Comprehensive analysis of patients with neuromyelitis optica spectrum disorder (NMOSD) combined with chronic hepatitis B (CHB) infection and seropositive for anti-aquaporin-4 antibody

Abstract

Previous research indicated the association between hepatitis B virus (HBV) infection/vaccination and the onset of demyelinating diseases. However, most of these studies were single case reports, and comprehensive data are still scarce. Here we present a comprehensive analysis of 10 patients with neuromyelitis optica spectrum disorder (NMOSD) combined with chronic hepatitis B (CHB) infection and seropositive for anti-aquaporin-4 antibody (AQP4-Ab). Demographic, clinical, laboratory, neuroimaging, outcome, and follow-up data of the 10 patients were retrospectively analyzed. The median age at the onset of NMOSD was 35 years (range 25-43). Nine patients were female (90%). All patients were positive for HBsAg and had been diagnosed with CHB earlier than with NMOSD. One patient had an autoimmune disease. All patients had normal thyroid function. Paresthesia and visual impairment were the most common clinical symptoms. The cerebrospinal fluid (CSF) parameters (protein and glucose) were normal in 10 cases, whereas slightly higher CSF white blood cell count was detected in 3 patients. The brain and spinal cord magnetic resonance imaging findings were abnormal in 8 patients. All patients were treated with hormone and immunosuppressive therapy, and anti-HBV agents. Patients with detectable serum HBV DNA were more prone to liver damage after receiving high doses of corticosteroids. In 8 patients, the symptoms improved before they were discharged. Two patients with optic neuritis (ON) maintained the symptoms. A month later, 1/8 patient had recurrence of symptoms, and one ON patient progressed to NMO. Overall, the characteristics of NMOSD patients with CHB and seropositive for AQP4-Ab are usually nonspecific. Abnormal liver function test results in NMOSD patients should be a warning of possible CHB infection, and the treatment should be modified accordingly.

Neuromyelitis optica spectrum disorder with active replication of hepatitis B virus and seropositive anti-aquaporin-4 antibody

“…Therefore, the diagnosis of HBV-associated NMOSD was confirmed after exclusion of other infectious factors. Liu et al [ 5 ] speculated that the molecular simulation and immune cross-reaction between HBsAg and myelin antigen of the CNS may potentially explain the primary pathophysiologic mechanisms underlying NMOSD with HBV infection. Molecular simulation of T cell infective factors has been suggested as a potential mechanism of demyelination of the CNS after HBV vaccination.…”

“…In both treatments, the patient's visual acuity improved after a few days; furthermore, in the second treatment, after 5 days of treatment with antiviral drugs, a rapid recovery of the liver function and gradual reduction of symptoms of systemic discomfort were observed. Liu et al [ 5 ] retrospectively analyzed 10 patients with NMOSD with CHB infection who were seropositive for AQP4-Ab; they found an increased risk of liver damage in these patients after high-dose glucocorticoid therapy. Therefore, they suggested that patients with NMOSD should be aware of the possibility of HBV infection once liver damage occurs, which would necessitate adjustments to treatment.…”

“…[ 9 ] Zhao et al [ 7 ] found that patients with NMOSD and concomitant CHB infection exhibited severe manifestations. Liu et al [ 5 ] analyzed the clinical features of 10 Chinese patients with NMOSD combined with CHB infection who were seropositive for aquaporin-4; they explained the possible pathologic mechanism between the association of NMOSD and HBV infection. However, the role of HBV infection in the emergence of NMOSD was not specified, and no recommendations regarding the use of corticosteroids in patients with NMOSD and HBV infection were outlined.…”

New-onset neuromyelitis optica spectrum disorder in a patient with COVID-19 and chronic Hepatitis B co-infection

“…( Mormile, 2015 May ) Despite one study of 10 patients with chronic HBV and seropositive NMOSD hypothesizing a cross-reactivity between HBsAg and myelin proteins, we believe there is currently insufficient evidence to suggest that chronic HBV increases the risk for developing a demyelinating disorder. ( Liu et al, 2018 Feb 20 ) COVID-19 is far more likely to be an immunological trigger to developing autoimmune neurological disorders.…”

Induction of aquaporin 4-reactive antibodies in Lewis rats immunized with aquaporin 4 mimotopes

“…The combined results of the following searches were pooled for this table: unlimited search, search limited to H. pylori (taxid: 210), search limited to Mycobacterium tuberculosis typus humanus (taxid: 1773), and search limited to RNA viruses (taxid: 2559587). The limited searches were done due to possible associations of NMOSD with infections by H.pylori[56], M. tuberculosis[57][58][59][60], and Hepatitis viruses (RNA viruses][61][62][63]. The top Blast Hits on 100 subject sequences were analyzed.…”