How Hepatitis B virus causes cirrhosis and liver cancer

Hepatitis B virus is a major pathogen infecting the liver, causing high morbidity and mortality worldwide, particularly in developing countries. The mechanism underlying progression from infections of Hepatitis B virus to cirrhosis and liver cancer is not fully determined. Here we propose that the HBV X protein traps protons and Cl^-, and induces the expression of collagen in the liver, which forms potent hydrogen bonds with trapped protons. The presence of collagen in the liver marks the progression to fibrosis. The X protein and collagen concertedly build up HCl locally, triggering disease advances to liver cancer in some patients with liver cirrhosis. The hypothesis can be tested in Hepatitis B primate model with the administration of calcium and weak acids to ascertain physiological changes and monitor tumorigenesis rate. The experiments will pave the way for better intervention of human infections with Hepatitis B virus.