Cause-Specific Mortality Following Sustained Virologic Response in hepatitis C patients Treated with Direct-Acting Antivirals: A Standardized Mortality Ratio Analysis

Background Direct-acting antivirals (DAAs) achieve high sustained virologic response (SVR) rates in patients with hepatitis C virus (HCV) infection. However, the long-term prognosis and cause-specific mortality following SVR remain incompletely defined. Methods This study analyzed 1,753 HCV-infected patients without a history of hepatocellular carcinoma (HCC) treatment who achieved SVR with DAAs. Liver disease-related (LDR) and non-LDR mortality were assessed using age- and sex-adjusted standardized mortality ratios (SMR) compared with the general population. Results During a mean follow-up of 59.2 months, 122 patients died. The SMR for all-cause mortality was 1.050 ( p  = 0.588). The SMR for LDR and non-LDR mortality were 7.819 (p < 0.001) and 0.566 (p < 0.001), respectively. The SMR for extrahepatic malignancy-related mortality was significantly lower at 0.593 (p = 0.013), whereas cardiovascular disease (CVD)–related mortality did not differ significantly at 0.884 (p = 0.554). These findings were consistent regardless of age, sex, presence of LC, diabetes, or chronic kidney disease. Conclusions Overall mortality after SVR in patients with HCV was comparable with that of the general population. Nevertheless, LDR mortality remained significantly elevated, whereas non-LDR and extrahepatic malignancy-related mortality were significantly reduced. These results underscore the importance of continued liver disease surveillance post-SVR, while CVD management should parallel that of the general population.