Smoking has a number of negative consequences on organs that do not come into direct touch with the smoke, such as the liver. It has three key negative effects on the liver : direct or indirect toxicity, immunological effects, and carcinogenic consequences. Tobacco use produces chemical compounds with cytotoxic potential, which contribute to necroinflammation and fibrosis. Furthermore, smoking promotes the production of pro-inflammatory cytokines (IL-1, IL-6, and TNF-), which are implicated in liver cell damage. It promotes secondary polycythemia and, as a result, increased red cell mass and turnover, which may be a contributing factor to secondary iron overload illness by boosting oxidative stress in hepatocytes. Increased red cell mass and turnover are linked to increased purine catabolism, which promotes excessive uric acid generation. Smoking impairs both cell-mediated and humoral immune responses by inhibiting lymphocyte growth and promoting lymphocyte death. Smoking also raises