version 3.2009, AZE Ltd, Tokyo, Japan) before and 6 months after liver donation. The CT volumetry was calculated from 2-mm cut slices. The liver and spleen volumes were measured by automatic tracing of the organ outline on the axial portal venous phase images in the CT examination. Major vessels, including the inferior vena cava and extra-hepatic portal vein, caudate lobe, and major fissures were excluded manually. Liver volumetry of RL and LL were determined based on the location of the MHV. The dominant MHV donors were defined by a large drainage area of segment 5 and segment 8 hepatic veins (S5V and S8V), which drained into the dominant MHV, respectively. The dominant RHV donors were defined by a large drainage area of RHV or dominant inferior RHV and relatively smaller caliber of S8V and S5V drainage into the MHV. The total liver volume (TLV) was assumed to be the actual liver weight because the liver had nearly the same density as water. The RLV of the donors was measured 6 months after liver donation. The RLV at 6 months divided by the TLV before donation was calculated as the RLRR.
Statistical Analysis All statistical analyses were performed using SPSS 16. All variables were expressed as mean standard deviation (SD). The statistical analysis of demographic data, postoperative laboratory data, complications, RLV, and RLRR between the different groups was evaluated using the 2-sample t test. P < .05 was considered significant.
TSANG, TUNG, HSU ET AL
RESULTS
All donors were alive and well at the end of follow-up. There was no significant difference between the 2 groups in the donor’s age, transient liver enzyme elevation, operation time, postoperative minor complications, and RLRR after 6 months; however, there were significant differences in gender, body mass index (BMI), PT, TB, blood loss, and ICU stay. Donor age was similar in both groups, but donor weight and BMI were slightly higher in the LL group, which also included a higher percentage of male donors. There were transient increases of PT and TB after RL compared with the LL groups (P < .001). The peak level was observed at postoperative day 3. The levels of PT and TB gradually decreased and returned to normal until 1 month after operation. The LL group had the most increased blood loss among the 2 groups (P < .05). The mean blood loss in the LL group was 390 mL. There were no statistical differences among the 2 groups with regard to operation times. The RL group had a significantly longer ICU stay compared with the LL group (P < .001). The LL group had no significantly better RLRR (6 months) after surgery than the RL group. However, the dominant RHV and LLS groups had significantly better RLRR than the RL group (89.2% vs 86% and 95.1% vs 86%, respectively: P < .05), but no significance in the dominant MHV group (82.5%). DISCUSSION
LDLT is an excellent option for patients with end-stage liver disease in situations of donor shortage. The indications for LDLT have successfully been extended from pediatric to adult cases in the last decade. During this period, the graft type has been shifted from LL to RL. Preference for RL grafting is mainly because of its advantage in graft size, and perhaps partly because of the technical ease of right hepatectomy. In LDLT, success for the recipient is important for sure, but the most important concern is donor safety, in which safety of the donor must also be respected. Therefore, the donor surgeon has the duty to ensure normal life to the donor after LDLT as early as possible. There are many factors related to donor safety, such as age, obesity, fatty liver, major medical problems, RLV, anatomic variations, operation time, blood loss, and vascular inflow and outflow [4]. RLV is known to be a major concern in donor surgery, especially for donors undergoing right hepatectomy in LDLT. Recent studies focused on the relationship between RLV and donor safety. Some studies reported that RLV is correlated to liver dysfunction, postoperative adverse events, and longer hospital stays [2]. In RL LDLT, some studies reported the optimal hepatic venous tributary flow is correlated with liver regeneration [5]. The liver regenerates faster with preservation of the MHV in remnant livers and grafts [6]. However, the correlation between remnant liver regeneration and the influence of different drainage patterns of hepatic veins in LL LDLT has not been discussed clearly. In
REMNANT LIVER REGENERATION
LL LDLT, the MHV is harvested along with LL graft to the recipient. The stump of S5V and S8V are ligated without performing hepatic tributary reconstruction. The hepatic venous outflow of S5V and S8V thus may be compromised. Thus, it is reasonable to assume that the more dominant of the MHV (with more dominant S5V and S8V) may lead into more congestion of the drainage area of the remnant RL liver than the dominant RHV and the LLS groups. The larger the area of liver congestion may also lead to the higher peak postoperative aspartate aminotransferase (AST) and alanine amimotransferase (ALT) and longer hospital stays. The liver congestion ratio is inversely correlated with remnant liver regeneration [7]. This explains why the dominant RHV and LLS groups have significantly better RLRR than the RL group (89.2% vs 86% and 95.1% vs 86%, respectively; P < .05), but no significance in the dominant MHV group in our study. However, the RLV is not the main concern in LL LDLT due to the relatively large volume of remnant liver after liver donation. However, left hepatectomy is not always safe in adult LDLT. Sometimes it may lead to critical situations during the donor sugery. One study reported a LL donor who developed massive hepatic venous congestion of >50% of RL volume after clamping the MHV-LHV trunk. The surgical plan was adjusted to harvest only the LL without the MHV trunk for the donor’s safety [8]. Another study suggested the conversion of the graft from the LL to the RL might be appropriate for donors with severe remnant liver congestion [7].
