Socioeconomic deprivation is associated with worse patient and graft survival following adult liver transplantation.

BACKGROUND: The impact of social determinants of health (SDOH) on adult liver transplant recipient outcomes is not clear at a national level. Further understanding of the impact of SDOH on patient outcomes can inform effective equitable healthcare delivery. METHODS: Unadjusted and multivariable models were used to analyze the Scientific Registry of Transplant Recipients to evaluate the association between the Social Deprivation Index (SDI) based on liver transplant recipient's residential location and patient and graft survival. We included adult recipients between 1/1/2008-12/1/2021. RESULTS: Patient and graft survival were lower in adults living in areas with deprivation scores above the median. Five-year patient and graft survival were 78.7% and 76.5% respectively in the cohort above median SDI compared to 80.5% and 78.3% below median SDI. Compared to the recipients in low deprivation residential areas, recipients residing in highest deprivation (SDI quintile=5) cohort had 6% higher adjusted risk of mortality (Adjusted Hazard Ratio [AHR]=1.06,95%C.I. 1.01-1.13) and 6% higher risk of graft failure (AHR=1.06,95% C.I. 1.001-1.11). The increased risks for recipients residing in more vulnerable residential areas were higher (AHR=1.11,95% CI 1.03-1.20 for both death and graft loss) following the first-year post-transplantation. Importantly, overall risk for graft loss associated with SDI was not linear but instead accelerated above the median level of deprivation. DISCUSSION: In the United States, SDOH, as reflected by residential distress, significantly impact 5-year patient and graft survival. The overall effect of residential deprivation are modest, but importantly, results illustrate they are more strongly associated with longer-term follow up and accelerate at higher deprivation levels. Further research is needed to evaluate effective interventions and policies to attenuate disparities in outcomes among recipients in highly disadvantaged areas.

Psychosocial evaluation of living liver donors-State of current practices in the United States.

We surveyed living donor liver transplant programs in the United States to describe practices in the psychosocial evaluation of living donors focused on (1) composition of psychosocial team; (2) domains, workflow, and tools of the psychosocial assessment; (3) absolute and relative mental health-related contraindications to donation; and (4) postdonation psychosocial follow-up. We received 52 unique responses, representing 33 of 50 (66%) of active living donor liver transplant programs. Thirty-one (93.9%) provider teams included social workers, 22 (66.7%) psychiatrists, and 14 (42.4%) psychologists. Validated tools were rarely used, but domains assessed were consistent. Respondents rated active alcohol (93.8%), cocaine (96.8%), and opioid (96.8%) use disorder, as absolute contraindications to donation. Active suicidality (97%), self-injurious behavior (90.9%), eating disorders (87.9%), psychosis (84.8%), nonadherence (71.9%), and inability to cooperate with the evaluation team (78.1%) were absolute contraindications to donation. There were no statistically significant differences in absolute psychosocial contraindications to liver donation between geographical areas or between large and small programs. Programs conduct postdonation psychosocial follow-up (57.6%) or screening (39.4%), but routine follow-up of declined donors is rarely conducted (15.8%). Psychosocial evaluation of donor candidates is a multidisciplinary process. The structure of the psychosocial evaluation of donors is not uniform among programs though the domains assessed are consistent. Psychosocial contraindications to living liver donation vary among the transplant programs. Mental health follow-up of donor candidates is not standardized.

Practice patterns of the medical evaluation of living liver donors in the United States.

Living donor liver transplantation (LDLT) can help address the growing organ shortage in the United States, yet little is known about the current practice patterns in the medical evaluation of living liver donors. We conducted a 131-question survey of all 53 active LDLT transplant programs in the United States to assess current LDLT practices. The response rate was 100%. Donor acceptance rate was 0.33 with an interquartile range of 0.33-0.54 across all centers. Areas of high intercenter agreement included minimum age cutoff of 18 years (73.6%) and the exclusion of those with greater than Class 1 obesity (body mass index, 30.0-34.9 m/kg 2 ) (88.4%). Diabetes mellitus was not an absolute exclusion at most centers (61.5%). Selective liver biopsies were performed for steatosis or iron overload on imaging (67.9% and 62.3%, respectively) or for elevated liver enzymes (60.4%). Steatohepatitis is considered an exclusion at most centers (84.9%). The most common hypercoagulable tests performed were factor V Leiden (FVL) (88.5%), protein C (73.1%), protein S (71.2%), antithrombin III (71.2%) and prothrombin gene mutation (65.4%). At 41.5% of centers, donors were allowed to proceed with donation with FVL heterozygote status. Most programs discontinue oral contraceptive pills at least 28 days prior to surgery. At most centers, the need for cardiovascular ischemic risk testing is based on age (73.6%) and the presence of one or more cardiac risk factors (68.0%). Defining areas of practice consensus and variation underscores the need for data generation to develop evidence-based guidance for the evaluation and risk assessment of living liver donors.

