Investigation of hepatic gluconeogenesis pathway in non-diabetic Asian Indians with non-alcoholic fatty liver disease using in vivo (31P) phosphorus magnetic resonance spectroscopy

Non-alcoholic fatty liver disease (NAFLD) is poised to dominate the landscape of clinical hepatology in the 21st century. Its complex, interdependent aetiologies, non-linear disease progression and uncertain natural history have presented great challenges to the development of effective therapies. Progress will require an integrated approach to uncover molecular mediators, key pathogenic milestones and response to intervention at the metabolic level. The advent of precision imaging has yielded unprecedented insights into these processes. Quantitative imaging biomarkers such as magnetic resonance imaging (MRI), spectroscopy (MRS) and elastography (MRE) present robust, powerful tools with which to probe NAFLD metabolism and fibrogenesis non-invasively, in real time. Specific advantages of MRS include the ability to quantify static metabolite concentrations as well as dynamic substrate flux in vivo. Thus, a vast range of key metabolic events in the natural history of NAFLD can be explored using MRS. Here, we provide an overview of MRS for the clinician, as well as key pathways exploitable by MRS in vivo. Development, optimisation and validation of multinuclear MRS, in combination with other quantitative imaging techniques, may ultimately provide a robust, non-invasive alternative to liver biopsy for observational and longitudinal studies. Through enabling deeper insight into inflammatory and fibrogenic cascades, MRS may facilitate identification of novel therapeutic targets and clinically meaningful endpoints in NAFLD. Its widespread use in future could conceivably accelerate study design, data acquisition and availability of disease-modifying therapies at a population level.

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Key points of etiopathogenesis of non-alcoholic fatty liver disease

Vestnik of Russian military medical Academy ◽

10.17816/brmma25948 ◽

2019 ◽

Vol 21 (2) ◽

pp. 219-222

Author(s):

I I Zhirkov ◽

A V Gordienko ◽

D Yu Serdyukov ◽

G Yu Dorokhov

Keyword(s):

Liver Disease ◽

Magnetic Resonance ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Atherogenic Dyslipidemia ◽

Resonance Spectroscopy ◽

Alcoholic Fatty Liver ◽

Nonalcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

Based on the analysis of Russian and foreign literature sources, the definition of non-alcoholic fatty liver disease is given, modern data on the etiology, prevalence, risk factors for the development and progression of non-alcoholic fatty liver disease are presented. Nonalcoholic fatty liver disease found in at least a quarter of the world’s population and the main target of this disease is the most able-bodied and economically active part of the population. These circumstances give this problem special medical, social and humanitarian significance. Two different pathomorphological states represent non-alcoholic fatty liver disease: nonalcoholic fatty liver and nonalcoholic steatohepatitis, which, in turn, includes liver fibrosis, liver cirrhosis, and hepatocellular carcinoma. Non-alcoholic fatty liver disease is determined not only on the basis of the results of histological studies in the presence of steatosis in more than 5% of hepatocytes, but also in excess of proton density of more than 5.6% during proton magnetic resonance spectroscopy, or when performing selective magnetic resonance imaging with quantitative determination of fat and water. Modern data on the pathogenesis of nonalcoholic fatty liver disease are presented. Attention is focused on such key mechanisms in the development of the disease as insulin resistance, lipotoxicy, oxidative stress, systemic aseptic inflammation, mitochondrial dysfunction and endoplasmic reticulum, which served as the basis of the pathogenetic theory of «multi hit». The pathogenesis of nonalcoholic fatty liver disease plays an important role visceral adipose tissue, which also synthesized proinflammatory cytokines and adipokines, as well as the syndrome of excessive bacterial growth, due to the formation of endotoxemia and atherogenic dyslipidemia.

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