Elevated serum CA19-9 indicates severe liver inflammation and worse survival after curative resection in hepatitis B-related hepatocellular carcinoma

We explored the prognostic value of preoperative CA19-9 in α-fetoprotein (AFP)-positive and -negative HCC with hepatitis B virus (HBV) background (HBV-HCC), and explored the underlying mechanism. Recurrence-free survival (RFS) and overall survival (OS) were assessed in HBV-HCC patients who underwent curative resection (Cohort 1). Immunohistochemical staining of CA19-9 in HCC and liver parenchyma were quantified in another cohort of 216 patients with resected HCC (Cohort 2). Immunohistochemical staining of CA19-9 and serum CA19-9 level was also compared between patients with HCC and intrahepatic cholangiocarcinoma (ICC) (Cohort 3). 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). CA19-9 ≥ 39 U/mL was also associated with significantly higher incidence of macrovascular invasion (MaVI) compared with CA19-9 < 39 U/mL (23.0% vs. 7.2%, p = 0.002), and elevated aminotransferase and aspartate aminotransferase to platelet ratio index (APRI), and lower albumin. Immunohistochemical staining of CA19-9 revealed that 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. CA19-9 ≥ 39 U/mL was associated with worse OS and RFS in both AFP-positive and negative HCC patients. CA19-9 indicated more severe inflammation and cirrhosis in the liver of HCC patients.