Liver and obesity: a narrative review

Obesity is a multifactorial chronic disease characterized by an excess of adipose tissue, placing a growing burden on individual health and public health systems worldwide. Here we aim to elucidate how obesity contributes to liver dysfunction and highlight the preventive, diagnostic, and management strategies that are most relevant to healthcare providers, researchers, and policy makers. To this end, a comprehensive literature search using major scientific databases was conducted. Various clinically heterogenous pathophenotypes, such as android, gynoid, sarcopenic, metabolically healthy and unhealthy obesity, exhibit variable associations with liver health in the context of chronic liver disease (CLD), including alcohol-related CLD, viral hepatitis B and C, and, particularly, metabolic dysfunction-associated steatotic liver disease (MASLD), which is the prototypic manifestation of obesity-associated CLD. Regardless of the etiology of CLD, obesity is a major risk factor for the progression to cirrhosis and hepatocellular carcinoma through a variety of lipotoxic, proinflammatory, pro-fibrotic, and carcinogenic pathomechanisms involving genetics and epigenetics, altered adipokine profile, oxidative stress, endoplasmic reticulum stress, apoptosis, intestinal dysbiosis, and altered gut-liver axis. Various strategies are available to address obesity-associated CLD, including lifestyle changes, endoscopic techniques, and metabolic/bariatric surgery. Integrative approaches bringing together clinicians, basic researchers, and public health experts will be crucial in developing a coherent, holistic framework to address, with a precision medicine approach, the rising tide of obesity-related CLD on a global scale.