Background: Nonalcoholic steatohepatitis (NASH) is a severe immune-mediated stage of nonalcoholic fatty liver disease that is rapidly becoming the most common etiology requiring liver transplantation (LT), with Hispanics bearing a disproportionate burden. This study aimed to uncover the underlying immune mechanisms of the disparities experienced by Hispanic patients undergoing LT for NASH.
Methods: We enrolled 164 LT recipients in our institutional review board-approved study, 33 of whom presented with NASH as the primary etiology of LT (20%), with 16 self-reported as Hispanic (48%). We investigated the histopathology of prereperfusion and postreperfusion biopsies, clinical liver function tests, longitudinal soluble cytokines via 38-plex Luminex, and immune cell phenotypes generated by prereperfusion and postreperfusion blood using 14-color flow cytometry and enzyme-linked immunosorbent assay.
Results: Hispanic LT recipients transplanted for NASH were disproportionately female (81%) and disproportionately suffered poor outcomes in the first year posttransplant, including rejection (26%) and death (38%). Clinically, we observed increased pro-inflammatory and apoptotic histopathological features in biopsies, increased AST/international normalized ratio early posttransplantation, and a higher incidence of presensitization to mismatched HLA antigens expressed by the donor allograft. Experimental investigations revealed that blood from female Hispanic NASH patients showed significantly increased levels of leukocyte-attracting chemokines, innate-to-adaptive switching cytokines and growth factors, HMGB1 release, and TLR4/TLR8/TLR9/NOD1 activation, and produced a pro-inflammatory, pro-apoptotic macrophage phenotype with reduced CD14/CD68/CD66a/TIM-3 and increased CD16/CD11b/HLA-DR/CD80.
Conclusions: A personalized approach to reducing immunological risk factors is urgently needed for this endotype in Hispanics with NASH requiring LT, particularly in females.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10593264 | PMC |
| http://dx.doi.org/10.1097/TXD.0000000000001550 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Thyromimetics and MASLD: Unveiling the Novel Molecules Beyond Resmetirom.
J Gastroenterol Hepatol
January 2025
Department of Pharmacology, Hepatology and Molecular Medicine Lab, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, Tamil Nadu, India.
Background: Resmetirom, the first FDA-approved drug for nonalcoholic steatohepatitis (NASH) with fibrosis in obese patients, when combined with lifestyle modifications, improves NASH resolution and reduces fibrosis by at least one stage. Low thyroid hormone (T) levels are linked to a higher risk of developing metabolic dysfunction-associated steatotic liver disease (MASLD). Epidemiological studies have confirmed the positive correlation between hypothyroidism and MASLD.
View Article and Find Full Text PDFAssociation of diet quality scores with risk of metabolic-associated fatty liver disease in Iranian population: a nested case-control study.
J Diabetes Metab Disord
June 2025
Gastroenterology and Liver Disease Research Center, Research Institute for Gastroenterology and Liver Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Background And Aim: A healthy diet has been recommended for non-alcoholic fatty liver disease (NAFLD). We aim to investigate the associations of diet quality indices with the risk of developingmetabolic-associated fatty liver disease (MAFLD).
Methods: We conducted this nested case-control study by recruiting 968 cases with MAFLD and 964 controls from the participants of the baseline phase of the Sabzevar Persian Cohort Study (SPCS).
Balancing anticancer therapy efficacy and safety in advanced hepatocellular carcinoma: a case report.
J Gastrointest Oncol
December 2024
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Background: Hepatocellular carcinoma (HCC) is a significant health problem associated with several risk factors, increasingly driven by non-alcoholic steatohepatitis and metabolic syndrome. This association poses a challenge for the primary treatments of HCC, which may include immune checkpoint inhibitors and vascular endothelial growth factor inhibitors, due to their potential cardiotoxic effect. Therefore, it is imperative to balance the therapeutic effects of these agents with their potential cardiovascular adverse events.
View Article and Find Full Text PDFCorrelation between metabolic dysfunction-associated steatotic liver disease and subclinical coronary atherosclerosis in eastern China.
Diabetol Metab Syndr
January 2025
Department of Radiology, Shanghai Health and Medical Center, No. 67 Dajishan, Binhu District, Wuxi, 214065, China.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by the presence of at least one cardiovascular disease (CVD) risk factor, underscoring its potential to elevate CVD risk in affected individuals. However, evidence linking MASLD to subclinical coronary atherosclerosis remains scarce, and further investigations are necessary to elucidate the independent role of varying MASLD severities as a CVD risk factor.
Methods: This study analyzed 7,507 participants aged ≥ 40 who underwent comprehensive health evaluations at the Shanghai Health and Medical Center.
Design, synthesis and biological evaluation of Alisol B derivatives for potential treatment of non-alcoholic steatohepatitis.
Bioorg Chem
January 2025
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201 China; University of Chinese Academy of Sciences, Beijing 100049 China. Electronic address:
Non-alcoholic fatty liver disease (NAFLD), also known as metabolic dysfunction- associated with fatty liver disease (MAFLD), is one of the most prevalent chronic liver diseases globally. NAFLD is characterized by the accumulation of liver fat unrelated to excessive alcohol consumption. Non-alcoholic steatohepatitis (NASH) is the disease progression of NAFLD and could develop into cirrhosis and hepatocellular carcinoma.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!