Description
Metabolically-driven fatty liver disorders are a growing worldwide burden, mostly tied to the increasing prevalence of all cardiometabolic disorders such as obesity, insulin resistance and type 2 diabetes. These conditions are currently the most common liver disorders in the world and are one of the leading causes of liver transplantation in the United States. Metabolically-driven fatty liver disorders initiate with accumulation of fat within hepatocytes (steatosis), but can progress to inflammatory hepatitis, fibrosis and even hepatic carcinoma. In the past few decades, much has been learned about the pathophysiology of this progressive chronic disease, especially the interplay between hepatic fatty acid metabolism and the gut microbiome, intestinal permeability, mitochondrial function and innate immune activation. This new knowledge has greatly expanded the search for therapeutic agents to prevent or reverse hepatic steatosis, though no pharmaceutical therapies have yet been approved in the United States. Instead, lifestyle-based therapies designed to reduce weight and improve insulin sensitivity remain the foundation for slowing or reversing these disorders. In this narrative review, we will discuss the underlying pathophysiology of metabolically-driven fatty liver disorders, focusing on how depletion of important metabolic reserves creates metabolic vulnerabilities in susceptible subjects. Along with established lifestyle recommendations, we will explore non-pharmacological agents that may prove helpful to clinicians treating patients with these progressive disorders.
