Hepatitis B virus reactivation in HBsAg-negative patients is associated with emergence of viral strains with mutated HBsAg and reverse transcriptase

Colson, Philippe; Borentain, Patrick; Coso, Diane; Motte, Anne; Aurran-Schleinitz, Thérèse; Charbonnier, Aude; Stoppa, Anne Marie; Chabannon, Christian; Serrero, Mélanie; Bertrand, Julie; Barlési, Fabrice; Serratrice, Jacques; Portal, Isabelle; Botta-Fridlund, Danièle; Tamalet, Catherine; Gerolami, René

doi:10.1016/j.virol.2015.06.017

Cited by 22 publications

(28 citation statements)

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“…A number of additional or missing N‐linked glycosylation sites have been found in all three groups of anti‐HBs(+)/HBV DNA(+) patients. Additional glycosylation sites had been found lately in viral strains of patients with HBV reactivation and chronic hepatitis B infection . The 146N‐linked glycosylation site was detectable in all samples, except in a minority variant sequence (NGS <5%) of one patient undergoing HBV reactivation.…”

Section: Discussionmentioning

confidence: 90%

“…5 Simultaneous anti-HBs and HBV DNA detection has also been reported in patients receiving immunosuppression that develop HBV reactivation. 10 HBV reactivation is marked by the reappearance or rise of HBV DNA in the serum of patients with previously inactive or resolved HBV infection. It usually occurs under immunosuppression, but can in rare cases occur in immunocompetent hosts.…”

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confidence: 99%

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Clinical patterns associated with the concurrent detection of anti‐HBs and HBV DNA

Anastasiou

Widera

Korth

et al. 2017

Journal of Medical Virology

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Simultaneous detection of anti-HBs and HBV DNA is a rare serological combination and has been described in acute and chronic HBV infection. To scrutinize viral and clinical patterns associated with concurrent detection of anti-HBs and HBV DNA. Simultaneous detection of anti-HBs and HBV DNA was observed in 64/1444 (4.4%) patients treated for HBV infection at the University Hospital of Essen from 2006 to 2016 (8 with acute, 20 with reactivated, and 36 chronic HBV infection). Clinical data and laboratory parameters were analyzed. Regions of the small hepatitis B surface antigen (SHB) and the reverse transcriptase (RT) were sequenced using next generation sequencing (NGS). Among the 64 patients with detectable HBV DNA and anti-HBs, 17 were HBsAg negative (HBsAg[-]), and two had acute liver failure. Patients with acute HBV infection had fewer genotype specific amino acid substitutions in the SHB region than patients with reactivated HBV infection (4 [4.5] vs 9 [16.25], P = 0.043). However, we could observe a significantly higher number of mutations in the a-determinant region when comparing chronically infected patients to patients with acute infection (0 [1] vs 1 [1], P = 0.044). The ratio of nonsynonymous to synonymous mutations (Ka/Ks) was on average >1 for the SHB region and <1 for the RT region. The Ka/Ks ratio (>1) in the SHB region indicates that anti-HBs might have exerted selection pressure on the HBsAg. In three cases the diagnosis of acute HBV infection would have been at least delayed by only focusing on HBsAg testing.

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Section: Discussionmentioning

confidence: 90%

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confidence: 99%

Clinical patterns associated with the concurrent detection of anti‐HBs and HBV DNA

Anastasiou

Widera

Korth

et al. 2017

Journal of Medical Virology

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“…HBV RT/HBsAg sequencing detected HBV genotype D with several immune-escape mutations in HBsAg (V96 A/V, M103I, T123N, C124Y, T126I, and G145 K/R) and some RT mutations that were potentially associated with drug resistance (A181S and V214A) ( Table 4). The T123N HBsAg mutation introduces a new Nlinked glycosylation site in HBsAg, which drastically hampers the detection of HBsAg [35]. This mutation can explain this patient's negativity to HBsAg.…”

Section: Description Of the Four Hbv-reactivated Patientsmentioning

confidence: 99%

Persistent risk of HBV reactivation despite extensive lamivudine prophylaxis in haematopoietic stem cell transplant recipients who are anti-HBc-positive or HBV-negative recipients with an anti-HBc-positive donor

