Direct-Acting Antivirals Do Not Adversely Affect Hepatocellular Carcinoma Development

Hepatocellular Carcinoma
Hepatocellular Carcinoma
Findings support the urgent initiation of direct‐acting antivirals (DAAs) in all patients with chronic HCV and cirrhosis. The short‐term influence of DAAs on hepatocellular carcinoma in patients with a history of decompensated cirrhosis must still be clarified.

While there appears to be a small risk of short-term hepatocellular carcinoma (HCC) associated with direct‐acting antiviral (DAAs) in patients with cirrhosis, the initiation of DAAs in these patients results in a decreased occurrence of HCC compared with no treatment. This is according to a study in the Journal of Viral Hepatitis.

Patients who had cirrhosis and chronic hepatitis C virus (HCV) at time of entry into the French ANRS CO22 HEPATHER cohort study were enrolled (n=3292; mean age, 59.3 years old). A platelet count of <150,000/μL or a prothrombin time of <70% at entry was used to define cirrhosis. All patients who had started DAAs in this study were considered exposed to the agents until the end of the 36.8-month median follow-up period. Using data from this cohort, the researchers characterized the time‐varying impact of DAAs on HCC risk in patients with cirrhosis, including those with a history of decompensated cirrhosis (DC) and without a history of DC.

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A total of 3292 patients started DAAs during the follow-up period, whereas a total of 303 patients remained untreated in this observational study. There were 356 HCCs (3.4/100 person-years), representing 275 (3.1/100 person-years) patients exposed to DAAs and 81 (4.7/100 person-years) patients unexposed to DAAs.  A total of 2779 treated patients as well as 2406 without a history of DC and 373 with a history of DC achieved a sustained virological response (SVR).

In individuals without an SVR and with a history of DC, there was a nonsignificant increase in HCC in DAA-exposed vs untreated patients over the first 6 months. The researchers observed similar findings in patients with an SVR. In patients with a history of DC, a significant reduction in the hazard ratio (HR) for HCC was observed for DAA-exposed patients at 14 months (HR, 0.39; 95% CI, 0.18-0.85) to reach a minimum at 22 months (HR, 0.18; 95% CI, 0.07-0.47).

Limitations of the study included reverse causality. If patients with more advanced liver disease and a higher risk of HCC had a reduced chance of initiating therapy, this may have contributed to the association between HCC and treatment exposure in the first year.

The researchers concluded that their “findings support the urgent initiation of DAAs in all patients with chronic HCV and cirrhosis.”

Disclosure: This clinical trial was supported by several pharmaceutical organizations. Please see the original reference for a full list of authors’ disclosures.


Lusivika-Nzinga C, Fontaine H, Dorival C, Simony M, Pol S, Carrat F; ANRS/AFEF Hepather study group. The dynamic effect of direct-acting antiviral treatments on the risk of hepatocellular carcinoma in patients with cirrhosis and chronic hepatitis C [published online August 6, 2019]. J Viral Hepat. doi:10.1111/jvh.13186