1Department of Gastroenterology and Hepatology, Flinders Medical Centre, Bedford Park, South Australia 2Metabolic Clinic, Women's and Children's Hospital, North Adelaide, South Australia 3College of Medicine and Public Health, Flinders University, Bedford Park, South Australia Abbreviations: ACLF, acute-on-chronic liver failure; ALT, alanine transaminase; AST, aspartate transaminase; CPT, carnitine palmitoyl transferase; INR, international normalized ratio; NAS, NAFLD activity score. Correspondence Kate R. Muller, Department of Gastroenterology and Hepatology, Flinders Medical Centre, Flinders Drive, Bedford Park SA 5042, Australia. Email [email protected]

Brubaker, Aleah L.; Bensard, Claire; MacConmara, Malcolm; Elbetanony, Ahmed; Attia, Magdy; Sanchez, Ramon; Schnickel, Gabriel Author Information

To the editor, In rare cases where the living liver donor has a large right half liver and a small left half liver, a partial liver allograft can be obtained from the right posterior section. However, because the right posterior section is located deep under the costal arch, with many anatomical variations, many liver tissues need to be severed, and since the hepatic portal vein is complex to deal with, it is a challenge to use pure laparoscopic resection. The recent study by Cho et al,1 published in Liver Transplantation, comparing pure laparoscopic donor right posterior sectionectomy (PLDRPS) versus pure laparoscopic donor right hemihepatectomy, found PLDRPS in living liver donor with portal vein anomaly and insufficient left lobe was technically feasible and safe with experienced surgeons. We applaud their efforts to further promote the application of laparoscopy in living donor liver transplantation, and it would be nice if the authors could elaborate on the following points. First, in the process of obtaining the right posterior section graft, subtle displacement of the liver resection plane can lead to significant deviation between the mass of the grafts actually obtained and the estimated mass. How do we determine the accurate cutting plane during parenchymal transection under pure laparoscopy? Second, there are many variations in the right posterior section of the bile duct, such as double branches of the right posterior section of the bile duct or the right posterior section of the bile duct from the dorsal side of the portal vein out of shape. If we encounter these situations, how do we solve the problems? Third, we note that Cho et al have achieved complete transition from an open to laparoscopic approach in liver donor surgery.2 However, most audiences of Liver Transplantation may have to face the important issue of PLDRPS conversion to open surgery. Switching to open surgery will change “minimally invasive” surgery into “invasive” surgery, threatening the safety of the donor seriously. How to avoid conversion to open surgery and how to deal with it after conversion to minimize damage to the donor may be an urgent need for the audience to understand. Last, as a recently developed technique, PLDRPS has limited follow-up time, and its long-term effects are still unclear. Although no serious complications or deaths have been reported in these reports, the small number of reported cases does not allow reliable conclusions to be drawn from the limited data. Therefore, we should be cautious about widely using minimally invasive techniques in right posterior sectionectomy before conducting a comprehensive evaluation of donor safety and postoperative prognosis.

Liver transplantation continues to face significant organ shortages and efficient utilization of marginal donors is paramount. This study evaluates the practice patterns and outcomes in liver transplantation when utilizing allografts from marginal donors who required extracorporeal membrane oxygenation (ECMO) support. We performed a retrospective review of the Gift of Life (PA, NJ, DE) organ-procuring organization database for transplants performed using donors supported on ECMO for nondonation purposes. These were cross-referenced to the transplant recipients within the Organ Procurement and Transplantation Network database, and the outcomes of liver transplants using donors on ECMO support were compared with those not requiring ECMO. Organ use and nonuse patterns were then evaluated in ECMO-supported donors, identifying the factors associated with nonuse compared with the factors associated with graft failure. Thirty-nine of the 84 ECMO-supported donors contributing at least one intra-abdominal organ for transplant donated a liver. Graft survival and patient survival up to 5 years were comparable between transplants from ECMO and non-ECMO-supported donors, and no cases of primary nonfunction were seen in the ECMO group. ECMO support was not associated with 1-year graft failure on regression modeling. Additional regression analyses within the ECMO donor population identified bacteremia (HR: 19.81) and elevated total bilirubin at donation (HR: 2.44) as predictive of post-transplant graft failure. Livers from donors supported on ECMO before donation appear safe to use in select transplant settings. Better understanding of the impact of predonation ECMO on liver allograft function will help guide the optimal use of these scarcely used donors.

