Small Hepatocellular Carcinomas and Thrombocytopenia

Abstract

Background: Clinical phenotypes of small and large hepatocellular carcinomas (HCCs) are not well characterized. Aim: To evaluate the characteristics of small HCCs diagnosed by screening. Method: A cohort of 430 small HCCs that were diagnosed through screening, were dichotomized according to a size of ≤3 cm or >3 cm maximum tumor diameter and compared for radiological and blood-test parameters. Results: There were 330 males and 100 females. A higher percent of females had smaller tumors. The majority of patients had single tumors, but 15% of those with larger tumors had portal vein thrombosis (PVT) compared to 5% of those with smaller tumors. Significant differences between the tumor-size groups included alpha-fetoprotein (AFP) values and platelet counts, with thrombocytopenia and elevated bilirubin levels being associated with smaller tumors. In comparing PVT-positive and PVT-negative patients, AFP levels and platelet counts were also significantly different between the 2 groups. A mean multinomial multiple logistic regression model was developed for maximum tumor diameter plus PVT. Conclusions: The finding of larger tumors being associated with normal platelets and bilirubin levels in comparison to smaller tumors having thrombocytopenia reveals 2 different patterns of HCC presentation.

Platelet-Related Phenotypic Patterns in Hepatocellular Carcinoma Patients

“…Thrombocytopenia is a risk for HCC in predisposed patients (3, 12–15), and associated with small HCC size (16, 17). We combined terciles II and III to create a manageable large tumor category for this analysis.…”

“…Thrombocytopenia is a cirrhosis surrogate, an HCC risk factor, prognostic factor, and is associated with small HCCs (7–13, 16, 17). Non-cirrhotic HCCs can be large (22, 23, 24), and associated with thrombocytosis (25), which is a general sign of early malignancy (26).…”

Hepatocellular Carcinoma Size: Platelets, γ-Glutamyl Transpeptidase, and Alkaline Phosphatase

“…Thrombocytopenia, a surrogate marker for cirrhosis, is associated with subsequent HCC development [2,15-18] and is associated with smaller HCCs [7,8]. In non-cirrhotic livers, HCCs tend to be larger [19-22], probably since they can grow with less liver damage, whereas HCC growth in cirrhosis is often associated with parenchymal damage.…”

“…They include male gender, age, cirrhosis with portal hypertension and its surrogate marker, thrombocytopenia [4-6]. We recently found a relationship between thrombocytopenia and HCC size, with lower platelet levels associated with smaller tumors [7, 8]. The current study was undertaken to further explore this relationship.…”

Retrospective Analyses of Cancer Trials or Existing Clinical Databases: Potential for Highly Clinically Relevant Hypothesis Generation

“…In one report, while examining an extensive database consisting of 430 patients with hepatocellular carcinomas diagnosed through the individual’s participation in a well-organized screening program, investigators noted somewhat surprising and quite provocative features associated with screened tumors that were ≤3 versus >3 cm in diameter at diagnosis [3]. Specifically, as a group, patients with the smaller sized tumors were found to have lower platelet counts and higher serum bilirubin levels at presentation.…”