Innate and Adaptive Immunity Alterations in Metabolic Associated Fatty Liver Disease and Its Implication in COVID-19 Severity.

The coronavirus infectious disease 2019 (COVID-19) pandemic has hit the world, affecting health, medical care, economies and our society as a whole. Furthermore, COVID-19 pandemic joins the increasing prevalence of metabolic syndrome in western countries. Patients suffering from obesity, type II diabetes mellitus, cardiac involvement and metabolic associated fatty liver disease (MAFLD) have enhanced risk of suffering severe COVID-19 and mortality. Importantly, up to 25% of the population in western countries is susceptible of suffering from both MAFLD and COVID-19, while none approved treatment is currently available for any of them. Moreover, it is well known that exacerbated innate immune responses are key in the development of the most severe stages of MAFLD and COVID-19. In this review, we focus on the role of the immune system in the establishment and progression of MAFLD and discuss its potential implication in the development of severe COVID-19 in MAFLD patients. As a result, we hope to clarify their common pathology, but also uncover new potential therapeutic targets and prognostic biomarkers for further research.

Bacterial antigen translocation and age as BMI-independent contributing factors on systemic inflammation in NAFLD patients.

BACKGROUND & AIMS: Low-grade systemic inflammation is a crucial landmark in NAFLD favouring disease progression and comorbidities. We evaluated the input of circulating bacterial antigens on systemic markers of inflammation in NAFLD patients. PATIENTS & METHODS: Multicenter cross-sectional study including consecutive patients with biopsy-proven NAFLD. Demographic, metabolic and fibrosis-related variables were collected. Circulating bacterial antigens were quantified in blood. Toll-like receptor SNPs were genotyped. Serum cytokine levels were evaluated. Peripheral blood mononuclear cell response to bacterial antigens was evaluated in vitro. RESULTS: Three hundred and fifteen patients from five Spanish hospitals were distributed by BMI. At least, one bacterial antigenic type was found in 66 patients with BMI < 30 (63.4%) and 163 patients with BMI > 30 (77.3%) (P = .014). HOMA-IR was significantly higher in the presence of circulating antigens among patients with BMI < 30. NASH and significant fibrosis in non-obese patients were more frequent in the presence of at least two circulating antigenic types. Allelic frequencies of TLR variants were similar to controls and did not affect clinical or laboratory parameters. Pro-inflammatory cytokines were significantly increased in patients with bacterial antigens, regardless of BMI. TLR gene and protein expression levels were significantly increased in PBMCs from patients with bacterial antigens. Antigen concentrations independently influenced TNF-α and IL-6, in both BMI subgroups of patients. Age independently influenced TNF-α and IL-6 in non-obese patients, and TNF-α in obese patients. CONCLUSION: Serum circulating bacterial antigens as well as age were BMI-independent factors related to increased systemic inflammation in NAFLD and provides insight on the multifaceted sources of inflammation in these patients.