Annette C. and Harold C. Simmons Transplant Institute

Fallahzadeh, M. A. and R. S. Rahimi (2019). “Hepatic Encephalopathy and Nutrition Influences: A Narrative Review.” Nutr Clin Pract Dec 23. [Epub ahead of print].

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Hepatic encephalopathy (HE) is a potentially reversible neurocognitive condition seen in patients with advanced liver disease. The overt form of HE has been reported in up to 45% of patients with cirrhosis. This debilitating condition is associated with increased morbidity and mortality and imposes a significant burden on the caregivers and healthcare system. After providing an overview of HE epidemiology and pathophysiology, this review focuses on the interaction of HE and frailty, nutrition requirements and recommendations in cirrhotic patients with HE, and current dietary and pharmacologic options for HE treatment.

Ramani, A., G. Testa, Y. Ghouri, E. C. Koon, M. Di Salvo, G. J. McKenna, J. Bayer, A. M. Warren, A. Wall and L. Johannesson (2019). “DUETS (Dallas UtErus Transplant Study):Complete report of 6-month and initial 2-year outcomes following open donor hysterectomy.” Clin Transplant Nov 22. [Epub ahead of print].

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INTRODUCTION: Uterus transplantation has shown success in treating women with uterine-factor infertility who want to carry their own pregnancy. METHODS: We report the medical, sexual, and psychological outcomes of our first cohort of 13 living-donor hysterectomies. As we have transitioned from open to robotically assisted hysterectomy, this report represents the complete series of open-donor hysterectomies at our center, all with >/=6-month postoperative outcomes. RESULTS: The open donor hysterectomy had a median of a 6.5-hour surgical time, 0.8 L estimated blood loss, 6-day hospital stay, and 28-day sick leave. Three donors had a grade III or IV complications, one reported new-onset psychological symptoms, and 9 experienced transient sexual discomfort. All complications were addressed and resolved, and all donors returned to their presurgical social and physical activities. CONCLUSION: Since uterus transplantation is not life-saving or life-extending, the risks in living uterus donation must be weighed against the benefit of giving another woman the opportunity to give birth to her own child. This report provides data to support more detailed informed consent regarding the medical, psychological, and sexual complications of open living donor hysterectomy and allows for further evaluation of the ethical acceptability of this procedure.

Kristek, J., L. Johannesson, G. Testa, R. Chmel, M. Olausson, N. Kvarnstrom, N. Karydis and J. Fronek (2019). “Limited Availability of Deceased Uterus Donors: A Transatlantic Perspective.” Transplantation 103(12): 2449-2452.

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Women with absolute uterine-factor infertility (AUFI) had until recently only the opportunity to have children through adoption, foster parenting, or gestational surrogacy. However, for some women with AUFI, none of these options is possible because of religious, societal, personal, or other reasons. Uterus transplantation (UTx) has recently been introduced as a unique opportunity for both genetic and gestational motherhood. To date, most UTx were accomplished with uterus transplants procured from living donors. Although deceased donor (DD) UTx have been performed successfully, the overall experience remains rare. Notably, most (10/13) DD UTx have been performed by the teams in Dallas, TX and Prague, Czech Republic. Recently, the first baby was born to a recipient after DD UTx in São Paulo, demonstrating proof of concept for DD UTx. DD UTx is desirable, as it avoids risks associated with complex live donor hysterectomies and (2) not every patient in need may have a qualifying living donor available. Thus, it appears critical to analyze the potential of DD UTx. Several unknowns and limitations to this pursuit need to be addressed and include (1) the lack of standardized evaluation criteria of uterus DD (both standard and extended criteria), (2) information on the availability of potential uterus DDs, (3) assuring that potential donors will be identified by organ procurement organizations (OPOs), and (4) issues of consent beyond that taken for the procurement of solid organs for transplantation. Here, we address those issues in a transatlantic approach with an analysis in the Czech Republic, Sweden, the United Kingdom, and the United States. We aimed to roughly approximate the volume of potential uterus donors, demand for transplantation linked to geographical region. Moreover, we suggest criteria allowing OPOs to identify uterus DD and introduce the experience at our institutions on getting consent. (Excerpt from text, p. 2449; no abstract available.)