Sex and racial disparities in deceased donor liver transplantation (DDLT) have been described, but this has not been well studied in living donor liver transplantation (LDLT). We aim to examine these disparities in the US LDLT population and identify potential predictors of these differences. From 2002 to 2021, the Organ Procurement and Transplant Network database was queried to characterize the adult LDLT population and evaluate differences between LDLT and DDLT recipients with regard to sex and race. Donor demographics, Model for End-stage Liver Disease (MELD), and socioeconomic data were all included. Of the 4961 LDLT and 99,984 DDLT recipients, males received the majority of LDLT (55% vs. 45%, p < 0.001) and DDLT (67% vs. 33%, p < 0.001) compared to females. There was a significant difference in race between male and female LDLT recipients ( p < 0.001); 84% of male recipients were White and 78% of females. In both groups, females had lower levels of education and were less likely to have private insurance. There were more female living donors (N = 2545, 51%); 50% of female donors donated to males but only 40% of males donated to females. Donor-recipient relationships varied significantly by sex ( p < 0.001); males received more donations from spouses (62% vs. 39%) and siblings (60% vs. 40%). In the LDLT population, significant disparities exist with respect to sex and race that disadvantage women, but these disparities are less pronounced than in the DDLT population. Although further studies are needed, complex clinical and socioeconomic differences as well as donor factors may explain these variations.

1Department of Transplant, Mayo Clinic Florida, Jacksonville, Florida 2Department of Surgery, Mayo Clinic Arizona, Phoenix, AZ, USA Correspondence Amit K. Mathur. Email: [email protected]

Surgery (Organ Transplantation) and Interventional Radiology Correspondence Division of Gastroenterology and Hepatology Northwestern University Feinberg School of Medicine, 676 N St. Clair 19th Floor, Chicago, IL 60607 Email: [email protected]

The deleterious effect of donor-specific anti-HLA antibodies (DSA) after liver transplantation (LT) has been increasingly recognized during the past decade. Antibody-mediated rejection (AMR) represents a rare but severe complication in the presence of DSA. However, little is known concerning the treatment of AMR after LT. The nationwide French study aimed to describe LT recipients who received specific treatment of AMR. We performed a multicenter retrospective study on 44 patients who were treated with B-cell targeting agents from January 2008 to December 2020. Median patient age at the time of AMR treatment was 51.6 years (range: 17.9-68.0). AMR was classified as acute (n = 19) or chronic (n = 25). The diagnosis of AMR was made after a median time of 16.8 months (range: 0.4-274.2) after LT. The main therapeutic combination was plasma exchange/rituximab/IVIG (n = 25, 56.8%). The median follow-up after the treatment of AMR was 32 months (range: 1-115). After the treatment, 1-, 5- and 10-year patient and graft survivals were 77%, 55.9%, and 55.9%, and 69.5%, 47.0%, and 47.0%, respectively. Initial total bilirubin (Q1-Q3 vs. Q4) was significantly associated with patient survival (log-rank test, p = 0.005) and graft survival (log-rank test, p = 0.002). After a median follow-up of 21 months (range: 12-107), DSA became undetectable in 15/38 patients (39.5%) with available DSA monitoring. In conclusion, specific treatment of AMR in LT recipients has slowly emerged in France during the past decade and has probably been considered in the most severe patients; this explains the global poor outcome, even if the outcome was favorable in some cases.

