A Target to Cure Chronic Hepatitis B?

Chronic hepatitis B may be curable by targeting liver immune cells called hepatic microphages and eliminating them, which in turn reactivates cells that can destroy the virus, according to a University of Southern California study published in the journal Immunity.

Jing-Hsiung James Ou, PhD, Professor of Molecular Microbiology and Immunology at the University of Southern California’s Keck School of Medicine in Los Angeles and colleagues created a mouse model to examine vertical hepatitis B virus (HBV) transmission from mother to child, which researchers said causes chronic infection in offspring. 

Dr Ou and colleagues noted that while adult horizontal transmission is usually limited to acute infection and cleared by the adult immune system, the mechanism for chronic infection has not been well understood. The Centers for Disease Control and Prevention (CDC) report that in 2013, approximately 1.1 million people in the United States have chronic HBV infection, which highlights the needs for treatment.

In the mouse model, one group of mice were offspring of mothers with HBV, while the control group was uninfected offspring. Researchers injected HBV-DNA into livers of all offspring mice and monitored over a 28-week period.

During the study period, researchers located the mechanism in the test group that HBV uses – the HBV e antigen, which comes from the mother and makes the offspring’s hepatic microphages – immune cells in the liver that remove invaders – subdue the white blood cells called CTLs that would normally attack the virus, effectively betraying the mouse’s own system.

Dr Ou and colleagues injected a drug into the chronically infected mice that was able to deplete these hepatic microphages, which resulted in the activation of white blood cell CTLs that were then able to clear the virus. The drug was given 2 days before the HBV-DNA and one every 5 days after, for a total of 4 administrations. Researchers reported HBV had been cleared after a 4-week period.

“Depletion of hepatic macrophages led to CD8+ T cell activation and HBV clearance in the offspring, raising the possibility of targeting macrophages to treat chronic HBV patients,” researchers said in the study.

The study, which may offer a path to a cure for chronic HBV with more research and clinical trials, was funded by the National Institute of Health and a grant from the LK Whittier Foundation.

Reference

Tian Y, Kuo C, Akbari O et al. Maternal-derived hepatitis B virus e antigen alters macrophage function in offspring to drive viral persistence after vertical transmission. Immun. 2016; 44(5):1204-14