Recent studies have suggested a negative impact of hepatocellular carcinoma (HCC) on sustained virologic response (SVR) to hepatitis C virus (HCV) direct acting antivirals (DAAs). We compared the effectiveness of DAAs in patients with cirrhosis, with and without HCC, and in those with HCC partially treated or untreated (PT/UT-HCC) versus completely treated (CT-HCC). HCC status was based on imaging 6 months before or 2 months after start of DAA therapy. Absence and presence of enhancing lesions after HCC treatment defined CT-HCC and PT/UT-HCC, respectively. Using minimally adjusted logistic regression, the association between the presence of HCC and SVR rates was estimated. Among the 1,457 patients with cirrhosis from HCV-TARGET with complete virologic data (per-protocol population) who did not undergo liver transplantation during treatment and followup, 1,300 were without HCC, 91 with CT-HCC, and 66 with PT/UT-HCC. Most patients were genotype 1 (81%) and treatment-experienced (56%), 41% had history of prior decompensation, and the median pretreatment Model for End-Stage Liver Disease was 9 (range 6-39). The SVR rates were 91% for patients without HCC, 84% for CT-HCC, and 80% for PT/UT-HCC. The presence of HCC (versus not having HCC) was associated with significantly lower odds of achieving SVR (odds ratio [OR] = 0.51, 95% confidence interval [CI]: 0.33-0.81; P = 0.003). However, among those with HCC, HCC treatment status (PT/UT-HCC versus CT-HCC) did not show association with SVR (OR = 0.79, 95% CI: 0.35-1.79, P = 0.569). Conclusions: The presence of HCC reduces the likelihood of SVR by 50%, but with no evident difference in those with completely treated HCC versus partially treated/untreated HCC.
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