Therefore, beside the structural alterations (fibrosis, nodule formation), there is a complex dynamic component that contributes to increasing hepatic vascular resistance and splanchnic vasodilata-tion. Understanding this pathophysiology has revealed markers that are associated with the presence of PH and varices. On the other hand, variation of the genes that encode proteins involved in sys-temic and splanchnic vasodilatation have been found to be associated with the presence of esophageal varices. 8 Therefore, variation of these genes could play a role in addition to predicting the presence of esophageal varices, as well as their likelihood of bleeding. In this issue of the journal, Yang and colleagues have analyzed 951 patients with cirrhosis of various etiologies. The main aim was to evaluate additional blood markers and genetic risk for the prediction of the presence of esophageal varices in cirrhosis. Also, they performed a 2-year follow-up to evaluate predictors for esophageal varices (EV) bleeding. The authors also studied another 650 independent patients to confirm the association between genetic variants and presence of EVs, namely for validation cohort. 9 The factors analyzed in this study included plasma levels of soluble CD163 (sCD163), VEGF and HO-1, genetic polymorphisms of HO-1, VEGF, and vascular endothelial growth factor receptor 2 (VEGFR2). Soluble CD163 is a specific marker of activated macrophages, another potential biomarker for PH in cirrhosis. The activation of Kupffer cells may be involved in PH by the release of vasoconstrictor substances. Recently, Grønbaek et al. have shown that sCD163 plasma concentration in cirrhosis is almost three times higher than in controls, and sCD163 was an independent predictor of the hepatic venous pressure gradient. 10 Yang et al. 9 found that serum sCD163 level was elevated in patients with cirrhosis complicated by esophageal varices, and this marker could potentially be used to predict the presence of EVs in clinical practice. The genetic elements of the Yang study identified that patients with esophageal varices showed significantly higher frequencies of risk genotypes of HO-1, SS in (GT)n repeat, and AA in T(-413)A than corresponding wild-type genotypes. Further, cir-rhotic patients carrying C(+405)G GG and C(+936)T TT risk genotype of VEGF, and Val(-297)Ile Ile/Ile risk genotype of VEGFR2 had a higher likelihood of developing EVs than those carrying wild-type genotype. Therefore, in addition to traditional markers (platelet count and splenomegaly), the authors showed that high serum sCD163 level and these polymorphisms in the HO-1 and VEGF predict the presence of esophageal varices in patients with cirrhosis. Further, the combination of platelet count, serum sCD163 level, and those risk haplotypes of HO-1 and VEGF conferred higher predictive values for varices than platelet count alone. Finally, patients with these same risk haplotypes (HO-1 and VEGF) have a higher chance of esophageal variceal bleeding than those not carrying these haplotypes. In con...