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).

Fatal coincidence of inapparent SARS-CoV-2 infection and drug toxicity in the field of immunosuppression in a 33-year old woman.

The COVID-19 pandemic represents a wide-ranging form of involvement from asymptomatic through mild respiratory form to bilateral bronchopneumonia with acute respiratory and multiorgan fatal failure. Patients with comorbidities (obesity, cardiovascular diseases, diabetes mellitus) are particularly at risk of a more severe course of infection. We present a 33-year old lean patient with a medical history of ulcerative colitis on immunosuppressive treatment with Azathioprine, after unsuccessful in vitro fertilization one week before the onset of symptoms, admitted to hospital for two-week-long cough with sore throat with fever ap to 40°C. CT confirmed bilateral bronchopneumonia without etiological detection of the infectious agent. Three PCR tests (two of nasopharyngeal swabs and one of bronchoalveolar lavage (BAL)) were negative for COVID-19, including antigen and antibody tests. Complex parenteral ATB treatment with high-flow nasal oxygen therapy was ineffective, and artificial lung ventilation was indicated for acute respiratory failure. After 4 days antifungal treatment of Fluconazole, condition of patient progressed to hepatic and multiorgan failure and the patient died on day 14 of hospitalization. Post-mortem histological examination revealed the presence of coronavirus in the cells of lung parenchyma. The case recalls that even young patients with immunosuppressive treatment are at risk for the critical course of COVID-19 disease. The negativity of the tests was due to the capture of the patient only after the second week of infection, at the time of the diagnostic window between the positive PCR test and the formation of antibodies. The persistent effect of immunosuppression was most likely the reason for the lack of antibody response.

[Drug and herbal hepatotoxicity: an overview of clinical classifications]. / Lieková a herbálna hepatotoxicita: prehlad klinických klasifikácií.

Drug induced liver injury (DILI) is often underdiagnosed disease with increasing incidence. In developed countries it belongs to the leading causes of acute liver failure. Risk groups are women and persons older than 60 years. The work summarizes the up to date information on diagnosis and mostly used classifications on DILI. It is quite often and serious complication of medicament therapy. DILI belongs to the most often cause of acute hepatic failure in the old age in developed countries. Diagnostic procedure includes medical history (time correlation with drug intake), clinical symptoms and blood tests. Laboratory tests may be helpful to specify immunopathogenetic origin, but negative results does not exclude diagnosis. The exclusion of other possible etiological factors is the crucial condition of diagnosis statement. Key words: DILI/drug induced liver toxicity - DILIn network - RUCAM classification.