Living donor liver transplantation for colorectal cancer liver metastases: Midterm outcomes at a single center in North America.

In recent years, liver transplantation has emerged as a treatment for patients with stage IV colorectal liver metastases (CRLM). Given the limited number of available deceased donor grafts, the use of living donor liver transplantation (LDLT) can be an important option. We performed a retrospective analysis of 10 patients that underwent LDLT for CRLM at our institution. A total of 90% of patients were male, with median age of 58 years and median model for end-stage liver disease score of 11 (range: 6-32). The rectum was the most common primary location (40%). Synchronous liver tumors were found in 50%. Pretransplant patients underwent resection (60%), hepatic-artery infusion pumping (50%), and/or radiofrequency ablation (50%). Everybody underwent adjuvant chemotherapy. Median cold ischemia time was 103 minutes (range: 93-207 minutes), and median total OR time was 11.5 hours (range: 8.5-13.9 hours). In total, 30% of patients had postoperative complications requiring reoperation. Mean recurrence-free survival was 2.2 years (95% confidence interval, 1.2-3.2 years), and mean overall survival was 3.0 years (95% confidence interval, 2.5-3.6 years). In total, 30% of patients suffered a recurrence, and 90% of patients are currently alive. This study represents the largest single-center analysis in North America of patients undergoing LDLT for CRLM. LDLT is a safe and effective alternative for patients with CRLM who do not have progressive disease or extrahepatic metastasis.

Advances and innovations in living donor liver transplant techniques, matching and surgical training: Meeting report from the living donor liver transplant consensus conference.

The practice of LDLT currently delivers limited impact in western transplant centers. The American Society of Transplantation organized a virtual consensus conference in October 2021 to identify barriers and gaps to LDLT growth, and to provide evidence-based recommendations to foster safe expansion of LDLT in the United States. This article reports the findings and recommendations regarding innovations and advances in approaches to donor-recipient matching challenges, the technical aspects of the donor and recipient operations, and surgical training. Among these themes, the barriers deemed most influential/detrimental to LDLT expansion in the United States included: (1) prohibitive issues related to donor age, graft size, insufficient donor remnant, and ABO incompatibility; (2) lack of acknowledgment and awareness of the excellent outcomes and benefits of LDLT; (3) ambiguous messaging regarding LDLT to patients and hospital leadership; and (4) a limited number of proficient LDLT surgeons across the United States. Donor-recipient mismatching may be circumvented by way of liver paired exchange. The creation of a national registry to generate granular data on donor-recipient matching will guide the practice of liver paired exchange. The surgical challenges to LDLT are addressed herein and focuses on the development of robust training pathways resulting in proficiency in donor and recipient surgery. Utilizing strong mentorship/collaboration programs with novel training practices under the auspices of established training and certification bodies will add to the breadth and depth of training.

Living donor liver transplant candidate and donor selection and engagement: Meeting report from the living donor liver transplant consensus conference.

INTRODUCTION: Living donor liver transplantation (LDLT) is a promising option for mitigating the deceased donor organ shortage and reducing waitlist mortality. Despite excellent outcomes and data supporting expanding candidate indications for LDLT, broader uptake throughout the United States has yet to occur. METHODS: In response to this, the American Society of Transplantation hosted a virtual consensus conference (October 18-19, 2021), bringing together relevant experts with the aim of identifying barriers to broader implementation and making recommendations regarding strategies to address these barriers. In this report, we summarize the findings relevant to the selection and engagement of both the LDLT candidate and living donor. Utilizing a modified Delphi approach, barrier and strategy statements were developed, refined, and voted on for overall barrier importance and potential impact and feasibility of the strategy to address said barrier. RESULTS: Barriers identified fell into three general categories: 1) awareness, acceptance, and engagement across patients (potential candidates and donors), providers, and institutions, 2) data gaps and lack of standardization in candidate and donor selection, and 3) data gaps regarding post-living liver donation outcomes and resource needs. CONCLUSIONS: Strategies to address barriers included efforts toward education and engagement across populations, rigorous and collaborative research, and institutional commitment and resources.

The John S. Najarian symposium: The past, present, and future of surgery and transplantation, May 20, 2022, Minneapolis, MN.

