Pretransplant Hepatic Malignancy Increases Risk of De Novo Malignancy after Liver Transplantation.

BACKGROUND: Hepatocellular carcinoma (HCC) recurrence and development of de novo malignancy (DNM) after liver transplantation (LT) are the major causes of late recipient death. METHODS: We analyzed the incidence of extrahepatic DNM following living donor LT according to the status of pretransplant hepatic malignancy. We selected 2,076 adult patients who underwent primary LDLT during 7 years from January 2010 to December 2016. RESULTS: The pretransplant hepatic malignancy group (n = 1,012) showed 45 cases (4.4%) of the following extrahepatic DNMs: posttransplant lymphoproliferative disease (PTLD) in 10; lung cancer in 10; stomach cancer in 6; colorectal cancer in 5; urinary bladder cancer in 3; and other cancers in 11. The pretransplant no hepatic malignancy group (n = 1,064) showed 25 cases (2.3%) of the following extrahepatic DNMs: colorectal cancer in 3; stomach cancer in 3; leukemia in 3; lung cancer in 3; PTLD in 2; prostate cancer in 2; and other cancers in 9. Incidences of extrahepatic DNM in the pretransplant hepatic malignancy and no hepatic malignancy groups were as follows: 1.1% and 0.5% at 1 year, 3.2% and 2.0% at 3 years, 4.6% and 2.5% at 5 years, and 5.4% and 2.8% at 8 years, respectively (P = 0.006). Their overall patient survival rates were as follows: 97.3% and 97.2% at 1 year, 91.6% and 95.9% at 3 years, 89.8% and 95.4% at 5 years, and 89.2% and 95.4% at 8 years, respectively (P < 0.001). Pretransplant hepatic malignancy was the only significant risk factor for posttransplant extrahepatic DNM. CONCLUSION: Our results suggest that patients who had pretransplant hepatic malignancy be followed up more strictly because they have a potential risk of primary hepatic malignancy recurrence as well as a higher risk of extrahepatic DNM than patients without pretransplant hepatic malignancy.

Prolonged hepatic inflow occlusion to reduce bleeding during recipient hepatectomy in living donor liver transplantation.

Background: Living donor liver transplantation (LDLT) causes bleeding in recipients during the careful preservation of most perihilar structures during this surgery. This case-control study aimed to analyze the effect of prolonged hepatic inflow occlusion (PHIO) when applied during recipient hepatectomy in LDLT. Methods: The study group comprised patients who underwent PHIO with Model for End-Stage Liver Disease (MELD) scores ranging from 26 to 35 (n=20). The following two control groups were selected according to their MELD scores: the low-MELD score group (MELD scores of 15-20, n=40) and the high-MELD score group (MELD scores of 26-35, n=40). Total dissection time for hepatic mobilization and dissection and blood loss during these procedures were compared between the two groups. Results: In the PHIO study group, mean total dissection time and mean PHIO duration were 226.3±59.4 and 68.2±19.1 minutes, respectively. Twelve patients underwent PHIO twice, and the other eight patients underwent PHIO once. The low-MELD score control group and the PHIO study group showed similar dissection duration (216.0±43.9 vs. 226.3±59.4 minutes, P=0.82) and similar blood loss volume during dissection (2,112.5±1,614.9 vs. 2,350.0±951.9 mL, P=0.17). The high-MELD score control group and the PHIO study group showed similar dissection duration (241.0±41.9 vs. 226.3±59.4 minutes, P=0.71), but the PHIO group showed a significantly lower blood loss during dissection than the high-MELD score group (2,350.0±951.9 vs. 2,815.0±1,813.9 mL, P=0.002). During and after PHIO, no adverse complication was observed, except for transient splanchnic congestion. Conclusions: Our findings suggest that PHIO is a simple effective method to reduce intraoperative bleeding during hepatic mobilization and dissection during LDLT operation requiring difficult dissection.

Changes in the indications for living donor liver transplantation: single-institution experience of 3,145 cases over 10 years.

