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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 作者: StephenW 时间: 2014-10-30 12:33