Dr John S Najarian (1927-2020), chairman of the Department of Surgery at the University of Minnesota from 1967 to 1993, was a pioneer in surgery, clinical immunology and transplantation. A Covid-delayed Festschrift was held in his honor on May 20, 2022. The speakers reflected on his myriad contributions to surgery, transplantation, and resident/fellow training, as well as current areas of ongoing research to improve clinical outcomes. Of note, Dr Najarian was a founder of the journal Clinical Transplantation.

Poor Outcomes of Patients With NAFLD and Moderate Renal Dysfunction or Short-Term Dialysis Receiving a Liver Transplant Alone.

The outcomes of patients with moderate renal impairment and the impact of liver disease etiology on renal function recovery after liver transplant alone (LTA) are largely unknown. We explored whether NAFLD patients with pre-LTA moderate renal dysfunction (GFR 25-45 ml/min/1.73 m2) may be more susceptible to develop post-LTA severe renal dysfunction (GFR<15 ml/min/1.73 m2) than ALD patients, as well as other overall outcomes. Using the UNOS/OPTN database, we selected patients undergoing liver transplant for NAFLD or ALD (2006-2016), 15,103 of whom received LTA. NAFLD patients with moderate renal dysfunction were more likely to develop subsequent GFR<15 ml/min/1.73 m2 than ALD patients (11.1% vs. 7.38%, p < 0.001). Patients on short-term dialysis pre-LTA (≤12 weeks) were more likely to develop severe renal dysfunction (31.7% vs. 18.1%), especially in NAFLD patients, and were more likely to receive a further kidney transplant (15.3% vs. 3.7%) and had lower survival (48.6% vs. 50.4%) after LTA (p < 0.001 for all). NAFLD was an independent risk factor for post-LTA severe renal dysfunction (HR = 1.2, p = 0.02). NAFLD patients with moderate renal dysfunction and those receiving short-term dialysis prior to LTA are at a higher risk of developing subsequent severe renal dysfunction. Underlying etiology of liver disease may play a role in predicting development and progression of renal failure in patients receiving LTA.

Back Table Preparation of the Right Lobe Live Donor Liver Allograft: A Crucial Part of the Adult Live Donor Liver Transplant Procedure.

INTRODUCTION: We aimed to describe our procedure for vascular reconstruction and back table bench preparation for the right lobe live donor allograft. Live donor liver transplantation (LDLT) remains an important option for the expansion of the donor pool. The procedure has been widely used, and its success is dependent on a technically perfect operation with appropriate inflow and outflow of the allograft. Adequate preparation of the right lobe (RL) allograft prior to implantation remains a vital part of the procedure. METHODS: Our technique of back table vascular reconstruction of the RL allograft has been performed using a hepatic vein patch venoplasty, inferior hepatic vein inclusion, portal vein reconstruction, and segment V and VIII reconstruction for all of our LDLTs. RESULTS: Between March 2009 and January 2020, 321 consecutive adult LDLTs were performed and underwent back table reconstruction with the techniques described. During that time period, no patients had hepatic insufficiency. There was a single thrombosis of a superior mesenteric vein (SMV) to PV jump conduit. CONCLUSIONS: Our technique of back table reconstruction of the LDLT right lobe graft remains a crucial part of the operative procedure. Our experience with RL grafts without middle hepatic vein (MHV) and our systematic approach for inflow and outflow reconstruction has yielded excellent results with no technical outflow issues and minimal inflow complications.

Characterization of hepatic steatosis using controlled attenuation parameter and MRI-derived proton density fat fraction in living donor liver transplantation.

