Despite the tremendous progresses toward our understanding of the mechanisms of how liver cancer was developed

the therapeutic outcomes of liver cancer in the clinic have very limited improvement within the past three decades or so. In addition

both the incidence and mortality of liver cancer worldwide are not dropping

but increasing steadily

in the last decade. Thus

it is time for us to rethink what has been wrong and how could we do better in the upcoming years

in order to achieve our goal of improving the therapeutic outcomes of patients with liver cancer in the clinic

and at the meantime

effectively reducing the incidence of liver cancer by blocking malignant transformation of hepatocytes from chronic viral infection. This is also one of the main reasons why we try to organize this special issue on primary liver cancer in the journal of

Genes & Diseases

. In this perspective

I will summarize the major obstacles confronted with in the prevention and management of patients with chronic hepatitis B infection and subsequent development of liver cirrhosis and liver cancer. Next

I will delineate the pitfalls and underlying mechanisms of why the current anti-viral strategies and therapeutic agents are not as effective as one expected in terms of successful reduction or prevention chronic hepatitis B infection associated liver cirrhosis and liver cancer. I will then provide my personal perspectives on potential approaches and strategies for effective prevention and management of hepatitis B-related liver cancer.