Direct Antiviral Therapy of Hep C May Not Boost Hepatocellular-Carcinoma Risk

By Reuters Staff

August 03, 2018

NEW YORK (Reuters Health) - Treatment of hepatitis C (HCV) with direct-acting antiviral agents does not appear to increase the risk of hepatocellular carcinoma (HCC) in individuals with cirrhosis, researchers from France report.

Cirrhotic patients who achieve sustained viral response (SVR) after interferon-based treatment for HCV infection have a reduced risk of HCC. Recent retrospective studies have found unexpectedly high rates of HCC following DAA regimens.

Dr. Pierre Nahon from Hopital Jean Verdier and Universite Paris 13, in Saint-Denis, France, and colleagues in the ANRS CO12 CirVir group investigated the incidence of HCC under or following DAA therapy and compared it with that observed under DAA-free regimens in 1,270 patients with cirrhosis.

The three-year cumulative incidence of HCC was significantly higher in the DAA group (5.9%) than in the interferon-treated group that achieved SVR (SVR-IFN) (3.1%) but significantly lower than in the non-SVR group (12.7%).

Among patients treated with DAAs, the incidence of HCC was significantly lower for those who achieved SVR (2.6 per 100 person-years) than for those who did not (12.0 per 100 person-years).

Further analysis confirmed that patients who achieved SVR following DAA therapy did not have a significantly higher risk of developing HCC, compared with those who achieved SVR following interferon-based regimens, the team reports in Gastroenterology, online July 18.

DAA patients also had a similar three-year cumulative incidence of cardiovascular events and extrahepatic cancers, compared with SVR-IFN patients, and lower rates of liver decompensation and vascular events, compared with non-SVR patients.

Survival rates did not differ between the groups after multivariate adjustment for age, bilirubin, alpha-fetoprotein and platelet count.

Factors independently associated with the development of HCC included increased age, past excessive alcohol consumption, HCV genotype 1 and impaired liver function, but not DAA use.

"In summary, our experience of the CirVir cohort suggests that patients who received DAAs have an apparent increased risk of HCC development when compared to patients who achieved an SVR by means of an interferon-based regimen," the researchers conclude. "However, this 2-fold increase in risk is modest, limited in time, and can at least partially be explained by confounders linked to the specific profile of patients bearing higher risk factors for the development of liver cancer."

"Because it is not possible to rule out an influence of these molecules in promoting the growth of a preexisting tumor through their immunological effects, physicians should be encouraged to ensure rigorous recall procedures in the event of unspecified focal lesions," they suggest. "A pragmatic attitude could be to systematically perform a contrast-enhanced imaging technique if a suspicious nodule is detected on ultrasound examination before DAAs implementation; in case of doubt, all recommended procedures including sequential contrast-enhanced procedures at various time points should be performed and initiation of DAA therapy should be delayed until elimination of an emerging oncologic process."

"Apart from this specific situation and based on our data, DAAs implementation does not appear to be associated with an increased risk of HCC development and must be acknowledged as a major improvement in the management of patients with HCV-related cirrhosis," the authors add.

Dr. Nahon did not respond to a request for comments.

Seven of the 41 authors of this report had various relationships with one or more companies that produce DAAs.

SOURCE: https://bit.ly/2KlUlzl

Gastroenterology 2018.

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