BACKGROUND: The increasingly favorable outcomes of live donor liver transplant warrant development of screening techniques to expand current donor pool. Transient elastography (TE) with controlled attenuation parameter (CAP) is accessible and has promising diagnostic performance in non-obese individuals. Here, we demonstrate its utility in grading donor steatosis for risk assessment in living liver donors (LLD). STUDY DESIGN: In a prospective study of LLD and recipients, accuracy was determined using MRI-derived proton density fat fraction (PDFF) as reference. RESULTS: One hundred and one LLD underwent TE, 95 of whom had available PDFF. Median CAP and MRI-PDFF were 233 dB/m (206-270) and 2.9% (2.3-4.0), respectively. A CAP threshold of 270 dB/m captured all steatosis which was present in 13 (13%) LLD (AUROC .942, 100% sensitivity and 83% specificity). Performance further improved when excluding obese LLD and limiting analysis to M-probe (AUROC .971 and .974, respectively, with 87% specificity). There was no difference in CAP and MRI-PDFF between LLD and nondonors (P = .26 and .21, respectively). Early allograft dysfunction was observed in one recipient (CAP 316, PDFF 9.5%), zero underwent retransplant, and one died from sepsis. CONCLUSION: The specific role of CAP in living liver donation warrants further study, beginning with its use as screening tool across peripheral clinics.

The closing survival gap after liver transplantation for hepatocellular carcinoma in the United States.

BACKGROUND: Socio-economic inequalities among different racial/ethnic groups have increased in many high-income countries. It is unclear, however, whether increasing socio-economic inequalities are associated with increasing differences in survival in liver transplant (LT) recipients. METHODS: Adults undergoing first time LT for hepatocellular carcinoma (HCC) between 2002 and 2017 recorded in the Scientific Registry of Transplant Recipients (SRTR) were included and grouped into three cohorts. Patient survival and graft survival stratified by race/ethnicity were compared among the cohorts using unadjusted and adjusted analyses. RESULTS: White/Caucasians comprised the largest group (n=9,006, 64.9%), followed by Hispanic/Latinos (n=2,018, 14.5%), Black/African Americans (n=1,379, 9.9%), Asians (n=1,265, 9.1%) and other ethnic/racial groups (n=188, 1.3%). Compared to Cohort I (2002-2007), the 5-year survival of Cohort III (2012-2017) increased by 18% for Black/African Americans, by 13% for Whites/Caucasians, by 10% for Hispanic/Latinos, by 9% for patients of other racial/ethnic groups and by 8% for Asians (All P values<0.05). Despite Black/African Americans experienced the highest survival improvement, their overall outcomes remained significantly lower than other ethnic∕racial groups (adjusted HR for death=1.20; 95%CI 1.05-1.36; P=0.005; adjusted HR for graft loss=1.21; 95%CI 1.08-1.37; P=0.002). CONCLUSION: The survival gap between Black/African Americans and other ethnic/racial groups undergoing LT for HCC has significantly decreased over time. However, Black/African Americans continue to have the lowest survival among all racial/ethnic groups.

Sequential liver and kidney living donors: Making the ultimate gift twice.

There are nearly 150 living donors in the United States who donated more than one solid organ. Using our divisional database, we found 20 individuals who donated a liver and a kidney at different times. We performed a retrospective chart review of these donors, studying their motivating factors, complications and outcomes. The donors included 11 (55%) males and nine females. Thirteen (65%) donated the kidney before the liver. Fourteen (70%) were nondirected donors at the first donation, and four of the six directed donors in the first donation became nondirected in the second donation. Seventeen (85%) were nondirected at the second donation. Common reasons for donating the second time were a good experience with the first donation and knowing that one can donate again. Outcomes and the incidence of early complications were not significantly different after the 2nd versus the 1st donation. All donors recovered and currently are doing well. Our results show a significant number of dual organ donors are nondirected and motivated by their strong desire to help. A positive experience with the 1st donation often was the driving factor for the 2nd. A history of previous organ donation did not negatively impact the 2nd donation.

Increasing Living Donor Liver Transplantation Using Liver Paired Exchange.

BACKGROUND: Living donor liver transplantation (LDLT) continues to be the primary modality of liver transplantation in Asia, but it accounts for about 5% of all liver transplantations in the US. ABO incompatibility is the primary reason motivated donors are declined. Although kidney paired exchanges are common, liver paired exchange (LPE) is still evolving in the US. STUDY DESIGN: This is a retrospective review (between January 1, 2019, and July 31, 2021) of our initial experience with LPE. RESULTS: A total of 10 LPEs (20 LDLTs) were performed during the study period. Seven LPEs were initiated by a nondirected O donor. The other 3 pair sets involved 1 ABO compatible and 1 ABO incompatible pair. Transplantations in a pair set were completed within a mean of 4.8 (range 1-14) days of each other. All 20 donors are doing well with no major complications at 12.7 (range 1-20) months. Seventeen of 20 recipients are alive and have good allograft function. One recipient died in the early postoperative period. Two late deaths of patients with functioning allografts were due to COVID-19 (at 8 months) and peritoneal carcinomatosis and gram-negative sepsis (at 9 months). CONCLUSIONS: LPE is feasible in a high-volume LDLT center and is a useful option to increase LDLT by overcoming ABO incompatibility. Nondirected donors can be utilized to initiate an LPE.

