Direct-acting antiviral agents do not increase the incidence of hepatocellular carcinoma development: a prospective, multicenter study
- 308 Downloads
While achieving sustained virological response (SVR) following interferon-based or direct-acting antiviral agent (DAA) treatments reduces the incidence of hepatocellular carcinoma (HCC), an increase in unexpected early occurrence or recurrence of HCC after hepatitis C virus elimination by DAA treatments has been reported. We prospectively investigated the incidence and risk factors of HCC after DAA treatment in a large multicenter cohort in Japan.
Patients with chronic hepatitis C with or without cirrhosis who were treated with DAAs and obtained SVR were enrolled. DAAs were administered for 3 or 6 months. A total of 2552 patients were enrolled.
Of these, 70 patients (2.7%) developed HCC. The 12-, 24-, and 36-month cumulative HCC incidences were 1.3%, 2.9%, and 4.9% in all patients; 2.5%, 5.2%, and 10.0% in those with cirrhosis; and 0.9%, 2.1%, and 2.9% in those without cirrhosis, respectively. Multivariate analysis revealed age, sex, gamma-glutamyl transpeptidase level, and fibrosis-4 index to be independent factors associated with HCC. Patients with these four factors had an approximately six-to-sevenfold increased risk for HCC development. Five patients with large and early tumor occurrence did not receive contrast imaging examinations before treatment.
Although the results of our prospective study suggested that achieving SVR by DAA treatment reduces the incidence of HCC, HCC development still occurs. Careful follow-up is important in patients with risk factors.
KeywordsHepatitis C virus Sustained virological response Fibrosis-4 (FIB-4) index Hepatocarcinogenesis
Hepatitis C virus
Sustained virological response
AST to platelet count ratio index
Area under the curve
Magnetic resonance imaging
Tumor thrombus of the portal vein
We thank Editage (www.editage.jp) for English language editing.
Compliance with ethical standards
Conflict of interest:
Akio Ido has COI as follows: (1) Speaking fees or honoraria; AbbVie GK, Bristol Myers Squibb Co. Ltd., Gilead Sciences Inc., and Eisai Co. Ltd. (2) Research grants; AbbVie GK, Otsuka Pharmaceutical Co. Ltd., MSD K.K., Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Astellas Pharmaceutical Inc., and Takeda Pharmaceutical Co. Ltd. The other authors disclose no conflicts.
The protocol was approved by all hospital institutional review boards and carried out in compliance with the Declaration of Helsinki.
Written informed consent was obtained from all participating patients.
- 12.Kuzuya T, Nakagawa S, Satoh J, Kanazawa Y, Iwamoto Y, Kobayashi M, et al. Committee of the Japan Diabetes Society on the diagnostic criteria of diabetes mellitus. Report of the committee on the classification and diagnostic criteria of diabetes mellitus. Diabetes Res Clin Pract 2002;55:65-85.CrossRefGoogle Scholar
- 18.Ikeda K, Saitoh S, Arase Y, Chayama K, Suzuki Y, Kobayashi M, et al. Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis type C: a long-term observation study of 1,643 patients using statistical bias correction with proportional hazard analysis. Hepatology. 1999;29:1124–1130.CrossRefGoogle Scholar
- 20.Yoshida H, Shiratori Y, Moriyama M, Arakawa Y, Ide T, Sata M, et al. Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. IHIT Study Group. Inhibition of hepatocarcinogenesis by interferon therapy. Ann Intern Med 1999;131:174-181.CrossRefGoogle Scholar