Decisions on who requires simultaneous liver-kidney (SLK) transplantation are controversial. United Network for Organ Sharing implemented a “safety net” in 2017 providing prioritization on the kidney ...waitlist for patients with renal failure after liver transplantation. We aimed to compare survival after early kidney after liver transplantation (KALT) and SLK.
We compared SLK, KALT, and liver transplantation alone (LTA) in adult patients who underwent deceased donor (DD) liver transplantation in the US, from 2002 to 2018. Early KALT was defined as 60 to 365 days between liver and subsequent kidney transplantation (reflecting safety net listing criteria). Patients who died within 60 days were excluded to mitigate immortal time bias favoring KALT.
There were 6,774 SLK, 120 KALT at 60 to 365 days, and 11,501 LTA. Early KALT had equivalent survival compared with SLK, both for all KALT (hazard ratio HR 0.58, 95% CI 0.34–1.00, p = 0.05) and for DD KALT only (HR 0.72, 95% CI 0.37–1.38, p = 0.32). Simultaneous liver-kidney transplantation was associated with improved survival compared with LTA (HR 0.82. 95% CI 0.76–0.87, p < 0.01). Early KALT was associated with a greater reduction in mortality compared with LTA, but this was not significant (HR 0.58, 95% CI 0.39–1.00, p = 0.05). There was a lower proportion of early KALT in African Americans relative to SLK transplantations (7% vs 16%, p = 0.04).
Early KALT has equivalent survival compared with SLK transplantation, both for all KALT and for DD KALT only, supporting the promise of the “safety net.” There was a lower proportion of African-American patients undergoing early KALT, indicating the importance of monitoring access to early KALT under the “safety net” policy.
Display omitted
IMPORTANCE: Ischemic cold storage (ICS) of livers for transplant is associated with serious posttransplant complications and underuse of liver allografts. OBJECTIVE: To determine whether portable ...normothermic machine perfusion preservation of livers obtained from deceased donors using the Organ Care System (OCS) Liver ameliorates early allograft dysfunction (EAD) and ischemic biliary complications (IBCs). DESIGN, SETTING, AND PARTICIPANTS: This multicenter randomized clinical trial (International Randomized Trial to Evaluate the Effectiveness of the Portable Organ Care System Liver for Preserving and Assessing Donor Livers for Transplantation) was conducted between November 2016 and October 2019 at 20 US liver transplant programs. The trial compared outcomes for 300 recipients of livers preserved using either OCS (n = 153) or ICS (n = 147). Participants were actively listed for liver transplant on the United Network of Organ Sharing national waiting list. INTERVENTIONS: Transplants were performed for recipients randomly assigned to receive donor livers preserved by either conventional ICS or the OCS Liver initiated at the donor hospital. MAIN OUTCOMES AND MEASURES: The primary effectiveness end point was incidence of EAD. Secondary end points included OCS Liver ex vivo assessment capability of donor allografts, extent of reperfusion syndrome, incidence of IBC at 6 and 12 months, and overall recipient survival after transplant. The primary safety end point was the number of liver graft–related severe adverse events within 30 days after transplant. RESULTS: Of 293 patients in the per-protocol population, the primary analysis population for effectiveness, 151 were in the OCS Liver group (mean SD age, 57.1 10.3 years; 102 67% men), and 142 were in the ICS group (mean SD age, 58.6 10.0 years; 100 68% men). The primary effectiveness end point was met by a significant decrease in EAD (27 of 150 18% vs 44 of 141 31%; P = .01). The OCS Liver preserved livers had significant reduction in histopathologic evidence of ischemia-reperfusion injury after reperfusion (eg, less moderate to severe lobular inflammation: 9 of 150 6% for OCS Liver vs 18 of 141 13% for ICS; P = .004). The OCS Liver resulted in significantly higher use of livers from donors after cardiac death (28 of 55 51% for the OCS Liver vs 13 of 51 26% for ICS; P = .007). The OCS Liver was also associated with significant reduction in incidence of IBC 6 months (1.3% vs 8.5%; P = .02) and 12 months (2.6% vs 9.9%; P = .02) after transplant. CONCLUSIONS AND RELEVANCE: This multicenter randomized clinical trial provides the first indication, to our knowledge, that normothermic machine perfusion preservation of deceased donor livers reduces both posttransplant EAD and IBC. Use of the OCS Liver also resulted in increased use of livers from donors after cardiac death. Together these findings indicate that OCS Liver preservation is associated with superior posttransplant outcomes and increased donor liver use. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02522871