The use of nondirected donor organs in living donor liver transplantation: Perspectives and guidance.

Interest in anonymous nondirected living organ donation is increasing in the United States and a small number of transplantation centers are accumulating an experience regarding nondirected donation in living donor liver transplantation. Herein, we review current transplant policy, discuss emerging data, draw parallels from nondirected kidney donation, and examine relevant considerations in nondirected living liver donation. We aim to provide a consensus guidance to ensure safe evaluation and selection of nondirected living liver donors and a schema for just allocation of nondirected grafts.

Current approach to health care transition and integration into adult care for pediatric liver transplant recipients: A call for partnership.

Despite the increased risk of non-adherence, allograft rejection, and mortality following transfer from pediatric to adult care in liver transplantation (LT), there is no standardized approach to health care transition (HCT). Two electronic national surveys were developed and distributed to members of the Society for Pediatric Liver Transplantation and all adult LT programs in the United States to examine current HCT practices. Responses were received from 40 pediatric and 79 adult centers. Pediatric centers were more likely to focus on HCT noting the presence of a transition/transfer policy (60.2% vs. 39.2%), transition clinic (51.6% vs. 16.5%), and the routine use of transition readiness assessment tools (54.8% vs. 10.2%). Perceived barriers to HCT were similar among pediatric and adult respondents and included patient willingness to transfer and participate in care, failure to show for appointments, and lack of sufficient time and staffing. These results highlight the need for an increased awareness of HCT at both pediatric and adult LT centers. The path to improvement requires a partnership between pediatric and adult providers. Recognizing the importance of a comprehensive HCT program initiated in pediatrics and continued throughout young adulthood with ongoing support by the adult team is essential.

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.

Can non-directed living liver donation help improve access to grafts and correct socioeconomic disparities in pediatric liver transplantation?

BACKGROUND: Each year, children die awaiting LT as the demand for grafts exceeds the available supply. Candidates with public health insurance are significantly less likely to undergo both deceased donor LT and D-LLD LT. ND-LLD is another option to gain access to a graft. The aim of this study was to evaluate if recipient insurance type is associated with likelihood of D-LLD versus ND-LLD LT. METHODS: The SRTR/OPTN database was reviewed for pediatric LDLT performed between January 1, 2014 (Medicaid expansion era) and December 31, 2019 at centers that performed ≥1 ND-LLD LDLT during the study period. A multivariable logistic regression was performed to assess relationship between type of living donor (directed vs. non-directed) and recipient insurance. RESULTS: Of 299 pediatric LDLT, 46 (15%) were from ND-LLD performed at 18 transplant centers. Fifty-nine percent of ND-LLD recipients had public insurance in comparison to 40% of D-LLD recipients (p = .02). Public insurance was associated with greater odds of ND-LLD in comparison to D-LLD upon multivariable logistic regression (OR 2.37, 95% CI 1.23-4.58, p = .01). CONCLUSIONS: ND-LLD allows additional children to receive LTs and may help address some of the socioeconomic disparity in pediatric LDLT, but currently account for only a minority of LDLT and are only performed at a few institutions. Initiatives to improve access to both D-LLD and ND-LLD transplants are needed.

Practices and Perceptions of Living Donor Liver Transplantation, Nondirected Donation, and Liver Paired Exchange: A National Survey.

