Article Abstract

Serum cytokeratin-18 is a non-invasive biomarker for evaluating disease severity in patients with liver cirrhosis and hepatocellular carcinoma

Authors: Huayu Yang, Lejia Sun, Langqing Sheng, Xiaowei Wang, Haifeng Xu, Shunda Du, Haitao Zhao, Xin Lu, Xinting Sang, Yilei Mao

Abstract

Background: To investigate the dynamic changes in cytokeratin-18 (CK18) levels in patients with liver cirrhosis and hepatocellular carcinoma (HCC) undergoing surgery, and to evaluate its diagnostic value for HCC and acute liver injury.
Methods: Serum levels of total CK18 and CK18 fragments were measured using specific enzyme-linked immunosorbent assays in patients with liver cirrhosis and HCC, and control patients with liver cavernous hemangioma. Clinical parameters were measured 1 day before and 1, 3, and 5 days after surgery.
Results: CK18 levels were markedly elevated in patients with liver cirrhosis and HCC compared with control patients with non-cirrhotic liver disease (total CK18: 262.9±130.0 U/L, control 158.7±44.5 U/L, P=0.038; CK18 fragments: 145.1±69.6 U/L, control 81.6±15.2 U/L, P=0.005), but fell to near preoperative levels at postoperative day (POD) 5. CK18 levels paralleled perioperative changes in alanine transaminase (ALT), reaching peak values on POD 1, and then decreasing gradually to near preoperative levels by POD 5. The correlation coefficients for the relationships between serum CK18 released by hepatocyte necrosis and ALT levels were 0.659 in the cancer group and 0.922 in the control group. Serum ALT levels remained above preoperative levels at POD 5. The levels of total CK18 and CK18 fragment released by hepatocyte necrosis were remarkably higher on POD 1 than the levels before operation.
Conclusions: Serum levels of total CK18 and CK18 fragments were higher in HCC patients with chronic hepatitis B-related liver cirrhosis compared with levels in patients with liver cavernous hemangioma. Liver cancer may have a greater impact on serum CK18 levels than cirrhosis. Surgical injury can increase serum CK18 levels, and CK18 may be a more sensitive marker of liver injury than ALT.