User:Oddvector/Seroconversion

Seroconversion in Hepatitis B
Seroconversion plays a major role in the diagnosis and treatment of hepatitis B infections. As in other viral infections, seropositivity indicates that an individual has a sufficiently high concentration of antibody or antigen in the blood to be detectable by standard techniques. While assays for other infections such as COVID-19 and HIV primarily test for seroconversion of antibodies to antigens, assays for HBV also test for antigens. The standard serology panel for seroconversion include hepatitis B surface antigen, hepatitis B surface antibody for IgM and IgG, hepatitis B core antibody for IgM and IgG, and hepatitis B e-antigen.

In the typical disease course for hepatitis B, the individual will first seroconvert for hepatitis B surface antigen (HBsAg); while some can convert within one week, most individuals take about four weeks after initial infection to convert. Anti-core antibodies are the first antibodies produced by the body, first in short-term IgM (anti-HBc IgM), and subsequently in long-term IgG; while levels of IgM anti-HBc will peak around sixteen weeks after exposure and fall within about seven to eight months, IgG anti-HBc will remain detectable in the serum as a sign of chronic infection for years. IgM anti-HBc concentration will fall regardless of whether or not the individual clears the infection. The window period occurs as concentration of HBsAg falls and before the body develops anti-HBs antibodies, lasting approximately six to eight weeks in most individuals. During this time, serology assays can test for total anti-HBc. Levels of anti-surface antibody (anti-HBs) generally become detectable after thirty-two weeks and peak around thirty-six to forty; the production of anti-HBs antibodies indicates imminent resolution of the HBV infection. Anti-HBs concentration falls as the infection resolves but not serorevert completely, and anti-HBs IgG remains positive for years as a sign of immunity.

Hepatitis B e-antigen (HBeAg) is a sign of current infectivity. An individual who is seropositive for HBeAg can infect others, but an individual who is infected with HBV and who never becomes seropositive for HBeAg can still be infective, because not all HBV infections produce HBeAg. For most individuals, those who seroconvert positive for HBeAg during their disease course and subsequently serorevert negative as their infection progresses are no longer infective. Seroreversion from HBeAg is thus used as one marker of resolution of infection.

On a serological assay, the presence of hepatitis B surface antigen (HBsAg) indicates an individual with a currently active hepatitis B infection, whether acute or chronic; the presence of core antibody (anti-HBc) indicates an individual with an infection in general, whether current or previously resolved; and the presence of surface antibody (anti-HBs) indicates an individual with immunity to hepatitis B, whether due to previously resolved infection or due to hepatitis B vaccination. For example, an individual who has never had any exposure to HBV, either by vaccine or by infection, would test negative for the entire serology panel. An individual who has been vaccinated and never had an infection will test seropositive for anti-HBs due to vaccination and negative for markers of infection. An individual with an acute HBV infection would test positive for HBsAg and anti-HBc (total and IgM) while negative for anti-HBs. An individual with a chronic infection would test positive for HBsAg and total anti-HBc, but negative for IgM anti-HBc. An individual who has successfully resolved their HBV infection will test negative for HBsAg, positive for anti-HBc, and may test negative or positive for anti-HBs, although most will test positive.

Some studies have suggested that a significant minority across all population cohorts fails to seroconvert after the standard three-dose series. For these individuals, a booster is recommended. Other studies have indicated that even for those who seroconvert as children or as adults, the immunity conferred may decrease over time, and boosters are also recommended for immunocompromised individuals after five years. However, those who are immunocompetent may forego testing or boosters after the five year period. Individuals who receive vaccination for HBV should undergo serology testing to confirm seroconversion following the initial vaccine series as well as any boosters. Those who are persistent non-responders to the booster series are unlikely to benefit from additional boosters and should instead be cautioned on prevention.