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

 

AUGUST 2003

TOPIC REVIEW

Antiviral prophylaxis of HBV carriers who receive immunosuppressive or cytotoxic chemotherapy.  Reactivation of HBV replication with increase in serum HBV DNA and ALT levels has been reported in 20-50% of HBV carriers undergoing immunosuppressive or cancer chemotherapies. In most cases, the hepatitis flares are asymptomatic, but icteric flares, and even hepatic decompensation and death have been observed. Uncontrolled studies showed that prophylactic therapy with lamivudine (LAM) can reduce the rate of HBV reactivation, severity of associated hepatitis flares, and mortality compared to historical controls. Although there are limitations with these studies, it seems prudent to administer prophylactic antiviral therapy to HBV carriers at the onset of chemotherapy or immunosuppressive therapy, and to maintain antiviral therapy for 3-6 months afterwards. The benefit versus risk of prophylactic antiviral therapy in HBV carriers who require life-long immunosuppressive therapy, such as renal transplant recipients, is less certain. One approach would be to monitor these patients and initiate antiviral therapy when there is a significant increase in serum HBV DNA or ALT levels, but frequent quantitative HBV DNA testing is expensive and the threshold HBV DNA and ALT values for initiation of antiviral therapy are unclear. In addition, a recent study found that the vast majority (11/12) of HBsAg (+) patients who were closely monitored during the first year after renal transplantation met predefined criteria for LAM treatment, suggesting that prophylactic therapy for all patients may be more practical.  Interferon (IFN) should not be used in this setting because of its marrow suppressive effects and the risk of hepatitis flares. Studies to date have focused on LAM, although adefovir (ADV) may be used as an alternative in patients who are not at risk of renal insufficiency. While HBV reactivation can occur in persons who are HBsAg (-) but anti-HBc and anti-HBs (+), this is infrequent and there is not enough information to recommend prophylaxis at this time.

 

RANDOMIZED STUDIES

Steroid-free chemotherapy and the risk of HBV reactivation.  Glucocorticoids have been linked to an increased risk of hepatitis reactivation in lymphoma patients who are HBsAg carriers.  Ann-Lii Chen and colleagues conducted a study in which 50 patients with non-Hodgkin's lymphoma who were HBsAg (+) were randomized to receive combination chemotherapy with either epirubicin, cyclophosphamide, and etoposide (ACE) or ACE plus prednisolone (PACE).  Nine months after the initiation of chemotherapy, the cumulative incidence of HBV reactivation was 38% in patients treated with ACE compared to 73% in those treated with PACE.  In addition, 11 PACE-treated patients (44%) compared to 3 ACE-treated patients (13%) had a serum ALT elevation >10-fold of normal, and only one ACE-treated patient (4%) versus 7 PACE-treated patients (28%) had icteric hepatitis.  Tumor response and survival rates were similar in both treatment groups.  The results of this study indicate that steroid-free chemotherapy reduces the incidence and severity of HBV reactivation in HBsAg (+) lymphoma patients.  (Cheng A-L, et al. Hepatology 2003;37:1320-1328)

 

Serum HBV DNA as marker for treatment efficacy.  H. Mommeja-Marin and coworkers reviewed the literature to investigate the relationship of treatment-induced changes in HBV DNA levels to activity of chronic HBV infection.  The review included 26 prospective studies with 33 evaluable treatment arms.  Consistent and statistically significant correlations between viral load and histological, biochemical, and serologic evidence of disease activity were observed.  More specifically, the authors observed that a treatment-induced reduction in serum HBV DNA levels of >1 log10 was associated with disease response.  Moreover, the authors found that analyses of serum HBV DNA levels had a broader dynamic range than histology, allowing use to assess results in studies using nucleoside regimens to treat HBV infection.  This review indicates that HBV DNA is potentially a useful and easily measured alternative to histology for assessing HBV disease activity.  (Mommeja-Marin H, et al. Hepatology 2003;37:1309-1319)

 

LAM vs. LAM + hepatitis B immune globulin (HBIg) to prevent post-transplant HBV recurrence.  Maria Buti and colleagues performed a multicenter study in which 29 patients with HBV cirrhosis who had received LAM plus HBIg for one month following liver transplantation were randomized to receive continued therapy with LAM plus HBIg or LAM alone for 17 months.  All patients had been treated with LAM prior to transplantation and HBV DNA was undetectable in all cases at the time of liver transplantation.  After 18 months of follow-up, all patients survived without HBV recurrence.  HBV DNA became detectable by PCR analysis in 4 patients (3 pts in combination arm; 1 pt in LAM monotherapy arm).  The study therapies were well tolerated.  This study did not demonstrate a difference in the post-transplantation HBV recurrence rate in patients treated with LAM monotherapy or the more expensive combination therapy consisting of LAM and repeated HBIg infusions.  (Buti M, et al. J Hepatol 2003;38:811-817)

 

LAM-containing therapy for IFN nonresponders.  Eugene Schiff et al randomized 238 patients with HBeAg (+) chronic hepatitis B who had previously failed IFN therapy to receive a 52-week course of LAM monotherapy (100 mg) or placebo or a 24-week regimen of LAM + IFN.  At week 52, histological response occurred more commonly in the LAM monotherapy group (52%) than in either the placebo group (25%) or the combination therapy group (32%).  HBeAg loss also occurred more frequently in the LAM monotherapy-treated patients.  Durable responses 16 weeks post-treatment were observed in 71% of patients with HBeAg loss.  These results show that LAM monotherapy for 52 weeks is more effective than placebo or a 24-week regimen of LAM plus IFN for IFN-resistant chronic hepatitis B.  More studies of combination therapy are needed.  (Schiff E, et al. J Hepatol 2003;38:616-826)

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