Background: To understand the changing demands and recent trends in the indications for living donor liver transplantation (LDLT), the present study aimed to analyze the indications for LDLT performed in a high-volume transplantation center over 10 years. Methods: The liver transplantation database at our institution was searched to identify patients who underwent LDLT during a 10-year period from January 2008 to December 2017. The study subjects (n=3,145) were divided into two groups: adult patients (n=3,019, 92.7%) and pediatric patients (n=126, 3.9%). Results: In the adult recipients, the primary diagnoses were hepatitis B virus (HBV)-associated liver cirrhosis (n=1,898, 62.9%), alcoholic liver disease (n=482, 16.0%), hepatitis C virus-associated cirrhosis (n=203, 6.7%), acute liver failure (n=127, n=4.2%), and other diseases (n=157, 5.2%). The mean Model for End-Stage Liver Disease score was 15.6±8.8 (range, 6-40). The proportion of patients with HBV-associated liver disease gradually decreased, but the proportion of those with alcoholic liver disease increased. Hepatocellular carcinoma (HCC) was diagnosed in 1,467 patients (48.6%). The mean proportion of patients with HCC was 63.1% among those with HBV-associated liver disease. In pediatric recipients, the primary diagnoses were biliary atresia (n=51, 40.5%), liver failure of various causes (n=37, 29.4%), metabolic disease (n=22, 17.5%), hepatoblastoma (n=12, 9.5%), and infectious diseases (n=4, 3.2%). Conclusions: Our results showed that there were some significant changes in the indications of LDLT. We believe that our results may reflect the real changes in the indications of LDLT and they will be useful for predicting further changes in the future.

Long-term patency and complications of ringed polytetrafluoroethylene grafts used for middle hepatic vein reconstruction in living-donor liver transplantation.

Background: Homologous vein allografts are adequate for reconstruction of the middle hepatic vein (MHV) in living-donor liver transplantation (LDLT). However, supply is a matter of concern. To replace homologous vein allografts, polytetrafluoroethylene (PTFE) grafts were used. This study aimed to assess the long-term patency rates and complications of PTFE grafts used for MHV reconstruction of LDLT in a high-volume liver transplantation center. Methods: We analyzed the patency rates of PTFE-interposed MHV in 100 LDLT recipients and reviewed complications including PTFE graft migration. Results: The mean age was 53.5±5.4 years and male to female ratio was 73:27. Primary diagnoses were hepatitis B virus infection (n=71) and other (n=28). Mean model for end-stage liver disease score was 16.2±8.3. V5 reconstruction was performed as either single anastomosis (n=85) or double anastomoses (n=14). No V5 reconstruction was required in one patient. V8 reconstruction was performed as single anastomosis, double anastomoses, and no reconstruction in 75, 0, and 25 patients, respectively. During a mean follow-up of 6 years, three recipients required early MHV stenting within 2 weeks. After 3 months, there were no episodes of congestion-associated infarct, regardless of MHV patency. Patency rates of PTFE-interposed MHV were 54.0%, 37.0%, and 37.0% at 1, 3, and 5 years, respectively. Unwanted PTFE graft migration occurred in two recipients, and the actual incidence was 2% at 5 years. Conclusions: PTFE grafts combined with small-artery patches demonstrated acceptably high short- and long-term patency rates. Since the risk of unwanted migration of PTFE graft is not negligibly low, lifelong surveillance is necessary to detect unexpected rare complications.

Is renal replacement therapy necessary in deceased donor liver transplantation candidates with hepatorenal syndrome?: a 2-year experience at a high-volume center.

