4Ps medicine of the fatty liver: the research model of predictive, preventive, personalized and participatory medicine-recommendations for facing obesity, fatty liver and fibrosis epidemics

Abstract

Relationship between adipose tissue and fatty liver, and its possible evolution in fibrosis, is supported by clinical and research experience. Given the multifactorial pathogenesis of non-alcoholic fatty liver disease (NAFLD), treatments for various contributory risk factors have been proposed; however, there is no single validated therapy or drug association recommended for all cases which can stand alone. Mechanisms, diagnostics, prevention and treatment of obesity, fatty liver and insulin resistance are displayed along with recommendations and position points. Evidences and practice can get sustainable and cost-benefit valuable outcomes by participatory interventions. These recommendations can be enhanced by comprehensive research projects, addressed to societal issues and innovation, market appeal and industry development, cultural acceptance and sustainability. The basis of participatory medicine is a greater widespread awareness of a condition which is both a disease and an easy documented and inclusive clue for associated diseases and unhealthy lifestyle. This model is suitable for addressing prevention and useful for monitoring improvement, worsening and adherence with non-invasive imaging tools which allow targeted approaches. The latter include health psychology and nutritional and physical exercise prescription expertise disseminated by continuous medical education but, more important, by concrete curricula for training undergraduate and postgraduate students. It is possible and recommended to do it by early formal teaching of ultrasound imaging procedures and of practical lifestyle intervention strategies, including approaches aimed to healthier fashion suggestions. Guidelines and requirements of research project funding calls should be addressed also to NAFLD and allied conditions and should encompass the goal of training by research and the inclusion of participatory medicine topics. A deeper awareness of ethics of competences in health professionals and the articulation of knowledge, expertise and skills of medical doctors, dieticians, health psychologists and sport and physical exercise graduates are the necessary strategy for detectin a suboptimal health status and achieving realistically beneficial lifestyle changes. "The devil has put a penalty on all things we enjoy in life. Either we suffer in health or we suffer in soul or we get fat" (Albert Einstein); the task of medical research and intervention is to make possible to enjoy life also without things that make sufferance in health and souls and which excessively increase body fat.

Keywords: Adipose tissue; Diet; Fashion; Fatty liver; Interactome; Lifestyle; Liver fibrosis; Obesity; Suboptimal Health.

Figure 1

Relative prevalence of disease from fatty liver to hepatocarcinoma; the most likely associated mechanisms.

Figure 2

Cause and co-factors leading fatty liver to HCC.

Figure 3

Fatty liver pathogenesis. Representation of the step-by-step progression of the fatty liver pathogenesis, with its respective pathologic features.

Figure 4

Morphological and histological analysis of a liver sample.Haematoxylin and eosin (H&E) staining in liver tissue demonstrated no sign of tissue degeneration, with a good preservation and absence of lipid droplets. NAFLD activity score = 0 for every histological feature. Magnification × 20; scale bar: 100 μm.

Figure 5

Morphological and histological analysis of a liver sample. H&E staining in liver tissue demonstrated no sign of tissue degeneration, with a good preservation and the beginning of formation of lipid droplets (black arrows). NAFLD activity score = 1 for steatosis, 0 for lobular inflammation, 1 for hepatocellular ballooning and 0 for fibrosis. Magnification × 20; scale bar: 100 μm.

Figure 6

Bright liver score. The severity of steatosis can be evaluated by ultrasonography as fatty infiltration in the liver produces a diffuse increase in echogenicity.

Figure 7

PUFAs molecular mechanism of action. ω-3 PUFAs regulate gene transcription factors, i.e. peroxisome proliferator-activated receptor alpha (PPARα), PPARγ and sterol regulatory element-binding protein-1 (SREBP-1), having a beneficial impact on most of the cardiometabolic risk factors (hypertension, hyperlipidemia, endothelial dysfunction and atherosclerosis). Activation of PPARs stimulates lipid oxidation, decreases the endogenous lipid production and determines IR, besides a significant reduction of the expression of pro-inflammatory molecules (TNF-α and IL-6) and of oxygen reactive species, leading to amelioration of hepatic steatosis.

Figure 8

Is the clinic of NAFLD a hazard? It is not true that the choices in the management of NAFLD are scarcely relevant, so that can be taken by chance addressing more to one aspect or the other. A great level of attention should be present in the assessment of established or new knowledge: the drift caused by inconsistent articles and reports, and scarcely supported conclusions, prevents the dissemination of more robust studies and valid approaches. A lie gets halfway around the world before the truth has a chance to get its pants on. The clinic of liver disease is a comprehensive approach, and the concept that one special issue can be the definite answer for diagnosis or therapy is not achieved. “Luck is not chance, it’s toil; fortune’s expensive smile is earned”.