AbstractObjective:To identify potential early diagnostic markers for hepatitis B progression to primary liver carcinoma using routine immunological tests based on 6 cytokine combinations.Methods:Eight hundred and ninety-nine patients with hepatitis B progressing to early primary liver carcinoma admitted to and treated at Changhai Hospital, Naval Military Medical University, Shanghai, China between March 2015 and June 2017 were included in this observational study, including 666 patients with HBsAg+, HBeAb+, HBcAb+ liver carcinoma and 233 patients with HBsAg+, HBeAg+, HBcAb+ liver carcinoma. Receiver operating characteristic (ROC) curves were used to evaluate the efficiency of the different cytokine in the diagnosis of hepatocellular carcinoma in patients with hepatitis B. This study was approved by the Institutional Review Board of Changhai Hospital, Naval Military Medical University, China (approval No. CHEC2020-080) on June 6, 2020.Results:Changed levels of interleukin (IL)-1β, IL-2R, IL-8, and tumor necrosis factor (TNF)-α were statistically significant (P < 0.05). The area under the ROC curve, sensitivity, specificity, positive predictive value, negative predictive value, and Youden index for the diagnosis of primary liver carcinoma using the combination of IL-1β, IL-2R, IL-8, and TNF-α were 0.938, 79.2%, 96.7%, 96%, 82.0%, 0.759, respectively. The serum alpha-fetoprotein level in patients with primary liver carcinoma was positively correlated with IL-2R (r=0.3502, P < 0.001), IL-8 (r=0.1558, P=0.0273), and TNF-α (r=0.2544, P < 0.001) levels. The equation fitted to the results was logit(P)=0.086+ 0.01 × IL-2R-0.001 × IL-8-0.033 × TNF-α-0.041 × IL-1β.Conclusion:Our study establishes a novel, potentially valuable diagnostic model based on four cytokines related to the early stages of liver carcinoma.
