Extrahepatic Malignancies After Treatment with Direct Antiviral Agents for Chronic HCV Infection
Direct antiviral agents (DAAs) have become the treatment of choice for chronic hepatitis C virus (HCV). A safety concern was raised about a possible relationship between DDAs and malignancies. We report unexpected development of extrahepatic malignancies after DAA treatment.
Four hundred thirty-one patients were treated with DAAs in our unit between January 2015 and February 2018. The most common regimen used the combination of paritaprevir/ritonavir/ombitasvir with/without dasabuvir (PrOD) (141 patients, 32.7%). The most common genotype was G1b (317 patients, 73.5%).
Nine patients (2.08%) were diagnosed with malignancies after treatment: three patients developed lymphoma, one laryngeal carcinoma, one pancreatic adenocarcinoma, one cervix carcinoma, one lung carcinoma, one developed recurrent transitional cell carcinoma of the urinary bladder, and one developed recurrent metastatic breast cancer. The incidence of these malignancies in the cohort was 696 to 100,000 for lymphoma and 232 to 100,000 for each one of the other malignancies described, while the incidence in the general population is 20, 8.8, 1.7, 44.7, 142, and 89.7 to 100,000, respectively. Five of these patients were treated with PrOD, two with sofosbuvir and daclatasvir, one with simeprevir and sofosbuvir, and one with ledipasvir and sofosbuvir. The occurrence of the malignancies was 3 months to 4 years after the end of the treatment. Besides, 10 patients (2.3%) developed HCC and one developed recurrent aggressive HCC.
This report raises a question about a possible relationship between treatment with DAAs and development of extrahepatic malignancies. Thus, data collection from larger cohorts is critical to determine the relationship possibility.
KeywordsDirect antiviral agents HCV Extrahepatic Hepatocellular carcinoma Lymphoma
Hepatitis C virus
Direct antiviral agent
Paritaprevir/ritonavir/ombitasvir with/without dasabuvir
Sustained viral response
Modification of Diet in Renal Disease
- CHOP + R
Cyclophosphamide, hydroxydaunorubicin, oncovine, prednisone, and rituximab
Compliance with Ethical Standards
The study was approved by the institutional review board (IRB).
Conflict of Interest
The authors declare that they have no conflict of interest.
- 5.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;131:174–81.CrossRefGoogle Scholar
- 10.Conteduca V, Sansonno D, Russi S, et al. Therapy of chronic hepatitis C virus infection in the era of direct-acting and host-targeting antiviral agents. J Inf Secur. 2014;68:1–20.Google Scholar
- 21.Ioannou GN, Green PK, Berry K. HCV eradication induced by direct-acting antiviral agents reduces the risk of hepatocellular carcinoma. J Hepatol. 2017;(17):32273–0. https://doi.org/10.1016/j.jhep.2017.08.030.
- 27.Hinotsu S, Akaza H, Miki T, Fujimoto H, Shinohara N, Kikuchi E, et al. Bladder cancer develops 6 years earlier in current smokers: analysis of bladder cancer registry data collected by the cancer registration committee of the Japanese Urological Association. Int J Urol. 2009;16:64–9.CrossRefGoogle Scholar
- 28.Alfsen GC, Thoresen SO, Kristensen GB, Skovlund E, Abeler VM. Histopathologic subtyping of cervical adenocarcinoma reveals increasing incidence rates of endometrioid tumors in all age groups: a population based study with review of all nonsquamous cervical carcinomas in Norway from 1966 to 1970, 1976 to 1980, and 1986 to 1990. Cancer. 2000;89:1291–9.CrossRefGoogle Scholar