Hepatocellular carcinoma decreases the effectiveness of hepatitis C antiviral treatment: Do direct‐acting antiviral regimens matter?
Authors: Fanpu Ji, Yee Hui Yeo, Mike Tzuhen Wei, Bin Wei, Shuangsuo Dang, Zongfang Li, Mindie H. Nguyen
Journal: Hepatology (2017)

Potential conflict of interest: Dr. Nguyen consults for, advises for, and received grants from Gilead, Bristol‐Myers Squibb, and Janssen. She consults for and received grants from Pfizer. Author names in bold designate shared co‐first authorship. TO THE EDITOR: We read with interest two articles recently published in Hepatology.1 Both studies showed that hepatocellular carcinoma (HCC) patients treated with all‐oral direct‐acting antiviral (DAA) regimens for hepatitis C virus (HCV) infection had lower sustained virological response 12 weeks after end of treatment (SVR12). In the study by Saberi et al., only 67% (14 of 21) of HCC patients achieved SVR12.1 In another study, all 5 patients who developed HCC within 6 months of therapy experienced virological relapse compared to 12 of 150 patients without HCC (100% vs. 8%; P < 0.0001).2 Similarly, Beste et al. showed that only 74.4% of patients with HCC achieved SVR12 compared to 91.1% in those without HCC.3 Prenner et al. also showed that patients with cirrhosis with active HCC (viable tumor on imaging) were almost 8 times more likely to fail HCV treatment than those without active HCC.4 Although the vast majority of the patients in these studies were non‐Asians,1 their results are consistent with our recent meta‐analysis of HCV genotype 1 (GT 1) patients from Asia, in which we showed a lower SVR12 in HCC patients treated with ledipasvir (LDV)/sofosbuvir (SOF) regimen (94.1% vs. 98.7% in non‐HCC patients; P = 0.001; Fig. 1A).5Figure 1: Pooled estimates of SVR rates in HCV genotype 1 patient with HCC from Asia. (A) With LDV/SOF regimen, patients with past history of HCC (n = 177) showed a lower SVR than those without HCC (n = 1,365; 94.1%; 95% confidence interval [CI], 89.9‐97.3 vs. 98.7%; 95% CI, 97.5‐99.6; P = 0.001). (B) With DCV/ASV regimen, patients with past history of HCC (n = 234) achieved a similar SVR to those without HCC (n = 1,064) (88.7%; 95% CI, 82.7‐93.6 vs. 88.0%; 95% CI, 86.0‐89.9; P = 0.9776).Though the most commonly used regimens in these studies were SOF‐based regimens and all showed lower SVR in HCC patients, results for subanalysis of the various individual DAA regimens were conflicting.1 In one subanalysis, SVR12 for HCC with HCV GT1 patients treated with paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD) plus ribavirin (RBV) was 97.4%, which was similar to non‐HCC patients (92.3%); however, this finding should be interpreted with caution because this analysis only included 39 HCC patients.3 For GT1 patients treated with LDV/SOF ± RBV in the same study, the SVR12 in non‐HCC patients was significantly higher than those with HCC (93% vs. 76%), and this analysis included 303 HCC patients.3 In our meta‐analysis of patients treated with daclatasvir (DCV)/asunaprevir (ASV) with 234 HCC patients in Asia, SVR12 rates were similar for HCC and non‐HCC patients (88.7% vs. 88.0%; P = 0.98; Fig. 1B). Of note, although similar to SVR12 in non‐HCC patients treated with the same medications, SVR12 for DCV/ASV‐treated HCC patients was still lower than SVR12 for LDV/SOF‐treated HCC patients (94.1%).5 Further investigations with large, well‐controlled studies are needed to clarify the effect of HCC in response to different DAA regimens and to help identify the optimal regimen(s) for this population.