S2151 Impact of Direct-Acting Antivirals on Hematologic, Oncologic, Healthcare Utilization, and Mortality Outcomes in Hepatitis C: A Matched Cohort Analysis

Introduction: Direct-acting antivirals (DAAs) have revolutionized the treatment of hepatitis C virus (HCV), but their broader systemic effects, particularly on extrahepatic outcomes, remain incompletely characterized. This study evaluated the impact of DAA therapy on hematologic, oncologic, healthcare utilization, and mortality outcomes in a large real-world cohort of HCV-infected adults. Methods: A retrospective cohort study was conducted using the TriNetX Global Network. Adults with HCV infection were included, excluding individuals with HIV or chronic hepatitis B. Patients treated with DAAs were matched 1:1 to untreated HCV patients using propensity scores based on demographics and comorbidities. Each group included approximately 91,000 patients. Outcomes were assessed using Cox proportional hazards modeling. Results: DAA therapy was associated with significantly reduced risk of hematologic complications including thrombocytopenia (hazard ratio [HR] 0.67; 95% confidence interval [CI] 0.60–0.75), iron deficiency anemia (HR 0.78; 95% CI 0.70–0.87), coagulopathy (HR 0.53; 95% CI 0.43–0.66), and aplastic anemia (HR 0.58; 95% CI 0.46–0.73). No significant differences were observed for hemolytic anemia, cryoglobulinemia, amyloidosis, porphyria cutanea tarda, or autoimmune hemolytic anemia. Oncologic outcomes favored DAA use, with reduced hepatocellular carcinoma (HR 0.86; 95% CI 0.82–0.90) and AFP >20 ng/mL (HR 0.58; 95% CI 0.55–0.61), while monoclonal gammopathy of undetermined significance (MGUS) was more common (HR 1.22; 95% CI 1.08–1.39). Other oncologic outcomes including lymphomas and solid tumors showed no significant differences. DAA-treated patients had lower healthcare utilization, including hospitalizations (HR 0.72; 95% CI 0.68–0.75) and outpatient visits (HR 0.77; 95% CI 0.74–0.81), as well as fewer elevated liver enzyme events (HR 0.79; 95% CI 0.76–0.82). All-cause mortality was significantly lower in the DAA-treated group (HR 0.58; 95% CI 0.55–0.60). Conclusion: In a large matched cohort of HCV-infected adults, DAA therapy was associated with significant reductions in hematologic complications, hepatocellular carcinoma, healthcare utilization, and all-cause mortality. These findings support the broad systemic benefits of antiviral therapy and highlight the need for continued research on long-term outcomes after HCV eradication.