Innate Pathways of Immune Activation in Transplantation

Studies of the immune mechanisms of allograft rejection have predominantly focused on the adaptive immune system that includes T cells and B cells. Recent investigations into the innate immune system, which recognizes foreign antigens through more evolutionarily primitive pathways, have demonstrated a critical role of the innate immune system in the regulation of the adaptive immune system. Innate immunity has been extensively studied in its role as the host's first-line defense against microbial pathogens; however, it is becoming increasingly recognized for its ability to also recognize host-derived molecules that result from tissue damage. The capacity of endogenous damage signals acting through the innate immune system to lower immune thresholds and promote immune recognition and rejection of transplant grafts is only beginning to be appreciated. An improved understanding of these pathways may reveal novel therapeutic targets to decrease graft alloreactivity and increase graft longevity

Dangerous dietary supplements: Garcinia cambogia-associated hepatic failure requiring transplantation.

Commercial dietary supplements are marketed as a panacea for the morbidly obese seeking sustainable weight-loss. Unfortunately, many claims cited by supplements are unsupported and inadequately regulated. Most concerning, however, are the associated harmful side effects, often unrecognized by consumers. Garcinia cambogia extract and Garcinia cambogia containing products are some of the most popular dietary supplements currently marketed for weight loss. Here, we report the first known case of fulminant hepatic failure associated with this dietary supplement. One active ingredient in this supplement is hydroxycitric acid, an active ingredient also found in weight-loss supplements banned by the Food and Drug Administration in 2009 for hepatotoxicity. Heightened awareness of the dangers of dietary supplements such as Garcinia cambogia is imperative to prevent hepatoxicity and potential fulminant hepatic failure in additional patients

Gender and Racial Disparity Among Liver Transplantation Professionals: Report of a Global Survey.

Equality, diversity, and inclusion (EDI) are fundamental principles. Little is known about the pattern of practice and perceptions of EDI among liver transplant (LT) providers. International Liver Transplant Society (ILTS) EDI Committee survey around topics related to discrimination, mentorship, and gender. Answers were collected and analyzed anonymously. Worldwide female leadership was also queried via publicly available data. The survey was e-mailed to 1312 ILTS members, 199 responses (40.7% female) were collected from 38 countries (15.2% response rate). Almost half were surgeons (45.7%), 27.6% hepatologists and 26.6% anesthetists. Among 856 LT programs worldwide, 8.2% of leadership positions were held by females, and 22% of division chiefs were female across all specialties. Sixty-eight of respondents (34.7%) reported some form of discrimination during training or at their current position, presumably related to gender/sexual orientation (20.6%), race/country of origin (25.2%) and others (7.1%). Less than half (43.7%) received mentorship when discrimination occurred. An association between female responses and discrimination, differences in compensation, and job promotion was observed. This survey reveals alarmingly high rate of experience with racial and gender disparity, lack of mentorship, and very low rates of female leadership in the LT field and calls to action to equity and inclusion

Addressing the Burden and Management Strategies for Disparities and Inequities Among Liver Transplant Professionals: The ILTS Experience.

Medical professional environments are becoming increasingly multicultural, international, and diverse in terms of its specialists. Many transplant professionals face challenges related to gender, sexual orientation or racial background in their work environment or experience inequities involving access to leadership positions, professional promotion, and compensation. These circumstances not infrequently become a major source of work-related stress and burnout for these disadvantaged, under-represented transplant professionals. In this review, we aim to 1) discuss the current perceptions regarding disparities among liver transplant providers 2) outline the burden and impact of disparities and inequities in the liver transplant workforce 3) propose potential solutions and role of professional societies to mitigate inequities and maximize inclusion within the transplant community

The Role of Surgical Resection and Liver Transplantation for the Treatment of Intrahepatic Cholangiocarcinoma

Intrahepatic cholangiocarcinoma (iCCA) is a rare and complex malignancy of the biliary epithelium. Due to its silent presentation, patients are frequently diagnosed late in their disease course, resulting in poor overall survival. Advances in molecular profiling and targeted therapies have improved medical management, but long-term survival is rarely seen with medical therapy alone. Surgical resection offers a survival advantage, but negative oncologic margins are difficult to achieve, recurrence rates are high, and the need for adequate future liver remnant limits the extent of resection. Advances in neoadjuvant and adjuvant treatments have broadened patient treatment options, and these agents are undergoing active investigation, especially in the setting of advanced, initially unresectable disease. For those who are not able to undergo resection, liver transplantation is emerging as a potential curative therapy in certain cases. Patient selection, favorable tumor biology, and a protocolized, multidisciplinary approach are ultimately necessary for best patient outcomes. This review will discuss the current surgical management of locally advanced, liver-limited intrahepatic cholangiocarcinoma as well as the role of liver transplantation for select patients with background liver disease

Liver transplantation and sleeve gastrectomy in the medically complicated obese: New challenges on the horizon.

In the last 30 years, operative, technical and medical advances have made liver transplantation (LT) a life-saving therapy that is used worldwide today. Global industrialization has been a contributor to morbid obesity and this has brought about the metabolic syndrome along with many downstream complications of such. Non-alcoholic steatohepatitis (NASH) has become a recognized hepatic manifestation of the metabolic syndrome and NASH cirrhosis is predicted to be the primary indication for LT in the United States by 2025. Several case series and database reviews have begun analyzing the efficacy of weight reduction surgery in the LT recipient. These data have reasonably demonstrated that weight reduction surgery in the LT recipient is a feasible endeavor. However, several questions have been raised regarding the type of weight reduction surgery, timing of surgery in relation to LT, patient and allograft survival and post-LT maintenance of weight loss to name a few. We look forward to a time when weight reduction surgery will work to improve the technical conduct of LT, improve perioperative benchmarks such as blood transfusions, intensive care unit length of stay and help to prevent recurrence of NASH cirrhosis in the medically complicated obese patient. In the meantime, well-designed prospective clinical trials that focus on the issues highlighted will help guide us in the care of these complicated patients who will soon account for the majority of the patients in our clinics

Equitable Access to Liver Transplant: Bridging the Gaps in the Social Determinants of Health

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/170891/1/hep31986_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/170891/2/hep31986.pd

Equitable access to liver transplant: Bridging the gaps in the social determinants of health

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/170891/1/hep31986_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/170891/2/hep31986.pd