The Combined Elevation of Tumor Markers CA 19-9 and CA 125 in Liver Disease Patients Is Highly Specific for Severe Liver Fibrosis

Increased tumor markers in patients with liver cirrhosis are often considered to be unspecific. The use of this unspecific elevation to discriminate minimal fibrosis from severe fibrosis has never been explored. We aimed to answer the question, Do tumor markers predict severe liver fibrosis? The study group consisted of 125 patients with alcoholic liver disease, hepatitis B, or hepatitis C with available liver biopsy. Tumor markers CA 19-9, CA 15-3, and CA 125 were determined using routine laboratory methods and correlated with the extent of liver fibrosis. Fibrosis stages 1 and 2 were classified as minimal fibrosis; stages 3 and 4, as severe fibrosis. Tumor markers CA 19-9, CA 125, and CA 15-3 increased with stage of fibrosis. For separating patients with mild fibrosis (F1+F2) from patients with severe fibrosis (F3+F4), CA 19-9 had a sensitivity of 70.5% and a specificity of 88.6, CA 125 had 38.1% and 89.7%, and CA 15-3 had 19.0% and 93.0%, respectively. Logistic regression of a combined score of CA19-9 and CA 125 values revealed that an increase of 1 point of the CA 19-9/CA125 score resulted in a 1.6 times increase in likelihood of the presence of severe fibrosis. The CA 19-9/CA 125 score achieved a similar specificity (97.1% vs. 100%) but a higher sensitivity (42.9% vs. 33.3%) than the widely used cirrhosis discriminant score of Bonacini. A specificity (98.5%) similar to that of the CA 19-9/CA 125 score was reached by the easier determination of the combined elevation of CA 19-9 and CA 125, which had the best positive predictive value, 92.9%. The excellent predictive ability of the combined elevation of CA 19-9 and CA 125 for severe liver fibrosis (F3+F4) was confirmed in an independent group of patients with liver disease. The combined elevation of CA 19-9 and CA 125 is useful for identifying patients with advanced fibrosis or cirrhosis with high specificity. Patients without a combined elevation of CA 19-9 and CA 125 still require histological examination to identify severe fibrosis or cirrhosis.