Hepatologists in Israel are questioning whether there’s a link between direct-acting antiviral agents (DAAs) and cancer development. In a new article published in Journal of Clinical Gastroenterology, the researchers reported that 7 of 110 patients (6.4%) treated with DAAs for chronic hepatitis C virus (HCV) developed malignancies.
“The rapid appearance of these malignancies, the aggressiveness of the tumors, and the high incidence compared with the general population raise important questions about the relationship to DAA treatment,” wrote Tarek Saadi, MD, and Johad Khoury, MD, of Rambam Health Care Campus, Haifa, Israel.
Other studies have suggested a possible link between DAA therapy and the development of new or recurrent hepatocellular carcinoma (HCC). However, these studies have reported conflicting findings—some showed a higher incidence of HCC recurrence and some didn’t.
In the current study, all 110 HCV patients finished DAA treatment, and all but 2 patients achieved sustained virologic response (SVR). Most patients were treated with paritaprevir/ritonavir/ombitasvir (with or without dasabuvir) because it was the only DAA approved in Israel for much of the study.
During or shortly after finishing DAA treatment, 7 patients developed malignancies. Three of these patients had HCC; 2 developed de novo HCC and 1 developed recurrent aggressive HCC. Four patients developed malignancies that didn’t involve the liver, including laryngeal carcinoma, pancreatic adenocarcinoma, oropharyngeal lymphoma, and recurrent aggressive transitional cell carcinoma of the urinary bladder.
The incidence of non-HCC malignancies among patients was notably higher than the incidence found in the general population, the authors noted. Such a high incidence occurring during or shortly after completing DAA treatment suggests that any pre-existing tumors were of a low-grade status, they speculated.
In addition, two patients had tumors before starting DAA treatment. After they began treatment, the recurrence of these tumors was very aggressive, the researchers observed.
“It is possible that DAAs can affect the immunologic system and change the balance in favor of tumor progression,” Drs. Saadi and Khoury speculated. “Another possibility is that DAAs have a direct effect on dysplastic and malignant cells that potentiate the aggressiveness of these tumors.”
Examine these questions
Whatever the process, the researchers don’t believe that DAA treatment is directly causing aggressive malignancies. “It is more logical to think that the treatment may accelerate progression of existing tumors,” they wrote.
Drs. Saadi and Khoury acknowledged that their finding can’t demonstrate a causal relationship. Nevertheless, they added, their study raises important questions about a possible link between DAAs and malignancy.
“Further studies from clinical trials and real-life experience need to be performed to examine these questions,” they wrote. “If a real correlation is found, it will be important to define the risk factors for the development of malignancies in DAA-treated patients so that treatment guidelines and potential screening guidelines can be established.”