Incidence of Hepatocellular Carcinoma after Treatment with Sofosbuvir-Based or Sofosbuvir-Free Regimens in Patients with Chronic Hepatitis C

Simple Summary The development of hepatocellular carcinoma (HCC) has not been well-controlled, even after the elimination of hepatitis C virus (HCV), especially for those with cirrhosis or of high-age. Fibrosis-related biomarkers have been recognized as useful predictors for the development of HCC; however, there are few analyses of the HCC incidence for the various regimens with direct-acting antivirals (DAA). We found that DAA treatment with sofosbuvir, an oral nucleotide analogue inhibitor of HCV NS5B polymerase, was not associated with the development of de novo HCC within five years by propensity score matched analysis. Moreover, the distribution of the early stage of HCC (the Barcelona Clinic Liver Cancer stage 0/A) was similar for all treatment regimens, irrespective of the use of sofosbuvir. Advanced fibrosis/cirrhosis and related biomarkers have been recognized as useful predictors of the development of hepatocellular carcinoma (HCC) by patients with chronic hepatitis C (CHC) following hepatitis C virus (HCV) cure by direct-acting antivirals (DAAs). However, it remains unclear if DAAs themselves have an influence on or facilitate the development of HCC. This multicenter cohort study included CHC patients without a history of HCC who achieved HCV elimination by DAAs. Cohorts of 835 patients treated with a sofosbuvir (SOF)-based regimen and 835 treated with a SOF-free regimen were matched 1:1 by propensity scoring with nine variables to evaluate differences in HCC incidence. The median observation period was 3.5 years. Sixty-nine cases of HCC were found during 5483.9 person-years (PY) over the entire follow-up period. The annual incidence was similar for both groups (SOF-based 1.25 and SOF-free 1.27 per 100 PY, respectively: adjusted hazard ratio (HR) 1.26, 95% confidence interval (CI) 0.75-2.12, p = 0.39). However, the annual incidence within the first two years was higher for patients treated with SOF than for those without, but did not reach significance (1.50 and 0.97 per 100 PY incidence rates, respectively: adjusted HR 2.05, 95% CI 0.98-4.25, p = 0.06). In summary, DAA treatment with SOF was not associated with an increase in the development of de novo HCC.