Background The 2014 Medicaid expansion in participating states increased insurance coverage among people with chronic health conditions, but its implications for access to surgical care remain ...unclear. We investigated how Medicaid expansion influenced the insurance status of candidates for liver transplantation (LT) and transplant center payor mix. Study design Data on LT candidates aged 18 to 64 years, in 2012 to 2013 (pre-expansion) and 2014 to 2015 (post-expansion), were obtained from the United Network for Organ Sharing registry. Change between the 2 periods in the percent of LT candidates using Medicaid was compared between expansion and nonexpansion states. Multivariable logistic regression was used to determine how Medicaid expansion influenced individual LT candidates' likelihood of using Medicaid insurance. Results The study included 33,017 LT candidates, of whom 29,666 had complete data for multivariable analysis. Medicaid enrollment increased by 4% after Medicaid expansion in participating states. One-quarter of the transplant centers in these states experienced ≥10% increase in the proportion of LT candidates using Medicaid insurance. Multivariable analysis confirmed that Medicaid expansion was associated with increased odds of LT candidates using Medicaid insurance (odds ratio 1.49; 95% CI 1.34, 1.66; p < 0.001). However, the absolute number and demographic characteristics of patients listed for LT did not change in Medicaid expansion states during the post-expansion period. Conclusions Candidates for LT became more likely to use Medicaid after the 2014 Medicaid expansion policy came into effect. Enactment of this policy did not appear to increase access to LT or address socioeconomic and demographic disparities in access to the LT wait list.
In April 2012, the Organ Procurement and Transplantation Network (OPTN) implemented an online explant pathology form for recipients of liver transplantation who received additional wait‐list priority ...for their diagnosis of hepatocellular carcinoma (HCC). The purpose of the form was to standardize the data being reported to the OPTN, which had been required since 2002 but were submitted to the OPTN in a variety of formats via facsimile. From April 2012 to December 2014, over 4500 explant forms were submitted, allowing for detailed analysis of the characteristics of the explanted livers. Data from the explant pathology forms were used to assess agreement with pretransplant imaging. Explant data were also used to assess the risk of recurrence. Of those with T2 priority, 55.7% were found to be stage T2 on explant. Extrahepatic spread (odds ratio OR = 6.8; P < 0.01), poor tumor differentiation (OR = 2.8; P < 0.01), microvascular invasion (OR = 2.6; P < 0.01), macrovascular invasion (OR = 3.2; P < 0.01), and whether the Milan stage based on the number and size of tumors on the explant form was T4 (OR = 2.4; P < 0.01) were the strongest predictors of recurrence. In conclusion, this analysis confirms earlier findings that showed an incomplete agreement between pretransplant imaging and posttransplant pathology in terms of HCC staging, though the number of patients with both no pretransplant treatment and no tumor in the explant was reduced from 20% to <1%. In addition, several factors were identified (eg, tumor burden, age, sex, region, ablative therapy, alpha‐fetoprotein, Milan stage, vascular invasion, satellite lesions, etc.) that were predictive of HCC recurrence, allowing for more targeted surveillance of high‐risk recipients. Continued evaluation of these data will help shape future guidelines or policy recommendations. Liver Transplantation 22 757–764 2016 AASLD.
Meeting the metabolic demands of donor livers using normothermic ex vivo liver perfusion (NEVLP) preservation technology is challenging. The delta opioid agonist D-Ala2, D-Leu5 enkephalin (DADLE) has ...been reported to decrease the metabolic demand in models of ischemia and cold preservation. We evaluated the therapeutic potential of DADLE by investigating its ability to protect against oxidative stress and hepatic injury during normothermic perfusion.
Primary rat hepatocytes were used in an in vitro model of oxidative stress to determine the minimum dose of DADLE needed to induce protection and the mechanisms associated with protection. NEVLP was then used to induce injury in rat livers and determine the effectiveness of DADLE in preventing liver injury.
