Abstract
BackgroundThere are conflicting data regarding the risk of hepatocellular carcinoma (HCC) after direct-acting antiviral agent (DAA) treatment. Risk of HCC in HCV genotype-3 infected persons after DAA therapy is not well known.MethodsWe prospectively studied HCV infected persons initiated on a DAA regimen between October 2014 and March 2017 at two centers in Pakistan. All persons were free of HCC at study initiation. HCC was confirmed based on characteristic CT scan findings. Patients were followed for 12 months after the completion of therapy.ResultsA total of 662 persons initiated treatment. Median age (IQR) was 50 (41, 57) years and 48.8% were male. At baseline, 49.4% were cirrhotic, 91% were genotype 3 and 91.9% attained SVR. Treatment regimens used were: Sofosbuvir (SOF)/ribavirin (RBV)/pegylated interferon (PEG-IFN), 25.2%; SOF/RBV, 62.4%; SOF/RBV/daclatasavir (DCV), 10.6%; SOF/DCV, 2.0%. Incident HCC was detected in 42 patients (12.8%) in the 12-month period after treatment completion and was exclusively observed in those with cirrhosis. In multivariable Cox regression analysis, SVR was associated with a reduction in HCC risk (HR, 95% CI: 0.35, 0.14,0.85). In Kaplan-Meier plots by treatment regimen, those treated with SOF/RBV, SOF/RBV/DCV, or SOF/DCV regimens had a shorter HCC-free survival compared with those treated with a SOF/RBV/PEG-IFN regimen.ConclusionIn a predominantly genotype 3 cohort, incident HCC occurred frequently and early after treatment completion, and exclusively in those with pre-treatment cirrhosis. SVR reduced the risk of HCC. Treating HCV infected persons before development of cirrhosis may reduce risk of HCC.
Highlights
There are conflicting data regarding the risk of hepatocellular carcinoma (HCC) after direct-acting antiviral agent (DAA) treatment
The median age was 50 years and 48.8% were male. (Table 1) Mean weight of the participants was 71.8 kg, 6.9% had hypertension, 28.2% had diabetes and 1.4% were coinfected with hepatitis B virus
While at least one study has reported a lower incidence of HCC in persons with hepatitis C virus (HCV) non-genotype 1 infection, another large national study observed a clear association between HCV genotype 3 infection and HCC cirrhosis [33, 34]
Summary
There are conflicting data regarding the risk of hepatocellular carcinoma (HCC) after direct-acting antiviral agent (DAA) treatment. Treatment of hepatitis C virus (HCV) has been revolutionized by the use of direct acting antiviral agents (DAAs) against HCV These regimens are more efficacious compared with the older interferon based regimens, with sustained virologic response (SVR) rates consistently exceeding 90–95% [1,2,3,4,5]. The risk of HCC among persons with HCV genotype 3 infection who are treated with newer DAA-based regimens is unknown. We undertook this to determine the association between DAA-based regimen and incident HCC in a predominantly HCV genotype 3 population in Pakistan
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