Female Hispanic Health Disparities in Orthotopic Liver Transplantation During Ischemia-Reperfusion Injury. (July 2018)

• Record Type: Journal Article
• Authors: Sosa, Rebecca A; Nevarez-Mejia, Jessica; Rossetti, Maura; Kaldas, Fady M; Datta, Nakul; Zarrinpar, Ali; Lassman, Charles R; Naini, Bita V; Busuttil, Ronald W; Gjertson, David W; Kupiec-Weglinski, Jerzy W; Reed, Elaine F
• Is Part Of: Transplantation. Volume 102(2018)Supplement 7S-1
• Publication Date: 2018-07
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; Transplantation immunology -- Periodicals; 617.95
• DOI: 10.1097/01.tp.0000543023.01197.f0
• Languages: English
• ISSNs: 0041-1337

Abstract

Abstract : Obesity and the metabolic syndrome have become a worldwide epidemic with Hispanics bearing a disproportionate burden. Nonalcoholic fatty liver disease (NAFLD) is the most common liver pathology associated with obesity, diabetes and metabolic syndrome. NAFLD includes the whole spectrum of fatty liver, ranging from simple steatosis to steatohepatitis (NASH) which can progress to liver cirrhosis and end-stage liver disease (ESLD) requiring orthotopic liver transplant (OLT) for survival. It is not well understood why some patients progress and others do not, however NASH is linked to a 50% higher death rate compared with NAFLD. Hispanics in the US have the highest prevalence of ESLD due to NAFLD (58.3% vs. 44.4%), as well as its most clinically-relevant subset of patients, those with NASH (19.4% vs. 9.8%) and are particularly at risk for requiring OLT. OLT success is hampered by cellular damage elicited by ischemia-reperfusion injury (IRI) which lowers both short-and long-term allograft survivals. There is growing experimental and clinical evidence that recipient steatosis exacerbates the mechanisms of injury related to IRI, and therefore may be a major contributing factor to racial and ethnic disparities related to OLT. Therefore, we investigated IRI, recipient steatosis, and OLT outcomes in a cohort of Hispanic NASH OLT recipients at our center. Over the past three years we have enrolled 104 OLT recipients in our IRB-approved study, 19 of which were diagnosed with NASH that contributed to their ESLD requiring OLT (18%). Of these patients, 9 had biopsy-proven IRI (50% IRI+), and 9 did not (50% IRI-), based on the presence of necrotic hepatocytes and inflammatory infiltrates. Of note, 6/9 IRI+ patients with NASH were Hispanic (67%), but only 2/9 IRI- NASH patients were Hispanic (22%). Additionally, most Hispanic NASH patient biopsies already exhibited large-droplet macrovesicular steatosis in hepatocytes at 2 hours post-reperfusion (5/8=63%) whereas only 1/11 of the Non-Hispanic NASH patients had macrovesicular steatosis by this early time point (9%). In the first year post-transplant, most Hispanic NAFLD/NASH patients required for-cause biopsies (6/8=75%) and had worse outcomes than Non-Hispanics, including ACR, AMR, chronic IRI and NASH whereas only 9% of Non-Hispanics (1/11) required a for-cause biopsy and had HCV at the time of biopsy. Interestingly, despite our overall cohort being predominantly male (69/104=66%), Hispanic NASH OLT-IRI patients with for-cause biopsies associated with worsened outcomes were almost entirely female (5/6=83%). Taken together, female Hispanics with NASH in our OLT cohort disproportionately suffered from IRI leading to worsened outcomes within the first year post-transplant. As such, reduction of IRI risk factors should be considered in Hispanics with NASH requiring OLT, particularly females. Ruth L. Kirschstein National Research Service Award T32CA009120 (RAS). NIH Health Disparities LRP Award MPEG6329 (RAS). NIH PO1 AI120944 (JWKW and EFR).