The impact of genetic risk on liver fibrosis in non‐alcoholic fatty liver disease as assessed by magnetic resonance elastography

Abstract The FNDC5 gene encodes the fibronectin type III domain-containing protein 5 that is a membrane protein mainly expressed in skeletal muscle, and the FNDC5 rs3480 polymorphism may be associated with liver disease severity in non-alcoholic fatty liver disease (NAFLD). We investigated the influence of the FNDC5 rs3480 polymorphism on the relationship between sarcopenia and the histological severity of NAFLD. A total of 370 adult individuals with biopsy-proven NAFLD were studied. The association between the key exposure sarcopenia and the outcome liver histological severity was investigated by binary logistic regression. Stratified analyses were undertaken to examine the impact of FNDC5 rs3480 polymorphism on the association between sarcopenia and the severity of NAFLD histology. Patients with sarcopenia had more severe histological grades of steatosis and a higher prevalence of significant fibrosis and definite non-alcoholic steatohepatitis than those without sarcopenia. There was a significant association between sarcopenia and significant fibrosis (adjusted OR 2·79, 95 % CI 1·31, 5·95, P = 0·008), independent of established risk factors and potential confounders. Among patients with sarcopenia, significant fibrosis occurred more frequently in the rs3480 AA genotype carriers than in those carrying the FNDC5 rs3480 G genotype (43·8 v. 17·2 %, P = 0·031). In the association between sarcopenia and liver fibrosis, there was a significant interaction between the FNDC5 genotype and sarcopenia status (P value for interaction = 0·006). Sarcopenia is independently associated with significant liver fibrosis, and the FNDC5 rs3480 G variant influences the association between sarcopenia and liver fibrosis in patients with biopsy-proven NAFLD.

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Cardiovascular Diseases and Non-Alcoholic Fatty Liver Disease: Relationship and Pathogenetic Aspects of Pharmacotherapy

Rational Pharmacotherapy in Cardiology ◽

10.20996/1819-6446-2021-12-14 ◽

2022 ◽

Vol 17 (6) ◽

pp. 880-888

Author(s):

A. V. Nelidova ◽

M. A. Livzan ◽

N. A. Nikolaev ◽

T. S. Krolevets

Keyword(s):

Cardiovascular Risk ◽

Liver Disease ◽

Cardiovascular Diseases ◽

Liver Fibrosis ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Cardiovascular Risks ◽

Alcoholic Fatty Liver ◽

The Impact ◽

Alcoholic Fatty Liver Disease

The association of non-alcoholic fatty liver disease (NAFLD) and cardiovascular risk is currently one of the actively studied areas. The incidence of non-alcoholic fatty liver disease continues to grow worldwide. In the structure of mortality rate of patients with non-alcoholic fatty liver disease, the first place is occupied by cardiovascular events: stroke and myocardial infarction. Studies have shown that the presence of severe liver fibrosis (F3-4) in NAFLD not only increases the risk of cardiovascular diseases (CVD), but also increases the risk of overall mortality by 69% due to mortality from cardiovascular causes. The degree of increased risk is associated with the degree of activity of non-alcoholic steatohepatitis (NASH). Despite the large number of works on this topic, we do not have a clear opinion on the impact on cardiovascular risk, interaction and the contribution of various factors, as well as algorithms for managing patients with non-alcoholic fatty liver disease to reduce the risk of cardiovascular diseases. This article describes the pathogenetic factors of formation of cardiovascular risks in patients with non-alcoholic fatty liver disease, proposed the idea of stratification of cardiovascular risks in these patients, taking into account changes in the structure of the liver (fibrosis) and function (clinical and biochemical activity) and also it describes the main directions of drug therapy, taking into account the common pathogenetic mechanisms for non-alcoholic fatty liver disease and cardiovascular diseases. The role of obesity, local fat depots, adipokines, and endothelial dysfunction as the leading pathogenetic factors of increased cardiovascular risk in patients with NAFLD is discussed. Among pathogenetically justified drugs in conditions of poly and comorbidity, hypolipidemic (statins, fibrates), angiotensin II receptor antagonists, beta-blockers, etc. can be considered. According to numerous studies, it becomes obvious that the assessment of cardiovascular risks in patients with NAFLD will probably allow prescribing cardiological drugs, selecting individualized therapy regimens, taking into account the form of NAFLD, and on the other hand, building curation taking into account the identified cardiovascular risks.

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