拉米在防御HBsAg阳性化疗病人HBV再活动上的效应

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Effect of Epivir-HBV (Lamivudine) to Prevent HBV Reactivation in HBsAG Positive Patients Undergoing Chemotherapy

Hepatitis B virus (HBV) exacerbation is a serious cause of morbidity and mortality in hepatitis B surface antigen (HBsAg) positive patients treated with cytotoxic or immunosuppressive therapy.

The purpose of the current study was to compare the efficacy of pre-emptive and deferred Epivir-HBV (lamivudine) therapy in reducing the incidence of HBV reactivation in HBsAg positive lymphoma patients who had chemotherapy.

The investigators studied 22 HBsAg positive lymphoma patients who were treated with chemotherapy. They were randomized (1:1) to receive lamivudine 100 mg daily 1 week prior to chemotherapy (Group 1) or upon diagnosis of 'HBV virological reactivation' during or after chemotherapy (Group 2) and then continue until 6 weeks after completion of chemotherapy.

Pre-chemotherapy serum HBV genotype was determined by sequencing, serum HBV DNA by Digene Capture II assay and intrahepatic cccDNA was quantitated by real-time fluorescent-probe PCR (TaqMan), using primers specific for cccDNA. Serial ALT and serum HBV DNA were determined at 2 weekly intervals till 6 week after completion of chemotherapy.

Definition of HBV virological reactivation: Elevation of serum HBV DNA > 10 times that of the baseline pre-chemotherapy level or the serum HBV DNA turned from negative to positive (by Digene Capture II assay), and remained positive for two consecutive readings for 7 days apart. Results: Five (45.5%) patients in group 2 and none in group 1 had HBV virological reactivation after chemotherapy (p=0.035).

Despite the administration of lamivudine with the onset of virological reactivation, 3 patients in group 2 still suffered from hepatitis (2 anicteric hepatitis and 1 hepatic failure). For group 2 patients, gender, HBV genotype, age and pre-chemotherapy serum ALT had no significant influence on HBV reactivation based on simple logistic regression analysis.

However, the median intrahepatic cccDNA/cell in subjects with HBV reactivation (79.5, min-max=19-272) was significantly higher than among those without HBV reactivation (1.2, min-max=0-3; p=0.029 by exact Wilcoxon rank sum test).

Conclusions: (1) Preemptive use of lamivudine is preferable to deferred lamivudine treatment for HBsAg positive patients undergoing chemotherapy and (2) a high intrahepatic cccDNA level is associated with HBV reactivation in HBsAg positive patients undergoing chemotherapy.

01/20/03

Reference
G K Lau and others. A RANDOMIZED STUDY OF LAMIVUDINE FOR PREVENTION OF HBV REACTIVATION IN HBSAG POSITIVE PATIENTS UNDERGOING CYTOTOXIC CHEMOTHERAPY. Abstract 836. 53rd AASLD. November 1-5, 2002. Boston, MA. Hepatology 2002: Vol 36 No 4, Pt 2 of 2.