Questions remain about the effect of hepatocellular carcinoma (HCC) on response to interferon-free direct-acting antiviral (DAA) therapy for chronic hepatitis C (CHC) patients compared to those without HCC. Using a systematic review and meta-analysis approach, we aimed to investigate the effect of DAA therapy on sustained virologic response among CHC patients with active, inactive and no HCC.PubMed, Embase, Web of Science, and the Cochrane Controlled Trials Register were searched from 1/1/2013 to 9/24/2018. The pooled sustained virologic response (SVR) rates were computed using DerSimonian-Laird random-effects models.We included 49 studies from 15 countries, comprised of 3,341 HCC and 35,701 non-HCC patients. Overall, the pooled SVR was lower in HCC than in non-HCC patients (89.6%, 95% CI 86.8-92.1%, I2=79.1% vs. 93.3%, 95% CI 91.9-94.7%, I2=95.0%, P=0.0012), translating to a 4.8% (95% CI 0.2-7.4%) SVR reduction by meta-regression analysis. Also on meta-regression analyses, the largest SVR reduction (18.8%) occurred in patients with active/residual HCC vs. inactive/ablated HCC (SVR 73.1% vs. 92.6%, P=0.002). Meanwhile, HCC patients with prior liver transplant (LT) had higher SVR compared to non-LT HCC patients (P<0.001). Regarding specific DAA regimens, HCC patients treated with ledipasvir/sofosbuvir had lower SVR rates than non-HCC patients (92.6%, n=884 vs. 97.8%, n=13,141, P=0.026) but heterogeneity was high (I2=84.7%, P<0.001). For the few HCC patients treated with paritaprevir/ritonavir, ombitasvir ± dasabuvir (n=101), SVR was similar to non-HCC patient (97.2% vs. 94.8%, P=0.79). Daclatasvir/asunaprevir-treated HCC and non-HCC patients also had similar SVR rates though both were low (91.7% vs. 89.8%, P=0.66).Overall, SVR was lower in HCC compared to non-HCC patients, especially in those with active HCC though heterogeneity was high. Continued efforts are needed to aggressively screen, diagnose and treat HCC to ensure higher CHC cure rates.There are now medications ("DAAs") that can "cure" hepatitis C virus, but patients with hepatitis C and liver cancer may be less likely to achieve cure than those without liver cancer. However, liver cancer patients are also more likely to have advanced liver disease and risk factors that can decrease cure rates, so better controlled studies are needed to confirm these findings.
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