The prognosis of hepatitis B inactive carriers in Japan: a multicenter prospective study.
BACKGROUND
Hepatitis B e antigen (HBeAg)-negative inactive carriers, the majority of hepatitis B virus (HBV) carriers, are considered to have a good prognosis. The definition of the inactive HBV carrier state has been based on HBV DNA and alanine aminotransferase (ALT) levels. Here we conducted a prospective study involving 18 hospitals to clarify the prognosis of HBeAg-negative inactive carriers.


METHODS
Three hundred eighty-eight HBeAg-negative inactive carriers at the baseline were observed prospectively from January 2011 to November 2015. We evaluated the primary end point, defined as the development of cirrhosis, hepatocellular carcinoma (HCC), or liver-related death. Also, we analyzed the factors associated with inactive carrier dropout and markedly increased levels of ALT or HBV DNA or both during the follow-up period.


RESULTS
At the baseline, the mean age was 57.5 ± 13.1 years and 42 % of patients were male. No individual developed cirrhosis, HCC, or liver-related death during the follow-up period (1035 ± 252 days). Loss of inactive carrier status was seen in 75 patients (19.3 %). Factors associated with failure to meet the inactive carrier criteria in the multivariate analysis were the levels of ALT (hazard ratio 1.13, 95 % confidence interval 1.07-1.19, p < 0.001), HBV DNA (hazard ratio 2.70, 95 % confidence interval 1.63-4.49, p < 0.001), and γ-glutamyl transpeptidase (hazard ratio 1.01, 95 % confidence interval 1.00-1.02, p = 0.003) at the baseline.


CONCLUSIONS
Most inactive carriers in Japan had a good prognosis. However, despite the short observation period, some patients had loss of IC status. The long-term prognosis of inactive carriers remains unclear; therefore, careful follow-up of inactive carriers is needed.
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chiba, 260-8670, Japan.
Takashi
T
Taida
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chiba, 260-8670, Japan. araim-cib@umin.ac.jp.
Makoto
M
Arai
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chiba, 260-8670, Japan.
Tatsuo
T
Kanda
Department of Gastroenterology, Sapporo-Kosei General Hospital, Sapporo, Hokkaido, Japan.
Shuhei
S
Hige
Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan.
Yoshiyuki
Y
Ueno
Safety and Health Organization, Chiba University, Chiba, Japan.
Fumio
F
Imazeki
Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Tokyo, Japan.
Namiki
N
Izumi
Department of Internal Medicine, Division of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
Eiji
E
Tanaka
Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
Noboru
N
Shinkai
Department of Liver, Biliary Tract and Pancreas Diseases, Fujita Health University, Toyoake, Aichi, Japan.
Kentaro
K
Yoshioka
Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Yasunari
Y
Nakamoto
Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
Shuhei
S
Nishiguchi
Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.
Masataka
M
Tsuge
Departments of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Ehime, Japan.
Masanori
M
Abe
Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Michio
M
Sata
Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, Omura, Nagasaki, Japan.
Hiroshi
H
Yatsuhashi
Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Akio
A
Ido
Department of Gastroenterology, Chiba Kaihin Municipal Hospital, Chiba, Japan.
Kazuhiko
K
Kita
Department of Gastroenterology, Kimitsu Chuo Hospital, Kisarazu, Chiba, Japan.
Ryousaku
R
Azemoto
Department of Gastroenterology, Chiba Aoba Municipal Hospital, Chiba, Japan.
Yoshio
Y
Kitsukawa
Department of Gastroenterology, Numazu City Hospital, Numazu, Shizuoka, Japan.
Nobuaki
N
Goto
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chiba, 260-8670, Japan.
Osamu
O
Yokosuka
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D002353:Carrier State / Q000821:virology*; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006509:Hepatitis B / Q000821:virology*; D006513:Hepatitis B e Antigens / Q000097:blood; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies
D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D000410:Alanine Transaminase
Chronic hepatitis; Hepatitis B virus; Inactive carrier; Prognosis