Serum CA19-9 Level is Correlated with Liver Inflammation, Cirrhosis, and Poor Prognosis after Curative Resection in Hepatitis B-related Hepatocellular Carcinoma

Abstract Background: The relationship between serum carbohydrate antigen 19-9 (CA19-9) and hepatocellular carcinoma (HCC) is unclear. To explore the prognostic value of preoperative CA19-9 in α-fetoprotein (AFP)-positive and -negative HCC with hepatitis B virus (HBV) background (HBV-HCC).Methods: We evaluated HBV-HCC patients who underwent curative resection (Cohort 1). Recurrence-free survival (RFS) and overall survival (OS) were assessed, and the clinicopathological characteristics were compared according to a CA19-9 cutoff of ≥ 39 U/ml. Immunohistochemical staining of CA19-9 in HCC tumor tissue and background liver were quantified in another cohort of 216 patients with resected HCC (Cohort 2). Immunohistochemical staining or serum CA19-9 level was also compared between patients with intrahepatic cholangiocarcinoma (ICC) (Cohort 3).Results: In Cohort 1, CA19-9 ≥ 39 U/ml was an independent risk factor for RFS (HR=1.507, 95% CI=1.087-2.091, p=0.014) and OS (HR=1.646, 95% CI=1.146-2.366, p=0.007) in both AFP-positive and AFP-negative patients. CA19-9 ≥ 39 U/ml was also associated with significantly higher incidence of macrovascular invasion compared with CA19-9 < 39 U/ml (23.0% vs. 7.2%, p=0.002), elevated aminotransferase and aspartate aminotransferase to platelet ratio index, and lower albumin. In contrast, no association was found between CA19-9 and systemic inflammation. CA19-9 expression was found exclusively in the background liver but not in HCC tumor cells. In contrast, tumor tissue was the main source of CA19-9 in ICC patients.Conclusions: CA19-9 ≥ 39 U/ml was associated with lower OS and RFS in both AFP-positive and negative HCC patients. CA19-9 is secreted by the background liver but not by tumor cells. Thus, CA19-9 is a prognostic marker for liver inflammation and cirrhosis in HCC.