Optimal Timing of Administration of Direct-acting Antivirals for Patients With Hepatitis C-associated Hepatocellular Carcinoma Undergoing Liver Transplantation.

OBJECTIVE: To investigate the optimal timing of direct acting antiviral (DAA) administration in patients with hepatitis C-associated hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). SUMMARY OF BACKGROUND DATA: In patients with hepatitis C (HCV) associated HCC undergoing LT, the optimal timing of direct-acting antivirals (DAA) administration to achieve sustained virologic response (SVR) and improved oncologic outcomes remains a topic of much debate. METHODS: The United States HCC LT Consortium (2015-2019) was reviewed for patients with primary HCV-associated HCC who underwent LT and received DAA therapy at 20 institutions. Primary outcomes were SVR and HCC recurrence-free survival (RFS). RESULTS: Of 857 patients, 725 were within Milan criteria. SVR was associated with improved 5-year RFS (92% vs 77%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 92%, and 82%, and 5-year RFS of 93%, 94%, and 87%, respectively. Among 427 HCV treatment-naïve patients (no previous interferon therapy), patients who achieved SVR with DAAs had improved 5-year RFS (93% vs 76%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 93%, and 78% (P < 0.01) and 5-year RFS of 93%, 100%, and 83% (P = 0.01). CONCLUSIONS: The optimal timing of DAA therapy appears to be 0 to 3 months after LT for HCV-associated HCC, given increased rates of SVR and improved RFS. Delayed administration after transplant should be avoided. A prospective randomized controlled trial is warranted to validate these results.

Post-operative outcomes in anonymous living liver donors: What motivates individuals to donate to strangers.

BACKGROUND: Anonymous living donor liver transplantation (LDLT) is a strategy to address the shortage of available transplantable livers; however, few studies have been conducted on this population. The objective of this study was to describe the motivations and medical, psychosocial, and financial outcomes of anonymous living liver donors. METHODS: Between 2010-2019, 116 anonymous living liver donors were evaluated, 59 (51.7%) of whom proceeded to surgery. A subset of 21 anonymous donors were matched to biologically/emotionally related donors according to age, gender, race, and duration since surgery. A medical chart review and post-surgical interviews were performed to assess medical and financial outcomes. RESULTS: The primary motivation for donors was an unselfish desire to help others (43, 72.9%). A total of 13 (22%) anonymous donors experienced complications. Of these, 7 (11.9%) were grade I Clavien-Dindo classification, 5 (8.5%) grade II, 1 was grade III (1.7%); and no patients had grade IV-V Clavien-Dindo complications. Increased anxiety was reported by 3 (5.1%) donors, and one donor reported clinical levels of depression (1.7%). Within the matched controls, anonymous donors were not significantly different to biologically/emotionally related donors with regard to surgical complications, psychosocial, or financial outcomes. CONCLUSIONS: Allowing a greater number of anonymous donors may facilitate the reduction of the waitlist for liver transplant candidates.

Magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) is a viable alternative to liver biopsy for steatosis quantification in living liver donor transplantation.

