A roadmap for serum biomarkers for hepatitis B virus: current status and future outlook

Abstract

Globally, 296 million people are infected with hepatitis B virus (HBV), and approximately one million people die annually from HBV-related causes, including liver cancer. Although there is a preventative vaccine and antiviral therapies suppressing HBV replication, there is no cure. Intensive efforts are under way to develop curative HBV therapies. Currently, only a few biomarkers are available for monitoring or predicting HBV disease progression and treatment response. As new therapies become available, new biomarkers to monitor viral and host responses are urgently needed. In October 2020, the International Coalition to Eliminate Hepatitis B Virus (ICE-HBV) held a virtual and interactive workshop on HBV biomarkers endorsed by the International HBV Meeting. Various stakeholders from academia, clinical practice and the pharmaceutical industry, with complementary expertise, presented and participated in panel discussions. The clinical utility of both classic and emerging viral and immunological serum biomarkers with respect to the course of infection, disease progression, and response to current and emerging treatments was appraised. The latest advances were discussed, and knowledge gaps in understanding and interpretation of HBV biomarkers were identified. This Roadmap summarizes the strengths, weaknesses, opportunities and challenges of HBV biomarkers.

Serum cytokine change profile associated with HBsAg loss during combination therapy with PEG-IFN-α in NAs-suppressed chronic hepatitis B patients

“…As important immune system components, cytokines may introduce immune dysregulation or tolerance and be associated with progression in CHB (15)(16)(17)(18). Inflammatory cytokines, such as IFN-a, CXCL8, CXCL9, and CXCL10, can induce inflammatory immune cell recruitment and promote hepatocyte apoptosis in CHB (15,(19)(20)(21). For instance, an elevated serum IFN-a and CXCL8 could promote NK-cell-mediated liver cell injury (20,21), high serum CXCL9 and CXCL10 levels were reported to correlate with the development of hepatitis flares (20)(21)(22), IL-2 and IFN-g were upregulated with high ALT levels (21).…”

“…Otherwise, patients can become chronically infected when the host immune response is inadequate or inappropriate ( 13 , 14 ). As important immune system components, cytokines may introduce immune dysregulation or tolerance and be associated with progression in CHB ( 15 – 18 ). Inflammatory cytokines, such as IFN-α, CXCL8, CXCL9, and CXCL10, can induce inflammatory immune cell recruitment and promote hepatocyte apoptosis in CHB ( 15 , 19 – 21 ).…”

Commentary: Serum hepatitis B virus large and medium surface proteins as novel tools for predicting HBsAg clearance

“…What is also similar to our findings is that a combination of baseline MHBs and LHBs levels as well as the decrease at treatment week 12 seemed to be stronger associated with subsequent functional cure than total HBsAg levels at baseline or week 12. (7,8) We believe that there is now enough evidence for the high potential of HBsAg components to develop them further as treatment markers and to validate them in clinical trials.…”

Hepatitis B virus pathogenesis relevant immunosignals uncovering amino acids utilization related risk factors guide artificial intelligence-based precision medicine

“…Chronic hepatitis B virus (HBV) infection remains a major health concern worldwide (Kramvis et al, 2022). First-line anti-HBV drugs approved by FDA including PEG IFN-α and nucleoside (acid) analogs (NAs) are not yet effective in achieving functional cure referring to hepatitis B surface antigen (HBsAg) and covalently closed circular DNA (cccDNA) elimination (Levrero et al, 2018;Fanning et al, 2019;Yang et al, 2019;Tout et al, 2020).…”