Hiroko Nagata1, Mina Nakagawa2, Yasuhiro Asahina3, Ayako Sato1, Yu Asano1, Tomoyuki Tsunoda1, Masato Miyoshi1, Shun Kaneko1, Satoshi Otani1, Fukiko Kawai-Kitahata4, Miyako Murakawa5, Sayuri Nitta1, Yasuhiro Itsui4, Seishin Azuma1, Sei Kakinuma6, Toshihiko Nouchi7, Hideki Sakai8, Makoto Tomita9, Mamoru Watanabe1. 1. Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Japan. 2. Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Japan; Institute of Education, Tokyo Medical and Dental University, Japan. 3. Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Japan; Department of Liver Disease Control, Tokyo Medical and Dental University, Japan. Electronic address: asahina.gast@tmd.ac.jp. 4. Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Japan; Department of General Medicine, Tokyo Medical and Dental University, Japan. 5. Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Japan; Department of Clinical Laboratory, Tokyo Medical and Dental University, Japan. 6. Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Japan; Department of Liver Disease Control, Tokyo Medical and Dental University, Japan. 7. Showa General Hospital, Tokyo Medical and Dental University, Tokyo, Japan. 8. Kashiwa Municipal Hospital, Tokyo Medical and Dental University, Tokyo, Japan. 9. Clinical Research Center, Tokyo Medical and Dental University, Tokyo, Japan.
Abstract
BACKGROUND AND AIMS: Although treatment for hepatitis C virus has been dramatically improved by the development of direct-acting antiviral agents (DAAs), whether interferon (IFN)-free therapy reduces hepatocarcinogenesis in an equivalent manner to IFN-based therapy remains controversial. The aims of this study were to evaluate the occurrence and recurrence of hepatocellular carcinoma (HCC) in chronic hepatitis C (CHC) patients treated with DAAs and to identify biomarkers of HCC development after antiviral treatment. METHODS: A restrospective review of a prospective database of 1,897 CHC patients who were treated with IFN-based (1,145) or IFN-free therapies (752) was carried out. Cumulative HCC occurrence and recurrence rates were compared using propensity score-matched analysis. Predictors of HCC development after viral eradication were identified by multivariate analysis. RESULTS: Propensity score-matched analysis showed no significant difference in HCC occurrence (p=0.49) and recurrence rates (p=0.54) between groups treated with IFN-based or IFN-free therapies. In multivariate analysis, higher levels of post-treatment α-fetoprotein (AFP) or Wisteria floribunda agglutinin positive Mac-2 binding protein (WFA+M2BP) were independently associated with HCC occurrence and recurrence after viral eradication. Only post-treatment WFA+M2BP level was significantly associated with HCC occurrence and recurrence among patients without severe fibrosis. The area under the receiver operating characteristic (ROC) curve for WFA+M2BP levels was greater than that for AFP levels in ROC analysis. CONCLUSION: The risks of early HCC occurrence and recurrence after viral eradication were similar between IFN-based and IFN-free therapies. Post-treatment levels of WFA+M2BP may be helpful screening biomarkers for assessing the risk of HCC after IFN-free therapy. Patients with high WFA+M2BP levels after antiviral treatment, even without severe fibrosis, must be followed up carefully for HCC development. Lay summary: The risks of early HCC occurrence and recurrence after viral eradication were similar between IFN-based and IFN-free therapies. Post-treatment levels of WFA+M2BP may be helpful screening biomarkers for assessing the risk of HCC after IFN-free therapy.
BACKGROUND AND AIMS: Although treatment for hepatitis C virus has been dramatically improved by the development of direct-acting antiviral agents (DAAs), whether interferon (IFN)-free therapy reduces hepatocarcinogenesis in an equivalent manner to IFN-based therapy remains controversial. The aims of this study were to evaluate the occurrence and recurrence of hepatocellular carcinoma (HCC) in chronic hepatitis C (CHC) patients treated with DAAs and to identify biomarkers of HCC development after antiviral treatment. METHODS: A restrospective review of a prospective database of 1,897 CHCpatients who were treated with IFN-based (1,145) or IFN-free therapies (752) was carried out. Cumulative HCC occurrence and recurrence rates were compared using propensity score-matched analysis. Predictors of HCC development after viral eradication were identified by multivariate analysis. RESULTS: Propensity score-matched analysis showed no significant difference in HCC occurrence (p=0.49) and recurrence rates (p=0.54) between groups treated with IFN-based or IFN-free therapies. In multivariate analysis, higher levels of post-treatment α-fetoprotein (AFP) or Wisteria floribunda agglutinin positive Mac-2 binding protein (WFA+M2BP) were independently associated with HCC occurrence and recurrence after viral eradication. Only post-treatment WFA+M2BP level was significantly associated with HCC occurrence and recurrence among patients without severe fibrosis. The area under the receiver operating characteristic (ROC) curve for WFA+M2BP levels was greater than that for AFP levels in ROC analysis. CONCLUSION: The risks of early HCC occurrence and recurrence after viral eradication were similar between IFN-based and IFN-free therapies. Post-treatment levels of WFA+M2BP may be helpful screening biomarkers for assessing the risk of HCC after IFN-free therapy. Patients with high WFA+M2BP levels after antiviral treatment, even without severe fibrosis, must be followed up carefully for HCC development. Lay summary: The risks of early HCC occurrence and recurrence after viral eradication were similar between IFN-based and IFN-free therapies. Post-treatment levels of WFA+M2BP may be helpful screening biomarkers for assessing the risk of HCC after IFN-free therapy.
Authors: Carmen M Preda; Cristian Baicus; Irina Sandra; Alexandru Oproiu; Teodora Manuc; Ileana Constantinescu; Daniel Gavrila; Mircea Diculescu; Radu Dumitru; Catalin Vasilescu; Cristian Tieranu; Doina Istratescu; Theodor Voiosu; Mircea Manuc Journal: United European Gastroenterol J Date: 2019-03-29 Impact factor: 4.623