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

October 2004

Editorial

Prevention of HBV-related hepatocellular carcinoma (HCC). Therapy of chronic HBV infection that reduces associated hepatic necroinflammation is hypothesized to decrease the incidence of HCC. Reports of long-term follow-up data in support of this hypothesis have focused on studies of interferon therapy because lamivudine and adefovir dipivoxil have been available only in recent years. Only one randomized controlled trial investigating the incidence of HCC among interferon-treated patients has been conducted (Lin S-M, et al. Hepatology 1999; 29:971-975). In this study 101 HBeAg-positive Taiwanese men were randomized (2:1 ratio) to receive either interferon or no therapy. After a follow-up that ranged from 1 to 12 years, HCC was detected in 1.5% of interferon-treated patients compared to 12% of untreated patients (p = 0.04). The results of other non-randomized studies and case series of interferon therapy on the incidence of HCC have been mixed. A meta-analysis (Camma CM, et al. J Hepatol 2001; 34:593-602) including 7 studies with 853 interferon-treated patients and 652 untreated controls found interferon to have a significant protective effect. However, there was marked heterogeneity among the studies. In the August 2004 issue of the Journal of Viral Hepatitis, S-M Lin and others pooled data from 2 randomized controlled studies of HBeAg-positive patients conducted at the Chang Gung University and Memorial Hospital (Taipei, Taiwan). These studies included 34 patients who received placebo, 67 patients treated with natural lymphoblastoid interferon-alpha (IFN-αnl) (86 after prednisolone priming), and 109 patients treated with recombinant IFN α-2a (56 after prednisolone priming). Patients treated with IFN-αnl after prednisolone priming had the highest sustained response rate. After 11 years of follow-up, a greater percentage of placebo-treated patients (14.7%) than IFN-αnl-treated patients (1.5%, p <0.05) or IFN α-2a-treated patients (3.7%, p <0.05) developed HCC. In addition, the cumulative survival rate was lowest in the placebo group. Multivariate analysis identified IFN therapy as a significant predictor of decreased risk of HCC development and mortality. These data suggest that IFN therapy may reduce the incidence of HCC and prolong survival in patients with chronic HBV infection. A beneficial effect of IFN therapy on HCC development has not yet been observed in studies outside Asia possibly related to the short duration of follow-up and a lower incidence of HCC among Caucasians. (Lin S-M, et al. J Viral Hepat 2004; 11:349-357)

Reactivation of Chronic HBV INFECTION

Occurrence after infliximab therapy for Crohn's disease. Infliximab is the current standard therapy for patients with fistulizing Crohn's disease that is unresponsive to conventional treatment. The use of infliximab is contraindicated in the presence of active infection, and recommendations have been issued concerning the prevention and treatment of bacterial and opportunistic infections prior to the initiation of infliximab infusions. However, little is known about the effects of this immunomodulatory agent on the course of patients with chronic viral hepatitis, and there are no recommendations for the surveillance and treatment of HBV infection before infliximab infusions. Recently 2 cases of severe or fulminant hepatitis B related to infliximab treatment have been reported in patients with rheumatic diseases. In the current article, M. Esteve and associates report the reactivation of HBV in 2 patients with Crohn's disease treated with infliximab. The authors prospectively determined hepatitis markers and liver function tests in 80 Crohn's disease patients treated with infliximab in 3 hospitals in Spain. Chronic HBV infection was identified in 3 patients. Two of these patients developed a severe reactivation of hepatitis B following the withdrawal of infliximab and 1 patient died. The third patient was treated with lamivudine at the time of infliximab therapy and had no clinical or biochemical evidence of liver disease. HBV vaccination was given to 6 other patients, and no changes in hepatic function were detected in these patients. This report indicates the need for screening Crohn's disease patients who require infliximab therapy for HBV infection. The authors recommend antiviral therapy for HBsAg-positive patients who are to receive infliximab treatment and HBV vaccination for patients without natural immunity to HBV at the diagnosis of Crohn's disease. (Esteve M, et al. Gut 2004; 53:1363-1365)

Occurrence during chemotherapy for hematologic malignancies. Anna Maria Pelizzari and colleagues reviewed 32 courses of primary lamivudine prophylaxis given to 23 adult HBV carriers with hematologic malignancies who underwent chemotherapy in order to determine the frequency and clinical significance of the occurrence of HBV YMMD mutants. Lamivudine was administered for a median of 6 months (range, 2-24+ months). After a median follow-up time of 19.5 months (range, 5-40 months), 4 episodes of HBV reactivation with mild hepatitis were observed. YMMD mutation (associated with normal aminotransferase levels) was detected in only one patient who had received lamivudine continuously for 20 months (3.1% of prophylactic lamivudine courses). Prophylactic lamivudine treatment during chemotherapy for patients with hematologic malignancies was associated with a low frequency of YMMD mutant development that was of little clinical significance; this may be related to low pretreatment HBV DNA levels and the short duration of lamivudine treatment in many of the patients. (Pelizzari AM, et al. The Hematology Journal 2004; 5:325-328)

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