Background A serious consequence of long-term hepatitis B virus (HBV) and hepatitis C virus (HCV) infections is hepatocellular carcinoma (HCC), particularly in co-infected individuals, who are at a significantly higher risk of malignant transformation. Objective The main objective of this study is to determine the frequency and identify associated risk factors of HCC in patients co-infected with HBV and HCV through a retrospective cross-sectional analysis. Methodology This retrospective cross-sectional study was conducted at Hayatabad Medical Complex, Peshawar, Pakistan, using medical records of HBV-HCV co-infected patients from January 2023 to December 2024. A total of 348 patients aged ≥18 years, with complete clinical, biochemical, and radiological/histopathological data, were included. Data were analyzed using IBM SPSS Statistics for Windows, Version 25 (Released 2017; IBM Corp., Armonk, NY, USA), evaluating demographics, comorbidities, alpha-fetoprotein (AFP) levels, liver function tests, and HCC diagnosis. Chi-square and logistic regression analyses were used to identify significant risk factors, with p-values <0.05 considered statistically significant. Results Out of 348 HBV-HCV co-infected patients, 73 (20.98%) were diagnosed with HCC. The majority of patients were aged between 31 and 60 years, with a mean age of 47.8 ± 12.6 years. Males comprised 58.91% (n = 205) of the cohort. Among the HCC patients, age >45 years was significantly associated with HCC occurrence (71.23% vs. 47.27%, p = 0.002). Cirrhosis was found in 68.49% of HCC patients versus 35.64% without HCC (p < 0.001). Infection duration ≥5 years was observed in 72.60% of HCC cases compared to 60.36% of non-HCC cases (p = 0.054). Elevated AFP >20 ng/mL was significantly associated with HCC (61.64% vs. 24.36%, p < 0.001), as was elevated alanine aminotransferase (ALT) (76.71% vs. 57.82%, p = 0.006). Comorbidities were more common in HCC patients (39.73%) compared to non-HCC patients (21.82%, p = 0.004). Logistic regression analysis identified several independent predictors of HCC: age >45 years (adjusted odds ratio (AOR): 2.45; 95% CI: 1.38-4.36; p = 0.002), cirrhosis (AOR: 3.87; 95% CI: 2.15-6.96; p < 0.001), infection duration ≥5 years (AOR: 1.62; 95% CI: 1.01-2.59; p = 0.046), AFP >20 ng/mL (AOR: 3.09; 95% CI: 1.74-5.48; p < 0.001), and presence of comorbidities (AOR: 1.85; 95% CI: 1.09-3.15; p = 0.022). Conclusion Among HBV-HCV co-infected patients, a high proportion of HCC was observed. Significant risk factors independently associated with HCC included age over 45 years, presence of cirrhosis, longer infection duration, elevated AFP levels, and comorbidities. These findings underscore the importance of early risk stratification and regular surveillance in co-infected individuals to enable timely diagnosis and intervention.
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