Tsugiko Oze1, Naoki Hiramatsu2, Takayuki Yakushijin1, Masanori Miyazaki1, Akira Yamada3, Masahide Oshita4, Hideki Hagiwara5, Eiji Mita6, Toshifumi Ito7, Hiroyuki Fukui8, Yoshiaki Inui9, Taizo Hijioka10, Masami Inada11, Kazuhiro Katayama12, Shinji Tamura13, Harumasa Yoshihara14, Atsuo Inoue15, Yasuharu Imai16, Eijiro Hayashi17, Michio Kato18, Takuya Miyagi1, Yuichi Yoshida1, Tomohide Tatsumi1, Akinori Kasahara1, Toshimitsu Hamasaki19, Norio Hayashi5, Tetsuo Takehara1. 1. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. 2. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. Electronic address: hiramatsu@gh.med.osaka-u.ac.jp. 3. Sumitomo Hospital, Osaka, Osaka, Japan. 4. Osaka Police Hospital, Osaka, Osaka, Japan. 5. Kansai Rosai Hospital, Amagasaki, Hyogo, Japan. 6. National Hospital Organization Osaka National Hospital, Osaka, Osaka, Japan. 7. Osaka Koseinenkin Hospital, Osaka, Osaka, Japan. 8. Yao Municipal Hospital, Yao, Osaka, Japan. 9. Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Hyogo, Japan. 10. National Hospital Organization Osaka Minami Medical Center, Kawachinagano, Osaka, Japan. 11. Toyonaka Municipal Hospital, Toyonaka, Osaka, Japan. 12. Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Osaka, Japan. 13. Minoh City Hospital, Minoh, Osaka, Japan. 14. Osaka Rosai Hospital, Sakai, Osaka, Japan. 15. Osaka General Medical Center, Osaka, Osaka, Japan. 16. Ikeda Municipal Hospital, Ikeda, Osaka, Japan. 17. Kinki Central Hospital of Mutual Aid Association of Public School Teachers, Itami, Osaka, Japan. 18. National Hospital Organization Minami Wakayama Medical Center, Tanabe, Wakayama, Japan. 19. Department of Biomedical Statistics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Abstract
BACKGROUND & AIMS: In patients with chronic hepatitis C virus (HCV) infection, lack of sustained virologic response (SVR) 24 weeks after the end of interferon therapy is a significant risk factor for hepatocellular carcinoma (HCC). Although many pretreatment factors are known to affect HCC incidence, less is known about post-treatment factors-many change during the course of interferon therapy. METHODS: We performed a prospective study, collecting data from 2659 patients with chronic hepatitis C without a history of HCC who had been treated with pegylated interferon (Peg-IFN) plus ribavirin from 2002 through 2008 at hospitals in Japan. Biopsy specimens were collected before treatment; all patients received Peg-IFN plus ribavirin for 48 to 72 weeks (HCV genotype 1) or 24 weeks (HCV genotype 2). Hematologic, biochemical, and virologic data were collected every 4 weeks during treatment and every 6 months after treatment. HCC was diagnosed based on angiography, computed tomography, and/or magnetic resonance imaging findings. RESULTS: HCC developed in 104 patients during a mean observation period of 40 months. Older age, male sex, lower platelet counts and higher levels of α-fetoprotein at baseline, and lack of an SVR were significant risk factors for HCC. The cumulative incidence of HCC was significantly lower in patients without SVRs who relapsed than those with no response to treatment. Levels of α-fetoprotein 24 weeks after the end of treatment (AFP24) were significantly lower than levels of α-fetoprotein at baseline in patients with SVRs and those who relapsed, but not in nonresponders. Post-treatment risk factors for HCC among patients with SVRs included higher AFP24 level and older age; among those without SVRs, risk factors included higher AFP24 level, integrated level of alanine aminotransferase, older age, and male sex. AFP24 (≥10 ng/mL, 10-5 ng/mL, and then <5 ng/mL) was a better predictor of HCC incidence than pretreatment level of AFP among patients with and without SVRs. CONCLUSIONS: In patients with chronic HCV infection, levels of α-fetoprotein decrease during interferon therapy. High post-treatment levels of α-fetoprotein predict HCC, regardless of whether patients achieve an SVR. University Hospital Medical Information Network Clinical Trials Registry: C000000196, C000000197.
BACKGROUND & AIMS: In patients with chronic hepatitis C virus (HCV) infection, lack of sustained virologic response (SVR) 24 weeks after the end of interferon therapy is a significant risk factor for hepatocellular carcinoma (HCC). Although many pretreatment factors are known to affect HCC incidence, less is known about post-treatment factors-many change during the course of interferon therapy. METHODS: We performed a prospective study, collecting data from 2659 patients with chronic hepatitis C without a history of HCC who had been treated with pegylated interferon (Peg-IFN) plus ribavirin from 2002 through 2008 at hospitals in Japan. Biopsy specimens were collected before treatment; all patients received Peg-IFN plus ribavirin for 48 to 72 weeks (HCV genotype 1) or 24 weeks (HCV genotype 2). Hematologic, biochemical, and virologic data were collected every 4 weeks during treatment and every 6 months after treatment. HCC was diagnosed based on angiography, computed tomography, and/or magnetic resonance imaging findings. RESULTS: HCC developed in 104 patients during a mean observation period of 40 months. Older age, male sex, lower platelet counts and higher levels of α-fetoprotein at baseline, and lack of an SVR were significant risk factors for HCC. The cumulative incidence of HCC was significantly lower in patients without SVRs who relapsed than those with no response to treatment. Levels of α-fetoprotein 24 weeks after the end of treatment (AFP24) were significantly lower than levels of α-fetoprotein at baseline in patients with SVRs and those who relapsed, but not in nonresponders. Post-treatment risk factors for HCC among patients with SVRs included higher AFP24 level and older age; among those without SVRs, risk factors included higher AFP24 level, integrated level of alanine aminotransferase, older age, and male sex. AFP24 (≥10 ng/mL, 10-5 ng/mL, and then <5 ng/mL) was a better predictor of HCC incidence than pretreatment level of AFP among patients with and without SVRs. CONCLUSIONS: In patients with chronic HCV infection, levels of α-fetoprotein decrease during interferon therapy. High post-treatment levels of α-fetoprotein predict HCC, regardless of whether patients achieve an SVR. University Hospital Medical Information Network Clinical Trials Registry: C000000196, C000000197.