Editorial Board: Emmet B. Keeffe, MD (Chair); Anna Lok, MD; Brian McMahon, MD; Albert Min, MD; Myron Tong, MD; Naoky Tsai, MD; Bruce Tung, MD
HBV Watch^™
Timely Information for Practicing Physicians

SEPTEMBER 2005

HEPATITIS B VIRUS (HBV) DNA levels and hepatocellular carcinoma (HCC)

An etiologic association between chronic HBV infection and HCC is well established. Among patients with chronic HBV infection, male gender, older age, cirrhosis, heavy alcohol consumption, and aflatoxin exposure increase the risk of HCC. Recently, viral factors, including HBV genotype (C>B), HBV core promoter variants, and high levels of HBV replication (the presence of hepatitis B e antigen [HBeAg] and high levels of HBV DNA) have also been reported to be associated with an increased risk of HCC. The study by Yu and others found that Taiwanese hepatitis B surface antigen (HBsAg) carriers who had higher serum HBV DNA levels at presentation were significantly more likely to develop HCC during follow-up. Similar findings had been reported in Senegal and mainland China. Unfortunately, none of these studies monitored serum HBV DNA and aminotransferase levels over time. It is likely that the duration of high levels of HBV replication as well as the intensity and duration of hepatitis activity are more important than a high HBV DNA level on a random occasion in predicting the risk of HCC in individual carriers. Similarly, the prognostic significance of a high serum HBV DNA level at a single time point in a 40-year-old man may be different from that in a 20-year-old woman. Thus, caution must be exercised in initiating antiviral therapy to prevent HCC based on a single high serum HBV DNA level.

HEPATOCELLULAR CARCINOMA

Association with HBV DNA level and genotype. Yu and others report the results of a nested case-control study in which blood samples were collected from 4,841 male HBsAg carriers aged ≥30 years between 1988 and 1992. HCC developed in 154 of these patients. A total of 316 patients among the cohort of HBsAg carriers who had not been diagnosed with HCC were matched to the case patients by age and date of blood collection and were selected as controls. An increased risk of HCC was associated with increasing HBV DNA level and genotype C disease. The adjusted odds ratio for a patient with genotype C HBV with a viral load in the highest quintile was 26.49 (95% confidence interval, 10.41 to 67.42). These data demonstrate that HBV DNA level and HBV genotype may help define HBV carriers at a higher risk for HCC. (Yu M-W, et al. J Natl Cancer Inst. 2005;97:265–272.)

POST- TREATMENT EXACERBATION OF HBV

Analysis of long-term emtricitabine trials. Mondou and colleagues evaluated data across three randomized, double-blind clinical studies (n = 251) of emtricitabine and found that post-treatment exacerbation of HBV occurred in 23% of patients. Post-treatment exacerbation of hepatitis was limited to elevations of aminotransferase levels in most patients, but seven patients had evidence of decompensation and one patient with marked bridging fibrosis required liver transplantation. Development of antibody to HBeAg did not prevent hepatic flares. This analysis shows that patients with chronic HBV infection are at risk for hepatic flares with decompensation following the withdrawal of nucleoside or nucleotide therapy and should be closely monitored for several months. Therapy should probably not be withdrawn in persons with cirrhosis. (Mondou E, et al. Clin Infect Dis. 2005:41:e45–e47.)

NEW AGENTS

Telbivudine trial. Previous preclinical and early clinical studies have demonstrated that telbivudine, an oral nucleoside, has activity against HBV. These findings led Lai and others to conduct a multicenter, double-blind study in which 104 patients with HBeAg-positive chronic hepatitis B were randomized to one of five treatment groups: telbivudine 400 or 600 mg/day, telbivudine 400 or 600 mg/day plus lamivudine 100 mg/day, or lamivudine 100 mg/day. At week 52, patients treated with telbivudine monotherapy had a greater mean reduction in HBV DNA levels (P <0.05), clearance of HBV DNA (P <0.05), and normalization of alanine aminotransferase levels (P <0.05) than did patients receiving lamivudine monotherapy. HBeAg seroconversion occurred in 31% and 22% and viral breakthrough occurred in 4.5% and 15.8% of patients who received telbivudine and lamivudine monotherapy, respectively. Both patients with telbivudine resistance had the rtM204I mutation involving the YMDD motif. Combination therapy did not improve the results achieved with telbivudine monotherapy. All treatments were well tolerated. (Lai C-L, et al. Gastroenterology. 2005;129:528–536.)

REVERSE SEROCONVERSION

Association with disappearance of anti-HBs following allogeneic hematopoietic stem cell transplantation (SCT). Reverse seroconversion (RS), the reactivation of latent HBV infection, has been reported as a complication of allogeneic hematopoietic SCT. Onozawa and associates retrospectively studied serologic markers in 14 SCT recipients who were anti-HBs–positive. Decreases in anti-HBs titer were observed in all patients, and in 12 patients the anti-HBs titer decreased to under the protective value. RS occurred in seven patients after anti-HBs became undetectable. The risk of anti-HBs disappearance and RS were estimated to be 75% and 39.8%, respectively, at 2 years and 100% and 70%, respectively, at 5 years. These data demonstrate that RS is a late-onset complication of allogeneic hematopoietic SCT that can be predicted by monitoring anti-HBs titers. (Onozawa M, et al. Transplantation. 2005;79:616–619.)

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