1017
In conclusion, different hepatic venous drainage patterns of remnant liver grafts may affect the regeneration rate in LL LDLT, especially with dominant RHV donors, may have more comparable outcomes with that of RL, and should be a favorable option during donor selection.
REFERENCES [1] Taketomi A, Kayashima H, Soejima Y, et al. Donor risk in adult-to-adult living donor liver transplantation: impact of left lobe graft. Transplantation 2009;87(3):445e50. [2] Reichman TW, Sandroussi C, Azouz SM, et al. Living donor hepatectomy: the importance of the residual liver volume. Liver Transpl 2011;17(12):1404e11. [3] Umeshita K, Fujiwara K, Kiyosawa K, et al. Operative morbidity of living liver donors in Japan. Lancet 2003;362(9385): 687e90. [4] Sharma A, Ashworth A, Behnke M, et al. Donor selection for adult-to-adult living donor liver transplantation: well begun is half done. Transplantation 2013;95(3):501e6. [5] Cheng YF, Huang TL, Chen TY, et al. Liver graft regeneration in right lobe adult living donor liver transplantation. Am J Transplant 2009;9(6):1382e8. [6] Haga J, Shimazu M, Wakabayashi G, et al. Liver regeneration in donors and adult recipients after living donor liver transplantation. Liver Transpl 2008;14(12):1718e24. [7] Fukuhara T, Umeda K, Toshima T, et al. Congestion of the donor remnant right liver after extended left lobe donation. Transpl Int 2009;22(8):837e44. [8] Hwang S, Lee SG, Kim KH, et al. Intraoperative assessment of hepatic venous congestion with direct clamping of the hepatic vein trunk for living donor liver transplantation. Transplant Proc 2004;36(5):1462e5.
Departments of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; and bDepartments of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
ABSTRACT Objectives. Liver regeneration and donor safety in right-lobe (RL) and left-lobe (LL) grafts are essential for donors in living donor liver transplantation (LDLT). Our aim was to compare the liver regeneration rate and postoperative outcome between different donor graft types in LDLT. Materials and Methods. A total of 95 donors were divided into 2 groups: RL (n ¼ 42) and LL (n ¼ 53). The remnant liver of LL donors were subdivided into 3 subgroups according to the different hepatic venous drainage pattern that dominates from right hepatic vein (dominant RHV; n ¼ 34), middle hepatic vein (dominant MHV; n ¼ 10), and include MHV for left lateral segment (LLS) graft (n ¼ 9). The demographic data, postoperative laboratory data, complications, remnant liver volume (RLV), and remnant liver regeneration rate (RLRR) 6 months after surgery were compared. Results. The postoperative total bilirubin (TB), prothrombin time (PT), and intensive care unit (ICU) stays of the LL group were lower than the RL group (P < .05). The LL group has no significant better regeneration rate 6 months after surgery than the RL group. However, dominant RHV and LLS groups have significantly better RLRR than the RL group (89.2% vs 86% and 95.1% vs 86%, respectively, P < .05), but no significance in the dominant MHV group. Conclusion. In conclusion, different hepatic venous drainage patterns of remnant liver grafts may affect the regeneration rate in LL LDLT, especially with dominant RHV donors, may have more comparable outcomes with that of RL, and should be a favorable option during donor selection.
