Direct-acting antiviral therapy reduces variceal rebleeding and improves liver function in hepatitis C virus-related cirrhosis: A multicenter retrospective cohort study

Abstract

BACKGROUND Hepatitis C virus (HCV) infection remains a major public health issue in Egypt, with a high prevalence of genotype 4. Direct-acting antivirals (DAAs) achieve > 95% sustained virologic response (SVR), but their impact on variceal rebleeding in genotype 4 cirrhotic patients is underexplored. This study evaluated the association between DAA therapy and variceal rebleeding in Egyptian patients with HCV-related cirrhosis. AIM To evaluate the association between DAA therapy and variceal rebleeding in Egyptian patients with HCV-related cirrhosis. METHODS A multicenter retrospective cohort study included HCV genotype 4 cirrhotic patients from five Egyptian centers with a first variceal bleeding episode. Patients were divided into DAA-treated (Group A) and non-treated (Group B) groups and followed for 5 years. Propensity score matching (PSM), Cox regression, and competing risk analysis were adjusted for confounders. RESULTS DAA treatment significantly reduced variceal rebleeding (HR 2.57; 95%CI: 1.39-4.72; P = 0.002), ascites development over 5 years (6.8% vs 27.1%, P = 0.006), and hepatic dysfunction progression. During treatment, it improved liver function [lower model for end-stage liver disease (MELD), stable Child-Pugh class] and reduced complications. All Group A patients achieved SVR by PCR, while Group B remained HCV-positive, likely contributing to the observed reductions in rebleeding and hepatic decompensation. These benefits persisted over 5 years, with longer survival without rebleeding (4.5 years vs 3.2 years), lower MELD (7 vs 12, P < 0.001), and reduced hepatic decompensation (Child-Pugh progression: 5.1% vs 35.6%, P < 0.001). At 5 years, the DAA group had better liver function (higher albumin, lower international normalized ratio, improved platelets), while the non-DAA group worsened. PSM confirmed these findings (HR: 0.45, 95%CI: 0.27-0.75, P = 0.002), and competing risk analysis showed sustained protection (sub-distribution HR: 0.44, 95%CI: 0.26-0.74, P = 0.002). Endoscopy revealed variceal regression with DAA but progression in the non-DAA group. DAA therapy significantly reduced variceal rebleeding, hepatic decompensation, and mortality (8.5% vs 20.3%, P = 0.045), with survival benefits linked to SVR. Additionally, it was associated with improved survival, with a lower 5-year mortality rate in the DAA group (8.5% vs 20.3%, P = 0.045). The protective effect of DAA therapy remained consistent across multivariable Cox regression, time-dependent modeling, and competing risk analyses. CONCLUSION DAA treatment in HCV-related cirrhosis significantly reduces variceal rebleeding, ascites development, and hepatic dysfunction progression. The 5-year follow-up data demonstrate sustained improvements in liver function and hematologic parameters, underscoring the long-term benefits of DAA therapy.