Novel strategies for the early diagnosis of hepatitis B virus reactivation

Abstract

Hepatitis B virus (HBV) reactivation under systemic chemotherapy or immunosuppressive therapy is a serious complication among HBV‐resolved patients. Some medications, such as more than 2 weeks of corticosteroid therapy, can influence HBV reactivation; therefore, screening tests that measure hepatitis B surface antigen (HBsAg), hepatitis B core antibody, and hepatitis B surface antibody before therapy are required. Additionally, because HBV reactivation has been reported in patients positive for HBsAg treated with immune checkpoint inhibitors (ICIs), the prophylactic administration of nucleos(t)ide analogues prior to administering ICIs is recommended for HBsAg‐positive patients. Under these circumstances, highly sensitive novel biomarkers are expected to be used for the early diagnosis of HBV reactivation. A fully automated high‐sensitivity HBsAg assay (detection limit: 5 mIU/ml) by Lumipulse HBsAg‐HQ, with 10‐fold higher sensitivity than that of conventional assays, is currently used. Furthermore, ultra‐sensitive HBsAg assays using a semi‐automated immune complex transfer chemiluminescence enzyme immunoassay (ICT‐CLEIA; detection limit: 0.5 mIU/ml) have been developed. Recently, a fully automated, novel high‐sensitivity hepatitis B core‐related antigen assay (iTACT‐HBcrAg; cut‐off value: 2.1 Log U/mL) has been developed and reported. The utility of ICT‐CLEIA and iTACT‐HBcrAg for the diagnosis of HBV reactivation appears comparable to the use of HBV DNA. In this review, we provide the latest information related to medications that influence HBV reactivation and recently developed novel biomarkers that predict and monitor HBV reactivation.

Drug Discovery Study Aimed at a Functional Cure for HBV

“…More recently, Inoue et al have reported that a fully automated, high-sensitivity CLEIA for HBcrAg detection (iTACT-HBcrAg; Fujirebio Corporation, Tokyo, Japan) is useful for the management of HBV reactivation and of HBeAg-negative CHB patients [ 95 , 96 ]. The iTACT-HBcrAg assay is inexpensive and simpler to use than the HBV DNA assay, and provides results within 30 min.…”

Mesenchymal stem cells-based therapy in liver diseases

“…However, before the use of MSCs in AVH patients, reducing the risk of self-infection with MSCs and whether the immunosuppressive effect of MSCs impairs the body's ability to clear the virus, leading to persistent or chronic viral infection, as well as affecting the therapeutic efficacy of antiviral drugs, need to be further investigated. In patients with oncologic and autoimmune diseases complicated by chronic viral infections, viral reactivation has been reported after the use of some drugs, such as corticosteroid therapy and immune checkpoint inhibitors (ICIs) for more than 2 weeks [ 464 ], and viral reactivation significantly increases the risk of acute liver failure and death [ 465 ]. It is worthwhile to investigate when and how MSCs can be applied to strike a balance between antiviral immunity and mitigation of liver pathological damage.…”

Blood-Based Biomarkers in Hepatitis B Virus-Related Hepatocellular Carcinoma, Including the Viral Genome and Glycosylated Proteins

“…More recently, Inoue et al demonstrated that a fully automated, high-sensitivity CLEIA for HBcrAg detection (iTACT-HBcrAg; Fujirebio, Inc., Tokyo, Japan), is about 10-fold more sensitive than the conventional HBcrAg assay, and is even more useful for monitoring transcriptional activity of cccDNA and detecting HBV reactivation before the onset of hepatitis [ 98 , 99 ]. Since iTACT-HBcrAg does not require any special technology and provides results within 30 min; it is expected to be used in clinical practice and research in the future.…”