Prognostic value of keratin 18 for the patients with hepatitis B virus-related acute-on-chronic liver failure

Abstract

Objective To analyze the serum keratin 18 (K18) level of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF) and its correlation with prognosis. Methods From December 2012 to October 2014, 120 patients who visited Fuzhou Infectious Diseases Hospital and diagnosed with HBV-ACLF were enrolled, and 20 chronic hepatitis B (CHB) patients and 20 healthy controls were enrolled with matched gender and age. Enzyme linked-immunosorbent assay was used for the detection of K18 (M30, M65) and the differences of M30, M65, M30/M65 and other laboratory results were analyzed among the first enrolled 40 patients with HBV-ACLF, 20 CHB patients and 20 healthy controls. All HBV-ACLF patients were followed up for 3 months and divided into two groups (death group and survival group). And M30 and M65 in both groups were detected and their clinical data were collected. Continuous variables between groups were compared using t test and one-way analysis of varicmce. Categorical variables were compared using χ2 test. Receiver operating characteristic (ROC) curve was used for prognostic analysis. Results The serum M30 in HBV-ACLF group, CHB group and healthy controls group were (2.99±0.29), (3.12±0.26) and (2.16±0.12) lg U/L, respectively (F=95.36, P<0.01). The serum M65 in the three groups were (3.41±0.29), (3.38±0.29) and (2.01±0.11) lg U/L, respectively (F=217.60, P<0.01). And M30/M65 the three groups were 0.39±0.11, 0.55±0.09 and 1.45±0.34, respectively (F=202.63, P<0.01). The white blood cell, total bilirubin, alanine aminotransferase and aspartate aminotransferase in HBV-ACLF patients were the highest, and platelet, albumin, serum sodium and prothrombin time activity were the lowest. After following up for 3 months of 120 patients with HBV-ACLF, 40 of them died with fatality rate of 33.3%. The area under ROC curve (AUC) of the M30/M65 was 0.871, and that of score of model for end-stage liver disease (MELD) was 0.668 (Z=3.011, P<0.01). The M30/M65 ratio was significantly negatively correlated with the MELD score (r=-0.389, P<0.01). Conclusions K18 (M65 and M30) are strongly associated with liver disease severity. The M30/M65 ratio may be a potential diagnostic and prognostic marker for the patients with HBV-ACLF. Key words: Keratin-18; Hepatitis B virus; Acute-on-chronic liver failure; Prognosis