Extrahepatic Malignancies After Treatment with Direct Antiviral Agents for Chronic HCV Infection

  • Johad Khoury
  • George Nassar
  • Rimma Kramsky
  • Tarek SaadiEmail author
Original Research



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.


Direct antiviral agents HCV Extrahepatic Hepatocellular carcinoma Lymphoma 



Hepatitis C virus


Non-Hodgkin lymphoma


Direct antiviral agent


Paritaprevir/ritonavir/ombitasvir with/without dasabuvir


Hepatocellular carcinoma


Sustained viral response


Modification of Diet in Renal Disease


Therapy week




Alpha-feto protein


Cyclophosphamide, hydroxydaunorubicin, oncovine, prednisone, and rituximab


Computed tomography


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.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Johad Khoury
    • 1
  • George Nassar
    • 2
  • Rimma Kramsky
    • 3
  • Tarek Saadi
    • 2
    • 3
    • 4
    Email author
  1. 1.Pulmonology DivisionLady Davis Carmel Medical CenterHaifaIsrael
  2. 2.Bruce Rappaport Faculty of MedicineThe Technion-Israel Institute of TechnologyHaifaIsrael
  3. 3.Liver Unit, Rambam Health Care CampusHaifaIsrael
  4. 4.Department of GastroenterologyRambam Health Care CampusHaifaIsrael

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