L
IVER transplantation has been considered to be a main therapy for patients with end-stage liver disease. Living donor liver transplantation (LDLT) has become a popular treatment option. The safety of donors is the first priority during the whole procedure in LDLT. Remnant liver volume (RLV) is known to be a major concern in donor surgery, especially for donors undergoing right hepatectomy in LDLT [1]. Some studies reported that RLV is correlated with liver dysfunction, postoperative adverse event, and longer hospital stays [2]. Some studies showed that left-lobe (LL) donor operations potentially carry a lower complication rate than those using RL graft donations [3] and
This work was supported by grants from Health and welfare surcharge of tobacco products, Ministry of Health and Welfare, Taiwan (MOHW103-TD-B-111-07, MOHW104-TDU-B-212-124004, MOHW105-TDU-B-212-134006 to Chen CL). and Chang Gung Medical Foundation Institutional Review Board, Taiwan approval has been obtained (104-8523B and 101-3673B). *Address correspondence to Yu-Fan Cheng, MD, Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao-Sung, Kaosiung 833, Taiwan. E-mail: [email protected]
ª 2016 Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/16 http://dx.doi.org/10.1016/j.transproceed.2015.12.123
Transplantation Proceedings, 48, 1015e1017 (2016)
1015
1016
suggest that LL donation is thought to be a favorable option in LDLT for donor safety [2]. However, the influence of different dominate hepatic vein patterns in regeneration of remnant liver of LL donors after operation compared with the right-lobe (RL) groups has not been discussed clearly. In general, the remnant liver of LL groups after LDLT could be subdivided into 3 subgroups according to the drainage patterns of hepatic veins, dominates from right hepatic vein (dominant RHV), dominates from middle hepatic vein (dominant MHV), and remnant liver includes MHV for left lateral segment (LLS). The purpose of this study was to compare the liver regeneration rates and postoperative outcomes between different types of donor grafts, which include RL and LL liver grafts with different territories of venous drainage in LDLT. MATERIALS AND METHODS From January 2013 to November 2013, 95 donors underwent hepatectomy for LDLT in Kaohsiung Chang Gung Memorial Hospital. Right hepatectomy (without MHV), left hepatectomy (with MHV), and left lateral segmentectomy were performed in 42, 44, and 9 donors, respectively. The remnant liver of LL donors were subdivided into 3 subgroups according to the territories of venous drainage, including dominant RHV (n ¼ 34), dominant MHV (n ¼ 10), and LLS (n ¼ 9). The demographic data, postoperative laboratory data, complications, RLV, and remnant liver regeneration rate (RLRR) 6 months after surgery were compared.
Computed Tomography Volumetry of the Donor Spleen and Remnant Liver The total liver and spleen volumes of donors were measured using multislice-computed tomography (CT) and semiautomatic volumetry (AZE liver manual, VirtualPlace Version 3.2009, AZE Ltd, Tokyo, Japan) before and 6 months after liver donation. The CT volumetry was calculated from 2-mm cut slices. The liver and spleen volumes were measured by automatic tracing of the organ outline on the axial portal venous phase images in the CT examination. Major vessels, including the inferior vena cava and extra-hepatic portal vein, caudate lobe, and major fissures were excluded manually. Liver volumetry of RL and LL were determined based on the location of the MHV. The dominant MHV donors were defined by a large drainage area of segment 5 and segment 8 hepatic veins (S5V and S8V), which drained into the dominant MHV, respectively. The dominant RHV donors were defined by a large drainage area of RHV or dominant inferior RHV and relatively smaller caliber of S8V and S5V drainage into the MHV. The total liver volume (TLV) was assumed to be the actual liver weight because the liver had nearly the same density as water. The RLV of the donors was measured 6 months after liver donation. The RLV at 6 months divided by the TLV before donation was calculated as the RLRR.
Statistical Analysis All statistical analyses were performed using SPSS 16. All variables were expressed as mean standard deviation (SD). The statistical analysis of demographic data, postoperative laboratory data, complications, RLV, and RLRR between the different groups was evaluated using the 2-sample t test. P < .05 was considered significant.