In hepatocytes, DADLE was protective against oxidative stress and led to a decrease in phosphorylation of JNK and p38. Naltrindole, a δ-opioid receptor antagonist, blocked this effect. DADLE also activated the PI3K/Akt signaling pathway, and PI3K/Akt inhibition decreased the protective effects of DADLE treatment. In addition, DADLE treatment during NEVLP resulted in lower perfusate alanine aminotransferase and tissue malondialdehyde and better tissue adenosine triphosphate and glutathione. Furthermore, perfusion with DADLE compared with perfusate alone preserved tissue architecture.
DADLE confers protection against oxidative stress in hepatocytes and during NEVLP. These data suggest that the mechanism of protection involved the prevention of mitochondrial dysfunction by opioid receptor signaling and subsequent increased expression of prosurvival/antiapoptotic signaling pathways. Altogether, data suggest that opioid receptor agonism may serve as therapeutic target for improved liver protection during NEVLP.
Summary
Domino liver transplantation (DLT) utilizes the explanted liver of one liver transplant recipient as a donor graft in another patient. While there may be unique risks associated with DLT, it ...is unclear if DLT has less favorable long‐term outcomes than deceased donor liver transplantation (DDLT). We used a propensity score matching approach to compare the outcomes of DLT recipients to DDLT recipients. The United Network for Organ Sharing (UNOS) registry was queried for patients undergoing DLT or DDLT in 2002–2016. Each DLT recipient was matched to a unique DDLT recipient to compare mortality and graft failure. There were 126 DLT and 62 835 DDLT recipients meeting inclusion criteria. After propensity score matching on recipient pre‐transplant characteristics, 123 DLT cases were matched to DDLT controls from the same UNOS region. On stratified Cox proportional hazards regression, DLT incurred no increase in the hazard of mortality hazard ratio (HR) = 1.4; 95% confidence interval (CI): 0.8, 2.7; P = 0.265 or graft failure (HR = 1.2; 95% CI: 0.7, 2.1; P = 0.556) compared to DDLT. Using a large national registry, a propensity‐matched analysis found no increased risk of mortality or graft failure associated with DLT compared to DDLT.
Liver transplantation (LT) recipients in the United States have low rates of paid employment, making some eligible for Medicaid public health insurance after transplant. We test whether recent ...expansions of Medicaid eligibility increased Medicaid enrollment and insurance coverage in this population. Patients of ages 18‐59 years receiving first‐time LTs in 2009‐2013 were identified in the United Network for Organ Sharing registry and stratified according to insurance at transplantation (private versus Medicaid/Medicare). Posttransplant insurance status was assessed through June 2015. Difference‐in‐difference multivariate competing‐risks models stratified on state of residence estimated effects of Medicaid expansion on Medicaid enrollment or use of uninsured care after LT. Of 12,837 patients meeting inclusion criteria, 6554 (51%) lived in a state that expanded Medicaid eligibility. Medicaid participation after LT was more common in Medicaid‐expansion states (25%) compared to nonexpansion states (19%; P < 0.001). Multivariate analysis of 7279 patients with private insurance at transplantation demonstrated that after the effective date of Medicaid expansion (January 1, 2014), the hazard of posttransplant Medicaid enrollment increased in states participating in Medicaid expansion (hazard ratio HR = 1.5; 95% confidence interval CI = 1.1‐2.0; P = 0.01), but not in states opting out of Medicaid expansion (HR = 0.8; 95% CI = 0.5‐1.3; P = 0.37), controlling for individual characteristics and time‐invariant state‐level factors. No effects of Medicaid expansion on the use of posttransplant uninsured care were found, regardless of private or government insurance status at transplantation. Medicaid expansion increased posttransplant Medicaid enrollment among patients who had private insurance at transplantation, but it did not improve overall access to health insurance among LT recipients. Liver Transplantation 22 1075–1084 2016 AASLD
PDF
![[D-Ala2, D-Leu5] Enkephalin...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0022-4804/small "[D-Ala2, D-Leu5] Enkephalin Improves Liver Preservation During Normothermic Ex Vivo Perfusion")
