Hepatitis B virus infection and diabetes mellitus: the Kailuan prospective cohort study in China
HEPATOLOGY INTERNATIONAL
Authors: Lei, Shaoyuan; Chen, Shuohua; Zhao, Xinyu; Zhang, Yanmin; Cheng, Kailiang; Zhang, Xiaohui; Wang, Zhenyu; Sun, Yuanyuan; Wu, Shouling; Wang, Li
Abstract
Background and aims The effect of hepatitis B virus (HBV) infection on diabetes has remained unclear. We thus conducted a prospective cohort study to investigate the association between different HBV infection status and new-onset diabetes in a Chinese population. Methods We enrolled 55,520 participants with HBV serological markers and diabetes free in 2010 in Kailuan cohort. Cox regression models were used to analyze the relationship between different HBV infection status and incidence of diabetes after adjusting different confounders. Results During an average follow-up of 5.6 years, we identified 6008 incident patients with diabetes. Compared to the participants with hepatitis B surface antigen (HBsAg) negative/hepatitis B surface antibody (anti-HBs) negative/hepatitis B core antibody (anti-HBc) negative, those with chronic HBV infection or with HBsAg negative/anti-HBc positive had a higher risk to occur diabetes. The hazard ratios were 1.18 (95% CI 0.99-1.40,p = 0.0588) and 1.22 (95% CI 1.08-1.36,p = 0.0009), respectively. The association between chronic HBV infection, anti-HBc positive and diabetes was different between those with different levels of high density lipoprotein cholesterol, blood pressure, body mass index, and age. Conclusion The individuals with chronic HBV infection or anti-HBc positive may have an increased risk of diabetes, and the association may be modified by the different status of metabolism related variables and age. Effective management of HBV infection may contribute to the reduction of the burden of both hepatitis B and diabetes.
The incorporation of cationic property and immunopotentiator in poly (lactic acid) microparticles promoted the immune response against chronic hepatitis B
JOURNAL OF CONTROLLED RELEASE
Authors: Lu, Ting; Hu, Fumin; Yue, Hua; Yang, Tingyuan; Ma, Guanghui
Abstract
Biodegradable microparticles (MPs) as vaccine adjuvants have sparked the passion of researchers in recent decades. However, it is still a huge challenge to develop an efficient vaccine delivery system to reverse chronic hepatitis B (CHB). Herein, we integrated a physiochemical merit and an immunopotentiator property in poly (lactic acid) (PLA) MPs and verified the therapeutic effect on CHB model mice. We prepared uniform MPs with insertion of cationic lipid didodecyldimethylammonium bromide (DDAB), which endowed a physiochemical merit for MPs. Such a DDAB-PLA (DP) group raised the recruitment of immune cells to the injection site along with the secretion of chemokines and pro-inflammatory cytokines, promoting the activation of antigen-presenting cells (APCs). Further combination of stimulator of interferon genes (STING) agonist 5,6-dimethylxanthenone-4-acetic acid (DMXAA) (DP-D) elevated 5.8-fold higher interferon regulatory factor 7 (IRF-7) expression compared to that for DP group. The DP group showed preferred lysosome escape advantage, which was in line with the DMXAA release behavior and the intracellular target of DMXAA. In addition, DP-D vaccine augmented the IFN-gamma secreting splenocytes and motivated Th1-biased antibodies in a more efficient way than that for the DP group. In the CHB model, the MPs based vaccines achieved 50% HBsAg seroconversion rate, and HBcAg in the liver also got a reduction. DP-D produced higher amount of memory T/B cells to confer protection in a sustained manner. Present work thus provided a promising strategy, via integrating a fine-tuned physiochemical property and an immunopotentiator virtue in the MPs, which synergistically reinforced both humoral and cellular immune responses against CHB.