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HCC in presence of HCV decreases cure rate in DAA treatment

Patients with hepatocellular carcinoma and hepatitis C were less likely to achieve sustained virologic response while receiving direct-acting antiviral therapy compared with patients without HCC, according to results of a retrospective study.

“Our data demonstrate that the presence of active HCC at the initiation of HCV therapy is significantly associated with DAA treatment failure,” Stacey B. Prenner, MD, from Northwestern University, Chicago, and colleagues wrote. “In contrast, DAA therapy in the presence of inactive tumor or post removal of tumor (resection/transplant) resulted in excellent SVR rates, similar to patients without HCC. There may be a trade-off in optimizing HCV clearance and risk of recurrent HCC depending upon the immunologic properties of an individual tumor.”

To better qualify the efficacy of DAA therapy in patients with HCC, Prenner and colleagues identified 419 patients who underwent DAA therapy for HCV between January 2014 and November 2015. Overall, 135 patients had HCC. Mean patient age was 61 years and 288 were men. Most patients had HCV genotype 1 (86%), had undergone previous treatment (60%) and were Child-Turcotte-Pugh class A (74%).

Initial treatment failed in 7 patients with HCC and 12 without HCC. At 12 weeks, treatment failed for 62 patients: a failure rate of 21% in patients with HCC compared with 12% of patients without HCC (P = .009).

Compared with patients who achieved sustained virologic response, the characteristics among patients with treatment failure included higher international normalized ratio (1.3 vs. 1.2; P = .01), higher aspartate aminotransferase (98 vs. 78 units/L; P = .02), lower platelet count (103 vs. 133 mL; P = .007) and were more likely to be Caucasian (17% vs. 11%; P = .02), be among Child-Turcotte-Pugh class B or C (40% vs. 24%; P = .01), have ascites (25% vs. 12%; P = .003), have active tumors (93% vs. 30%; P < .0001) and have genotype 1 (81%). Additionally, higher failure rates occurred among patients who did not receive liver transplantation compared with those who did (18% vs. 9%; P = .01).

Tumor presence was the primary predictor of DAA treatment failure in this study (adjusted odds ratio = 8.49; 95% CI, 3.9-18.49). Of the 64 patients with tumor present, failure rates were 42% compared with 3% of the 71 patients who no longer had tumor present (P < .0001). Of the 58 patients with active tumors at treatment initiation, failure rates were 48% compared with no failures among the 5 patients with non-active tumors.

“The biological explanation for the diminished SVR in patients with active HCC is not entirely clear. HCC may serve as a sanctuary for HCV, where virus particles may evade DAA therapy. HCC has been implicated as a viral reservoir for hepatitis B,” the researchers wrote. “Increased knowledge of these mechanisms will improve understanding of the ideal timing for treatment of HCV in patients with concomitant HCC.” – by Talitha Bennett

Disclosure: The researchers report no relevant financial disclosures.