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.