This study aimed to investigate whether magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) can be a viable noninvasive alternative to liver biopsy for the quantification of living liver donor steatosis. Hepatic steatosis for 143 donors was graded by MRI-PDFF. Study endpoints included liver volume regeneration in donors, recipient outcomes including length of hospital stay, deaths, primary non-function (PNF), early allograft dysfunction (EAD), and small for size syndrome (SFSS). Correlation between MRI-PDFF determined donor steatosis and endpoints were analyzed. Donors had lower steatosis grade than non-donors. Donor remnant liver regenerated to an average of 82% of pre-donation volume by 101 ± 24 days with no complications. There was no correlation between percent liver regeneration and steatosis severity. Among recipients, 4 underwent redo-transplantation and 6 died, with no association with degree of steatosis. 52 recipients (36%) fulfilled criteria for EAD (driven by INR), with no difference in hepatic steatosis between groups. MRI-PDFF reliably predicted donor outcomes. Living donors with no or mild steatosis based on MRI-PDFF (ie, <20%) and meeting other criteria for donation can expect favorable post-surgical outcomes, including liver regeneration. Recipients had a low rate of death or retransplantation with no association between mild hepatic steatosis and EAD.

Expanding Donor Selection and Recipient Indications for Living Donor Liver Transplantation.

There is an acute shortage of deceased donor organs for liver transplantation in the United States. Nearly a third of patients either die or become too sick for transplant while on the transplant waitlist. Living donor liver transplantation (LDLT) bridges the gap between demand and supply of organs for liver transplantation. This article reviews current living donor selection criteria, and avenues for expansion of criteria with novel surgical techniques and ongoing outcomes research. Ways in which institutions can establish and expand LDLT programs using the Living Donor Champion model are discussed. Efforts to expand recipient indications for LDLT are described.

An evaluation of the safety and preliminary efficacy of peri- and post-operative treprostinil in preventing ischemia and reperfusion injury in adult orthotopic liver transplant recipients.

BACKGROUND: Orthotopic liver transplantation (OLT) is the only treatment option for various end-stage liver diseases. Ischemia and reperfusion (I/R) injury is one of the unavoidable complications/conditions in OLT. In 2019, a total of 8896 livers were transplanted of which >94% organs were procured from deceased donors. An increase in the use of extended criteria donor (ECD) livers for transplantation further unraveled the role of hepatic I/R injury on short-term and long-term graft outcomes. Despite promising outcomes with the use of antioxidants, free radical scavengers, and vasodilators; I/R-mediated liver injury persists and significantly influences the overall clinical outcomes. Treprostinil, a synthetic prostacyclin I2  (PGI2 ) analog, due to its vasodilatory property, antiplatelet activity, and its ability to downregulate pro-inflammatory cytokines can potentially minimize I/R injury. AIM: We investigated the safety and preliminary efficacy of continuous intravenous infusion of treprostinil in liver transplant recipients in a prospective, single-center, non-randomized, interventional study. MATERIAL AND METHODS: This was a dose escalation (3 + 3 design) phase 1/2 study. Deceased donor liver transplant recipients received 5 ng/kg/min for two days, or 2.5, 5, and 7.5 ng/min/kg for 5 days as a continuous infusion. Multiple blood samples were collected for biochemical parameter assessment and for measuring treprostinil levels. Indocyanine green plasma disappearance rate was used as a measure of hepatic functional capacity. RESULTS: Subjects tolerated continuous infusion of treprostinil up to 5 ng/kg/min for 120 h with no occurrence of primary graft non-function (PNF), minimized need for ventilation support, reduced hospitalization time, 100% graft and patient survival, and improved hepatobiliary excretory function comparable to normal healthy adults. DISCUSSION: Treprostinil can be administered to liver transplant patients safely during the perioperative period. CONCLUSION: Based on this phase 1/2 study, further efficacy studies of treprostinil in preventing I/R injury of liver should be conducted to potentially increase the number of livers available for transplantation.

Portal vein thrombosis and renal dysfunction: a national comparative study of liver transplant recipients for NAFLD versus alcoholic cirrhosis.

