The suboptimal diagnostic performance of AFP in early stage HCC detection could be attributed to nonspecific increased levels in different scenarios, such as chronic hepatitis B infection, fatty liver disease, increased serum AST/ALT ratio, elevated serum ferritin, Mallory bodies in liver biopsies, liver disease with viral etiology, low albumin level, larger tumor size, multinodular HCC, and the presence of vascular invasion, which are also associated with elevated AFP levels in patients with HCC45–47. The gene discussed is AFP; the disease is chronic hepatitis B virus infection.