Monitoring of Hepatitis B Virus (HBV) DNA and Risk of HBV Reactivation in B-Cell Lymphoma: A Prospective Observational Study.
BACKGROUND
There is no standard management of reactivation of hepatitis B virus (HBV) infection in HBV-resolved patients without hepatitis B surface antigen (HBsAg), but with antibodies against hepatitis B core antigen and/or antibodies against HBsAg (anti-HBs).


METHODS
We conducted a prospective observational study to evaluate the occurrence of HBV reactivation by serial monthly monitoring of HBV DNA and to establish preemptive therapy guided by this monitoring in B-cell non-Hodgkin lymphoma (B-NHL) treated with rituximab plus corticosteroid-containing chemotherapy (R-steroid-chemo). The primary endpoint was the incidence of HBV reactivation defined as quantifiable HBV DNA levels of ≥ 11 IU/mL.


RESULTS
With a median HBV DNA follow-up of 562 days, HBV reactivation was observed in 21 of the 269 analyzed patients. The incidence of HBV reactivation at 1.5 years was 8.3% (95% confidence interval, 5.5-12.4). No hepatitis due to HBV reactivation was observed in patients who received antiviral treatment when HBV DNA levels were between 11 and 432 IU/mL. An anti-HBs titer of <10 mIU/mL and detectable HBV DNA remaining below the level of quantification at baseline were independent risk factors for HBV reactivation (hazard ratio, 20.6 and 56.2, respectively; P < .001). Even in 6 patients with a rapid increase of HBV due to mutations, the monthly HBV DNA monitoring was effective at preventing HBV-related hepatitis.


CONCLUSIONS
Monthly monitoring of HBV DNA is useful for preventing HBV reactivation-related hepatitis among B-NHL patients with resolved HBV infection following R-steroid-chemo (UMIN000001299).
Department of Hematology and Oncology.
Shigeru
S
Kusumoto
Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences.
Yasuhito
Y
Tanaka
Department of Hematopoietic Stem Cell Transplantation Data Management and Biostatistics, Nagoya University Graduate School of Medicine.
Ritsuro
R
Suzuki
Department of Hematology, National Cancer Center Hospital, Tokyo.
Takashi
T
Watanabe
Department of Internal Medicine, Sapporo Hokuyu Hospital.
Masanobu
M
Nakata
Department of Medical Oncology, Kanagawa Cancer Center, Yokohama.
Hirotaka
H
Takasaki
Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Saga University.
Noriyasu
N
Fukushima
Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University.
Takuya
T
Fukushima
Department of Hematology, Sasebo City General Hospital.
Yukiyoshi
Y
Moriuchi
Divisions of Oncology and Hematology, National Cancer Center Hospital East, Kashiwa.
Kuniaki
K
Itoh
Department of Hematology and Infectious Diseases, Kumamoto University School of Medicine.
Kisato
K
Nosaka
Division of Hematology, National Hospital Organization Kyushu Cancer Center, Fukuoka.
Ilseung
I
Choi
Department of Hematology and Oncology, Anjo Kosei Hospital.
Masashi
M
Sawa
Department of Chemotherapy, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital.
Rumiko
R
Okamoto
Division of Hematology-Oncology, Chiba Cancer Center.
Hideki
H
Tsujimura
Department of Hematology and Oncology, Nagoya Daini Red Cross Hospital.
Toshiki
T
Uchida
Department of Hematology, National Hospital Organization Hokkaido Cancer Center, Sapporo.
Sachiko
S
Suzuki
Department of Hematology and Medical Oncology, Fujita Health University School of Medicine, Toyoake.
Masataka
M
Okamoto
Department of Oncology/Hematology, Shimane University Hospital, Izumo.
Tsutomu
T
Takahashi
Division of Hematology and Oncology, Toyohashi Municipal Hospital.
Isamu
I
Sugiura
Department of Hematology and Rheumatology, Tohoku University Hospital, Sendai.
Yasushi
Y
Onishi
Department of Hematology, International Medical Center, Saitama Medical University, Hidaka.
Mika
M
Kohri
Department of Hematology, National Hospital Organization Nagasaki Medical Center, Ohmura.
Shinichiro
S
Yoshida
Department of Hematology, Yokohama City University Medical Center.
Rika
R
Sakai
Department of Hematology and Oncology, Tokai University School of Medicine, Isehara.
Minoru
M
Kojima
Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine.
Hiroyuki
H
Takahashi
Department of Hematology and Oncology, Nagoya University Graduate School of Medicine.
Akihiro
A
Tomita
Department of Hematology, National Cancer Center Hospital, Tokyo.
Dai
D
Maruyama
Department of Hematopoietic Stem Cell Transplantation Data Management and Biostatistics, Nagoya University Graduate School of Medicine.
Yoshiko
Y
Atsuta
Department of Medicine, Shinshu University School of Medicine, Matsumoto.
Eiji
E
Tanaka
Department of Hematology and Oncology, Shiga Medical Center for Adults, Moriyama.
Takayo
T
Suzuki
Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya.
Tomohiro
T
Kinoshita
Department of Hematology and Oncology, Nagoya Daini Red Cross Hospital.
Michinori
M
Ogura
The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa.
Masashi
M
Mizokami
Department of Tumor Immunology, Aichi Medical University School of Medicine, Japan.
Ryuzo
R
Ueda
D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D006509:Hepatitis B / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000150:complications* / Q000453:epidemiology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
D000998:Antiviral Agents; D004279:DNA, Viral
HBV DNA monitoring; HBV reactivation; preemptive antiviral therapy; resolved HBV infection; rituximab