Highly elevated sepsis biomarkers in advanced cholangiocarcinoma without sepsis: A case report and literature review

Rationale: Inflammatory markers such as C-reactive protein (CRP) and interleukin-6 (IL-6) are often elevated in liver cancer, making it difficult to monitor for bacterial infection. Hence, it is tempting to use more bacterial-specific sepsis markers such as procalcitonin (PCT) during immunosuppressive chemotherapy. This case study highlights the challenges of interpreting clinical chemistry sepsis biomarkers in patients with advanced cholangiocarcinoma (CCA). Patient concerns: A 55-year-old man presented with a liver mass on routine ultrasonography. MRI and CT showed multiple liver and bone metastases. The immunohistochemistry findings were consistent with an adenocarcinoma of the pancreaticobiliary system. After the diagnosis of primary hepatic CCA (NTM stage IV; FGFR2-SHROOM3 translocation) and 14 months of chemotherapy, the patient developed progressive liver lesions and new lung metastases. Diagnoses and interventions: During the last chemotherapy, PCT was highly elevated (>100 ng/mL), usually observed in severe sepsis or septic shock, whereas CRP was moderately elevated (<50 mg/L). The patient had mild leukopenia but no fever, systemic infection or septic shock. Blood and urine cultures were negative. Outcomes: After referral to best supportive care, the patient died of liver failure. Retrospective blood analysis revealed high levels of soluble CD14 subtype, a bacterial sepsis marker known as presepsin. Calcitonin and IL-6 levels were above normal, consistent with advanced CCA, but not with a PCT/calcitonin-secreting tumor or systemic inflammation. Lessons: Oncologists are aware that CRP and IL-6 values can be elevated in liver cancer. Here, we further demonstrate that highly elevated, septic shock-like PCT values can occur even in the absence of bacterial sepsis. In addition, presepsin may be elevated, although mechanistically unrelated to PCT. Therefore, sepsis markers should be interpreted with caution and in the clinical context, not only in patients with neuroendocrine or hepatocellular carcinoma, which are known to secrete PCT and calcitonin, but also in patients with advanced CCA.