Potential of ultra‐highly sensitive immunoassays for hepatitis B surface and core‐related antigens in patients with or without development of hepatocellular carcinoma after hepatitis B surface antigen seroclearance

2021

Microorganisms

The hepatitis B core-related antigen (HBcrAg) is an unprecedented novel HBV biomarker that plays an essential role in reflecting covalently closed circular DNA (cccDNA) in chronic hepatitis B (CHB) because its levels correlate with intrahepatic cccDNA and serum HBV DNA. In this review, we describe the clinical application of serum HBcrAg in CHB patients, with a particular focus on new therapies targeting intrahepatic HBV replication. (1) HBcrAg can be detected in clinical cases where serum HBV DNA is undetectable during anti-HBV therapy. (2) A highly sensitive HBcrAg assay (iTACT-HBcrAg) may be useful for monitoring HBV reactivation, as an alternative to HBV DNA. (3) Decreased HBcrAg levels have been significantly associated with promising outcomes in CHB patients, reducing the risk of progression or recurrence of hepatocellular carcinoma. Additionally, we focus on and discuss several drugs in development that target HBV replication, and monitoring HBcrAg may be useful for determining the therapeutic efficacies of such novel drugs. In conclusion, HBcrAg, especially when measured by the recently developed iTACT-HBcrAg assay, may be the most appropriate surrogate marker, over other HBV biomarkers, to predict disease progression and treatment response in CHB patients.

Section: High-sensitivity Hbcrag Assaymentioning

confidence: 99%

Hepatitis B Core-Related Antigen and New Therapies for Hepatitis B

Watanabe

2021

Microorganisms

“…As another clinical utility, a recent study reported that the prevalence of HBcrAg equal to or greater than 2.7 in the HCC group was significantly higher than that in non‐HCC group (100% [5/5] vs. 33% [4/12], p = 0.029), indicating that residual low HBcrAg might predict HCC development even if HBsAg seroclearance was achieved according to a conventional assay 52 …”

Section: Novel Biomarkers For the Diagnosis Of Hbv Reactivationmentioning

confidence: 99%

Novel strategies for the early diagnosis of hepatitis B virus reactivation

Matsui

2021

Hepatology Research

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.

“…Collectively, these reports show that serum HBcrAg can predict clinical outcomes, such as HBeAg seroconversion, response to therapy, HBV reactivation, and risk of HCC development [ 100 ].…”

Section: Hbcragmentioning

confidence: 99%

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

Hayashi

Nonomura

2021

IJMS

Hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC) development and is a global public health issue. High performance biomarkers can aid the early detection of HCC development in HBV-infected individuals. In addition, advances in the understanding of the pathogenesis of HBV infection and in clinical laboratory techniques have enabled the establishment of disease-specific tests, prediction of the progression of liver diseases, including HCC, and auxiliary diagnosis of HCC, using blood-based methods instead of biopsies of liver or HCC tissues. Viral factors such as the HBV genotype, HBV genetic mutations, HBV DNA, and HBV-related antigens, as well as host factors, such as tumor-associated proteins and post-translational modifications, especially glycosylated proteins, can be blood-based, disease-specific biomarkers for HCC development in HBV-infected patients. In this review, we describe the clinical applications of viral biomarkers, including the HBV genome and glycosylated proteins, for patients at a risk of HBV-related HCC, based on their molecular mechanisms. In addition, we introduce promising biomarker candidates for practical use, including colony stimulating factor 1 receptor (CSF1R), extracellular vesicles, and cell-free, circulating tumor DNA. The clinical use of such surrogate markers may lead to a better understanding of the risk of disease progression and early detection of HCC in HBV-infected patients, thereby improving their prognosis.