Open Access Highly Accessed Case report

Coexistence of HBsAg and HBsAb in a difficult-to-treat chronic hepatitis B: loss of HBsAg with entecavir plus tenofovir combination

Giovanni Galati1, Antonio De Vincentis1*, Umberto Vespasiani-Gentilucci1, Paolo Gallo1, Donatella Vincenti2, Maria Carmela Solmone2, Chiara Dell’Unto1 and Antonio Picardi1

Author Affiliations

1 Clinical Medicine and Hepatology Unit, Campus Bio Medico University of Rome, 200, Alvaro Del Portillo Street, Rome 00128, Italy

2 National Institute for Infectious Diseases “Lazzaro Spallanzani”, 292 Portuense Street, Rome 00149, Italy

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BMC Gastroenterology 2014, 14:94  doi:10.1186/1471-230X-14-94

Published: 17 May 2014



Some reports have documented the coexistence of Hepatitis B surfage Antigen (HBsAg) and anti-HBsAg antibodies (HBsAb) in patients with chronic hepatitis B (CHB), often in the absence of amino acid substitutions in the HBsAg sequences of the Hepatitis B Virus (HBV) genome able to explain an immunological escape variant.

HBV genome has a very compact coding organization, with four partially overlapping open reading frames (ORFs). Because the reverse transcriptase region (rt) of HBV polymerase overlaps the HBsAg ORF, it is possible that some mutations in the HBsAg region correspond to mutations in the rt ORF, conferring resistance to current antiviral therapies.

This unique case explores the response to antiviral therapies of a CHB with concurrent HBsAg and HBsAb positivity, and analyse the clinical implications of possible mutations in rt and HBsAg ORFs.

Case presentation

Here we describe the case of a 59 year-old Italian man suffering from Hepatitis B envelope Antigen (HBeAg) positive CHB with concurrent HBsAb positivity. By ultra-deep pyro-sequencing (UDPS) technique, mutations conferring immunological escape or resistance to antiviral therapies were found neither in HBsAg nor in HBV rt ORFs, respectively.

The patient was unsuccessfully treated with interferon, adefovir monotherapy and adefovir plus entecavir combination. Surprisingly, during entecavir plus tenofovir combination, anti-HBe seroconversion and HBsAg loss were observed, while the titer of HBsAb persisted.


Concurrent HBsAg/HBsAb positivity in active CHB is a clinical and virological dilemma. In this setting, there are not consistent data about the response to conventional therapies and the immunological balance between host and virus remains so far unexplained. This is, to our knowledge, the first case described of a CHB with HBsAg/HBsAb positivity, wild type for clinically relevant mutations in HBsAg and rt ORFs, successfully treated with a combination of nucleot(s)ide analogues (NAs).

HBeAg positive chronic hepatitis B; HBsAg; Anti-HBs; Coexistence; Ultra-deep pyro-sequencing; Immunological escape; Nucleos(t)ide analogues; Combination; Entecavir; Tenofovir