PURPOSE: Hepatorenal syndrome (HRS) is a fatal complication in patients with end-stage liver disease awaiting liver transplantation (LT). HRS often develops in patients with high model for end-stage liver disease (MELD) score. This study investigated the outcomes of peritransplant management of HRS in a high-volume LT center in Korea for 2 years. METHODS: A total of 157 recipients that deceased donor liver transplantation (DDLT) from January 2017 to December 2018 were included. In-hospital mortality (IHM) was analyzed in relation to pre- and posttransplant application of renal replacement therapy (RRT). RESULTS: Primary diagnoses for DDLT were alcoholic liver disease (n = 61), HBV-associated liver cirrhosis (n = 48), retransplantation for chronic graft failure (n = 24), and others (n = 24). Mean MELD score was 34.6 ± 6.2 with 72 patients at Korean Network for Organ Sharing MELD status 2 (45.9%), 43 at status 3 (27.4%), 36 at status 4 (22.9%), and 6 at status 5 (3.8%). Pretransplant RRT was performed in 16 patients (10.2%) that did not show IHM. Posttransplant RRT was performed in 69 patients (44.0%), for whom IHM incidence was 15.9%. In 53 patients that had undergone de novo posttransplant RRT, IHM incidence increased to 20.8%. IHM in the 88 patients not requiring RRT was 2.3%. CONCLUSION: The majority of adult DDLT recipients in Korean MELD score-based allocation system have very high MELD scores, which is often associated with HRS. Pretransplant RRT appears to improve posttransplant survival outcomes. We thereby recommend that, if indicated, pretransplant RRT be performed while awaiting DDLT.

Long-term results of conjoined unification venoplasty for multiple portal vein branches of the right liver graft in living donor liver transplantations.

Background: Autologous portal vein Y-graft (PYG) interposition has been the standard procedure for reconstruction of double portal vein (PV) orifices of right liver grafts during living donor liver transplantations. However, it has the disadvantage of being vulnerable to anastomotic stenosis. A refined technique of conjoined unification venoplasty (CUV) was developed to secure PV reconstruction. Methods: We reviewed the surgical outcomes in PV reconstructions using CUVs in 21 cases which were followed up for >3 years. Results: The mean age of recipients was 51.7±4.9 years. The model for end-stage liver disease score was 15.3±6.4. The graft-recipient weight ratio was 1.12±0.21. Recipient PYGs were harvested in all cases. All living donors were blood relatives or relatives through marriage with type III PV anomalies. The number of right liver graft PV orifices was two in 19 cases and three in two cases. For the central intervening vein patch, a PV segment was used in six cases, and an autologous greater saphenous vein patch was used in the remaining 15 cases. The 21 patient cohort displayed a 100% 4-year patient survival rate. None of them underwent any PV interventions including interventional stenting. Serial follow-up computed tomography scans revealed that the reconstructed PV showed early reshaping with a stable streamlined configuration for over 3 years. Conclusions: PV reconstruction using the CUV technique appears to be significantly more effective in preventing PV complications. We believe that CUV is a useful technique to reconstruct right liver grafts with multiple PV orifices.

Cross-sectional analysis of immunosuppressive regimens focused on everolimus after liver transplantation in a Korean high-volume transplantation center.

Background: The mammalian target of the rapamycin inhibitor has dual inhibitory effects on cell growth and angiogenesis. This study aimed to analyze the usage of everolimus on actual immunosuppression (IS) regimens through a cross-sectional study in a high-volume liver transplantation (LT) center. Methods: Our institutional LT database was searched for adult patients who underwent primary LT surgery between January 2010 and December 2016. We identified 2,093 LT recipients with observation periods of 1 to 8 years. Results: We divided the 2,093 recipients into three groups according to the posttransplant follow-up period as follows: group A (12-36 months; n=680), group B (37-60 months; n=560), and group C (>60 months; n=853). The individual IS agents were tacrolimus in 1,807 patients (86.3%), cyclosporine in 169 patients (8.1%), mycophenolate mofetil (MMF) in 1,310 patients (62.6%), and everolimus in 115 patients (5.5%). The most common IS regimens were tacrolimus-MMF combination and tacrolimus monotherapy, regardless of the posttransplant period. Patients with pretransplant malignancies were administered everolimus more frequently than those without pretransplant malignancies (P<0.001). In 102 patients with hepatocellular carcinoma recurrence or de novo malignancies, IS regimens included everolimus-tacrolimus in 41 patients (40.2%), tacrolimus-MMF in 27 patients (26.4%), tacrolimus in 20 patients (19.6%), MMF in 10 patients (9.8%), cyclosporine in three patients (2.9%), and cyclosporine-MMF in one patient (1.0%). Conclusions: Administration of everolimus after LT has been gradually increasing with the expansion of indications in our institutional practice. Currently, the role of everolimus is minimal and not comparable to that of tacrolimus, but it has a unique position in the field of IS after LT.

