Systemic and adipose tissue inflammation in NASH: correlations with histopathological aspects

Abstract

Introduction: Non-alcoholic steatohepatitis (NASH) is a progressive form of liver steatosis that involves a risk of progression towards fibrosis, cirrhosis, and end-stage liver disease. Low-grade inflammation is recognized to be involved in non-alcoholic fatty liver disease (NAFLD) pathogeny. Additionally, adipose tissue dysfunction plays an important role in the development of metabolic diseases. Patients, Materials and Methods:We conducted a study on 68 patients with liver steatosis confirmed through liver biopsy during the surgery. In all the patients, we recorded anthropometric parameters and we performed blood tests for systemic inflammation [high-sensitivity C-reactive protein (hs-CRP), fibrinogen] and serum adipokines related to adipose tissue inflammation (leptin, adiponectin). Additional to histopathological examination, we also performed the immunohistochemical study of inflammatory mononuclear cells. Results: The 68 patients had a mean age of 56.57±4.94 years old, had a mean value of hs-CRP of 2.30±0.91 mg/L, a mean value of leptin of 14.02±17.02 ng/mL and a mean value of adiponectin of 7.54±0.38 mg/L. In all the cases studied by liver biopsy, the steatosis exceeded 5% of hepatocytes, but the frequency of NASH was 26.47%. Cluster of differentiation (CD)45-positive, CD4-positive, and CD8-positive T-lymphocytes predominated in the studied cases. We obtained a statistically significant high association between definite NASH and the values of hs-CRP, serum adiponectin and leptin/adiponectin ratio (p<0.0001). Conclusions: Systemic and adipose tissue inflammation was statistically significant associated with histological lesions of steatosis and NASH, suggesting that the determination of hs-CRP and serum adipokines in dynamics in patients with NAFLD is predictive for the progression of the disease.

Predictive Power of Tissue and Circulating Biomarkers for the Severity of Biopsy-Validated Chronic Liver Diseases

“…Leptin concentrations in the peripheral blood of obese people is proportional to the degree of obesity [ 32 ], and hyper-leptinemia promotes steatosis with or without NAFLD [ 33 , 34 ]. Indeed, the adipose tissue disfunction in NAFLD is not completely understood but the inflammation of specific depots of white adipose tissue has a key role in NAFLD progression [ 35 , 36 ]. Thus, it is conceivable that in the cluster of NAFLD/NASH group with higher leptin levels, which strongly indicated that a higher BMI, the adipose tissues may be more responsible for circulating leptin.…”

Decoding the role of immune T cells: A new territory for improvement of metabolic‐associated fatty liver disease

“…Based on the cluster of differentiation T-lymphocytes, CD8 + T cells were recently found to infiltrate in the liver of MAFLD patients together with a higher degree of steatosis, similar to the Th cells that were derived from CD4 + T cells [114]. Another clinical study showed the higher frequencies of IL-7Rα low CD8 + T cells and IL-7Rα low CX3CR1 + CD8 + T cells but not CD4 + T cells in the serum of obese children, compared to the children without metabolic syndrome [115].…”

Emerging Links between Nonalcoholic Fatty Liver Disease and Neurodegeneration

“…64 Within the liver, resident macrophages (KCs) shift to an M1 proinflammatory macrophage phenotype during the transition from simple steatosis to NASH, increasing proinflammatory cytokine production and systemic inflammation correlating with the severity of steatosis and NASH. 65,66 Activated KCs in NASH become dysfunctional over time, leading to reduced filtration of bacterial components absorbed into the portal tract from the gut, 67 elevating serum proinflammatory cytokines that could reach the CNS. In fact, TNF-α correlates with severity of fibrosis in NASH patients and readily crosses the BBB.…”