Cerva

Colagrossi

Maffongelli

et al. 2016

Clinical Microbiology and Infection

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The overall rate of hepatitis B virus (HBV) reactivation was evaluated in a population of 373 haematological stem cell transplant (HSCT) patients treated with lamivudine (LMV) if they were anti-HBc-positive/HBV-DNA-negative recipients or if they were HBV-negative recipients with an anti-HBc-positive donor. The incidence of HBV reactivation was calculated in two groups of autologous (auto) or allogeneic (allo) HSCT patients who were stratified according to their HBV serostatus. The former group included 57 cases: 10 auto-HSCT and 27 allo-HSCT anti-HBc-positive recipients, two auto-HSCT and three allo-HSCT inactive carriers, and 15 allo-HSCT recipients with an anti-HBc-positive donor. Forty-seven (82.4%) patients in this group received LMV prophylaxis (the median (interquartile range, IQR) of LMV treatment was 30 (20-38) months). The second group consisted of 320 anti-HBc-negative auto-HSCT and allo-HSCT recipients with anti-HBc-negative donors. None of these patients received any prophylaxis. Two patients in the first group and two in the second group experienced reactivation of HBV infection, with an incidence of 3.5% (95% CI 0.4-12.1%) and 0.6% (95% CI 0.1-2.2%), respectively. Only one out of four reactivated patients was LMV-treated. The cumulative probability of HBV reactivation at 6 years from HSCT was 15.8% (95% CI 15.2-16.4%). Three of four viral isolates obtained from the HBV-reactivated patients harboured mutations in the immune-active HBsAg-region. In a HSCT population carefully evaluated for HBV prophylaxis, a risk of HBV reactivation persisted in the group of patients who were not LMV-treated. Only one LMV-treated patient experienced reactivation of HBV with a resistant HBV isolate.

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“…Reactivation of HBV infection in HBsAg positive patients treated with immunosuppressive or cytotoxic treatment is well known (11)(12)(13). Reactivation in patients with resolved HBV infection (HBsAg negative, anti-HBc positive) can also occur during and after immunosuppressive or cytotoxic therapy.…”

Section: Hbv Reactivationmentioning

confidence: 99%

Risk of HBV Reactivation in Patients Infected with HBV/HCV Treated with DAA

Pawłowska

Domagalski

2017

Hepat Mon

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The exact number of HBV/HCV co-infected patients is unknown. In many cases of HBV/HCV co-infection, HCV inhibits replication of HBV. After treatment and eradication of the dominant virus, the other one may then become active. The overall dominant effect appears to be hepatitis C over hepatitis B. Therefore, when planning treatment for eradication of HCV, the risk of HBV reactivation should be taken into account. In interferon-based therapies of patients with HBV/HCV co-infection, some cases of HBV reactivation without hepatitis were observed because IFN is effective against both viruses. In contrast, DAA treatment of hepatitis C in HBV/HCV co-infection is not well established. Currently, no clinical trials have been published regarding treatment of HBV/HCV co-infected patients with HCV DAA therapy. There is several research on HCV DAA therapy in HBV/HCV co-infection, which describes cases of HBV reactivation during and after DDA therapy for HCV. Result of the first available studies demonstrated that patients with HBV/HCV co-infection treated with DAA against HCV should be monitored for HBV reactivation during and after DAA treatment, even though HBV may be inactive at the time of treatment initiation.

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Hepatitis B virus reactivation in HBsAg-negative patients is associated with emergence of viral strains with mutated HBsAg and reverse transcriptase

Abstract: HBsAg and HBV-RT mutations are frequently encountered in patients with HBV-R, resulting in atypical serological testing and emergence of HBV strains resistant to nucleos(t)ides analogs.

Cited by 22 publications

References 50 publications

Clinical patterns associated with the concurrent detection of anti‐HBs and HBV DNA

Clinical patterns associated with the concurrent detection of anti‐HBs and HBV DNA

Persistent risk of HBV reactivation despite extensive lamivudine prophylaxis in haematopoietic stem cell transplant recipients who are anti-HBc-positive or HBV-negative recipients with an anti-HBc-positive donor

Risk of HBV Reactivation in Patients Infected with HBV/HCV Treated with DAA

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