Molecular mechanisms in the pathogenesis of metabolically associated fatty liver disease.

Inflammation is a common feature of all chronic liver diseases and atherosclerosis. The article discusses the participation of cytokines and inflammasomes in the process of development of metabolically associated fatty liver disease (MAFLD) and the ways of their activation under the influence of inductive stimuli (toxins, alcohol, fat, viruses, etc.), most often in the case of disruption of intestinal permeability through toll-like receptors with an imbalance in the composition of intestinal microflora and bile acids. Inflammasomes and cytokines are the sources of sterile inflammation in the liver in obesity and metabolic syndrome with subsequent lipotoxicity which is followed by fibrogenesis. The prospects for therapeutic modulation of diseases with the participation of inflammasomes are therefore sought precisely at the level of influencing the mentioned molecular mechanisms. The article emphasizes the importance of the liver-intestinal axis and modulation of microbiome, as well as calls attention to the influence of the circadian rhythm of the 12-hour pacemaker on gene production in NASH (non-alcoholic steatohepatitis) developing (Fig. 4, Ref. 56). Keywords: NASH, MAFLD, microbiome, lipotoxicity, bile acids, inflammasomes.

Biological Effects of Hydrogen Water on Subjects with NAFLD: A Randomized, Placebo-Controlled Trial.

Non-alcoholic fatty liver disease (NAFLD) is a liver pathology affecting around 25% of the population worldwide. Excess oxidative stress, inflammation and aberrant cellular signaling can lead to this hepatic dysfunction and eventual carcinoma. Molecular hydrogen has been recognized for its selective antioxidant properties and ability to attenuate inflammation and regulate cellular function. We administered hydrogen-rich water (HRW) to 30 subjects with NAFLD in a randomized, double-blinded, placebo-controlled manner for eight weeks. Phenotypically, we observed beneficial trends (p > 0.05) in decreased weight (≈1 kg) and body mass index in the HRW group. HRW was well-tolerated, with no significant changes in liver enzymes and a trend of improved lipid profile and reduced lactate dehydrogenase levels. HRW tended to non-significantly decrease levels of nuclear factor kappa B, heat shock protein 70 and matrix metalloproteinase-9. Interestingly, there was a mild, albeit non-significant, tendency of increased levels of 8-hydroxy-2'-deoxyguanosine and malondialdehyde in the HRW group. This mild increase may be indicative of the hormetic effects of molecular hydrogen that occurred prior to the significant clinical improvements reported in previous longer-term studies. The favorable trends in this study in conjunction with previous animal and clinical findings suggest that HRW may serve as an important adjuvant therapy for promoting and maintaining optimal health and wellness. Longer term studies focused on prevention, maintenance, or treatment of NAFLD and early stages of NASH are warranted.

Questionnaire for risk factors of alcoholic and nonalcoholic fatty liver disease.

OBJECTIVES: Non-communicable diseases are estimated to account for 90 % of total deaths and 19 % of premature deaths in Slovakia. Major preventable risk factors of premature mortality are overweight, obesity and alcohol consumption. BACKGROUND: Screening of risk factors related to alcoholic and nonalcoholic fatty liver diseases (AFLD and NAFLD, respectively) in Slovak outpatients with liver disease. METHODS: A total group of 923 patients, aged 19-91 years were included in the study. Self-administered anonymous questionnaires (Q) were filled in by them. Twelve questions were included relating to age, gender, education, BMI, intake of vegetable, fruit, fish, alcohol, and coffee, as well as to smoking and physical exercise. RESULTS: Overweight/obesity was detected in 59 % of patients, insufficient fiber intake in 87 % of patients, insufficient fish intake in 85 % of patients, and insufficient physical exercise in 68 % of patients. BMI over 25 together with the risk of alcohol consumption was present in 68 % of patients. Smoking was present in 19 % of patients and insufficient coffee intake (from its hepatoprotective point of view) was in 35 % of patients. A total proportion of 75 % of patients were at risk for NAFLD. The risk of alcohol consumption was present in 64 % of patients. CONCLUSIONS: An anonymous questionnaire is a useful screening tool for searching for the risks of NAFLD and AFLD in general practice. Recommendation of a screening schedule for general practitioners is implemented (Tab. 2, Fig. 4, Ref. 36).

[Coffee as hepatoprotective factor]. / Káva ako hepatoprotektívny faktor.

The mind about the coffee did change upon the recent studies and metaanalysis of the last years. Consensual protective effect of coffee on the progression of chronic liver diseases (NASH, viral hepatitis, liver cirrhosis, hepatocelullar carcinoma) was detected in experimental, clinical and large population studies together with decrease of mortality. Antioxidant, antifibrotic, insulinsensitizing and anticarcinogenic effect of coffee were detected. Modulation of genetic expression of key enzymes of fatty acid synthesis, modulation of mRNA included in autophagia, reduction of stress of endoplasmatic reticulum together with decrease of proinflammatory cytokines and decrease of fibrogenesis are main mechanisms. Chlorogenic acids, diterpens (cafestol, kahweol), caffein, polyfenols and melanoidins are key protective components of coffee. Inverse dose-dependent correlation of coffee consumption with liver diseases was found in clinical and population studies. Coffee is non-pharmacological tool of primary and secondary prevention of chronic liver diseases. Review of published data together with supposed mechanisms of hepatoprotection are given.Key words: coffee - hepatoprotective effect - metaanalysis.