AN INTEGRATED TGF-β1 AND CYP2E1 GENETIC INDEX FOR PREDICTING SEVERE LIVER CIRRHOSIS

This study evaluated the association between an integrated genetic index based on the TGF-β1 CT+TT and CYP2E1 c1/c2+c2/c2 risk genotypes and the clinical severity and unfavorable course of liver cirrhosis. The study in­cluded 180 patients with liver cirrhosis of various etiologies. According to the genetic index, the patients were classified into low-, intermediate-, and high-risk groups. Low, intermediate, and high genetic risk was identified in 28.3%, 52.2%, and 19.5% of patients, respectively. Increasing genetic risk was accompanied by a consistent rise in the frequency of Child–Pugh class C, ascites, and hepatic encephalopathy. The MELD/MELD-Na score increased from 13.9±4.0 to 19.2±5.0 points, whereas serum albumin decreased from 34.0±5.4 to 27.5±6.2 g/L. The genetic index showed positive correlations with Child–Pugh, MELD/MELD-Na, and total bilirubin and negative correlations with serum albumin and the SF-36 physical component score. A high genetic index was significantly associated with severe liver cirrhosis, with an odds ratio of 3.26. The findings indicate that the combined assessment of TGF-β1 and CYP2E1 genetic variants together with clinical and laboratory parameters may improve individualized risk stratification and prediction of an unfavorable course of liver cirrhosis.

Purpose – to evaluate the association of an integrated genetic index incorporating the TGF-β1 CT+TT and CYP2E1 c1/c2+c2/c2 risk genotypes with the severity and adverse course of liver cirrhosis.

Material and methods – The analysis included 180 patients with liver cirrhosis of various etiologies. The index was scored from 0 to 2: no risk genotype, 0; one risk genotype, 1; and both risk genotypes, 2. Disease severity was assessed using Child–Pugh, MELD/MELD-Na, ascites, hepatic encephalopathy, serum albumin, and the SF-36 physical component score. The χ² test, Spearman correlation, and logistic regression were applied.

Results – Low, intermediate, and high genetic risk was observed in 28.3%, 52.2%, and 19.5% of patients, re­spectively. Across increasing risk categories, Child–Pugh class C rose from 13.7% to 40.0%, ascites from 37.3% to 71.4%, and encephalopathy from 15.7% to 40.0%. MELD/MELD-Na increased from 13.9±4.0 to 19.2±5.0, whereas albumin decreased from 34.0±5.4 to 27.5±6.2 g/L. High genetic risk was associated with severe disease (OR=3.26; 95% CI: 1.48–7.19; p<0.01), while albumin <30 g/L showed the largest clinical effect (OR=3.72). Conclusion – Com­bining the TGF-β1/CYP2E1 genetic index with clinical and functional variables may improve individualized risk stratifi­cation; however, internal and external validation is required.