Mallory bodies and their role in the patho- and morphogenesis of alcoholic disease

The authors consider alcohol disease (AD) as an independent disease, the pathogenesis of which passes 3 stages: episodic alcohol intoxication, drunkenness and alcoholism. In the last 2 stages, severe changes in organs and tissues develop. In this case, Mallory bodies appear in the liver, which is considered to be a marker of chronic alcohol intoxication (CAI). They are observed in most patients with alcoholism and very rarely in those suffering from alcoholism. The authors believe that the alcoholic hyaline Mallory bodies, appearing in the liver and other organs in CAI, is an autoantigen to which the body responds with an autoimmune inflammatory response that is not curable. Therefore, drunkenness, in which there are no Mallory bodies, is curable when alcohol is consumed within the basal metabolism of the liver and treated by therapists, and the treatment of alcoholism is futile. Therefore, the problem of CAI can be solved only with the active treatment of the stage of drunkenness by therapists with the participation of psychiatrists.

Fat causes necrosis and inflammation in parenchymal cells in human steatotic liver

Adapted fixation methods for electron microscopy allowed us to study liver cell fine structure in 217 biopsies of intact human livers over the course of 10 years. The following novel observations and concepts arose: single fat droplets in parenchymal cells can grow to a volume four times larger than the original cell, thereby extremely marginalizing the cytoplasm with all organelles. Necrosis of single parenchymal cells, still containing one huge fat droplet, suggests death by fat in a process of single-cell steatonecrosis. In a later stage of single-cell steatonecrosis, neutrophils and erythrocytes surround the single fat droplet, forming an inflammatory fat follicle indicating the apparent onset of inflammation. Also, fat droplets frequently incorporate masses of filamentous fragments and other material, most probably representing Mallory substance. No other structure or material was found that could possibly represent Mallory bodies. We regularly observe the extrusion of huge fat droplets, traversing the peripheral cytoplasm of parenchymal cells, the Disse space and the endothelium. These fat droplets fill the sinusoid as a sinusoidal lipid embolus. In conclusion, adapted methods of fixation applied to human liver tissue revealed that single, huge fat droplets cause necrosis and inflammation in single parenchymal cells. Fat droplets also collect Mallory substance and give rise to sinusoidal fat emboli. Therefore, degreasing of the liver seems to be an essential therapeutic first step in the self-repairing of non-alcoholic fatty liver disease. This might directly reduce single-cell steatotic necrosis and inflammation as elements in non-alcoholic steatohepatitis progression.

Nonalcoholic Steatohepatitis: Case-Based Focused on Pediatric and Adult Guidelines

Nonalcoholic fatty liver disease (NAFLD) comprises a continuum of conditions associated with insulin resistance and obesity in the absence of secondary causes of hepatic steatosis (alcohol, medication, genetic disorders, hepatitis, etc.) The milder, benign form of NAFLD is simple fatty liver or steatosis. Fatty infiltration affects more than 5% of the liver.1 This is determined by histologic exam, direct quantification or imaging. The range progresses to nonalcoholic steatohepatitis (NASH) and culminates in fibrosis and cirrhosis. Histologic changes include ballooning degeneration of hepatocytes, the presence of Mallory bodies, macrovesicular steatosis, lobular or portal inflammation.2 NAFLD is now the foremost cause of childhood, adolescent and adult chronic hepatic disease. The pediatric and adult obesity epidemic makes NAFLD a potentially ubiquitous hepatic pathology amongst all patients.3,4,5The increase of obese children and adults with obesity correlates to the rise of NAFLD cases. In adults, the rate of NAFLD increase is paired with the epidemics of obesity and Type 2 Diabetes (T2DM).4,5 Data proposes hepatic-related mortality may be due to NASH ultimately progressing to cirrhosis.3,4 NAFLD is linked to pediatric and adult cardiovascular risk and morbidity.4,6Non-invasive biomarkers and the gold standard of liver biopsy not only diagnose but assist in targeted therapies.6 Most pharmacologic therapy for NAFLD is in trial stages for patients of all ages. Pioglitazone is favored in adults who have NAFLD/NASH and T2DM.7 The gut biome is also impactful. Lifestyle modifications of diet and exercise can reduce the public health burden of this disease.7,8,9,10