title: The co-inhibitory pathway and cellular immune imbalance in the progress of HBV infection.
abstract: OBJECTIVE
  Chronic hepatitis B (CHB) affects 400 million people and is the most common cause of liver cirrhosis (LC) and hepatocellular carcinoma (HCC) worldwide. Cellular immune regulation plays an important role in determining the infection outcome. Co-signal molecules and Th17/Treg were studied to explore their association with the progression of HBV infection.
  
  
  METHODS
  Ninety-four HBV-infected patients were categorized into three groups: 31 patients with LC caused by CHB, 30 with HCC caused by CHB and 33 with HCC caused by CHB. Co-signal molecules, Th17/Treg, and Stat3 and Stat5 were analyzed by flow cytometry.
  
  
  RESULTS
  CHB patients who progressed to LC or HCC showed a significantly higher level of co-inhibitory molecules such as BTLA and PD-1, while there was no significant difference in co-stimulatory molecules among LC, HCC and CHB. Stat3 and Stat5 were significantly increased in LC and HCC compared to CHB patients.
  
  
  CONCLUSIONS
  Co-inhibitory molecules play more important roles than co-stimulatory molecules. Increased PD-1 and BTLA/HVEM inhibited immune cells and the immune process. At the same time activated Stat3 and Stat5 stimulate the key factors in differentiation of Th17 and Treg, thus leading to imbalanced expansion of Th17 and Treg; immune tolerance was induced and HBV persistent. This resulted in hepatic inflammation that progressed to cirrhosis and carcinoma.
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China. wangll1015@163.com.
authors.forename: Lanlan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: Yangjuan
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: Limei
authors.initials: L
authors.lastname: Luo
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liao
keywords: BTLA; PD-1; Regulatory T cells; Stat; Th17