What does the test result "anti-HBc alone" mean? (i.e., an isolated finding of positive anti-HBc IgG in the presence of negative HBsAg and negative anti-HBs)

Author: Dr. Beat Helbling

Updated: 10 / 2007

Answer:

An isolated positive test for anti-HBc IgG is called "anti-HBc alone" and is defined as positive anti-HBc present simultaneously with negative HBsAg and negative anti-HBs (without further testing for anti-HBe, HBeAg and HBV-DNA).

The finding of "anti-HBc alone" occurs frequently in both normal and at-risk populations, such as intravenous drug users. During the course of an uncomplicated, self-limited HBV infection, "anti-HBc alone" is normally found after the disappearance of HBsAg and before the emergence of anti-HBs. This "core window" usually lasts for a few weeks. However in the majority of people who test positive for “anti-HBc alone”, this finding will persist for years to decades.

"Anti-HBc alone" also arises in cases of previous HBV infection which occurred years to decades ago, in particular, when anti-HBs disappear before anti-HBc is detected.

Many cases of "anti-HBc alone" are neither in the core window (early recovery phase of a self-limiting HBV infection) nor indicative of late immunity. In these cases the finding is interpreted as a possible chronic "low dose" HBV infection or an atypical infection with still poorly defined HBV mutants.

Only a small proportion (1% - 3%) of individuals with "anti-HBc alone" have circulating HBV DNA. However, the percentage of intravenous drug users or HCV-coinfected people with HBV DNA is between 30% and 40%, and in HIV-coinfected people it is as high as 70% - 80%. One unproven hypothesis is that some specific viral coinfections may restrain the expression of HBsAg.

Relatively few histological studies are available. Generally, liver histology in people with "anti-HBc alone" without performing further assays for circulating HBV DNA shows at most, discrete and usually non-specific evidence of liver inflammation with no further symptoms of hepatitis.

There are also few studies concerning infectivity of people with "anti-HBc alone" with or without circulating HBV DNA. Episodes of transmission of the infection from mother to newborns and in blood or organ donors have been reported, but their prevalence is not known.

As a result, the finding of "anti-HBc alone" cannot be clearly interpreted in terms of patient prognosis or infectivity. Patients are simply regarded as “potentially infectious”. Due to this uncertainty, different countries employ differing procedures when faced with "anti-HBc alone" findings. In the case of blood donation, many countries, including the United States test blood donations for anti-HBc, and blood from positive donors is discarded. In other countries, such as Switzerland, blood banks do not perform this assay. The question of how to treat "anti-HBc alone" cases faces similar controversy, particularly in those individuals who also test positive for circulating HBV DNA. Most experts recommend no treatment because the majority of cases exhibit normal liver enzymes.

Since individuals with “anti-HBc alone” are considered potentially infectious, standard precautions against infection should be observed. Regular sexual partners of "anti-HBc alone" individuals should be vaccinated against hepatitis B. “Anti-HBc alone” individuals who have multiple sexual partners should not engage in unprotected sex. Hepatitis B vaccination of newborns of "anti-HBc alone" positive mothers is recommended.

References:

Grob P, Jilg W et al. Serological Pattern "Anti-HBc Alone": Report on a Workshop. Journal of Medical Virology 2000;62:450-455.

Reichen J et al. Hepatitis B Virusinfektion: Diagnose, klinische Folgen, Therapie und Prophylaxe. PRAXIS 2002;91:307-319.

Dufour R.D. Lott J.A. Laboratory guidelines for screening, diagnosis and monitoring of hepatic injury. Clinical Chemistry 2000;12:1-60.