Living donor liver transplantation (LDLT) remains underutilized in the United States. Barriers to LDLT and acceptance of nondirected living liver donation (ND-LLD) and liver paired exchange (LPE) are unclear. The medical and surgical directors of 99 unique transplantation programs (56 LDLT programs and 43 non-LDLT programs) were surveyed to gain insight into perceptions and practices of LDLT and types of donors utilized. The response rate was 84%. Most LDLT programs (65%) reported performing ND-LLD, though opinions regarding allocation and the need for additional evaluation of these donors were mixed. Only a minority of LDLT programs reported performing LPE (12%), but most programs (78%) would be open to cross-institutional LPE barring logistical barriers. There were significant differences between LDLT and non-LDLT programs with regard to perceived barriers to LDLT, with LDLT programs reporting mainly donor and recipient factors and non-LDLT programs reporting institutional factors (P < 0.001). Understanding perceptions and practices of LDLT, ND-LLD, and LPE is important to aid in the growth of LDLT.

Does pre-operative counselling of the donor improve immediate and short-term outcomes after living liver donation? - A review of the literature and expert panel recommendations.

BACKGROUND: There is some evidence in the literature to suggest that pre-operative counselling improves pain scores postoperatively. However, it is unclear whether pre-operative counselling of the donor improves immediate and short-term outcomes after living liver donation. OBJECTIVES: This systematic review aimed to investigate the available quality of evidence (QOE) of pre-operative counselling for living donors on short term outcomes, provide expert opinion, grade recommendations and identify relevant components for Enhanced Recovery after Surgery (ERAS) protocols. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Endpoints were defined by the WHOQOL-BREF scale: physical health, psychological, social relationships, and environment. PROSPERO ID: CRD42021260677. RESULTS: Screening of 452 records and full texts led to 12 articles matching inclusion criteria, of which one was a randomized controlled trial (RCT), and 11 were observational retrospective cohort studies. A total of 933 individuals undergoing donor hepatectomy were included, of whom only 90 received dedicated perioperative ERAS protocols. Donors that received pre-operative counselling had fewer physical symptoms post donation, lower rates of fatigue, lower rates of pain, shorter recovery times and fewer unexpected medical problems, and less anxiety post donation. Female donors had higher affective and adverse effects scores, and 50% of donors reported adverse effects to analgesia that interfered with functional activity. Receiving information about analgesic options increased perception of care among donors. CONCLUSIONS: Providing comprehensive pre-operative counselling to living liver donors is associated with improved short-term outcomes after donation (QOE; moderate to low I Grade of Recommendation; Strong).

Health-related quality of life after anonymous nondirected living liver donation: A multicenter collaboration.

Literature on living nondirected liver donation is sparse. The purpose of this study was to assess health-related quality of life (HR-QOL) in anonymous nondirected living liver donors (ND-LLDs). ND-LLDs at 3 centers: University of Alberta (n = 12), University of Colorado (n = 12), and University of Southern California (n = 12), were surveyed. Thirty donors (83%) responded to the Donor Quality of Life (USC DQLS) and Short-Form 36 (SF-36). Most respondents (n = 15, 50%) donated their left lateral segment, 27% right lobe, and 23% left lobe. The majority were female (67%) and mean age was 38.9 ± 11.2 years at donation. Median follow-up was 1.1 (interquartile range 0.4-3.3) years. Approximately 37% had previously donated a kidney. Eleven experienced ≥1 postoperative complication, with only 1 Clavien-Dindo IIIb. Most reported minimal impact on school or work performance, all felt positive or neutral about their overall health since donation, and none expressed postdonation regrets. No donor reported impacts on health insurability, and 3 of 4 respondents attempting to purchase life insurance postdonation were successful. ND-LLD SF-36 outcomes were similar to US population norms. Overall, ND-LLDs demonstrated acceptable HR-QOL after donation and are appropriate candidates for partial liver donation. Based on evaluation of donation impact, consideration should be given to postdonation support strategies.

Challenging the Traditional Paradigm of Supply and Demand in Pediatric Liver Transplantation Through Nondirected Living Donation: A Case Series.