The prevalence of portal vein thrombosis (PVT), renal dysfunction (RD), and simultaneous PVT/RD in liver transplantation (LT) is poorly understood. We analyzed the prevalence of PVT, RD, simultaneous PVT/RD, and the outcomes of adult recipients of LT for nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) between 2006 and 2016 in the United States. We found that the prevalence of PVT (7.2% â†’ 11.3%), RD (33.8% â†’ 39.2%), and simultaneous PVT/RD (2.4% â†’ 4.5%) has increased significantly over the study period (all P-values <0.05). NAFLD patients had a higher proportion of PVT (14.8% vs. 9.2%), RD (45.0% vs. 42.1%), and simultaneous PVT/RD (6.5% vs. 3.9%; all P-values <0.05). 90-day mortality was 3.8%, 6.3%, 6.8%, and 9.8% for PVT(-)/RD(-), PVT(-)/RD(+), PVT(+)/RD(-), and PVT(+)/RD(+) recipients, respectively (P < 0.01). 5-year survival was 82.1%, 75.5%, 74.8%, and 71.1% for PVT(-)/RD(-), PVT(-)/RD(+), PVT(+)/RD(-), and PVT(+)/RD(+) recipients, respectively (P < 0.05). In conclusion, the prevalence of PVT, RD, and simultaneous PVT/RD has increased among LT recipients, especially for those with NAFLD. The short- and long-term outcomes of recipients with PVT, RD, and simultaneous PVT/RD were inferior to patients without those risk factors irrespective of their indication for LT. No differences in patient outcomes were found between ALD and NAFLD recipients after stratification by risk factors.

Adult Living Donor Versus Deceased Donor Liver Transplant (LDLT Versus DDLT) at a Single Center: Time to Change Our Paradigm for Liver Transplant.

OBJECTIVE: The aim of this study was to compare outcomes between living donor liver transplant (LDLT) and deceased donor liver transplant (DDLT) at a single center to demonstrate the advantages of LDLT and provide justification for the increased utilization and application of this procedure. SUMMARY OF BACKGROUND DATA: LDLT comprises a very small percentage of all liver transplants performed in the United States, this despite its advantages and a shortage of the availability of deceased donor organs. METHODS: A retrospective review of all adult LDLT (n = 245) and DDLT (n = 592) performed at a single center over 10 years (2009-2019), comparing survival outcomes by Kaplan-Meier analysis and comparing other measures of outcome such as recovery times, complications, costs, and resource utilization. RESULTS: Patient survival outcomes were superior in LDLT recipients (3-year 86% vs 80%, P = 0.03). Other outcomes demonstrated shorter length of hospital stay (11 vs 13 days, P = 0.03), less likelihood of intraoperative blood transfusion (52% vs 78%, P < 0.01), and less likelihood of need for posttransplant dialysis (1.6% vs 7.4%, P < 0.01). Early reoperation and biliary/vascular complication rates were similar. Hospital costs related to the transplant were 29.5% lower for LDLT. Complications in living donors were acceptable with no early or late deaths, 3-month reoperation rate of 3.1%, and overall complication rate of 19.5%. Given its advantages, we have expanded LDLT-in 2018, LDLT comprised 53.6% of our transplants (national average 4.8%), and our transplant rate increased from 44.8 (rate per 100-person years) in 2015 to 87.5 in 2018. CONCLUSIONS: LDLT offers advantages over DDLT including superior outcomes and less resource utilization. The time has come to change the paradigm of how LDLT is utilized in this country.

Evaluation of the enhanced recovery after surgery protocol in living liver donors.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocol has proven to be effective in many surgery fields in controlling pain and promoting early recovery. Application of the (ERAS) protocol in living donor liver patients is a new step to promote early recovery. METHODS: We analyzed outcomes in two groups. Group A included the living donors who had the ERAS protocol applied (n = 30), and Group B included donors who had their surgery before the ERAS protocol (n = 30). All donors had the same incision. The ERAS protocol involved a multimodality methods. This included intravenous ketamine and lidocaine intraoperatively with single dose intrathecal morphine and local injection of long-acting bupivacaine. The postoperative regimen included intravenous ketamine, lidocaine, ketorolac, and narcotics as PRN. RESULTS: Pain on the first three postoperative days was significantly lower in Group A (P < 0.05). Narcotics were also significantly lower in Group A (P < 0.01). Return of bowel function occurred earlier by 1 day in Group A (P < 0.003). Group A patients could tolerate a regular diet by postoperative day (POD) three vs four in Group B patients (P = 0.0057). Mean length of stay was lower in Group A, but not statistically significant. CONCLUSIONS: Enhanced recovery after surgery protocol was effective in minimizing postoperative pain and helped to decrease the postoperative narcotics and helped early recovery.