Paraneoplastic syndrome frequency and prognostic effect in hepatocellular carcinoma patients

Objective: Symptomatic hepatocellular carcinoma (HCC) patients may generally display constitutional symptoms such as abdominal pain, weight loss, anorexia and localized mass, or atypical clinical features of paraneoplastic syndrome (PNS) such as hypercholesterolemia, hypercalcemia, hypoglycemia, erythrocytosis and thrombocytosis. The most common PNS in HCC is hypercholesterolemia, hypercalcemia, hypoglycemia and erythrocytosis. The aim of this study isto evaluate the relationship of PNS in HCC patients.

Material and method: In this study, the data of 534 patients who were followed up with the diagnosis of HCC between January 2010 and December 2020 in the Gastroenterology clinic were evaluated retrospectively. Clinical data, age, gender, complete blood count of patients with and without PNS, liver biochemistry, alpha-fetoprotein (AFP) level, hepatitis B surface antigen, anti-hepatitis B virus, Child-Pugh score, model for end-stage liver disease score, tumor volume, portal vein thrombosis, liver biopsy histology and radiologic images were taken from the hospital data system and analyzed.

Results: Out of the 534 HCC patients, 120 (22.3%) were PNS-positive patients. There was a significant difference between the ages of PNS-positive and PNS-negative patients, and PNS-positive patients were older (64.60±12.97) (P=0.02). PNS-positive HCC was determined as hypoglycemia 5.8%, hypercalcemia 6.3%, erythrocytosis 3.9%, hypercholesterolemia 2.4% and thrombocytosis 3.9%. AFP level (22908 ± 60 ng/ml) and tumor diameter (>10 cm) were higher in the PNS-positive group. Multivariate analysis showed that stage C according to Child-Pugh score and tumor diameter >10 cm were independent predictors of poor prognosis, whereas PNS erythrocytosis and thrombocytosis were independent predictors of better prognosis.

Conclusion: In PNS-positive HCC patients, hypoglycemia and hypercalcemia were associated with poor prognosis according to Child-Pugh score, whereas erythrocytosis and thrombocytosis were associated with good prognosis.