Smoking and liver diseases: an updated review of pathogenesis, progression, and therapeutic implications

Abstract Cigarette smoking, a leading cause of preventable morbidity and mortality worldwide, has increasingly been recognized as a significant and independent risk factor for the development and progression of various liver diseases. Historically, the direct impact of smoking on liver health received limited attention compared to its well-established effects on the respiratory and cardiovascular systems. However, a growing body of evidence now unequivocally demonstrates that smoking negatively influences the incidence, severity, and outcomes of a wide spectrum of hepatic conditions, including metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-related liver disease (ALD), chronic viral hepatitis (HBV and HCV), primary biliary cholangitis (PBC), and hepatocellular carcinoma (HCC). The detrimental effects of tobacco extend to patients undergoing liver transplantation, where smoking is associated with increased post-transplant complications and mortality. The underlying mechanisms are complex, involving direct and indirect toxic effects, immunologic dysregulation, and oncogenic pathways, primarily driven by oxidative stress, systemic inflammation, insulin resistance, and the presence of numerous carcinogens in tobacco smoke. This comprehensive review synthesizes current knowledge, highlighting the multifaceted ways in which smoking impacts liver health, from cellular injury and fibrosis progression to increased cancer risk and compromised transplant outcomes. In addition, we explore the rising prevalence of electronic cigarette use and present the latest evidence regarding their potential impact on liver health. We emphasize the critical importance of smoking cessation as a therapeutic intervention across all stages of liver disease and discuss the challenges and strategies for its implementation. By integrating the updated research data and clinical insights, this review aims to underscore the urgent need for greater awareness among healthcare professionals and patients regarding the profound and pervasive link between smoking and liver disease, advocating for targeted interventions to alleviate this preventable burden.