Genetic Variants in Liver Cirrhosis: A Review of Classification, Mechanisms, and Clinical Relevance Cirrhosis

Background/Objectives: Cirrhosis represents a significant global health burden, driven by diverse etiologies including viral hepatitis, alcohol-associated liver disease, and non-alcoholic fatty liver disease (NAFLD). While environmental factors play a key role, individual susceptibility and disease progression vary widely, underscoring the importance of genetic predisposition. This review systematically examines the influence of inherited genetic variations on cirrhosis development and clinical outcomes, aiming to provide a mechanistic framework for understanding these associations and their implications for personalized hepatology. Methods: We conducted a comprehensive literature review of studies investigating genetic contributors to cirrhosis, focusing on germline variants with established or potential clinical relevance. Key databases (PubMed, Scopus, and Web of Science) were searched for peer-reviewed articles published up to [insert date]. Genetic variants were categorised into four functional groups: ethnicity-associated polymorphisms, liver enzyme–related genes, immune-modulating variants, and metabolism-related genetic changes. Polygenic risk scores and genotype-based prognostic tools were also evaluated. Results: Our analysis highlights critical genes, including PNPLA3, HSD17B13, and TM6SF2, which influence cirrhosis risk through mechanisms such as lipid metabolism dysregulation and hepatic inflammation. Ethnicity-specific polymorphisms and immune-related variants further modulate disease susceptibility. Polygenic risk scores demonstrate promise in stratifying patients, though clinical utility requires further validation. Conclusions: Genetic factors significantly contribute to cirrhosis heterogeneity, offering insights into individualized risk assessment and therapeutic targeting. Future research should prioritize translating these findings into actionable clinical strategies, integrating genetic profiling into hepatology practice. This review provides a structured foundation for understanding the genetic architecture of cirrhosis and its implications for precision medicine.