Factors associated with the effect of interferon-α sequential therapy in order to discontinue nucleoside/nucleotide analog treatment in patients with chronic hepatitis B

被引:38
作者
Matsumoto, Akihiro [1 ]
Yatsuhashi, Hiroshi [2 ]
Nagaoka, Shinya [2 ]
Suzuki, Yoshiyuki [3 ]
Hosaka, Tetsuya [3 ]
Tsuge, Masataka [4 ]
Chayama, Kazuaki [4 ]
Kanda, Tatsuo [5 ]
Yokosuka, Osamu [5 ]
Nishiguchi, Shuhei [6 ]
Saito, Masaki [6 ]
Miyase, Shiho [7 ]
Kang, Jong-Hon [8 ]
Shinkai, Noboru [9 ,10 ]
Tanaka, Yasuhito [9 ,10 ]
Umemura, Takeji [1 ]
Tanaka, Eiji [1 ]
机构
[1] Shinshu Univ, Sch Med, Dept Med, Matsumoto, Nagano 3908621, Japan
[2] Natl Hosp Org, Nagasaki Med Ctr, Clin Res Ctr, Omura, Japan
[3] Toranomon Gen Hosp, Dept Hepatol, Tokyo, Japan
[4] Hiroshima Univ, Inst Biomed & Hlth Sci, Dept Gastroenterol & Metab Appl Life Sci, Hiroshima, Japan
[5] Chiba Univ, Grad Sch Med, Dept Gastroenterol & Nephrol, Chiba, Japan
[6] Hyogo Coll Med, Dept Internal Med, Div Hepatobiliary & Pancreat Dis, Nishinomiya, Hyogo 6638501, Japan
[7] Kumamoto Shinto Gen Hosp, Dept Gastroenterol & Hepatol, Kumamoto, Japan
[8] Teine Keijinkai Hosp, Ctr Gastroenterol, Sapporo, Hokkaido, Japan
[9] Nagoya City Univ, Grad Sch Med Sci, Dept Virol, Nagoya, Aichi, Japan
[10] Nagoya City Univ, Grad Sch Med Sci, Liver Unit, Nagoya, Aichi, Japan
关键词
hepatitis B core-related antigen; hepatitis B surface antigen; interferon-alpha; nucleoside/nucleotide analogs; sequential therapy; CORE-RELATED ANTIGENS; CLOSED CIRCULAR DNA; SUSTAINED RESPONSE; VIRUS INFECTION; PEGINTERFERON ALPHA-2A; HBV INFECTION; LAMIVUDINE; JAPAN; MONOTHERAPIES; COMBINATION;
D O I
10.1111/hepr.12488
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Aim: The factors associated with the outcome of sequential therapy with interferon-alpha (IFN-alpha) in order to halt nucleoside/nucleotide analog (NUC) maintenance treatment for chronic hepatitis B were analyzed. Methods: A total of 50 patients with chronic hepatitis B who underwent IFN-alpha sequential therapy for cessation of NUC were enrolled retrospectively. The subjects received NUC plus IFN-alpha for 4 weeks followed by IFN-alpha alone for 20 weeks. Natural IFN-alpha of 6-MU doses was administrated three times a week. A successful response to NUC/IFN-alpha sequential therapy was defined as serum hepatitis B virus (HBV) DNA below 4.0 log copies/mL, serum alanine aminotransferase (ALT) below 30 IU/L, and hepatitis B e-antigen negativity at 24 months after completing the treatment. Results: Multivariate analysis revealed that hepatitis B surface antigen (HBsAg) of 3.0 log U/mL or more (P < 0.002) and hepatitis B core-related antigen (hepatitis B core-related antigen [HBcrAg]) of 4.5 log U/mL or more (P < 0.003) at the start of IFN-alpha administration were significant factors associated with a 24-month non-response. Maximal levels of ALT and HBV DNA during the follow-up period after completing IFN-alpha therapy were significantly related (P < 0.001), and receiver operating characteristic analysis showed that both maximal ALT (P < 0.001) and HBV DNA(P < 0.001) were significantly related to the final 24-month response. Conclusion: The combinational use of HBsAg and HBcrAg levels may be useful to predict the 24-month outcome of NUC/IFN-alpha sequential therapy. Maximal levels of ALT and HBV DNA during post-treatment follow-up may also help monitor responses to IFN-alpha sequential therapy.
引用
收藏
页码:1195 / 1202
页数:8
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