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Case Reports
. 2024 Feb 15:15:1351782.
doi: 10.3389/fimmu.2024.1351782. eCollection 2024.

Case report: Identification of Hepatitis B Virus in the cerebrospinal fluid of neuromyelitis optica spectrum disorders and successful treatment with ofatumumab and inebilizumab

Linjun Cai  1 , Xu Liu  1 , Hongyu Zhou  1 , Jinmei Li  1 , Dong Zhou  1   2 , Zhen Hong  1   2   3
Affiliations
Case Reports

Case report: Identification of Hepatitis B Virus in the cerebrospinal fluid of neuromyelitis optica spectrum disorders and successful treatment with ofatumumab and inebilizumab

Linjun Cai et al. Front Immunol. .

Abstract

Neuromyelitis optica spectrum disorder (NMOSD) is a rare demyelinating disease of the central nervous system primarily affecting the optic nerves, spinal cord, and brainstem. Viral infection may trigger NMOSD. Here, we report the case of a 34-year-old female presenting with a range of symptoms including nausea, vomiting, dysphagia, choking, and fatigue with unsteady gait, diplopia, hearing loss, left-sided facial paralysis, breathing difficulties, and hoarseness of voice. Her HBV DNA concentration, as determined by quantitative PCR analysis, exceeded 5×107 IU/ml in serum and 4.48×102 IU/ml in CSF. Next-generation sequencing of CSF revealed 1,528 HBV sequences in DNA analysis and 6 sequences in RNA analysis. Serum aquaporin-4 antibody (AQP4-Ab) titer was 1:10, and the CSF titer was 1:3.2. Brain magnetic resonance imaging showed high signal intensities in the brain stem, medulla oblongata, and left middle cerebellar peduncle with mild restricted-diffusion. The patient received antiviral and hepatoprotective medications before the high-dose methylprednisolone pulse therapy. However, the patient did not respond well to the first-line treatment. Subsequently, the patient received ofatumumab and inebilizumab. Throughout the follow-up period, there was a gradual improvement in her neurological symptoms, with no reactivation of hepatitis B or deterioration of liver function observed. Thereby, to the best of our knowledge, we report the first case of successful treatment with ofatumumab and inebilizumab in a patient with NMOSD concurrent with HBV infection.

Keywords: case report; hepatitis B virus; inebilizumab; neuromyelitis optica spectrum disorders; ofatumumab.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Timeline of disease disability course and different treatment regimes. The x-axis indicates the number of days after admission. The left y-axis indicates ALT (IU/L) and AST (IU/L). The right y-axis also indicated EDSS score. ALT: normal values < 40 IU/L ml; AST: normal values < 35 IU/L; EDSS is used to quantify the level of disability in NMOSD, ranging from 0 to 10, with higher scores representing increasing levels of disability; IVIG: 0.4 g/kg intravenous immunoglobulins daily for 5 days; IVMP, intravenous methylprednisolone 1000 mg for 5 consecutive days, followed by oral prednisone (1 mg/kg) with a weekly reduction of 5 mg. Throughout the entire immunotherapy process, ALT and AST showed some fluctuations without significant elevation. There was no clinical improvement after receiving IVMP and IVIG, and the EDSS score worsened to 9 on day 15 from admission. Ofatumumab was subcutaneously injection on days 39, 46, 53 (20 mg per dose) from admission; inebilizumab was intravenously infusion on days 83, 90 (300 mg per dose) from admission. After receiving ofatumumab and inebilizumab treatments, there was a gradual improvement in symptoms, and the EDSS score changed from 9 to 3. ALT, aspartate aminotransferase; AST, alanine aminotransferase; IVMP, intravenous methylprednisolone; IVIG, intravenous immunoglobulin; OP, oral prednisone; OFA, Ofatumumab; INE, inebilizumab; EDSS, Expanded Disability Status Scale.
Figure 2
Figure 2
Sequence reads mapped to HBV in CSF from NGS results. (A) Sequence reads of HBV DNA in CSF with a total coverage of 69.18% and an average depth of 6.22 X; (B) Sequence reads of HBV RNA in CSF with a total coverage of 1.57% and an average depth of 1.00 X. HBV, hepatitis B virus; CSF, cerebrospinal fluid; NGS, next generation sequencing.
Figure 3
Figure 3
Brain MRI. Lesions (arrowed) on brain MRI images before (A–E) and after (F-J) antiviral and immunotherapy showing obviously manifested shrinkage after treatment. (A) T2-weighted showed medulla oblongata lesion. Lesion area: 2.4 cm2; (B) T2-weighted showed dorsal aspect of the brainstem and left cerebellar peduncle lesions. Lesion area: 3.3 cm2; (C) T2-weighted showed dorsal aspect of the brainstem and left cerebellar peduncle lesions. Lesion area: 1.8cm2; (D) No significant enhancement before treatment; (E) Diffusion-weighted MRI (DWI) showed mild limited diffusion. Lesion area: 1.7 cm2; (F) T2-weighted showed a reduction in the area of medullary lesions, with an area of 1.0 cm²; (G) T2-weighted showed a reduction in the area of brainstem and left cerebellar peduncle lesions, with an area of 2.0 cm2; (H) T2-weighted showed a reduction in the area of brainstem and left cerebellar peduncle lesions, with an area of 0.7 cm2; (I) No significant enhancement after treatment; (J) Sagittal view showed medulla oblongata lesion.
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The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Open access funded by Helsinki University Library. This work was supported by the National Key Research and Development Program of China (Grant No. 2022YFC2503800), and Clinical Research Incubation Project of West China Hospital of Sichuan University (22HXFH022).

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