he pathogenesis of liver cirrhosis is a complex process for which the mechanisms are not completely elucidated. Although exogenous or environmental risk factors leading to chronic liver injury, such as viral hepatitis B and C infection, alcohol intake, or fatty liver disease, can be identified in most patients with cirrhosis, approximately 5% of patients with cirrhosis have no apparent risk factors. 1 In addition, patients with identical risk factors have a diverse spectrum of clinical manifestations. The reasons why some patients with identifiable risk factors progress to cirrhosis whereas others have a benign course remain unclear and cannot be completely explained by known environmental and/or obvious host factors (i.e., age and sex). Therefore, a genetic predisposition may contribute to the development of cirrhosis.
Evidence supporting the role of genetic factors as a risk for cirrhosis has been accumulating during the last decade. Data from epidemiologic studies reported the prevalence of cryptogenic cirrhosis as 3.1-fold higher in Hispanic Americans, but 3.9-fold lower in African Americans than in European Americans despite the same prevalence of diabetes in Hispanics and African Americans. 2 Studies of the National Academy of Sciences-National Research Council Twin Registry reported that concordance rates for developing alcoholic cirrhosis were significantly higher in monozygotic twins than in dizygotic twins (16.9% versus 5.3%, P < 0.001). 3 Recently, Huang et al. proposed a cirrhosis risk score based on a genetic marker panel (seven single-nucleotide polymorphisms [SNPs] in six genes: AP3S2 [adaptor-related protein complex 3, sigma 2 subunit], AQP2 [aquaporin 2], AZIN1 [antizyme inhibitor 1], STXBP5L [syntaxin binding protein 5-like], TLR4 [Toll-like receptor 4], and TRPM5 [transient receptor Abbreviations: HCC, hepatocellular carcinoma; HCV, hepatitis C virus; SNP, single-nucleotide polymorphism; TERT, telomerase reverse transcriptase; TERC, telomerase RNA component.