Ngaage, L. M., S. Ike, A. Elegbede, C. J. Vercler, S. Gebran, F. Liang, E. M. Rada, C. Cooney, G. Brandacher, R. J. Redett, L. Johannesson and Y. M. Rasko (2019). “The Changing Paradigm of Ethics in Uterus Transplantation: A Systematic Review.” Transplant International Nov 1. [Epub ahead of print].

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BACKGROUND: The first uterus transplantation was performed in 2000. As key milestones are reached (longlasting graft survival in 2011, and first birth from a transplanted womb in 2014), the ethical debate around uterus transplant evolves. METHODS: We performed a systematic review of articles on uterus transplantation. Ethical themes were extracted and categorised according to four bioethical principles. Papers were divided into time periods separated by key events in uterus transplant history: Phase I (first technical achievement, 2002-11), Phase II (clinical achievement, 2012-14), and Phase III (after the first childbirth, 2015-18). RESULTS: Eighty-one articles were included. The majority of ethics papers were published in Phase III (65%, p<0.0001), i.e. after the first birth. 80% of papers discussed non-maleficence making it the most discussed principle. The first birth acted as a pivotal point: non-maleficence was discussed by a lower proportion of articles (p=0.0073), as was beneficence (p=0.0309). However, discussion of justice increased to become the most discussed principle of the time period (p=0.0085). CONCLUSIONS: The ethical debate surrounding uterus transplantation has evolved around landmark events that signify scientific progress. As safety and efficacy become evident, the focus of ethical debate shifts from clinical equipoise to socioeconomic challenges and equitable access to uterus transplantation.

Levitsky, J., S. K. Asrani, G. Klintmalm, T. Schiano, A. Moss, K. Chavin, C. Miller, K. Guo, L. Zhao, L. W. Jennings, M. Brown, B. Armstrong and M. Abecassis (2019). “Discovery and Validation of a Biomarker Model (Preserve) Predictive of Renal Outcomes after Liver Transplantation.” Hepatology Sep 11. [Epub ahead of print].

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A high proportion of patients develop chronic kidney disease after liver transplantation. We aimed to develop clinical/protein models to predict future GFR deterioration in this population. In independent multicenter discovery (CTOT14) and single center validation (BUMC) cohorts, we analyzed kidney injury proteins in serum/plasma samples at month 3 after liver transplant in recipients with preserved GFR who demonstrated subsequent GFR deterioration vs. preservation by year 1, and year 5 in the BUMC cohort. In CTOT14, we also examined correlations between serial protein levels and GFR over the first year. A month 3 predictive model was constructed from clinical and protein level variables using the CTOT14 cohort (n=60). Levels of beta2-microglobulin and CD40 antigen and presence of HCV infection predicted early (year 1) GFR deterioration (AUC 0.814). We observed excellent validation of this model (AUC 0.801) in the BUMC cohort (n=50) who had both early and late (year 5) GFR deterioration. At an optimal threshold, the model had the following performance characteristics in CTOT14 and BUMC, respectively: accuracy (0.75, 0.8), sensitivity (0.71, 0.67), specificity (0.78, 0.88), positive predictive value (0.74, 0.75) and negative predictive value (0.76, 0.82). In the serial CTOT14 analysis, several proteins, including beta2-microglobulin and CD40, correlated with GFR changes over the first year. Conclusion: We have validated a clinical/protein model (PRESERVE) that early after liver transplantation can predict future renal deterioration vs. preservation with high accuracy. This model may help select recipients at higher risk for subsequent chronic kidney disease for early, proactive renal sparing strategies.