Meta-transcriptomic identification of hepatitis B virus in cerebrospinal fluid in patients with central nervous system disease.

Determining the etiological basis of central nervous system (CNS) infections is inherently challenging, primarily due to the multi-etiological nature. Using RNA sequencing, we aimed to identify microbes present in cerebrospinal fluid (CSF) of two patients suffering CNS infection, previously diagnosed with Cryptococcus sp. and Streptococcus pneumoniae infection, respectively. After meta-transcriptomic analysis, and confirmation with real-time PCR, hepatitis B virus (HBV) was detected in the CSF of two patients diagnosed with CNS syndrome. Phylogenetic analysis of the partial HBV genomes from these patients showed that they belonged to genotypes B and C and clustered with other viruses of Asian origin. In countries with high levels of HBV endemicity, the virus is likely to be found in patients diagnosed with CNS infections, although whether it contributes to symptoms and pathology, or is simply a coincidental infection, is unknown and merits further investigation.

Contribution of quantitative viral markers to document hepatitis B virus compartmentalization in cerebrospinal fluid during hepatitis B with neuropathies.

Extrahepatic manifestations linked to hepatitis B Virus (HBV) are usually indirect consequences of immune-mediated mechanisms triggered by the virus replication. Strong evidence of brain HBV replication is missing and direct involvement of HBV in nervous system symptoms has been rarely reported. We report two cases of neurological manifestations contemporary to HBV infection. In both cases, HBV-DNA and HBsAg could be quantified in the cerebrospinal fluid (CSF) at relatively high levels. Differential quantification of HBsAg and HBV viral load both in CSF and in blood as well as phylogenic studies on HBV genomic sequences obtained from blood and CSF provided strong arguments for central nervous system viral replication in both cases. Direct causality of HBV replication in the central nervous system in these clinical situations is certainly not demonstrated but these findings could expand the list of hepatitis viruses possibly involved in neurological disorders. Further studies should be promoted to better document possible HBV replication in the brain tissues and its consequences.

Hepatocyte growth factor (HGF) in patients with hepatitis B and meningitis.

OBJECTIVES: The present study investigates serum hepatocyte growth factor (HGF) levels in patients with acute and chronic hepatitis B and the relation between these levels and intrahepatic inflammatory markers of the liver and fibrosis, as well as the cerebrospinal fluid (CSF) HGF levels in patients with meningitis and the relation between these levels and CSF findings. To our knowledge this is the first study regarding CSF HGF levels in tuberculous meningitis. PATIENTS AND METHODS: The study consisted of 35 patients with chronic hepatitis B (HbeAg and HBV-DNA positive), 20 with acute hepatitis B, 20 with acute bacterial meningitis and 15 having tuberculous meningitis. HGF levels in the serum and CSF samples were measured by using the ELISA method. RESULTS: The mean serum HGF levels in acute hepatitis B group were found statistically significantly higher than those in the control group and chronic hepatitis B group (p<0.0001). It was established that serum HGF levels in patients with chronic hepatitis B were significantly correlated with serum alanine aminotransferase (ALT) and HBV-DNA levels (r: 0.816, 0.951; p<0.05, respectively). Similarly, serum HGF levels of patients with chronic hepatitis B were correlated with fibrosis score and hepatic activity index of the liver histopathology (r: 0.750, 0.459; p<0.05, respectively). The mean CSF HGF levels of patients with acute bacterial meningitis and tuberculous meningitis were higher than those in the control group (p<0.05). In addition, it was observed that mean CSF HGF levels in patients suffered from tuberculous meningitis were statistically significantly higher than those in acute bacterial meningitis (p<0.05). CONCLUSIONS: We suggest that serum HGF level in patients with chronic hepatitis B might reflect viral load, necro-inflammatory activity in the liver and the degree of structural progression. Our findings have demonstrated that tuberculous meningitis cause increased HGF concentrations in CSF. It is, therefore, suggested that examination of HGF levels in CSF may provide additional information in the differential diagnosis.

