DISCUSSION
In HBsAg negativity, OHB infection defined by anti HBc IgG +/-, anti HBs
+/- serological table, presence of HBV DNA in serum or plasma is
frequently reported in HIV-infected patients, especially those who have
not received treatment. The mechanisms responsible for HBsAg negativity
in occult infection are controversial. Among the causes of HBsAg
negativity, decrease or absence of HBsAg expression, decrease of HBsAg
secretion from hepatocytes, change of HBsAg antigenicity can be counted.
The presence of mutations in the HBV genome, particularly the envelope
gene, is an important cause of HBsAg negativity (1,8).
OHB infection has been investigated in many patient groups such as blood
donors, pregnant women, those receiving immunosuppressive therapy, and
hemodialysis patients, and OHB infection is encountered in HIV-infected
patients, especially those who have not received treatment. In the
literature, it has been reported that the prevalence of OHB infection in
HIV-infected individuals varies between 0% and 89.5% (9). In our
study, the frequency of OHB in 279 patients was found to be 1.4%. One
of the reasons for the difference in the prevalence of OHB infection is
the use of diagnostic methods with different sensitivity and specificity
(1).
In HIV / OHB co-infected individuals, although antibody (anti-HBc)
positivity against HBV core antigen is a marker of HBV exposure, OHB and
HIV / OHB co-infected cases have been reported in regions with high
endemicity where anti-HBc is negative (2). Recent studies show that
approximately 20% of OHB infections are serologically negative, and
anti-HBc positivity, which was used as a marker for the detection of
OHB, is not sufficient in the diagnosis of OHB infection. In a study,
serological evidence of HBV infection could not be shown in 2.2% of OHB
patients (2). In studies conducted in South Africa (2.2%) and the USA
(0.55%), HBV DNA positivity was reported in 2.2% and 0.55% of
seronegative individuals, respectively (8). In our study, it was
determined that 169 (60.6%) of the included HBsAg negative patients
were positive for Anti HBs and 125 (57.3%) of them were positive for
Anti HBc IgG. It was found that 2 out of four patients diagnosed with
OHB were Anti HBS positive, 4 were Anti HBc IgG positive, and the HBV
DNA levels of these patients were between 60-1128 IU / mL. These results
show that routine HBV antibody tests are not sufficient for OHB
screening. It is emphasized in the literature that the gold standard
test for the diagnosis of OHB is the demonstration of the presence of
HBV DNA in the liver. Since routine liver biopsy is not performed in
HIV-infected patients, blood samples are generally used in the diagnosis
of OHB infection. No evidence has been shown that HIV infection changes
the sensitivity or specificity of these tests (10).
Some studies have reported a trend towards elevated ALT and AST levels
in HIV / OHB co-infected individuals. In a study investigating the
prevalence of OHB and the long-term effects of OHB in HIV-infected
women, OHB infection was detected in 2% of HIV-infected women who were
anti-HBc positive, and it was observed that the increases in
aminotransferase levels were not associated with detectable HBV DNA
(17). In our study, no significant relationship was found between OHB
and liver enzyme elevation.
On the other hand, the clinical effect of OHB in HIV-infected patients
is still controversial. There is evidence that OHB is associated with
hepatic exacerbations, advanced liver fibrosis, decreased response to
interferon therapy, and hepatocellular carcinoma (HCC) (12). In patients
with HIV / OHB co-infection, HIV-induced immunodeficiency may accelerate
the progression to cirrhosis and hepatocellular carcinoma. Literature
data report that the fibrosis score is higher in patients with OHB (13).
However, since fibrosis scoring was not routinely performed in HIV / OHB
co-infected patients in centers participating in our study, no comment
could be made on this issue. These data indicate that large-scale
studies are needed regarding the clinical course, status of liver enzyme
levels, and fibrosis scoring in patients with suspected HIV / OHB.
In a study conducted with HIV-1 infected pregnant women, it was reported
that low CD4 count, cases over 35 years of age and HCV co-infection were
independent risk factors for isolated anti-HBc positivity (11).
Suppression of the immune system has been associated with a CD4 T cell
count of <100 cells / µL, birth in northern Thailand, loss of
anti-HBs and isolated anti-HBc in HIV-infected patients. It has been
argued that anti-HBs production decreases against HBV infection as the
age gets older (11). In the study conducted by Walz et al., It was
reported that 7 out of 105 babies born from isolated anti-HBc positive
women were infected with HBV. In the study of Khamduang et al., 47 women
with occult HBV infection had HBV DNA levels (> 15 IU /
mL). It was found that none of their babies were infected with HBV (11).
In our study, a significant correlation was found between OHB and CD4
count. Our data suggest that the possibility of OHB should be kept in
mind in cases with low CD4 cell count. Viremia is suppressed in OHB
patients due to the strong host defense that occurs during acute or
chronic infection (12). Similarly, in our study, HBV DNA levels in
patients with OHB are between 60-1128 IU / mL.
In our study, no significant difference was found in hemoglobin and
bilirubin levels and complete blood count in patients with HIV-OHB
co-infection. However, albumin values were found to be <3.5 in
three OHD patients (p = 0.043) (18).
Pooled HBV nucleic acid test (NAT) can be used to detect HIV / OHB
coinfection. In a study conducted in India, OHB infection was detected
in 10% of HIV-infected participants; It has been argued that the pooled
HBV NAT test used in the detection of HIV / OHB coinfection is a
cost-effective and highly specific test. It has been reported that the
sensitivity of this method is low in patients with low HBV DNA levels
(14). In a study conducted in Cameroon, anti-HBc positivity was detected
in more than 50% of blood donors; The presence of OHB has been shown in
1% of the patients with HBsAg negative and antiHBc positive. This study
reports that performing HBsAg test alone is not sufficient in
eliminating the risk of HBV transmission through transfusion and
screening potential donors; recommends the use of HBV NAT test in
addition to anti-HBc screening (16).
In our study, patients diagnosed with OHB were those under ART treatment
for 2-8 years. It was determined that 2 patients with a diagnosis of OHB
received tenofovir disoproxil / emtristabine / dolutegravir treatment,
and the other 2 patients received tenofovir alafenamide / emtristabine /
cobicistat / elvitegravir treatment. This shows that OHB can develop in
HIV patients under ART treatment (19).
Routine serological markers and especially isolated Anti-HBc positivity
may be insufficient in the diagnosis of OHB in HBsAg negative patients.
The most reliable method in the diagnosis of OHB in these patients is
HBV DNA detection. HBV DNA levels in these patients are usually low
(<1000 IU / mL). A low CD4 count and age> 35 are
among the independent risk factors for OHB. In our study, no significant
difference was found in patients with HIV-OHB co-infection in terms of
liver enzyme levels, hemoglobin and bilirubin levels, and complete blood
count, but a significant correlation was found between OHB and CD4
count. In addition, in our study, it was found that albumin values in
patients with OHB were significantly low. Hypoalbuminemia could be
showing hepatic failure and we can suggest the importance of treatment
that diseases. There was no significant relationship between
transmission routes, sexual preferences and OHB. It has been determined
that all patients with OHB are under ART treatment. The outputs we
obtained from our study clearly show that HIV-infected patients should
be evaluated in terms of OHB co-infection. For the diagnosis of OHB
infection, the HBV DNA test should be used, the test should be performed
before starting HAART, and accordingly, it should be decided to use
drugs effective against HBV in the treatment of patients. There is a
need for large-scale studies investigating the clinical course, liver
enzyme levels, histopathology, and treatment options of HIV-OHB
co-infected patients.