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DAAs for HCV do not increase liver cancer recurrence after local-regional therapy

Recently published data showed no association between direct-acting antiviral therapy and an increased risk for hepatocellular carcinoma recurrence among liver transplantation candidates with hepatitis C who experienced initial complete response to local-regional therapy.

Norah Terrault

“The majority of recent publications reveal no increased risk of liver cancer in patients treated with DAAs — both in terms of de novo HCC and recurrence after complete response to HCC treatment,” Norah Terrault, MD, from the University of California, San Francisco, told HCV Next. “These studies highlight the limitations of earlier studies that were uncontrolled and thus unable to account for differences in the patients in the current DAA era (older, more advanced cirrhosis) and prior pegylated-interferon era.”

The retrospective cohort study comprised 149 adult patients with HCV-associated cirrhosis and HCC listed for transplantation with MELD exception at UCSF between January 2014 and October 2016. According to Terrault and colleagues, they conducted the study prior to concerns about the adverse consequences of DAA therapy and HCC outcomes.

Sixty-two patients received DAA therapy while the rest represented an untreated group.

Patients underwent local-regional therapy (LRT) as bridge to transplantation and due to longer waiting times at the researchers’ center. LRT included trans-arterial chemoembolization (TACE); local ablation with radiofrequency ablation (RFA), cryotherapy, and ethanol injection; stereotactic body radiotherapy; and local surgical resection.

One hundred-twenty patients achieved complete tumor response after LRT with a median of one LRT (range, 1-2). Patients in the untreated group were less likely to achieve complete response (67.8% vs. 98.4%; P < .001).

Among patients who received DAA therapy, median alpha-fetoprotein decreased from 21 ng/mL (range, 9.1-55.4) prior to treatment to 8.1 ng/mL (range, 4.6-18.5) three months after completing therapy (P = .01).

Seventy-three of the patients who achieved complete response experienced HCC recurrence after a median of 6 months (range, 3.5-11.7). Median time from complete response to recurrence, 6-month incidence, and 1-year incidence were not significantly different between the untreated group and patients who received DAA therapy.

Similarly, both unweighted multivariate analysis and weighted multivariate analysis adjusted for the number of LRT received showed similar risk for HCC recurrence between patients who received DAA therapy and those who did not.

Twenty patients from the total cohort experienced waitlist dropout due to tumor progression and 16 patients died on the waitlist. Patients treated with DAAs had a significantly lower risk for dropout compared with the untreated group in unweighted univariate analysis (HR = 0.2; 95% CI, 0.09-0.48), unweighted multivariate analysis adjusted for Child-Pugh class (HR = 0.24; 95% CI, 0.1-0.59), and weighted univariate analysis (HR = 0.3; 95% CI, 0.13-0.69). No additional covariates were statistically significant in the weighted multivariate model.

After a median follow-up of 27.3 months (range, 17.6-35.1 months) from HCC diagnosis to death or last study follow-up, intention-to-treat survival for the entire study population was 92.1% (95% CI, 83.4-96.4) at 1 year and 89.6% (95% CI, 80.1-94.7) at 2 years. Overall, weighted survival was similar among patients treated with DAAs and those in the untreated group.

“Our study serves to remind clinicians that there are risks in not treating someone with advanced cirrhosis, in that they can die of cirrhosis-related complications,” Terrault concluded. “We know DAA therapy can help to improve symptoms of decompensation (in most, though not all patients), and thus in weighing the timing of DAA therapy in a patient with HCC, consider both the risks of their cirrhosis progressing while untreated as well as the potential risks of DAAs on their HCC.” – by Talitha Bennett

Disclosure: Terrault reports no relevant financial disclosures. Please see the full study for the other authors’ relevant financial disclosures.