The serological pattern, "anti-HBc alone", characterized by the presence of antibodies against the core antigen of hepatitis B virus (anti-HBc) as the only marker of hepatitis B, is not rare in a diagnostic setting. Depending on the prevalence of HBV infection and the patient group investigated, 1-31% of positive anti-HBc results are isolated positive findings. Anti-HBc alone is frequently observed in intravenous drug addicts, HIV-infected individuals, patients who are coinfected with HBV and hepatitis C virus, and pregnant women. However, it is not clear how this profile should be interpreted. Several studies have shown that anti-HBc alone is not only compatible with acute and resolved HBV infection but also with chronic infection. The reasons for the lack of HBsAg and anti-HBs in anti-HBc-alone individuals are not clear, but several mechanisms and possibilities have been suggested that could explain this phenomenon, some of which are delineated in this article.

The course of HBV infection is determined by the interplay between viral replication via HBV protein production and the host's immune response. Therefore, the diagnosis of infection in clinical practice is established by the serological detection of HBV protein products as well as antibodies produced by the host. Although the serological findings for assessing the clinical course of infection are already well established, the expression of viral proteins and the dynamics of antibody production may vary during the natural course of infection. This causes the HBV infection to be occasionally associated with the presence of unusual serologic profiles, which can lead to doubts in the interpretation of results and mistaken serological diagnosis. The simultaneous detection of HBsAg and anti-HBs in the blood stream comprises an atypical serological profile, somewhat incoherent, whose significance can be complicated to establish. Outlined in this article are some immunological and molecular mechanisms which could justify the existence of this profile in which there is a great laboratorial and clinical interest.

During hepatitis B virus (HBV) infection, at least four antigen-antibody systems are observed: HBsAg and anti-HBs; preS antigen and anti-preS antibody; HBcAg and anti-HBc; and HBeAg and anti-HBe. Through the examination of these antigen-antibody systems, hepatitis B infection is diagnosed and the course of the disorder may be observed. Although the serologic findings that allow both the diagnosis of HBV infection as well as assessing of its clinical course are already well established, the dynamics of viral proteins expression and of the antibodies production may vary during the infection natural course. This causes the HBV infection to be occasionally associated with the presence of uncommon serological profiles, which could lead to doubts in the interpretation of results or suspicion of a serological result being incorrect. This paper is dedicated to the discussion of some of these profiles and their significance.

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Although genomic detection is considered the gold standard test on HBV infection identification, the HBsAg investigation is still the most frequent clinical laboratory request to diagnose HBV infection in activity. However, the non-detection of HBsAg in the bloodstream of chronic or acutely infected individuals has been a phenomenon often observed in clinical practice, despite the high sensitivity and specificity of screening assays standardized commercially and adopted in routine. The expansion of knowledge about the hepatitis B virus biology (replication/life cycle, genetic variability/mutability/heterogeneity), their biochemical and immunological properties (antigenicity and immunogenicity), in turn, has allowed to elucidate some mechanisms that may explain the occurrence of this phenomenon. Therefore, the negativity for HBsAg during the acute or chronic infection course may become a fragile or at least questionable result. This manuscript discusses some mechanisms that could explain the negativity for HBsAg in a serological profile of individuals with HBV infection in activity, or factors that could compromise its detection in the bloodstream during HBV infection.

Viral hepatitis is a liver infection caused by one of the six hepatitis viruses: hepatitis A, B, C, D, E, and G virus (HAV to HEV and HGV). These agents differ in their biological, immunological, pathological and epidemiological characteristics. They cause infections that, when symptomatic, lead to clinical manifestations and laboratory findings that are not specific to a particular virus, often making differential diagnosis difficult, especially when no knowledge is available regarding the patient's medical history or the epidemiological background. A number of acute-phase serological markers, such as anti-HAV, anti-HBc, anti-HDV and anti-HEV IgM antibodies, are able to provide a clear indication of an infection caused by HAV, HBV, HDV or HEV. Anti-HCV antibodies and HGV/RNA are used for the diagnosis of HCV and HGV infections. The importance of each of these markers will be reviewed, and different factors that can interfere with the diagnosis of acute infections caused by these viruses will be described.

Hepatitis C virus infection is a global health problem that has important epidemiological and clinical consequences. It has been well established that exposure to infected blood is the main risk factor for HCV transmission. However, in 20% of cases the agent transmission occurs by unknown route or in the presence of an unidentified source of infection. Understanding of the epidemiology of HCV is needed to help us define future control and preventive strategies. Herein, we discuss about diagnosis of HCV infection and hepatitis C surveillance in the context of its transmission.

Acute exacerbations of chronic hepatitis B are common, and may even be the first presentation of hepatitis B virus (HBV) infection. Sometimes, patients involved in these scenarios may have mistaken diagnosis of acute hepatitis B. The reason for the confusion is that the two forms of infection manifestation resemble remarkably in clinical, biochemical, and serological features, such as apparent rapid onset of severe disease, advanced grades of encephalopathy, high aminotransferases and prolonged international normalized ratios (INRs), as well as positivity for HBsAg and for IgM anti-HBc antibodies and DNA detection. Therefore, these two entities cannot be distinguished easily without historical information of HBV-associated chronic infection or recent HBV exposure, information that is often inaccurate. Considering the different prognoses, treatment strategies, and the epidemiological impact in the public health context, the correct diagnosis is extremely important. Despite the lack of effective and reliable tests to differentiate between acute infection and acute exacerbation of chronic HBV infection, the expression and kinetic evaluation of viral markers present in the circulation of individuals infected, the observation of physical-chemical properties of specific antibodies, and the combination of these findings represent some strategies in serology that could assist in differentiating between the two entities, or at least in the guidance for the correct diagnosis.