Active Hepatocellular Carcinoma as a Risk Factor for DAA Treatment Failure

Active hepatocellular carcinoma was associated with nonsustained virologic response, while inactive hepatocellular carcinoma was not, suggesting that it is beneficial to defer direct-acting antiviral (DAA) treatment until after a complete radiological response, according to a study published in PLoS One.

A recent systematic review and meta-analysis reported that active hepatocellular carcinoma is associated with DAA treatment failure, but the heterogeneity was high and the studies were all from western countries. This retrospective cohort study was designed to examine this association in a population of Asian patients with hepatitis C and advanced fibrosis. Participants were treated with DAAs at Kaohsiung Chang Gung Memorial Hospital in Taiwan between January 2017 and June 2018. Advanced fibrosis was defined as the presence of transient elastography with a liver stiffness measurement ≥9.5 Kpa, a liver biopsy showing advanced fibrosis (METAVIR fibrosis score ≥3), a fibrosis-4 score ≥3.25, endoscopy showing gastroesophageal varices, or ultrasound-identified liver cirrhosis with splenomegaly. The presence of hepatocellular carcinoma was diagnosed by histological or image analysis, and sustained virologic response was defined as undetectable hepatitis C virus RNA 12 weeks after DAA therapy.

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Of the 976 patients with hepatitis C enrolled in per-protocol analysis, 57.2% (n=556) had genotype 1b infection, and 32.3% (n=314) had genotype 2. The mean age of the participants was 65.5±10.1 years, and 44.6% were men. Active hepatocellular carcinoma was present in 23 patients, inactive hepatocellular carcinoma in 172 patients, and no hepatocellular carcinoma in 781 patients. Of the 195 patients with hepatocellular carcinoma, the mean age was 69.7 years. Nonsustained virologic response was noted in 1.3% (n=10) patients without hepatocellular carcinoma, 2.9% (n=5) patients with inactive hepatocellular carcinoma, and 13.0% (n=4) patients with active hepatocellular carcinoma. After adjusting for confounders, when compared with inactive and nonhepatocellular carcinoma, active hepatocellular carcinoma was associated with nonsustained virologic response (adjusted odds ratio [OR], 24.5; 95% CI, 4.4-136.9; P <.001). Investigators excluded the 23 active hepatocellular carcinoma patients from multivariate analysis and after adjusting for confounders, inactive hepatocellular carcinoma was not associated with nonsustained virologic response (adjusted OR, 3.1; 95% CI, 0.94-9.95; P =.062).

Study limitations included the use of regimens that are no longer recommended, the presence of a potential confounder, and a potential lack of generalizability to other countries.

Study investigators concluded that, “the patients with [hepatocellular carcinoma] were older and had more advanced liver disease, which led them to be relatively intolerant of DAA treatment and caused a lower [sustained virologic response] rate. Furthermore, active [hepatocellular carcinoma] was associated with [nonsustained virologic response], while inactive [hepatocellular carcinoma] was not, so we suggest the deferral of DAA treatment until after complete radiological response to [hepatocellular carcinoma] treatment has been achieved.”


Yen YH, Chen CH, Hung CH, et al. Active hepatocellular carcinoma is an independent risk factor of direct-acting antiviral treatment failure: A retrospective study with prospectively collected data [published online October 3, 2019]. PLoS One. doi: 10.1371/journal.pone.0222605