Figure 1.

Immunopathogenic complement activation regulates progression to hepatocellular carcinoma. Exposure of the hepatic milieu to several triggers linked either to viral infections (Hepatitis B virus, Hepatitis C virus, etc.), severe obstructive and cholestatic diseases (Biliary atresia, Primary Sclerosing Cholangitis, Primary Biliary Cirrhosis, etc.), environmental stressors/toxin exposures (polychlorinated biphenyls, arsenic, androgenic steroids, etc.), and other etiopathogenic agents (aflatoxins, oral contraceptives, vinyl chloride, etc.) dictate the evolution of hepatocellular carcinoma (HCC). These triggers activate the innate immune complement cascade via classical (involving C1q complex), alternative (C3b-dependent activation), or lectin (triggered by carbohydrates) pathways. Abnormal activation of these complement pathways modulates functional effects of intrahepatic immune and epithelial cell compartments and disseminates significant perturbation of effector innate and adaptive cells, cytokine and chemokine expressions, and sustained cancer stem cell (CSC) activities. The collective net result of these processes defines the progression of HCC tumorigenesis.