The Inactive Carrier State in Chronic Hepatitis B Infection
The Inactive Carrier State in Chronic Hepatitis B Infection
I have a 41-year-old patient who is hepatitis B e antigen (HBeAg)-negative/HBe antibody (HBeAb)-positive, with normal serum aminotransferases. He is also HBsAg-positive, HB core total Ab-positive, and HB core IgM-negative. What is your diagnosis?
Despite advances in molecular biology, the routine diagnosis of hepatitis B virus (HBV) infection remains serologic. The presence of HBsAg indicates the patient is infected with HBV. The absence of IgM anti-core antibody implies that this patient has chronic rather than acute HBV infection. The patient is HBeAg negative with presence of antibody to e antigen (anti-HBe). In combination with the absence of e antigen, the patient's normal serum aminotransferases suggest an absence of viral replication and hepatic necroinflammatory activity. This patient can therefore be assumed to be in the inactive carrier state, or (in the older literature) a so-called "healthy carrier." However, there are a few important caveats. The term "healthy carrier" has fallen out of favor because chronic HBV infection, even in the absence of clinically overt liver disease, conveys an increased risk of hepatocellular carcinoma. Furthermore, reactivation of HBV replication, either spontaneously or iatrogenically induced by chemotherapy or immunosuppression, can lead to severe liver disease. Another important issue is whether this patient has detectable HBV DNA in serum. Although e antigen was for many years the conventional serum marker of HBV replication, it has become apparent that although many chronically infected patients shed e antigen in response to host immune pressure, they may have persistence of replication. This form of HBV, called e antigen negative chronic HBV, typically occurs after many years of infection. Recent literature has also drawn attention to the insensitivity of serum aminotransferases in excluding hepatic necroinflammatory activity. A number of reports have described extensive inflammatory changes and fibrosis in series of patients with chronic HBV infection and normal liver chemistries but persistent serum markers of replication, including HBV DNA.
Therefore, an important additional diagnostic test in this patient is a serum HBV DNA. If serum HBV DNA is absent, the patient is in the inactive carrier state. In contrast, if serum HBV DNA is detectable, particularly at a level of greater than 2000 IU/mL, the patient has e antigen chronic HBV infection. Irrespective of the presence or absence of detectable serum HBV DNA, this patient requires regular follow-up for surveillance for hepatocellular carcinoma and reactivation of HBV replication.
Question
I have a 41-year-old patient who is hepatitis B e antigen (HBeAg)-negative/HBe antibody (HBeAb)-positive, with normal serum aminotransferases. He is also HBsAg-positive, HB core total Ab-positive, and HB core IgM-negative. What is your diagnosis?
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Response from Paul Martin, MD, FACP Professor of Medicine and Chief, Division of Hepatology, Center for Liver Disease, University of Miami School of Medicine, Miami, Florida |
Despite advances in molecular biology, the routine diagnosis of hepatitis B virus (HBV) infection remains serologic. The presence of HBsAg indicates the patient is infected with HBV. The absence of IgM anti-core antibody implies that this patient has chronic rather than acute HBV infection. The patient is HBeAg negative with presence of antibody to e antigen (anti-HBe). In combination with the absence of e antigen, the patient's normal serum aminotransferases suggest an absence of viral replication and hepatic necroinflammatory activity. This patient can therefore be assumed to be in the inactive carrier state, or (in the older literature) a so-called "healthy carrier." However, there are a few important caveats. The term "healthy carrier" has fallen out of favor because chronic HBV infection, even in the absence of clinically overt liver disease, conveys an increased risk of hepatocellular carcinoma. Furthermore, reactivation of HBV replication, either spontaneously or iatrogenically induced by chemotherapy or immunosuppression, can lead to severe liver disease. Another important issue is whether this patient has detectable HBV DNA in serum. Although e antigen was for many years the conventional serum marker of HBV replication, it has become apparent that although many chronically infected patients shed e antigen in response to host immune pressure, they may have persistence of replication. This form of HBV, called e antigen negative chronic HBV, typically occurs after many years of infection. Recent literature has also drawn attention to the insensitivity of serum aminotransferases in excluding hepatic necroinflammatory activity. A number of reports have described extensive inflammatory changes and fibrosis in series of patients with chronic HBV infection and normal liver chemistries but persistent serum markers of replication, including HBV DNA.
Therefore, an important additional diagnostic test in this patient is a serum HBV DNA. If serum HBV DNA is absent, the patient is in the inactive carrier state. In contrast, if serum HBV DNA is detectable, particularly at a level of greater than 2000 IU/mL, the patient has e antigen chronic HBV infection. Irrespective of the presence or absence of detectable serum HBV DNA, this patient requires regular follow-up for surveillance for hepatocellular carcinoma and reactivation of HBV replication.