Aggiornamento
Malattia grassa del fegato: tra fattori ambientali e predisposizione genetica
Fatty liver disease: between environmental factors and genetic predisposition
Antonella Mosca, Giuseppe Maggiore
Epatogastroenterologia, Nutrizione, Endoscopia Digestiva e Clinica del Trapianto di Fegato, Ospedale Pediatrico “Bambino Gesù” IRCCS, Roma
Giugno 2023 - pagg. 355 -362 | DOI: 10.53126/MEB42355
Abstract
Non-alcoholic fatty liver disease (NAFLD) is now recognized as the hepatic manifestation of the metabolic syndrome and is the most common cause of chronic liver disease in both adults and children. It is assumed that a genetic predisposition associated with epigenetic
factors participates in the evolution of this condition. Visceral obesity and insulinresistance (IR) have always been considered as key factors linking Metabolic Syndrome (MetS) and NAFLD, but a multifactorial pathogenesis characterized by the interaction between genetic background and environmental factors is increasingly recognized as a key point in the development of metabolic disorders associated with NAFLD. In fact, in patients with NAFLD, insulin resistance, arterial hypertension, abdominal obesity, dyslipidemia and reduced intestinal permeability have often been observed, as well as a higher prevalence of comorbidities such as coronary artery disease, obstructive sleep
apnoea, polycystic ovary syndrome and osteopenia, which define a MetS framework. Early diagnosis is needed to prevent disease progression through primarily lifestyle interventions. Unfortunately, to date, there is no recommended pharmacological intervention
in a paediatric setting. However, a variety of new pharmacological agents are under clinical study. To achieve this, studies on the pathways that link the genetic background to the environment before and after birth to the development of NAFLD and MetS and on the molecular mechanisms that define NASH should be increased. Therefore, it is desirable that future studies may be useful in terms of population screening to identify individuals at risk for NAFLD and MetS.
Riassunto
La steatosi epatica non alcolica (NAFLD) è ora riconosciuta come la manifestazione epatica della sindrome metabolica ed è la causa più comune di malattia epatica cronica sia negli adulti che nei bambini. Si presume che una predisposizione genetica associata a fattori epigenetici partecipi all'evoluzione di questa condizione. L'obesità viscerale e l'insulino-resistenza (IR) sono sempre state considerate come fattori chiave che collegano la sindrome metabolica (MetS) e la NAFLD, ma una patogenesi multifattoriale caratterizzata dall'interazione tra background genetico e fattori ambientali è sempre più riconosciuta come un punto chiave nello sviluppo di disturbi metabolici associati a NAFLD. Infatti, nelle pazienti con NAFLD sono state spesso osservate insulino-resistenza, ipertensione arteriosa, obesità addominale, dislipidemia e ridotta permeabilità intestinale, oltre a una maggiore prevalenza di comorbilità quali coronaropatie, apnee ostruttive del sonno, sindrome dell'ovaio policistico e osteopenia, che definiscono un framework MetS. La diagnosi precoce è necessaria per prevenire la progressione della malattia principalmente attraverso interventi sullo stile di vita. Purtroppo, a oggi, non esiste un intervento farmacologico raccomandato in ambito pediatrico. Tuttavia, una varietà di nuovi agenti farmacologici è in fase di studio clinico. Per raggiungere questo obiettivo, dovrebbero essere incrementati gli studi sui percorsi che collegano il background genetico all'ambiente prima e dopo la nascita allo sviluppo di NAFLD e MetS e sui meccanismi molecolari che definiscono la NASH. Pertanto, è auspicabile che studi futuri possano essere utili in termini di screening della popolazione per identificare gli individui a rischio di NAFLD e MetS.
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Corrispondenza: giuseppe.maggiore@opbg.net