Woman With HBeAg-Negative HBV and Slightly Elevated AFP
The patient is a 42-year-old black woman with hepatitis B virus (HBV) infection (asymptomatic). Her serologies are as follows: hepatitis B surface antigen (HBsAg)-positive, HBs antibody (Ab)-negative, hepatitis B e antibody (HBeAb)-positive, HBeAg-negative, and hepatitis B core antibody (HBcAb)-positive. Her viral DNA quantified per PCR is 2000 copies/mL. Her alpha-fetoprotein (AFP) level is 16. She is immune to hepatitis A virus, and is hepatitis C virus-negative. Results of ultrasound are pending; she has not yet been biopsied. What are your suggestions?

There are 2 issues apparent in this patient. The first is her HBeAg-negative HBV infection. This likely represents a variant ("mutant") HBV virus that can be associated with an increased risk of progressive liver disease and of hepatocellular carcinoma (HCC). The second is the slight elevation in her AFP level, and we do not yet know her ultrasound screening results.

I would consider treating this patient initially with lamivudine, 100 mg daily. She is unlikely to respond to interferon. Lamivudine can initially be effective as therapy for HBeAg-negative patients. Although drug resistance may eventually develop, should that occur, other therapies, such as adefovir, would be possible. Why lamivudine at all? The drug safety profile of lamivudine is well known, it is less costly, and it is well tolerated, making it a good initial choice in my opinion. An alternative would be to use adefovir outright. In a recent study, adefovir was associated with biochemical and virologic response over 48 weeks. A longer study will be helpful in determining its long-term efficacy.

As to screening this patient for HCC, I would continue to do twice-yearly AFP levels and once-yearly ultrasound examinations. Ultrasound can be a cost-effective screening device for HCC, but the overall utility of AFP measurement and ultrasound in identifying early HCC lesions remains to be proven. If there is a progressive increase in AFP, even in the presence of a negative ultrasound for a liver mass, I would consider performing a magnetic resonance imaging (MRI) study of the liver. If this study is also negative, I would increase the frequency of radiologic screening to every 6 months and alternate ultrasound and MRI examination.