Clinical prediction of failure of Lamivudine prophylaxis for hepatitis B virus-infected patients undergoing cytotoxic chemotherapy for malignancy.
Although lamivudine (LAM) prophylaxis is recommended for patients infected with hepatitis B virus (HBV) undergoing chemotherapy for malignant disease, HBV reactivation sometimes occurs during or after LAM administration. The aim of this study was to determine predictors of LAM prophylactic failure in patients with malignancies. Patients with malignancies were routinely screened for serum hepatitis B surface antigen (HBsAg) from June 2002 to August 2008. All consecutive, HBsAg-positive patients received LAM prophylaxis during and after completion of chemotherapy. We assessed risk factors for virologic breakthrough and withdrawal hepatitis. Death without HBV reactivation was regarded as a competing risk event, which was adjusted by Fine and Gray's model. A total of 110 patients were included in this study. They received LAM prophylaxis for a median of 9.2 months. Virologic breakthrough occurred in 15 patients at a median of 10.9 months from the initiation of LAM prophylaxis. Withdrawal hepatitis occurred in 15 patients at a median of 2.4 months after cessation of LAM prophylaxis. Multivariable analysis showed that high baseline HBV DNA titer (≥2,000 IU/ml) (hazard ratio [HR], 9.94; P = 0.0063) and the use of rituximab (HR, 3.19; P = 0.027) were significant predictors of virologic breakthrough and that high baseline HBV DNA titer (HR, 5.90; P = 0.007), liver cirrhosis (HR, 10.4; P = 0.002), and distant metastasis (HR, 5.14; P = 0.008) were independent risk factors for withdrawal hepatitis. Patients with high viremia, liver cirrhosis, rituximab treatment, and distant metastasis are at high risk of prophylactic failure and need antiviral agents with a greater barrier to resistance.
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
In Kyoung
IK
Kim
Byeong Gwan
BG
Kim
Won
W
Kim
Donghee
D
Kim
Yoon Jun
YJ
Kim
Jung-Hwan
JH
Yoon
Hyo Suk
HS
Lee
D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004279:DNA, Viral / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D005260:Female; D006509:Hepatitis B / Q000150:complications / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000150:complications* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D011379:Prognosis; D000069283:Rituximab; D015996:Survival Rate; D017211:Treatment Failure; D019562:Viral Load / Q000187:drug effects
D058846:Antibodies, Monoclonal, Murine-Derived; D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D019259:Lamivudine; D000069283:Rituximab