Hemashield Vascular Graft Is a Preferable Prosthetic Graft for Middle Hepatic Vein Reconstruction in Living Donor Liver Transplantation.

BACKGROUND Because of the supply shortage for homologous vein allografts, we previously used ringed Gore-Tex vascular grafts for middle hepatic vein (MHV) reconstruction in living donor liver transplantation. However, owing to the subsequent unavailability of ringed Gore-Tex grafts, we replaced them with Hemashield vascular grafts. This study aimed to compare the patency of Hemashield grafts with that of ringed Gore-Tex grafts. MATERIAL AND METHODS This was a retrospective double-arm study between the study group that used Hemashield grafts (n=63) and the historical control group that used ringed Gore-Tex grafts (n=126). RESULTS In the Gore-Tex and Hemashield groups, mean age was 53.1±6.2 and 54.3±10.4 years; model for end-stage liver disease score was 16.5±8.3 and 17.5±9.9; and graft-recipient weight ratio was 1.11±0.23 and 1.12±0.25, respectively. In the Gore-Tex graft group, V5 reconstruction was done in single (n=107, 84.9%), double (n=17, 13.5%), and none (n=2, 1.6%). V8 reconstruction was done in single (n=95, 75.4%), double (n=1, 0.8%), and none (n=30, 23.8%). In the Hemashield group, V5 reconstruction was done in single (n=43, 68.3%), double (n=19, 30.2%), and triple (n=1, 1.6%). V8 reconstruction was done in single (n=45, 71.4%), double (n=9, 14.3%), and none (n=9, 14.3%). One-year conduit patency rates in the Gore-Tex and Hemashield groups were 54.8% and 71.6%, respectively (p=0.048). CONCLUSIONS MHV reconstruction using Hemashield vascular grafts demonstrated higher short-term patency rates than those associated with ringed Gore-Tex vascular grafts. We suggest that the Hemashield vascular graft is one of the best prosthetic materials for MHV reconstruction.

Successful introduction of Model for End-stage Liver Disease scoring in deceased donor liver transplantation in Korea: analysis of first 1 year experience at a high-volume transplantation center.

BACKGROUNDS/AIMS: Model for End-stage Liver Disease (MELD) score was adopted in June 2016 in Korea. METHODS: We analyzed changes in volumes and outcomes of deceased donor liver transplantation (DDLT) for 1 year before and after introduction of MELD scoring at Asan Medical Center. RESULTS: There were 64 cases of DDLT in 1 year before MELD introduction and 106 in 1 year after MELD introduction, an increase of 65%. The volume of DDLTs abruptly increased during first 3 months, but then returned to its usual level before MELD introduction, which indicated 3-month depletion of accumulated recipient pool with high MELD scores. The number of pediatric DDLT cases increased from 3 before MELD introduction to 11 after it, making up 21.4% and 47.8% of all cases of pediatric liver transplantation, respectively. The number of cases of retransplanted DDLTs increased from 4 to 27, representing 6.3% and 25.5% of all DDLT cases, respectively. The number of status 1 DDLT cases increased from 5 to 12, being 7.8% and 11.3% of all cases. Patient survival outcomes were similar before and after MELD introduction. CONCLUSIONS: The number of DDLTs temporarily increased after adoption of MELD scoring due to accumulated recipient pool with high MELD scores. The numbers of retransplanted and pediatric DDLT cases significantly increased. Patient survival in adult and pediatric DDLT was comparable before and after adoption of MELD scoring. These results imply that Korean MELD score-based allocation system was successfully established within its first year.