Abstract
BackgroundThe hepatitis B virus (HBV) is one of the leading causes of acute, chronic and occult hepatitis (OBI) representing a serious public health threat. Cytokines are known to be important chemical mediators that regulate the differentiation, proliferation and function of immune cells. Accumulating evidence indicate that the inadequate immune responses are responsible for HBV persistency. The aim of this study were to investigate the cytokines IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10 and IL-17A in patients with OBI and verify if there is an association between the levels of these cytokines with the determination of clinical courses during HBV occult infection.Methods114 patients with chronic hepatitis C were investigated through serological and molecular tests, the OBI coinfected patients were subjected to the test for cytokines using the commercial human CBA kit. As controls, ten healthy donors with no history of liver disease and 10 chronic HBV monoinfected patients of similar age to OBI patients were selected.ResultsAmong 114 HCV patients investigated, 11 individuals had occult hepatitis B. The levels of cytokines were heterogeneous between the groups, most of the cytokines showed higher levels of production detection among OBI/HCV individuals when compared to control group and HBV monoinfected pacients. We found a high level of IL-17A in the HBV monoinfected group, high levels of TNF-α, IL-10, IL-6, IL-4 and IL-2 in OBI/HCV patients.ConclusionThese cytokines could be involved in the persistence of HBV DNA in hepatocytes triggers a constant immune response, inducing continuous liver inflammation, which can accelerate liver damage and favor the development of liver cirrhosis in other chronic liver diseases.
Highlights
The hepatitis B virus (HBV) is one of the leading causes of acute, chronic and occult hepatitis (OBI) representing a serious public health threat
We found a significant increase in the median of IL-2 in occult HBV infection (OBI)/hepatitis C virus (HCV) patients when compared to healthy controls, other studies find overexpression of IL-2 exclusively in patients infected with OBI when compared to healthy individuals and patients who have resolved HBV infection [62] and in patients monoinfected with HCV [63]
We found high levels of IL-6 in the OBI/HCV group in our study and significant difference between OBI/HCV compared to monoinfected HBV group and healthy controls, this increase in IL-6 expression could be attributed to HCV co-infection, since several studies have already found that this cytokine is associated with HCV chronic infection [63, 72, 73]
Summary
The hepatitis B virus (HBV) is one of the leading causes of acute, chronic and occult hepatitis (OBI) representing a serious public health threat. The persistence of replication-competent HBV DNA (i.e. episomal HBV covalently closed circular DNA [cccDNA]) in the liver tissue and/or blood of patients with negative results for the hepatitis B surface antigen (HBsAg) antigen by currently available assays is called occult HBV infection [4,5,6] It can occur after the resolution of a self-limited acute infection or after a long time of infection, if there is any clinical evidence or biochemical change in liver function, using these virus carriers, Ribeiro et al Virol J (2021) 18:15 with a potential risk of transmitting the infection [5, 7, 8]. "False" OBI occurs due to the presence of mutations in the S gene (escape mutants) that produce modified HBsAg that are not recognized by commercially available detection assays [11,12,13]
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