scholarly journals Plasma oxylipin profile discriminates ethnicities in subjects with Non-alcoholic steatohepatitis: An exploratory analysis

2021 ◽  
Author(s):  
Tagreed A. Mazi ◽  
Kamil Borkowski ◽  
Oliver Fiehn ◽  
Christopher L. Bowlus ◽  
Souvik Sarkar ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Secondary Analysis ◽  
Arachidonic Acid Metabolism ◽  
Lipid Mediators ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Chain Pufa ◽  
Healthy Control ◽  
Underlying Causes ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) includes a range of liver pathologies from steatosis (NAFL) to non-alcoholic steatohepatitis (NASH). With no clear mechanism, it affects Hispanics in the U.S. disproportionately compared to other ethnicities. Polyunsaturated fatty acids (PUFAs) metabolism and downstream inflammatory lipid mediators including oxylipin (OXL) and endocannabinoid (eCB) are altered in NAFLD and thought to contribute to its pathogenesis. It is not clear if variations in PUFA metabolism and downstream lipid mediators characterize ethnicity in NAFLD. This pilot study employed targeted lipidomic profiling for plasma PUFAs, non-esterified OXLs and eCBs in White Hispanics (HIS, n =10) and Caucasians (CAU, n =8) with obesity and biopsy-confirmed NAFL, compared with healthy control subjects (HC; n =14 HIS; n =8 CAU). Results indicate diminished long chain PUFA profile in HIS with NAFL and NASH, independent of obesity and histological severity. The profiling data also detected differences in plasma OXLs and eCBs profiles by ethnicity group in NASH, including lower levels of arachidonic acid derived OXLs observed in HIS. We conducted a secondary analysis to compare ethnicities within NASH (n =12 HIS; n =17 CAU). Results showed that plasma OXL profiles distinguished ethnicities with NASH and confirmed ethnicity-related differences in arachidonic acid metabolism. Our data also suggest lower lipoxygenase(s) and higher soluble epoxide hydrolase(s) activities in HIS compared to CAU with NASH. The underlying causes and implications of these differences on NAFLD severity are not clear and worth further investigation. Our findings provide preliminary data suggesting ethnicity-specific plasma lipidomic signature characterizing NASH that requires validation.

Prevalence, diagnosis and treatment with 3 different statins of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in military personnel. Do genetics play a role?

2020 ◽  
Vol 18 ◽  
Author(s):  
Georgios Sfikas ◽  
Michael Psallas ◽  
Charalambos Koumaras ◽  
Konstantinos Imprialos ◽  
Evangelos Perdikakis ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Military Personnel ◽  
Fatty Liver Disease ◽  
Exercise Group ◽  
Severe Form ◽  
Laboratory Evaluation ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Alcoholic Fatty Liver Disease

Background: Non-alcoholic fatty liver disease (NAFLD) and its severe form, non-alcoholic steatohepatitis (NASH), are major health problems worldwide. Genetics may play a role in the pathogenesis of NAFLD/NASH. Aim: To investigate the prevalence of NAFLD/NASH in 5,400 military personnel and evaluate the effect of treatment with 3 statins on NAFLD/NASH using 2 non-invasive scores [NAFLD Activity Score (NAS); Fibrosis-4 score (FIB-4)]. Methods: During the mandatory annual medical check-up, military personnel underwent a clinical and laboratory evaluation. Participants with NAFLD/NASH were randomised to 4 groups (n=151 each): dietexercise, atorvastatin, rosuvastatin or pitavastatin for 1 year (i.e. until the next routine evaluation). Results: From all the participants, 613 had NAFLD/NASH (prevalence 11.3 vs 39.8% in the general population, p<0.001); 604 consented to participate in the study. After a year of treatment, the diet-exercise group showed no significant changes in both scores (NAS 4.98 baseline vs 5.62, p=0.07; FIB-4 3.42 vs 3.52, p=0.7). For the atorvastatin group, both scores were reduced (NAS 4.97 vs 1.95, p<0.001, FIB-4 3.56 vs 0.83, p<0.001), for rosuvastatin (NAS 5.55 vs 1.81, p<0.001, FIB-4 3.61 vs 0.79, p<0.001), and for pitavastatin (NAS 4.89 vs 1.99, p<0.001, FIB-4 3.78 vs 0.87, p<0.001). Conclusions : Atorvastatin, rosuvastatin and pitavastatin have a beneficial and safe effect in NAFLD/NASH patients as recorded by the improvement in the NAS (representing NAFLD activity) and FIB-4 (representing liver fibrosis) scores. Since both those with and without NAFLD/NASH shared several baseline characteristics, genetics may play a role in the pathogenesis of NAFLD/NASH and its treatment with statins.