Standard eligibility criteria for simultaneous liver-kidney transplantation (SLK) are in place in the United States. We hypothesize that the benefit associated with SLK over liver transplant alone differs by patient, depending on the specific SLK criteria met. We analyzed a retrospective US cohort of 5446 adult liver transplant or SLK recipients between January 1, 2015, and December 31, 2018, who are potentially qualified for SLK. Exposure was a receipt of SLK. We tested effect modification by the specific SLK eligibility criteria met (end-stage kidney disease, acute kidney injury, chronic kidney disease, or unknown). The primary outcome was death within 1 year of a liver transplant. We used a modified Cox regression analysis containing an interaction term of SLK * time from transplant. Two hundred ten (9%) SLK recipients and 351 (11%) liver-alone recipients died in 1 year. In the overall population, SLK was associated with a mortality benefit over liver transplant on the day of the transplant, without adjustment [HR: 0.59 (95% CI, 0.46-0.76)] and with adjustment [aHR: 0.50 (95% CI, 0.35-0.71)]. However, when SLK eligibility criteria were included, only in patients with end-stage kidney disease was SLK associated with a sustained survival benefit at day 0 [HR: 0.17 (0.08-0.35)] up to 288 (95% CI, 120-649) days post-transplant. Benefit within the first year post-transplant associated with SLK over liver-alone transplantation was only pronounced in patients with end-stage kidney disease but not present in patients meeting other criteria for SLK. A "strict SLK liberal Safety Net" strategy may warrant consideration at the national policy level.

To the editor, We read with interest the article by Long et al1 recently published in Liver Transplantation illustrating how digital imaging software analysis of liver biopsies provided a more precise estimation of the degree of macrovesicular steatosis in donor livers compared with the use of traditional histological procedures, thus reducing the number of discarded donor livers. In fact, the use of HALO lowered the estimates of the proportion of macrovesicular steatosis compared with both liver transplant centers and donor hospitals’ histological evaluations, a result that is more evident for the higher prevalence of macrovesicular steatosis. This finding, together with evidence that the percentage of macrovesicular steatosis estimated by HALO was associated with early allograft dysfunction, suggests that digital imaging software might be used to safely decrease the proportion of discarded donations and/or indicate potential for organ reconditioning to increase graft utilization.1 The prevalence of liver steatosis in the general population is on the rise, with a concurrent increase in the donor pool, rising from 20% in 2010 to 30% in 2016, and this parallels the steep increase in the number of discarded donations due to liver steatosis.2 Thus, an accurate, reproducible, operator-independent, and user-friendly method to assess the degree of macrovesicular steatosis is crucial, so as to improve organ selection and to base such relevant decisions as discarding a potential donor organ on more solid grounds.3 In this regard, however, it must be emphasized that the use of any software based on digital imaging analysis, such as HALO, needs periodic reevaluation of consistency and assessment of adherence to guidelines.3 In light of these findings, we recently devised an easy-to-use, innovative method that exploits artificial intelligence combined with a smartphone application that enables a physician to noninvasively classify steatosis (30% < or ≥30%) in liver grafts to a very high degree of accuracy.4 This methodology has the added advantage to avoid invasiveness and its related complications and to provide a more “panoramic” assessment of liver parenchyma, thus eluding the bias inherent to sampling variability and limited representativeness—potential pitfalls that cannot be excluded with the use of digital imaging software evaluation of histological specimens.5 We fully agree with the vision put forward by Long and colleagues that it is imperative to progress toward more objective evaluations of donor organs, and we feel that the use of noninvasive and accurate methods may be a further step in this direction.1,5 We also feel that it is urgent to evaluate whether the adoption of such tools may be associated not only with an expansion of the pool of potential donors but also with the absence of an increase in early allograft dysfunction, graft loss, and other relevant post-transplant outcomes. Finally, it remains to be assessed whether future improvement in functional assessment through dynamic evaluation of organ viability during machine perfusion, and of its modification following reconditioning, may render ancillary the (noninvasive) evaluation of macrovesicular steatosis.