Non‐liver‐related mortality in the DAA era: Insights from post‐SVR patients with and without previous HCC history

Abstract Background and Aims Mortality after sustained virological response (SVR) with interferon‐free direct‐acting antiviral (IFN‐free DAA) therapy is crucial for optimizing post‐SVR patient care, but it remains unclear, especially regarding non‐liver‐related mortality. Methods Consecutive post‐SVR patients from 14 institutions were stratified into three cohorts: A (without advanced fibrosis and without prior HCC), B (with advanced fibrosis and without prior HCC), and C (curative HCC treatment). We assessed mortality (per 1000 person‐years [/1000PY]) post‐SVR. Mortality rates were compared between cohorts A and B and the general population using age‐ and sex‐adjusted standardized mortality ratio (SMR). Comparison of survival between each cohort was performed using propensity‐score (PS) matching with sex, age, and comorbidity. Results In cohort A ( n = 762; median age, 65 years), 22 patients died (median follow‐up, 36 months); all‐cause mortality was 10.0/1000PY, with 86.4% non‐liver‐related deaths. In cohort B ( n = 519; median age, 73 years), 27 patients died (median follow‐up, 39 months); all‐cause mortality was 16.7/1000PY, with 88.9% non‐liver‐related deaths. In both cohorts, malignant neoplasm was the most common cause of death; all‐cause mortality was comparable to that of the general population (SMR: 0.96 and 0.92). In cohort C ( n = 108; median age, 75 years), 15 patients died (median follow‐up, 51 months); all‐cause mortality was 36.0/1000PY, with 53.3% liver‐related deaths. PS matching showed no significant survival differences between cohorts A and B, both of which had better survival than cohort C. Conclusions Mortality varies based on HCC history in the DAA era; nevertheless, attention should be paid to non‐liver‐related deaths in all post‐SVR patients.