AASLD2014:请问干扰素治疗降低肝癌的发病率在HBeAg阳性的慢性

StephenW

1910
Does interferon treatment reduce hepatocellular carcinoma incidence in HBeAg positive chronic hepatitis B patients?
Tetsuya Hosaka1, Fumitaka Suzuki1, Masahiro Kobayashi1, Taito Fukushima1, Yusuke Kawamura1, Hitomi Sezaki1, Norio Akuta1, Yoshiyuki Suzuki1, Satoshi Saitoh1, Yasuji Arase1, Kenji Ikeda1, Mariko Kobayashi2, Hiromitsu Kumada1;
1Hepatology, Torano-mon Hospital, Tokyo, Japan; 2Research institute for hepatology, Toranomon Hospital, Kawasaki, Japan
Background: Chronic hepatitis B virus (HBV) infection leads to hepatocellular carcinoma (HCC). Because interferon (IFN) alpha treatment for chronic hepatitis B (CHB) has the antiviral and immune modulatory effects, patients treated by IFN can achieve the inactive HBV infection state. We examined whether IFN treatment would reduce HCC incidence in CHB patients when compared with untreated patients.


Methods: We conducted a retrospective cohort study of in hepatitis B e antigen (HBeAg) positive 295 Japanese patients who received conventional IFN alpha (IFN group), and 391 untreated e-positive patients (control group). The IFN group comprised patients recruited from 1988 to 2011 and treated with IFN in our institute, and the control group patients from 1973 to 1999. Patients in IFN group received conventional 3-12 MU IFN alpha (lymphoblastoid or recombinant). The duration and regimens of treatment were 16-72 weeks (daily for 4 weeks followed by 2 or 3 times a week, or 2 or 3 times a week from the beginning). Responders (RP) were defined as normalized alanine aminotransferase, HBeAg loss, and low HBV DNA (< 5 log copies/mL) at 6 months after the end of IFN treatment (EOT). Patients treated with nucleos(t)ide analogues (NA) after IFN were defined as non-responders (NR). Primary outcome is HCC incidence for 10 years.


Results: The response rates at 6 months after EOT were 15.6% (46/295) in the IFN group. During follow-ups of 9.2 years in the IFN group and 9.9 years in the control group, 22 patients (7.5%) in the IFN group had developed HCC (81/10,000 person-years) compared with 62 patients (15.9%) in the control group (159/10,000 person-years). Propensity score (PS) matching eliminated the baseline differences of the two cohorts, resulting in a matched sample size of 119 patients in each cohort. The cumulative HCC incidence rates at 5- and 10-year were 2.7% and 15.9% for the PS-matched IFN, and 13.9% and 25.3% for the control group, respectively (P = 0.055). No patients with RP had developed HCC. Patients in the IFN group were divided into three groups (RP, NR-NA, and NR-noTx). Multivariate Cox regression analysis, adjusted for known HCC risk factors and PS quartiles, showed that patients in the RP or NR-NA group were less likely to develop HCC than those in the control group (hazard ratio (HR): 0.36; 95% CI: 0.16 to 0.84; P = 0.017). The beneficial effect was not observed in the NR-noTx group (HR: 0.71; 95% CI: 0.35 to 1.47).


Conclusion: IFN treatment marginally reduced HCC in CHB patients. The treatment effect was greater in the IFN responders compared with the control group. There was no benefit about the reduction of HCC incidence in IFN NRs.

Disclosures:
Norio Akuta - Patent Held/Filed: SRL. Inc.
Hiromitsu Kumada - Speaking and Teaching: Bristol-Myers Squibb,Pharma International, MSD, Dainippon Sumitomo, Tanabe Mitsubishi, Ajinomoto
The following people have nothing to disclose: Tetsuya Hosaka, Fumitaka Suzuki, Masahiro Kobayashi, Taito Fukushima, Yusuke Kawamura, Hitomi Sezaki, Yoshi-yuki Suzuki, Satoshi Saitoh, Yasuji Arase, Kenji Ikeda, Mariko Kobayashi

StephenW

1910

请问干扰素治疗降低肝癌的发病率在HBeAg阳性的慢性乙肝患者？
哲也Hosaka1，文孝Suzuki1，正弘Kobayashi1，台东区Fukushima1，介Kawamura1，瞳Sezaki1，夫Akuta1，富野Suzuki1，聪Saitoh1，安尔Arase1，贤治Ikeda1，圆子Kobayashi2，弘光Kumada1;
1Hepatology，Torano纹医院，日本东京; 2Research研究院肝病，虎之门医院，川崎，日本

背景：慢性乙型肝炎病毒（HBV）感染导致肝细胞癌（HCC）。因为干扰素（IFN）的α治疗慢性乙型肝炎（CHB）的抗病毒和免疫调节作用，通过干扰素治疗的患者可以实现非活动性HBV感染状态。我们研究的时候与未经治疗的患者相比，干扰素治疗是否会降低肝癌发病率的慢性乙型肝炎患者。方法：我们进行了乙肝e抗原（HBeAg），谁接受常规干扰素α（IFN组），391未处理的e抗原阳性患者（对照组）阳性295例日本患者的回顾性队列研究。干扰素组包括患者招募1988年至2011年，并与IFN在我院治疗，对照组病人从1973年到1999年的患者中IFN组给予常规3-12 MU IFNα（淋巴母细胞或重组）。的持续时间和治疗方案均16-72周（每日4周后，每周2或3次，或2或每周从开始3次）。应答器（RP）的被定义为归一化的丙氨酸氨基转移酶，HBeAg的损失，以及低的HBV DNA（<5日志拷贝/ mL），在6个月的IFN治疗（EOT）的端部之后。患者的核苷（酸）类似物（NA）后IFN被定义为无反应（NR）处理。主要的结果是肝癌发病率10年。结果：反应率在6个月后，EOT分别为15.6％（二百九十五分之四十六）干扰素组。在随访9.2年，干扰素组和9.9岁，对照组22例（7.5％），干扰素组制定了HCC（81/ 10,000人 - 年）有62例（15.9％）的比较对照组（159/ 10,000人 - 年）。倾向得分（PS）的匹配消除了两个队列的基线差异，导致119例中的每个队列匹配的样本大小。累积的HCC发病率在5年和10年分别为2.7％和对于PS匹配的IFN15.9％，和13.9％，而对照组中，分别为（P =0.055），25.3％。没有RP患者制定了肝癌。干扰素组中的患者分成三组（RP，N R-NA，和NR-noTx）。多因素Cox回归分析，调整称为肝癌的危险因素和PS四分位数，表明患者在RP或NR-NA组不太可能发展肝癌较对照组（危险比（HR）：0.36;95％CI ：0.16〜0.84; P =0.017）。使用NR-noTx组中未观察到的有益效果（HR：0.71; 95％CI：0.35〜1.47）。结论：干扰素治疗慢性乙型肝炎患者略微降低肝癌。与对照组相比，治疗效果是更大的干扰素应答。有没有关于肝癌的发病率在干扰素自然保护区的减少受益。

披露：

夫Akuta - 专利持有/归档：SRL。公司

熊田博光 - 口语与教学：施贵宝公司，制药国际，MSD，大日本住友，田边三菱，日本味之素

下面的人都没有透露：保坂哲也，铃木文孝，小林正博，台东福岛，川村雄介，濑崎瞳，耀西，雪铃木聪斋藤，安尔荒濑，池田健司，小林麻里子

肝肠欲断

这个骆抗先教授很早以前就说过！

咬牙硬挺

感谢分享