A gap exists between the demand for pediatric liver transplantation and the supply of appropriate size-matched donors. We describe our center's experience with pediatric liver transplantation using anonymous nondirected living liver donors (ND-LLD). First-time pediatric liver transplant candidates listed at our center between January 2012 and June 2020 were retrospectively reviewed and categorized by donor graft type, and recipients of ND-LLD grafts were described. A total of 13 ND-LLD pediatric liver transplantations were performed, including 8 left lateral segments, 4 left lobes, and 1 right lobe. Of the ND-LLD recipients, 5 had no directed living donor evaluated, whereas the remaining 8 (62%) had all potential directed donors ruled out during the evaluation process. Recipient and graft survival were 100% during a median follow-up time of 445 (range, 70-986) days. Of ND-LLDs, 69% were previous living kidney donors, and 1 ND-LLD went on to donate a kidney after liver donation. Of the ND-LLDs, 46% were approved prior to the recipient being listed. Over time, the proportion of living donor transplants performed, specifically from ND-LLDs, increased, and the number of children on the waiting list decreased. The introduction of ND-LLDs to a pediatric liver transplant program can expand the benefit of living donor liver transplantation to children without a suitable directed living donor while achieving excellent outcomes for both the recipients and donors.

Pregnancy Outcomes After Living Liver Donation: A Multi-Institutional Study.

Nearly half of living liver donors in North America are women of child-bearing age. Fetal and maternal outcomes after donation are unknown. We conducted a retrospective cohort study of female living liver donors (aged 18-50 years at donation) from 6 transplant centers. Participants were surveyed about their pregnancies and fertility. Outcomes were compared between predonation and postdonation pregnancies. Generalized estimating equations were clustered on donor and adjusted for age at pregnancy, parity, and pregnancy year. Among the 276 donors surveyed, 151 donors responded (54.7% response rate) and reported 313 pregnancies; 168/199 (68.8%) of the predonation pregnancies and 82/114 (71.9%) of the postdonation pregnancies resulted in live births, whereas 16.6% and 24.6% resulted in miscarriage, respectively. Women with postdonation pregnancies were older (32.0 versus 26.7 years; P < 0.001) and more frequently reported abnormal liver enzymes during pregnancy (3.5% versus 0.0%; P = 0.02) and delivery via cesarean delivery (35.4% versus 19.7%; P = 0.01). On adjusted analysis, there was no difference in cesarean delivery (odds ratio [OR], 2.44; 95% confidence interval [95% CI], 0.98-6.08), miscarriage (OR, 1.59; 95% CI, 0.78-3.24), combined endpoints of pregnancy-induced hypertension and preeclampsia (OR, 1.27; 95% CI, 0.36-4.49), or intrauterine growth restriction and preterm birth (OR, 0.91; 95% CI, 0.19-4.3). Of the 49 women who attempted pregnancy after donation, 11 (22.5%) self-reported infertility; however, 8/11 (72.7%) eventually had live births. Aside from increased reporting of abnormal liver enzymes and cesarean deliveries, there was no significant difference in pregnancy outcomes before and after living liver donation. One-fifth of women who attempt pregnancy after liver donation reported infertility, and although the majority went on to successful live births, further exploration is needed to understand the contributing factors. Future research should continue to monitor this patient-centered outcome across a large cohort of donors.

Provider Attitudes and Practice Patterns for Direct-Acting Antiviral Therapy for Patients With Hepatocellular Carcinoma.

BACKGROUND & AIMS: Direct-acting antivirals (DAAs) are effective against hepatitis C virus and sustained virologic response is associated with reduced incidence of hepatocellular carcinoma (HCC). However, there is controversy over the use of DAAs in patients with active or treated HCC and uncertainty about optimal management of these patients. We aimed to characterize attitudes and practice patterns of hepatology practitioners in the United States regarding the use of DAAs in patients with HCC. METHODS: We conducted a survey of hepatology providers at 47 tertiary care centers in 25 states. Surveys were sent to 476 providers and we received 279 responses (58.6%). RESULTS: Provider beliefs about risk of HCC recurrence after DAA therapy varied: 48% responded that DAAs reduce risk, 36% responded that DAAs do not change risk, and 16% responded that DAAs increase risk of HCC recurrence. However, most providers believed DAAs to be beneficial to and reduce mortality of patients with complete response to HCC treatment. Accordingly, nearly all providers (94.9%) reported recommending DAA therapy to patients with early-stage HCC who received curative treatment. However, fewer providers recommended DAA therapy for patients with intermediate (72.9%) or advanced (57.5%) HCC undergoing palliative therapies. Timing of DAA initiation varied among providers based on HCC treatment modality: 49.1% of providers reported they would initiate DAA therapy within 3 months of surgical resection whereas 45.9% and 5.0% would delay DAA initiation for 3-12 months and >1 year post-surgery, respectively. For patients undergoing transarterial chemoembolization (TACE), 42.0% of providers would provide DAAs within 3 months of the procedure, 46.7% would delay DAAs until 3-12 months afterward, and 11.3% would delay DAAs more than 1 year after TACE. CONCLUSIONS: Based on a survey sent to hepatology providers, there is variation in provider attitudes and practice patterns regarding use and timing of DAAs for patients with HCC. Further studies are needed to characterize the risks and benefits of DAA therapy in this patient population.