Safety of neonatal hepatitis B vaccine administration.

OBJECTIVE: To determine whether hepatitis B vaccination of newborns increases the incidence of fever and/or suspected sepsis. METHODS: A prospective clinical study was undertaken at the Kaiser Permanente San Francisco Medical Center involving normal full term newborns born between November 1, 1991, and April 30, 1994. During this time 3302 infants were vaccinated within 21 days of birth with hepatitis B vaccine, and 2353 were not. Clinical and demographic data were collected from Kaiser Permanente's existing clinical information systems, and laboratory data for blood and cerebrospinal fluid (CSF) cultures were obtained from the comprehensive automated regional laboratory reporting system. RESULTS: There were no significant differences between vaccinated and unvaccinated newborns in the proportion of infants who received care for fever (0.8% vaccinated and 1.1% unvaccinated, P = 0.28), allergic reactions, seizures or other neurologic events in the first 21 days of life. Vaccinated newborns were significantly less likely to undergo microbiologic evaluation for possible sepsis. Among vaccinated newborns 4.0% had blood cultures and 1.6% had CSF cultures. Among infants who were not vaccinated 8.3% had blood cultures and 1.6% had CSF cultures (P <0.001 for both tests). CONCLUSION: This study found no evidence that newborn hepatitis B vaccination is associated with an increase in the number of febrile episodes, sepsis evaluations or allergic or neurologic events. In addition our data did not support any increase in medical procedures attributed to receipt of hepatitis B vaccine.

Case report: psychosis associated with hepatitis B.

An acute disintegrative disorder in a child with acute hepatitis B virus (HBV) infection is described. Both hepatitis B surface antigen (HBsAg) and HBV-DNA were detected in cerebrospinal fluid (CSF) by means of enzyme-linked immunosorbent assay (ELISA) and the polymerase chain reaction (PCR) technique respectively. A markedly elevated level of CSF adenylate kinase (AK), which normalised as the patient recovered spontaneously, suggested an organic brain disorder. Demonstration of intra-blood-brain barrier production of IgG supported the possibility of local infection by HBV within the central nervous system.

Intra blood-cerebrospinal fluid-barrier detection of hepatitis B virus.

Hepatitis B, a major public health concern worldwide, is caused by hepatitis type B virus, a hepdnavirus that infects only human and certain nonhuman primates, and replicates strictly in hepatocytes. By using the techniques of slot and Southern blot DNA hybridization, and electron microscopy, the presence of HBV was identified in the cerebrospinal fluid of three affected individuals.

The spinal fluid of acute hepatitis B patients--an occupational hazard?

Spinal fluid and serum samples from 19 patients, with acute viral hepatitis, type B, already known to have HBs antigenemia, were tested for the detection of HBsAg by two techniques; Hemagglutination Inhibition (H.I.) and Enzyme Linked Immuno Sorbent assay (ELISA). HBsAg was detected in all serum samples by both techniques while all spinal fluid samples were free of that antigen except one sample that was found to contain HBsAg by the ELISA technique only. This sample was also proved to contain occult blood as shown by the positive benzidine reaction.

CSF cytology of acute viral meningitis and meningoencephalitis.

The CSF of 12 patients with acute meningitis and meningoencephalitis of viral nature (proven in 10 and probably in 2) was investigated by light microscopy. In early CSF, 1--31% reactive lymphocytes and 1--6% plasma cells were found consistently. In addition, various lymphoid cell features of marked immune activation were disclosed in association: cell polymorphism, normal-appearing mitosis and binucleation, abnormal nuclear lobulation and even partition, as well as Russell bodies, morular appearance and clasmatosis in plasma cells. The CSF findings are discussed with respect to those described in tuberculous meningitis and multiple sclerosis and distinguishing features are suggested to occur in early CSF of viral meningitis.