Faculty Bibliography

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.

BACKGROUND:In 2017, the American College of Gastroenterology (ACG) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition published clinical guidelines recommending the use of alanine aminotransferase (ALT) upper reference limits (URL) of 33, 25, 26, and 22 U/l for men, women, boys, and girls, respectively. This was opposed by laboratory experts who advocated for the use of higher URL of 59, 41, 33, and 24 U/l instead. We suspected that the variable inclusion of individuals who consumed alcohol to be a major contributing source of URL variability and debate. METHODS:Outpatient ALT data (n = 7379) were collected from unique individuals ≥13 y with BMIs of ≥19 and ≤25. A total of 222 (3%) were excluded due to suspected liver disease. Patients were split into a pediatric group (age 13-17 y), an alcohol-restricted adult group (age 18-20 y), and adults with access to alcohol by decade (i.e., age 21-29, 30-39, 40-49, 50-59, 60-69, 70-79, and ≥ 80 y). All ALT values were measured on Roche Cobas 8000 with pyridoxal phosphate and traceable to the IFCC-reference measurement procedure. RESULTS:We derived URL similar to CALIPER for our pediatric population, but closer to ACG-proposed URL in our alcohol-restricted adult group. The URL increased significantly in men and women for all other age groups. CONCLUSIONS:The discrepancy in ALT URL in clinical laboratories may be attributable in part due to the variable inclusion of individuals who recently consumed alcohol in local population derivation studies.

The COVID-19 pandemic and social justice movement have highlighted the impact of social determinants of health (SDOH) and structural racism in the United States on both access to care and patient outcomes. With the evaluation for liver transplantation being a highly subjective process, there are multiple ways for SDOH to place vulnerable patients at a disadvantage. This policy corner focuses on three different methods to reverse the deleterious effects of SDOH-identify and reduce implicit bias, expand and optimize telemedicine, and improve community outreach.

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.

Frailty, a global impairment of multiple organ systems resulting in increased vulnerability to health stressors, is common in end-stage liver disease, multifactorial in etiology, and impacts overall mortality as well as outcomes in liver transplantation. This is a review of the currently available data, a synopsis of expert consensus, and a framework for transplant centers to approach frailty. We suggest that centers use a multidisciplinary team of healthcare providers and approach frailty in a programmatic fashion to provide effective patient care and ensure optimal transplant outcomes. The utilization of standardized protocols to address both malnutrition and physical debility is ideal and can help ensure safety. A toolbox of resources has been made available by experts in the field to facilitate this approach. The incorporation of new technology tailored to overcome barriers is another resource under investigation.

During the coronavirus 2019 pandemic we converted our liver transplant waitlist candidate education and support program to a virtual format and expanded it to include ongoing engagement sessions aimed to educate and empower patients to maximize opportunity for live donor liver transplantation. Over a period of 6 months from April 2020 to Sept 2020 we included 21 patients in this pilot quality improvement program. We collected data regarding patient response and potential donor referral activity. Overall, patient response was positive, and some patients saw progress toward live donor liver transplantation by fostering inquiry of potential live liver donors. Optimization of logistical aspects of the program including program flow, technology access, and utilization is required to enhance patient experience. Long-term follow-up is needed to assess impact on the outcome of transplantation rates. Future data collection and analysis should focus on assessment of any potential disparity that may result from utilization of virtual programming. Herein we provide a framework for this type of virtual program and describe our experience.

BACKGROUND:Fontan circulation alters portal venous hemodynamics, causing chronic passive hepatic congestion and fibrosis. This congestion increases liver stiffness (LS) leading to overestimates of liver fibrosis as measured by ultrasound shear wave elastography (SWE) of the liver. We evaluated whether Fontan circulation has a similar effect on spleen stiffness (SS) and SS/LS ratio as measured by SWE. METHODS:We retrospectively compared the SS of adult Fontan patients to age and gender matched, control patients without congenital heart disease. We correlated SS measurements to LS measurements and also performed a limited subgroup analysis of SS in Fontan patients with various manifestations of Fontan Associated Liver Disease. RESULTS:SS in Fontan patients was similar to healthy controls (1.43 vs. 1.36 m/s, p = 0.26). LS was elevated in 78% of the Fontan patients (mean 1.68 m/s, SD 0.31, 95% CI 1.53-1.85). The correlation between LS and SS was modest (Pearson's correlation coefficient, r = 0.5) but did not reach statistical significance (p = 0.06). The mean SS/LS ratio was 0.85 (95% CI 0.77-0.94). CONCLUSION:Based on our study cohort, SS in Fontan patients is similar to age and gender matched control patients without congenital heart disease. The SS/LS ratio, however, is frequently less than 1, which is lower than that reported in both healthy patients and those with other forms of non-cardiac liver disease. SS and SS/LS ratio may be a useful indicator of portal hemodynamics in Fontan patients.