Olympia E Anastasiou1, Marek Widera2, Jens Verheyen2, Johannes Korth2, Guido Gerken3, Fabian A Helfritz4, Ali Canbay3, Heiner Wedemeyer5, Sandra Ciesek6. 1. Institute of Virology, University Hospital Essen, University Duisburg-Essen, Germany; Department of Gastroenterology and Hepatology, University Hospital of Essen, Germany. Electronic address: olympia_anastasiou@yahoo.com. 2. Institute of Virology, University Hospital Essen, University Duisburg-Essen, Germany. 3. Department of Gastroenterology and Hepatology, University Hospital of Essen, Germany. 4. Department of General, Visceral and Transplantation Surgery, University Hospital of Essen, Germany. 5. Department of Gastroenterology and Hepatology, Hannover Medical School, Germany; German Center for Infection Research, DZIF, Germany. 6. Institute of Virology, University Hospital Essen, University Duisburg-Essen, Germany; German Center for Infection Research, DZIF, Germany.
Abstract
BACKGROUND: The presence of anti-HBc antibodies indicates direct encounter of the immune system with hepatitis B virus (HBV). OBJECTIVES: Aim of our study was to seek for anti-HBc negative but HBV replicating patients and analyze their clinical course and preconditions. STUDY DESIGN: From 1568 HBV-DNA positive patients, 29 patients (1.85%) tested negative for anti-HBc. The absence of anti-HBc could be confirmed in 19 patients using an alternative assay. In 16 of 19 cases, a partial or full HBV genome analysis was performed with NGS sequencing to evaluate if specific mutations were associated with anti-HBc absence. As a control group samples from 32 matched HBV infected patients with detectable anti-HBc were sequenced. RESULTS: Patients with detectable HBV-DNA and sequenced HBV core region in the confirmed absence of anti-HBc were diagnosed with acute HBV infection (n=3), HBV reactivation (n=9) and chronic hepatitis B (n=4). Most patients (12/16) were immunosuppressed: 3/16 patients had an HIV coinfection, 7/16 patients suffered from a malignant disease and 4/16 patients underwent solid organ transplantation (from which 2/4 had a malignant disease). Compared to the control cohort, HBV variants from anti-HBc negative patients showed less variability in the core region. CONCLUSIONS: In the absence of anti-HBc, HBV-DNA was most often found in immunocompromised hosts. Distinct mutations or deletions in the core region did not explain anti-HBc negativity. It would be advisable not to rely only on a single result of anti-HBc negativity to exclude HBV infection in immunocompromised hosts, but to measure anti-HBc repeatedly or with different methods.
BACKGROUND: The presence of anti-HBc antibodies indicates direct encounter of the immune system with hepatitis B virus (HBV). OBJECTIVES: Aim of our study was to seek for anti-HBc negative but HBV replicating patients and analyze their clinical course and preconditions. STUDY DESIGN: From 1568 HBV-DNA positive patients, 29 patients (1.85%) tested negative for anti-HBc. The absence of anti-HBc could be confirmed in 19 patients using an alternative assay. In 16 of 19 cases, a partial or full HBV genome analysis was performed with NGS sequencing to evaluate if specific mutations were associated with anti-HBc absence. As a control group samples from 32 matched HBV infectedpatients with detectable anti-HBc were sequenced. RESULTS:Patients with detectable HBV-DNA and sequenced HBV core region in the confirmed absence of anti-HBc were diagnosed with acute HBV infection (n=3), HBV reactivation (n=9) and chronic hepatitis B (n=4). Most patients (12/16) were immunosuppressed: 3/16 patients had an HIV coinfection, 7/16 patients suffered from a malignant disease and 4/16 patients underwent solid organ transplantation (from which 2/4 had a malignant disease). Compared to the control cohort, HBV variants from anti-HBc negative patients showed less variability in the core region. CONCLUSIONS: In the absence of anti-HBc, HBV-DNA was most often found in immunocompromised hosts. Distinct mutations or deletions in the core region did not explain anti-HBc negativity. It would be advisable not to rely only on a single result of anti-HBc negativity to exclude HBV infection in immunocompromised hosts, but to measure anti-HBc repeatedly or with different methods.
Authors: Olympia E Anastasiou; Foteini Almpani; Anke Herrmann; Guido Gerken; Markus Ditschkowski; Sandra Ciesek Journal: Hepatol Commun Date: 2017-11-06
Authors: Adam Abdullahi; Olga Mafotsing Fopoussi; Judith Torimiro; Mark Atkins; Charles Kouanfack; Anna Maria Geretti Journal: Open Forum Infect Dis Date: 2018-10-05 Impact factor: 3.835