Successful liver transplantation in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE).

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a fatal disorder characterized by progressive gastrointestinal dysmotility, peripheral neuropathy, leukoencephalopathy, skeletal myopathy, ophthalmoparesis, and ptosis. MNGIE stems from deficient thymidine phosphorylase activity (TP) leading to toxic elevations of plasma thymidine. Hematopoietic stem cell transplant (HSCT) restores TP activity and halts disease progression but has high transplant-related morbidity and mortality. Liver transplant (LT) was reported to restore TP activity in two adult MNGIE patients. We report successful LT in four additional MNGIE patients, including a pediatric patient. Our patients were diagnosed between ages 14 months and 36 years with elevated thymidine levels and biallelic pathogenic variants in TYMP. Two patients presented with progressive gastrointestinal dysmotility, and three demonstrated progressive peripheral neuropathy with two suffering limitations in ambulation. Two patients, including the child, had liver dysfunction and cirrhosis. Following LT, thymidine levels nearly normalized in all four patients and remained low for the duration of follow-up. Disease symptoms stabilized in all patients, with some manifesting improvements, including intestinal function. No patient died, and LT appeared to have a more favorable safety profile than HSCT, especially when liver disease is present. Follow-up studies will need to document the long-term impact of this new approach on disease outcome. Take Home Message: Liver transplantation is effective in stabilizing symptoms and nearly normalizing thymidine levels in patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) and may have an improved safety profile over hematopoietic stem cell transplant.

Toxoplasmosis in non-cardiac solid organ transplant recipients: A case series and review of literature.

The risk of toxoplasmosis in high-risk cardiac transplant recipients is well recognized prompting universal donor and candidate screening with administration of targeted post-transplant chemoprophylaxis in high-risk (D+/R-) cardiac transplant patients. In contrast, until recently, there have been neither well-defined recommendations nor consensus regarding toxoplasmosis preventive strategies among non-cardiac solid organ transplant recipients. We report 3 cases of post-transplant toxoplasmosis in non-cardiac transplant recipients (one lung and two liver); all 3 infections presumed to be donor-derived. Not surprisingly, pre-transplant Toxoplasma serology was negative in all the patients. None of the patients were on trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis at the time of diagnosis of toxoplasmosis. The median time from transplant to onset of infection was 90 days (range: 30-120 days). Clinical presentations included cerebral (n = 1) and disseminated infections (n = 2). Two of the 3 patients, both with disseminated infection died (mortality ~ 67%).

Successful non-directed living liver donor transplant for an infant with biliary atresia during the COVID-19 pandemic.

Amidst the coronavirus (COVID-19) pandemic, the American Society for Transplant Surgeons has recommended that only urgent liver transplant with deceased donors should occur. However, young pediatric candidates rely on living donors for lifesaving transplant. We present a case of non-directed left lateral lobe living liver donor transplant for a 7-month-old child with biliary atresia experiencing repeated life-threatening episodes of sepsis and cholangitis from infected bile lakes. Using careful preoperative planning among the entire multidisciplinary team, paying meticulous attention to infection control pre- and post-operatively, and taking advantage of robust telehealth technology both in and out of the hospital, a successful transplant was achieved. Amidst the COVID pandemic, non-directed liver transplantation can be safely achieved for pediatric recipients.