Microbiota-Meditated Immunity Abnormalities Facilitate Hepatitis B Virus Co-Infection in People Living With HIV: A Review.

Hepatitis B virus (HBV) co-infection is fairly common in people living with HIV (PLWH) and affects millions of people worldwide. Identical transmission routes and HIV-induced immune suppression have been assumed to be the main factors contributing to this phenomenon. Moreover, convergent evidence has shown that people co-infected with HIV and HBV are more likely to have long-term serious medical problems, suffer more from liver-related diseases, and have higher mortality rates, compared to individuals infected exclusively by either HIV or HBV. However, the precise mechanisms underlying the comorbid infection of HIV and HBV have not been fully elucidated. In recent times, the human gastrointestinal microbiome is progressively being recognized as playing a pivotal role in modulating immune function, and is likely to also contribute significantly to critical processes involving systemic inflammation. Both antiretroviral therapy (ART)-naïve HIV-infected subjects and ART-treated individuals are now known to be characterized by having gut microbiomic dysbiosis, which is associated with a damaged intestinal barrier, impaired mucosal immunological functioning, increased microbial translocation, and long-term immune activation. Altered microbiota-related products in PLWH, such as lipopolysaccharide (LPS) and short-chain fatty acids (SCFA), have been associated with the development of leaky gut syndrome, favoring microbial translocation, which in turn has been associated with a chronically activated underlying host immune response and hence the facilitated pathogenesis of HBV infection. Herein, we critically review the interplay among gut microbiota, immunity, and HIV and HBV infection, thus laying down the groundwork with respect to the future development of effective strategies to efficiently restore normally diversified gut microbiota in PLWH with a dysregulated gut microbiome, and thus potentially reduce the prevalence of HBV infection in this population.

Quantitative detection of hepatitis B virus DNA in sera from patients with acute hepatitis B.

Two hundred forty-four serial serum samples from 30 adults hospitalized with benign (nonfulminant) acute hepatitis B were tested for the presence of hepatitis B virus (HBV) DNA by a quantitative solution hybridization assay using a 125I-labeled DNA probe complementary to HBV-DNA sequences. Acute hepatitis B was self-limiting in 28 and progressed to chronicity in the remaining two patients. Of the 28 patients with self-limiting hepatitis, 21 (75%) were hepatitis B e antigen (HBeAg) positive, 26 (93%) were HBV-DNA positive, and one patient (3.6%) was negative for both markers on admission to the hospital. HBV-DNA cleared after HBeAg clearance in 20 (71.4%), before HBeAg clearance in five (17.9%) and simultaneously with the loss of HBeAg in the remaining two (7.1%) of the 27 initially HBV-DNA- and/or HBeAg-positive patients. Moreover, HBV-DNA remained detectable in serum for 13.3 +/- 6.6 (range: 4-22) days after the appearance of anti-HBe in 71.4% of these patients. In contrast, HBV-DNA and HBeAg remained persistently positive in the two patients who developed chronic HBV infection. These data show that (1) viremia frequently persists after disappearance of HBeAg and (2) appearance of anti-HBe does not indicate the cessation of HBV replication in adults with acute self-limiting hepatitis B.

Hepatitis B virus in the colostra of HBeAg-positive carrier mothers.

To investigate the amount of hepatitis B virus (HBV) in colostra of hepatitis B e antigen (HBeAg)-positive carrier mothers and the relationship of HBV amount between colostrum and maternal blood, 50 HBeAg-positive carrier mothers were recruited and studied for hepatitis B surface antigen (HBsAg) titer, HBeAg titer, and HBV-DNA concentration in their sera and colostra. According to the presence or absence of seral HBV-DNA determined by dot hybridization, these 50 HBeAg-positive carrier mothers could be divided into two groups: group 1 (n = 28, HBV-DNA < 0.04 ng/ml), and group 2 (n = 22, HBV-DNA > or = 0.04 ng/ml). The colostral HBsAg and HBeAg titers were both significantly higher in group 2 than in group 1. In addition, both colostral HBsAg and HBeAg titers had positive correlation with each corresponding maternal blood. Although the colostral HBV-DNA was undetectable by dot hybridization, all were positive by polymerase chain reaction with Southern blot hybridization. Because HBV-DNA can be detected in all HBeAg-positive carrier mother's milk, it reinforces the necessity of hepatitis B vaccination for the neonates born to these carrier mothers, particularly in countries with a high carrier rate.

HB-antigen in serum and synovialis in acute hepatitis with and without polyarthritis.

In 27 patients suffering from acute hepatitis serum and synovial-fluid were tested for HB-Ag. It was detected in the serum in 19 cases, in the synovial fluid in 2 cases, but never in both serum and synovial-fluid. HB-Ag was not found in 6 patients. Polyarthritis was seen in 10 cases; 5 of them carried HB-Ag in the serum, 2 in the synovial-fluid. A hepatitis B however, was also suspected in the 3 cases with polyarthritis lacking HB-Ag. The results suggest that virus B may persist in joints too and that polyarthritis associated with acute hepatitis is coupled to an infection with virus B.

Electrn microscopic observations on virus-like particles associated with SH antigen.

The structural aspects of SH antigen-containing particles were investigated. These studies confirmed the existence of a large spherical particle (ca. 43 nm) and smaller (ca. 20 nm) rod- and sphere-shaped particles. The large particle consists of an outer and inner membrane and a core of "nucleic acid" as seen by positive staining techniques. The outer membrane of the large particle appears to be similar to that of the 20-nm diameter spheres and rods known to possess the SH antigen.