Fig. 2. Schematic representation of the sequence of events involved in the pathogenesis of N-nitrosodimethylamine (NDMA) induced hepatic fibrosis, cirrhosis, and hepatocellular carcinoma.

The metabolic activation and detoxification of NDMA cause hepatocyte injury, inflammation, neutrophilic infiltration, and massive hepatic necrosis, which results in oxidative stress and production of reactive oxygen species. These processes induce activation of hepatic stellate cells and increased synthesis of connective tissue components, especially collagens that end up in hepatic fibrosis. The chronic liver injury and perpetual fibrosis lead to liver cirrhosis, which could develop into hepatocellular carcinoma