scholarly journals Natural Progression of Non-Alcoholic Steatohepatitis to Hepatocellular Carcinoma

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 184
Author(s):  
Daryl Ramai ◽  
Waqqas Tai ◽  
Michelle Rivera ◽  
Antonio Facciorusso ◽  
Nicola Tartaglia ◽  
...  
Keyword(s):  
Public Health ◽  
Hepatocellular Carcinoma ◽  
Lipid Peroxidation ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Natural Progression ◽  
Public Health Threat ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic steatohepatitis (NASH) is a chronic and progressive form of non-alcoholic fatty liver disease (NAFLD). Its global incidence is increasing which makes NASH an epidemic and a public health threat. Due to repeated insults to the liver, patients are at risk for developing hepatocellular carcinoma (HCC). The progression of NASH to HCC was initially defined according to a two-hit model which involved the development of steatosis, followed by lipid peroxidation and inflammation. However, current research defines a “multi-hit” or “multi-parallel hit” model which synthesizes several contributing pathways involved in progressive fibrosis and oncogenesis. This perspective considers the effects of cellular, genetic, immunologic, metabolic, and endocrine pathways leading up to HCC which underscores the complexity of this condition. This article will provide an updated review of the pathogenic mechanisms leading from NASH to HCC as well as an exploration of the role of biomarkers and screening.

scholarly journals The Role of the Histone Methyltransferase EZH2 in Liver Inflammation and Fibrosis in STAM NASH Mice

Biology ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 93 ◽  
Author(s):  
Seul Lee ◽  
Dong-Cheol Woo ◽  
Jeeheon Kang ◽  
Moonjin Ra ◽  
Ki Hyun Kim ◽  
...  
Keyword(s):  
Liver Disease ◽  
Epigenetic Modification ◽  
Treatment Options ◽  
Histone Methyltransferase ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Promising Therapeutic Target ◽  
Alcoholic Fatty Liver Disease ◽  
Potential Therapeutics

Non-alcoholic fatty liver disease (NAFLD) is a leading form of chronic liver disease, with few biomarkers and treatment options currently available. Non-alcoholic steatohepatitis (NASH), a progressive disease of NAFLD, may lead to fibrosis, cirrhosis, and hepatocellular carcinoma. Epigenetic modification can contribute to the progression of NAFLD causing non-alcoholic steatohepatitis (NASH), in which the exact role of epigenetics remains poorly understood. To identify potential therapeutics for NASH, we tested small-molecule inhibitors of the epigenetic target histone methyltransferase EZH2, Tazemetostat (EPZ-6438), and UNC1999 in STAM NASH mice. The results demonstrate that treatment with EZH2 inhibitors decreased serum TNF-alpha in NASH. In this study, we investigated that inhibition of EZH2 reduced mRNA expression of inflammatory cytokines and fibrosis markers in NASH mice. In conclusion, these results suggest that EZH2 may present a promising therapeutic target in the treatment of NASH.

scholarly journals Portal lymphadenopathy predicts non-alcoholic steatohepatitis and advanced fibrosis in non-alcoholic fatty liver disease

PLoS ONE ◽  
2018 ◽  
Vol 13 (11) ◽  
pp. e0207479 ◽  
Author(s):  
Saleh Daher ◽  
Namma Lev Cohen ◽  
Muhammad Massarwa ◽  
Mahmud Mahamid ◽  
Mira Nasser ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Advanced Fibrosis ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Alcoholic Fatty Liver Disease
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