Background and Aim: The study aimed to identify the risk factors associated with hepatocellular 
carcinoma (HCC) development in patients with chronic hepatitis C virus (HCV) infection treated with 
direct-acting antivirals (DAAs) in Pakistan. 
Methods: A retrospective cohort study included 246 patients with chronic HCV infection who 
received DAA therapy between March 2020 and March 2024. Patients were followed for a median 
duration of 33 months to monitor the development of HCC. Baseline characteristics and potential 
risk factors were analyzed using univariate and multivariate analyses to determine their association 
with HCC occurrence. 
Results: Of the 246 patients, 34 (13.5%) developed HCC during the follow-up period. Univariate 
analysis revealed that older age (p<0.001), male gender (p=0.004), lower baseline platelet count 
(p<0.001), higher baseline alpha-fetoprotein (AFP) level (p<0.001), and the presence of liver cirrhosis 
(p<0.001) were significantly associated with the development of HCC. Multivariate analysis 
confirmed that advanced age (HR 1.06, 95% CI 1.03-1.08, p<0.001), male sex (HR 1.86, 95% CI 1.13
3.08, p=0.014), elevated baseline AFP (HR 1.28, 95% CI 1.18-1.39, p<0.001), and liver cirrhosis (HR 
4.84, 95% CI 2.78-8.42, p<0.001) were independent predictors of HCC development. Additionally, 
patients who achieved sustained virological response (SVR) had a significantly lower incidence of HCC 
compared to those who did not achieve SVR (1.1% vs. 6.9%, p<0.001). 
Conclusion: This study identifies key risk factors for HCC development in chronic HCV patients 
treated with DAAs, emphasizing the need for vigilant monitoring, especially in older males with 
cirrhosis and elevated AFP levels. Achieving SVR significantly reduces the risk of HCC, underscoring 
the importance of effective antiviral treatment in this population.