American University of Barbados, School of Medicine,  Wildey, Saint Michael, Barbados.

Recently re-named Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD), Non-Alcoholic Fatty Liver Disease (NAFLD) has risen to the level of a global Metabolic Pandemic with an estimated prevalence in the world of 25 to 30%. This disease is a progressive continuum of hepatic steatosis, starting with a simple hepatic steatosis and progressing to Non-Alcoholic Steatohepatitis (NASH) and cirrhosis, as well as hepatocellular carcinoma.

A complex, multiplexed, multiple-hit hypothesis pathogenesis results in convergent convergences of insulin resistance, lipotoxicity, mitochondrial oxidative stress, and gut-derived endotoxemia to initiate chronic inflammation. The disease exhibits a clinical paradox in the Indian subcontinent referred to as Lean NAFLD in which affected individuals develop massive hepatic pathology, but they have a normal Body Mass Index (BMI). The high visceral adiposity and genetic populations, namely, PNPLA3 polymorphism, are largely involved in this phenotype.

The synthesis of the world molecular developments and certain Indian epidemiological findings is reviewed and it assesses the current change of invasive biopsy to Non-Invasive Tests (NITs) which includes the FIB-4 Index and Transient Elastography. Therapeutic approaches are examined, including how dual PPAR agonists such as Saroglitazar have come to light and how the so-called Epi-therapeutics could be used to undo maladaptive epigenetic signatures. We end by concluding that this silent crisis needs a multi-systemic approach, focusing on the Gut-Liver-Heart axis, to reduce the long-term cardiovascular and hepatic burden associated with its impact.