Pathophysiology of liver cirrhosis and risk correlation between immune status and the pathogenesis of hepatocellular carcinoma

Chronic liver disease (CLD) and cirrhosis are leading contributors to global morbidity and mortality, with hepatocellular carcinoma (HCC) frequently arising in patients with advanced liver damage. This review explores the interplay between immune dysfunction and the progression of cirrhosis to HCC, emphasizing the pivotal role of immune status in HCC pathogenesis. Chronic inflammation, cirrhosis-associated immune dysfunction syndrome (CAIDS), and immunosenescence create a permissive environment for tumorigenesis by impairing immune surveillance and promoting hepatocyte stress. Key mechanisms include T cell exhaustion, dysregulated cytokine signaling, and gut-liver axis dysfunction, which collectively drive malignant transformation. Emerging immune biomarkers, such as PD-1/PD-L1, LAG-3, TIGIT, and soluble CD14/CD163, offer promise for refining HCC risk stratification and improving early detection. Integrating these biomarkers into existing surveillance protocols could enhance screening efficacy, particularly in high-risk populations such as the elderly and immunocompromised. Current guidelines recommend biannual ultrasound and alpha-fetoprotein testing for cirrhotic patients, but adherence remains suboptimal, and late diagnoses are common. A personalized approach combining clinical risk factors, immune markers, and patient demographics may improve surveillance outcomes. Future research should focus on validating immune biomarkers in large cohorts, exploring novel therapeutic targets like LAG-3 and TIGIT, and developing tools to quantify immune dysfunction for risk stratification. By addressing immune dysregulation as a critical factor in HCC development, this review highlights the potential for improved HCC screening adherence and early detection for better patient outcomes through immune-based strategies.