Mio Kurihara1,2, Masataka Tsuge1,2,3, Eisuke Murakami1,2, Nami Mori4, Waka Ohishi5, Takuro Uchida1,2, Hatsue Fujino1,2, Takashi Nakahara1,2, Hiromi Abe-Chayama2,6, Tomokazu Kawaoka1,2, Daiki Miki1,2,7, Akira Hiramatsu1,2, Michio Imamura1,2, Yoshiiku Kawakami1,2, Hiroshi Aikata1,2, Hidenori Ochi1,2,7, Yizhou Zhang1,2, Grace Naswa Makokha1,2, C Nelson Hayes1,2, Kazuaki Chayama1,2,7. 1. Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan. 2. Liver Research Project Center, Hiroshima University, Hiroshima, Japan. 3. Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, Japan. 4. Department of Hepatology, Hiroshima Red Cross Hospital and Atomic Bomb Survivors Hospital, Hiroshima, Japan. 5. Department of Clinical Studies, Radiation Effects Research Foundation, Hiroshima, Japan. 6. Center for Medical Specialist Graduate Education and Research, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. 7. Laboratory for Digestive Diseases, RIKEN Center for Integrative Medical Sciences, Hiroshima, Japan.
Abstract
BACKGROUND: Although nucleoside/nucleotide analogue therapy is thought to suppress chronic hepatitis B (CHB) via regulation of inflammatory cytokines/chemokines, the mechanism is still unclear. In this study, serum cytokine/chemokine levels were measured in CHB patients treated with entecavir, and the association with antiviral response was analysed. METHODS: A total of 78 Japanese patients with CHB were enrolled, and serum cytokine/chemokine levels were measured at baseline and at 12, 24 and 48 weeks of entecavir treatment using the MULTIPLEX kit. RESULTS: Antiviral response to entecavir treatment was significantly associated with hepatitis B surface antigen (HBsAg) titre and serum interferon-gamma-inducible protein 10 (IP-10) level (12w; P=0.0002; OR=0.020 [95% CI 0.002, 0.156], P=0.003; OR=0.042 [95% CI 0.005, 0.336], respectively). HBe-positive patients whose serum macrophage-derived chemokine (MDC) level was lower (<582.83 pg/ml) and IP-10 level was higher (≥1,323.13 pg/ml) achieved hepatitis B e antigen (HBeAg) loss earlier than those who remained HBeAg-positive (P=0.044). HBsAg reduction by entecavir treatment was significantly associated with higher initial tumour necrosis factor-alpha (TNF-α) level (≥15.20 pg/ml) and higher alanine aminotransferase level (≥73 IU/l; P=0.009; OR=18.460 [95% CI 2.044, 166.709], P=0.022; OR=7.709 [95% CI 1.341, 44.327], respectively). CONCLUSIONS: Results of the present study indicate that changes in cytokine/chemokine levels following entecavir therapy are associated with response to antiviral therapy in CHB patients. Monitoring of serum cytokine/chemokine levels could be useful for predicting reduction of HBV DNA and HBsAg and HBe seroconversion.
BACKGROUND: Although nucleoside/nucleotide analogue therapy is thought to suppress chronic hepatitis B (CHB) via regulation of inflammatory cytokines/chemokines, the mechanism is still unclear. In this study, serum cytokine/chemokine levels were measured in CHB patients treated with entecavir, and the association with antiviral response was analysed. METHODS: A total of 78 Japanese patients with CHB were enrolled, and serum cytokine/chemokine levels were measured at baseline and at 12, 24 and 48 weeks of entecavir treatment using the MULTIPLEX kit. RESULTS: Antiviral response to entecavir treatment was significantly associated with hepatitis B surface antigen (HBsAg) titre and serum interferon-gamma-inducible protein 10 (IP-10) level (12w; P=0.0002; OR=0.020 [95% CI 0.002, 0.156], P=0.003; OR=0.042 [95% CI 0.005, 0.336], respectively). HBe-positive patients whose serum macrophage-derived chemokine (MDC) level was lower (<582.83 pg/ml) and IP-10 level was higher (≥1,323.13 pg/ml) achieved hepatitis B e antigen (HBeAg) loss earlier than those who remained HBeAg-positive (P=0.044). HBsAg reduction by entecavir treatment was significantly associated with higher initial tumour necrosis factor-alpha (TNF-α) level (≥15.20 pg/ml) and higher alanine aminotransferase level (≥73 IU/l; P=0.009; OR=18.460 [95% CI 2.044, 166.709], P=0.022; OR=7.709 [95% CI 1.341, 44.327], respectively). CONCLUSIONS: Results of the present study indicate that changes in cytokine/chemokine levels following entecavir therapy are associated with response to antiviral therapy in CHB patients. Monitoring of serum cytokine/chemokine levels could be useful for predicting reduction of HBV DNA and HBsAg and HBe seroconversion.