Tobacco and MASLD

Tobacco use, both active and passive, significantly influences the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Active smoking increases MASLD risk through mechanisms such as oxidative stress, inflammation, and metabolic disruption. Tobacco-induced oxidative stress damages liver cells (hepatocytes), promotes insulin resistance, and facilitates fat deposition in the liver, which are hallmark features of MASLD. Smoking also elevates systemic inflammatory markers like C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), exacerbating hepatic inflammation and fibrosis. Additionally, smoking disrupts the gut–liver axis by altering gut microbiota, increasing intestinal permeability, and allowing endotoxins to enter the liver, further driving inflammation.

The risk of MASLD is dose-dependent, with smokers who consume ≥20 pack-years of tobacco experiencing a 32% higher risk, highlighting the cumulative effect of tobacco exposure. Passive smoking, or secondhand smoke exposure, also contributes to MASLD, increasing risk by 13%. This underscores the harmful effects of indirect tobacco exposure, which impacts liver function even in non-smokers.

Metabolic factors amplify the impact of smoking on MASLD. Individuals with obesity (BMI ≥24), hypertension, or high triglycerides face significantly higher risk due to the synergistic effects of smoking and metabolic dysfunction. Smoking impairs insulin signaling and lipid metabolism, worsening metabolic and hepatic health. Older adults and those with cardiometabolic conditions are particularly vulnerable.

Importantly, smoking cessation has a protective effect. Quitting for more than 10 years reduces MASLD risk close to that of non-smokers, though damage persists for those who quit less than 10 years ago. Public health initiatives targeting smoking cessation and secondhand smoke regulation are crucial for MASLD prevention.