Isolated Anti-HBc: Significance and Management

Abstract

Hepatitis B virus (HBV) infection is prevalent worldwide and is associated with dramatic levels of morbidity and mortality. Isolated anti-HBc (IAHBc) is a particular serological pattern that is commonly found in immunocompromised patients. There is ongoing debate regarding the management of patients with IAHBc. Herein, we summarize the current guidelines and the newest evidence. The frequency of IAHBc is variable, with a higher prevalence in some populations, such as persons living with HIV and others immunocompromised patients. The risk of HBV reactivation depends on host factors (including immunosuppression) and viral factors. It is now well established that immunocompromised patients can be classified into three groups for risk according to the type of immunosuppression and/or treatment. In patients at high risk, HBV therapy has to be considered systematically. In patients at moderate risk, the decision is based on the level of HBV DNA (preemptive treatment or monitoring and vaccination). In patients with low risk, HBV vaccination is another possible approach, although further studies are needed to assess the type of preemptive strategy.

Keywords: HBV reactivation; hepatitis B infection; immunosuppression; isolated anti-HBc antibodies; management; viral hepatitis.

Figure 1

Hepatitis B virus life in hepatocyte [3,4]. Modified from Ait-Goughoulte M, Lucifora J, Zoulim F, Durantel D. Innate antiviral immune responses to hepatitis B virus. Viruses. 2010;2(7):1394-410.

Figure 2

Level of anti-HBc depending on the stage of HBV infection. This figure represents the level of anti-Hbc according to the phase of HBV infection. It has been shown that anti-HBc level is higher in case of chronic HBV infection (especially in case of negative HbeAg) than in occult HBV infection and prior HBV infection. ¹ Prior HBV infection: HBsAg -, anti-HBc +, HBV DNA -, ALT/AST normal ² Cutoff 6.6 IU/mL: sensitivity of 60.7% and specificity of 75.3% ³ Occult HBV infection: HBsAg -, anti-HBc +, HBV DNA + ⁴ Cutoff 89 IU/mL: sensitivity of 95.8% and specificity of 98% ⁵ Chronic HBV infection: HBsAg + for ≥6 months HBV: Hepatitis B Virus anti-HBc: Hepatitis B core antibody; HBeAg: hepatitis B e-antigen.

Figure 3

Proposed algorithm for the management of patients with IAHBc and immunosuppressive treatment or condition. The figure represents our proposed algorithm to manage immunocompromised patients with IAHBc according to three different risk groups. ¹ High-risk group: B-cell depleting agents as rituximab ² Moderate-risk group: HIV infection, TNFα inhibitors, corticosteroids at high or moderate doses, systemic cancer chemotherapy, cytokine-based therapies, immunophilin inhibitors, tyrosine kinase inhibitors, proteasome inhibitors, histone deacetylate inhibitors ³ Low-risk group: corticosteroids at low dose or intra-articular, Abatacept, Tocilizumab, Methotrexate, Azathioprine, 6-mercaptopurine, Direct antiviral agents for HCV ⁴ HBV reactivation: seroconversion of HBsAg and detectability of HBV DNA ⁵ HBV vaccination: as in the general population with 3 doses of vaccine at 20µg with a control of anti-HBs one month after the last dose ETV: entecavir; TDF: tenofovir diproxil fumarate; TAF: tenofovir alafenamide; ALT: alanine-aminotransferase; AST: aspartate-aminotransferase.