New and Old Biomarkers for Diagnosis and Management of Chronic Hepatitis B Virus Infection

Abstract

Tests to detect the presence and activity of hepatitis B virus (HBV) are the cornerstones of diagnosis and management. Assays that detect or measure serum levels of HB surface antigen, HB surface antibody, and HB core antibody are used to identify patients with exposure to HBV, whereas other tests provide information on the level of virus replication, presence of specific variants, and presence of virus reservoirs. Newer diagnostic tests, used only in research settings so far, aim to quantify levels of intrahepatic HBV replication. Other tests have been developed to detect HBV infection in resource-limited settings. We review point-of-care tests (essential in global screening efforts), standard diagnostic tests used in routine clinical management, and newer tests that might be used in clinical trials of agents designed to cure HBV infection.

Keywords: HBV RNA; HBsAg; Point-of-Care; Quantitative.

Figure 1.. Point of Care Tests

POC tests are important for populations unable or unwilling to access regular medical care, such as among injection drug users, homeless, or the uninsured. POC tests use either fingersticks or dried blood spots. They are easy to use and inexpensive. Fingerstick POC tests provide immediate results whereas dry blood spots must be mailed for central testing.

Figure 2.. Phases of Chronic HBV Infection

Tests recommended for persons with chronic HBV infection include detection and quantification (q) of HBsAg, HBV DNA, HBeAg, and ALT, which indicate changes of the course of chronic HBV infection. There are 5 phase of infection: immune tolerance (also referred to as high-replicative, non-inflammatory phase), HBeAg-positive and HBeAg-negative chronic infection, inactive chronic infection (inactive carrier), and resolved chronic infection (functional cure). Transitions between phases are not unidirectional. Patients can revert back to an earlier phase or move back and forth between 2 phases over the course of their chronic infection.

Figure 3.. New Serum Markers of HBV

HBV cccDNA is the template for all known HBV RNA transcripts. These include (i) HBV full-length pregenomic RNA, which is eventually packaged to form progeny virions, (ii) shorter subgenomic RNAs, which are translated into HBsAg, and (iii) pre-core RNA, which encodes the secreted HBeAg and HBcrAg. HBsAg can also originate from noninfectious integrated viral DNA.