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.

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Fig. 1



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


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Correspondence to Tarek Saadi.

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Khoury, J., Nassar, G., Kramsky, R. et al. Extrahepatic Malignancies After Treatment with Direct Antiviral Agents for Chronic HCV Infection. J Gastrointest Canc 51, 584–590 (2020). https://doi.org/10.1007/s12029-019-00293-y

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  • Direct antiviral agents
  • HCV
  • Extrahepatic
  • Hepatocellular carcinoma
  • Lymphoma