Impact of Sustained Virologic Response with Direct-Acting Antiviral Treatment on Mortality in Patients with Advanced Liver Disease

The impact of sustained virologic response (SVR) on mortality after direct-acting antiviral treatment is not well documented. This study evaluated the impact of direct-acting antiviral-induced SVR on all-cause mortality and on incident hepatocellular carcinoma (HCC) in 15,059 hepatitis C virus-infected patients with advanced liver disease defined by a FIB-4 >3.25. Overall, 1,067 patients did not achieve SVR (no SVR) and 13,992 patients achieved SVR. In a mean follow-up period of approximately 1.6 years, 195 no SVR patients and 598 SVR patients died. Mortality rates were 12.3 deaths/100 patient years of follow-up for no SVR patients and 2.6 deaths/100 patient years for SVR patients, a 78.9% reduction (P < 0.001). Among patients without a prior diagnosis of HCC, 140 no SVR patients and 397 SVR patients were diagnosed with incident HCC. HCC rates were 11.5 HCCs/100 patient years for no SVR patients and 1.9 HCCs/100 patient years for SVR patients, an 83.5% reduction (P < 0.001). In multivariable Cox proportional hazard models controlling for baseline demographics, clinical characteristics, and comorbidities, SVR was independently associated with reduced risk of death compared to no SVR (hazard ratio, 0.26; 95% confidence interval, 0.22-0.31; P < 0.001). A history of decompensated liver disease (hazard ratio, 1.57; 95% confidence interval, 1.34-1.83; P < 0.001) and decreased albumin (hazard ratio, 2.70 per 1 g/dL decrease; 95% confidence interval, 2.38-3.12; P < 0.001) were independently associated with increased risk of death. Conclusion: Those achieving SVR after direct-acting antiviral treatment had significantly lower all-cause mortality and lower incident HCC rates than those who did not achieve SVR.