People with acute hepatitis who test positive for the hepatitis B surface antigen (HBsAg) face nine times the risk of developing a form of intensive, rapid liver failure, regardless of what strain of virus they contracted or the origins of their disease. That's the conclusion of a team of Taiwanese researchers who launched a study to determine if the underlying form of acute hepatitis in individual HBsAg-positive patients had any effect on their risk of developing this intensive, or fulminant, liver failure.

The study's findings were published in the June issue of the journal Infection.¹

The incidence of fulminant hepatitis is minute in hepatitis B and C, as well as other strains individually, but much higher when a person is infected with multiple strains, wrote researchers in the Liver Research Unit at Chang Gung Memorial Hospital in Taipei, Taiwan.

However, in that country, nearly two-thirds of those with sporadic acute hepatitis carry the hepatitis B surface antigen, but test negative for antibodies against HBV—a form of "occult" hepatitis, the researchers reported.

Antigens are substances in the body that stimulate an immune response. They may be contained within or on the surfaces of viruses, bacteria, other microorganisms, or cancer cells. In a normal immune response, an antigen is recognized as being foreign, prompting the immune system to consolidate its forces to defend the body against it, as well as attacking it.² In occult hepatitis, the antigen is present in the body, but when doctors use tests to search for evidence of antibodies that would normally be attacking the antigen (and thus, the virus), they don't appear.

In a previous study,³ the investigators determined that the risk of contracting a much more aggressive form of hepatitis was higher in those with pre-existing evidence of hepatitis B surface antigen in the acute phase of the infection compared to those with acute HAV, HBV or "non-A, non-B hepatitis" alone.

Link Between HBsAg and Fulminant Liver Disease

In patients with chronic evidence of hepatitis B surface antigen, as well as acute hepatitis, the causes can vary, such as a severe case of underlying chronic HBV infection combined with the acute infection, or a "superinfection" with other non-B strains of the virus, wrote the Taiwanese scientists. But whether this underlying cause has any relation to the risk of fulminant liver failure hasn't been evaluated much, they wrote.

To answer that question, the researchers enrolled 334 patients who had been hospitalized with acute hepatitis. Each patient underwent a range of hepatitis tests and the course of their individual disease was reviewed.

The cause of each person's acute hepatitis was then evaluated. In 177 patients who had tested positive for the hepatitis B surface antigen, about 20 percent had a form of aggressive acute disease, which was "significantly higher than in those with acute hepatitis A, B, C, E or non A-E," the researchers explained. They also found that older patients tended to have fulminant hepatitis more often than younger ones, but the difference in age was not significant. However, when the patients were classified as those with the antigen and those without, older age played a more significant role in whether they also had this aggressive form of the disease. In any event, regardless of age, the researchers noted that patients with the antigen "were at a 9-fold increased risk of fulminant hepatitis" compared to those who were not chronic carriers of HBsAg., the investigators noted.

Underlying Cause Not a Factor

In conclusion, the proportion of patients with aggressive liver failure was about 20 percent in the group who tested positive for the hepatitis B surface antigen. That contrasts with about 3 percent of the patients without this marker of infection. Thus, the only connection to fulminant hepatitis is the presence of the antigen, regardless of the underlying causes of the hepatitis infection, the researchers concluded.

For example, while it's well known that those with acute hepatitis D superinfection (a more aggressive form of HDV) in those who are chronic carriers of HBsAg, a more severe acute hepatitis typically erupts. However, in this study, the incidence of aggressive hepatitis in people with acute hepatitis D superinfection was not much different than in those with superinfections caused by other viral strains, the Taiwanese investigators found.

Further, the investigators learned that the incidence of fulminant hepatitis was not much different between those positive for HBV DNA (a more sensitive test than a serology exam that looks for genetic material in the virus as an indicator of disease) and those who tested negative, they wrote.

The findings are similar to those of other researchers in that many of the patients carrying the HBV antigen had no evidence of antibodies against the virus, based on serology tests.

More Research Needed

"These data suggested that the incidence of fulminant hepatitis in HBV s-antigen carriers with viral superinfection varied little, if any, with the different [origins] of viral superinfection," they wrote. "However, the number of patients in this cohort was relatively small; further studies of a larger cohort of patients are needed to confirm this finding."

In conclusion, an underlying chronic infection caused by the hepatitis B virus in those with other forms of acute hepatitis can significantly impact the outcome of the disease. Regardless of the origin, those with evidence of chronic HBV infection through the presence of the hepatitis B surface antigen face a significantly higher risk of developing a more aggressive form of liver disease, the investigators wrote.

1. Chu Cm, Liaw YF. Increased incidence of fulminant hepatic failure in previously unrecognized HBsAg carriers with acute hepatitis independent of etiology. Infection 2005 Jun;33(3):136-9.

2. The Merck Manual. Immune Disorders. Biology of the Immune System. Available at: http://www.merck.com/mmhe/sec16/ch183/ch183a.html?qt=antigen&alt=sh. Accessed June 23, 2005.

3. Chu CM, Liaw YF.  The incidence of fulminant hepatic failure in acute viral hepatitis in Taiwan: increased risk in patients with pre-existing HBsAg carrier state. Infection 1990 Jul-Aug;18(4):200-3.