Acute hepatitis B virus infection or acute exacerbation of chronic hepatitis B infection: the differential serological diagnosis

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.