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Effect of achieving drug-free status and HBs antigen decline in sequential therapy with Peg-IFN alfa-2a on long-term nucleoside analog treated patients
Ken Nishino, Miwa Kawanaka, Jun Nakamura, Takahito Oka, Noriyo Urata, Daisuke Goto, Mitsuhiko Suehiro, Hirofumi Kawamoto, Gotaro Yamada;General Iinenternal Medice2, Okayama, Japan
[Objectives] A sustained reduction in HBV DNA and alanine aminotransferase (ALT) levels and the elimination of hepatitis B surface antigen (HBsAg) are important to suppress chronic hepatitis B-induced liver carcinogenesis. We previously reported that in patients receiving long-term nucleoside analog (NA) therapy, HBsAg levels contributed to hepatocellular carcinoma (Kawanaka M et al. Liver Cancer 2014; 3: 41-52). However, long-term NA therapy is less likely to decrease HBsAg levels. Therefore, we administered sequential therapy with pegylated interferon alfa-2a (Peg-IFN alfa-2a) in patients who underwent long-term NA therapy and examined its ability to decrease HBsAg levels and render the patients drug-free.
[Methods] Fourteen patients (mean age, 51 [37-63] years; M/F: 12/2; genotype C: 13 patients) who were treated with NA for ≥2 years (mean, 6.6 years) that resulted in HBV DNA levels ≤2.1 Log IU/mL, ALT level normalization, and HBeAg negativity. Sequential therapy of Peg-IFN alfa-2a was conducted for 48 weeks and the capacity of the treatment to decrease ALT levels, HBsAg loss, and the patients drug free was examined. At the start of the Peg-IFN alfa-2a treatment, the mean serum ALT level was 23.5 IU/L, serum HBsAg level was 2.5 Log IU/mL, and serum hepatitis B core-related antigen (HBcrAg) level was 3.0 Log U/mL.
[Results] The decline of HBsAg levels over 24 weeks was greater after Peg-IFN alfa-2a treatment than after long-term NA therapy (0.43 vs. 0.12 Log IU/mL). Patients who showed a decline of HBsAg levels tended to have low HBsAg levels at the start of Peg-IFN alfa-2a treatment (1.8 vs. 3.1 Log IU/mL, p = 0.056). Among the 11 patients who completed sequential therapy, HBsAg negativity was achieved in two (18%) and a drug-free status was achieved in eight (73%). Three (27%) of the latter relapsed and required repeated NA, and their ALT levels were constantly within the reference values during PEG-IFN alfa-2a treatment and no immunostimulatory activity was found. Meanwhile, patients who reached a drug-free status had HBsAg levels of 1.0-3.9 Log U/mL and HBcrAg levels of 2.9-4.3 Log U/mL at the start of sequential therapy. The presence of ≥2 of the following criteria was a useful indicator of a drug-free status: HBsAg level <3.0 Log IU/mL, HBcrAg level <3.0 Log U/mL, and ALT level >60 IU/L during Peg-IFN alfa-2a treatment.
[Conclusions] For patients in whom Peg-IFN alfa-2a treatment has a stronger reducing effect on HBsAg levels than NA therapy, sequential therapy decreased HBsAg levels, achieved a drug-free status, and may lead to suppression of hepatocellular carcinoma.
Disclosures:
The following people have nothing to disclose: Ken Nishino, Miwa Kawanaka, Jun Nakamura, Takahito Oka, Noriyo Urata, Daisuke Goto, Mitsuhiko Suehiro, Hirofumi Kawamoto, Gotaro Yamada 作者: StephenW 时间: 2014-10-31 15:09