TSANG, TUNG, HSU ET AL
RESULTS
All donors were alive and well at the end of follow-up. There was no significant difference between the 2 groups in the donor’s age, transient liver enzyme elevation, operation time, postoperative minor complications, and RLRR after 6 months; however, there were significant differences in gender, body mass index (BMI), PT, TB, blood loss, and ICU stay. Donor age was similar in both groups, but donor weight and BMI were slightly higher in the LL group, which also included a higher percentage of male donors. There were transient increases of PT and TB after RL compared with the LL groups (P < .001). The peak level was observed at postoperative day 3. The levels of PT and TB gradually decreased and returned to normal until 1 month after operation. The LL group had the most increased blood loss among the 2 groups (P < .05). The mean blood loss in the LL group was 390 mL. There were no statistical differences among the 2 groups with regard to operation times. The RL group had a significantly longer ICU stay compared with the LL group (P < .001). The LL group had no significantly better RLRR (6 months) after surgery than the RL group. However, the dominant RHV and LLS groups had significantly better RLRR than the RL group (89.2% vs 86% and 95.1% vs 86%, respectively: P < .05), but no significance in the dominant MHV group (82.5%). DISCUSSION
LDLT is an excellent option for patients with end-stage liver disease in situations of donor shortage. The indications for LDLT have successfully been extended from pediatric to adult cases in the last decade. During this period, the graft type has been shifted from LL to RL. Preference for RL grafting is mainly because of its advantage in graft size, and perhaps partly because of the technical ease of right hepatectomy. In LDLT, success for the recipient is important for sure, but the most important concern is donor safety, in which safety of the donor must also be respected. Therefore, the donor surgeon has the duty to ensure normal life to the donor after LDLT as early as possible. There are many factors related to donor safety, such as age, obesity, fatty liver, major medical problems, RLV, anatomic variations, operation time, blood loss, and vascular inflow and outflow [4]. RLV is known to be a major concern in donor surgery, especially for donors undergoing right hepatectomy in LDLT. Recent studies focused on the relationship between RLV and donor safety. Some studies reported that RLV is correlated to liver dysfunction, postoperative adverse events, and longer hospital stays [2]. In RL LDLT, some studies reported the optimal hepatic venous tributary flow is correlated with liver regeneration [5]. The liver regenerates faster with preservation of the MHV in remnant livers and grafts [6]. However, the correlation between remnant liver regeneration and the influence of different drainage patterns of hepatic veins in LL LDLT has not been discussed clearly. In
REMNANT LIVER REGENERATION
LL LDLT, the MHV is harvested along with LL graft to the recipient. The stump of S5V and S8V are ligated without performing hepatic tributary reconstruction. The hepatic venous outflow of S5V and S8V thus may be compromised. Thus, it is reasonable to assume that the more dominant of the MHV (with more dominant S5V and S8V) may lead into more congestion of the drainage area of the remnant RL liver than the dominant RHV and the LLS groups. The larger the area of liver congestion may also lead to the higher peak postoperative aspartate aminotransferase (AST) and alanine amimotransferase (ALT) and longer hospital stays. The liver congestion ratio is inversely correlated with remnant liver regeneration [7]. This explains why the dominant RHV and LLS groups have significantly better RLRR than the RL group (89.2% vs 86% and 95.1% vs 86%, respectively; P < .05), but no significance in the dominant MHV group in our study. However, the RLV is not the main concern in LL LDLT due to the relatively large volume of remnant liver after liver donation. However, left hepatectomy is not always safe in adult LDLT. Sometimes it may lead to critical situations during the donor sugery. One study reported a LL donor who developed massive hepatic venous congestion of >50% of RL volume after clamping the MHV-LHV trunk. The surgical plan was adjusted to harvest only the LL without the MHV trunk for the donor’s safety [8]. Another study suggested the conversion of the graft from the LL to the RL might be appropriate for donors with severe remnant liver congestion [7].
1017
In conclusion, different hepatic venous drainage patterns of remnant liver grafts may affect the regeneration rate in LL LDLT, especially with dominant RHV donors, may have more comparable outcomes with that of RL, and should be a favorable option during donor selection.
REFERENCES [1] Taketomi A, Kayashima H, Soejima Y, et al. Donor risk in adult-to-adult living donor liver transplantation: impact of left lobe graft. Transplantation 2009;87(3):445e50. [2] Reichman TW, Sandroussi C, Azouz SM, et al. Living donor hepatectomy: the importance of the residual liver volume. Liver Transpl 2011;17(12):1404e11. [3] Umeshita K, Fujiwara K, Kiyosawa K, et al. Operative morbidity of living liver donors in Japan. Lancet 2003;362(9385): 687e90. [4] Sharma A, Ashworth A, Behnke M, et al. Donor selection for adult-to-adult living donor liver transplantation: well begun is half done. Transplantation 2013;95(3):501e6. [5] Cheng YF, Huang TL, Chen TY, et al. Liver graft regeneration in right lobe adult living donor liver transplantation. Am J Transplant 2009;9(6):1382e8. [6] Haga J, Shimazu M, Wakabayashi G, et al. Liver regeneration in donors and adult recipients after living donor liver transplantation. Liver Transpl 2008;14(12):1718e24. [7] Fukuhara T, Umeda K, Toshima T, et al. Congestion of the donor remnant right liver after extended left lobe donation. Transpl Int 2009;22(8):837e44. [8] Hwang S, Lee SG, Kim KH, et al. Intraoperative assessment of hepatic venous congestion with direct clamping of the hepatic vein trunk for living donor liver transplantation. Transplant Proc 2004;36(5):1462e5.