prognostic value of fever grade combined with neutrophil percentage in hepatocellular carcinoma patients presenting fever as the initial manifestation

Zi-Jun Gong,1,2 Wei Guo,1–3 Yun-Fan Sun,1,2 Xin Zhang,1,2 Shuang-Jian Qiu,1,2 Jian Zhou,1,2,4 Jia Fan,1,2,4 Xin-Rong Yang1,2 1Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, People’s Republic of China; 3Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 4Institutes of Biomedical Sciences, Fudan University, Shanghai, People’s Republic of China Background: Hepatocellular carcinoma (HCC) patients with fever as the initial presentation are extremely rare. Our aim was to investigate the clinical characteristics and prognosis of patients with this disease.Patients and methods: The clinical features were analyzed in a retrospective study of 63 HCC patients with fever as the first manifestation and 300 HCC patients without fever as the control group.Results: HCC patients with fever had a higher neutrophil percentage, larger tumor size, worse tumor differentiation, advanced Barcelona Clinic Liver Cancer stage, and more hilar lymph node metastasis than HCC patients without fever (all P<0.05). Compared with HCC patients without fever, patients presenting with fever had shorter overall survival (OS, median: 13 months, P<0.001) and time to recurrence (TTR, median: 7.5 months, P<0.001). In addition, HCC patients with fever also had shorter OS and TTR than those without fever in all clinical subgroups with aggressive features (all P<0.05). Multivariate analysis showed that neutrophil percentage >70%, fever grade ≥38.5°C, tumor size >5 cm, and hilar lymph node metastasis were independent factors for OS and TTR. A positive correlation was observed between body temperature and serum neutrophil percentage (r=0.527, P<0.001). Patients with a fever grade ≥38.5°C had more incomplete encapsulation and larger tumor size, while those with a neutrophil percentage >70% presented with more incomplete encapsulation, vascular invasion, and worse tumor differentiation. Patients with a fever grade ≥38.5°C combined with a neutrophil percentage >70% had worse OS and TTR than other groups.Conclusion: HCC patients presenting with fever have poorer prognosis than those without fever; however, their prognosis could be improved by timely surgical intervention. Patients with a neutrophil percentage >70% and a fever grade ≥38.5°C represent a rare HCC subgroup with an extremely dismal outcome and more aggressive clinical course. Keywords: hepatocellular carcinoma, fever, neutrophils, prognosis, hepatectomy