Tumor multifocality and serum albumin levels can identify groups of patients with hepatocellular carcinoma and portal vein thrombosis having distinct survival outcomes.

BACKGROUND: Macroscopic portal vein thrombosis (PVT) is a major poor prognosis factor in patients with hepatocellular carcinoma (HCC), but constitute a heterogeneous group. AIMS: To examine blood and tumor parameters of 1667 HCC patients who had PVT to identify factors that could differentiate different survival subsets. METHODS: a large HCC database was examined for presence of patients with PVT and analyzed retrospectively for PVT-associated factors and prognosis. RESULTS: A logistic regression model was calculated for presence of PVT. Highest odds ratios were found for tumor multifocality and serum albumin levels, as well as serum alpha-fetoprotein (AFP) and bilirubin levels. A Kaplan-Meier and Cox model on survival also showed the highest hazard ratios for tumor multifocality and serum albumin. A model was constructed on all 4 possible combinations of tumor focality and serum albumin in PVT patients. The longest survival group had <2 tumor nodules plus serum albumin >3.5 g/dL. Conversely, the shortest survival group had >2 tumor nodules plus serum albumin <3.5 g/dL. These 2 patient groups differed in maximum tumor diameter and levels of serum AFP, AST and bilirubin. CONCLUSIONS: Combination low tumor focality and high serum albumin identifies prognostically better PVT patient subgroups that might benefit from aggressive therapies.

Plasma lipids, tumor parameters and survival in HCC patients with HBV and HCV.

INTRODUCTION AND AIMS: Hepatocellular carcinoma (HCC) is a consequence of chronic liver disease, particularly from hepatitis B or C and increasingly from obesity and metabolic syndrome. Since lipids are an important component of cell membranes and are involved in cell signaling and tumor cell growth, we wished to evaluate the relationship between HCC patient plasma lipids and maximum tumor diameter and other indices of HCC human biology. METHODS: We examined prospectively-collected data from a multi-institutional collaborative Turkish HCC working group, from predominantly HBV-based patients, for plasma lipid profiles, consisting of triglycerides, total cholesterol, LDL-cholesterol (LDL) and HDL-cholesterol (HDL) and compared these with the associated patient maximum tumor diameter (MTD), portal vein thrombosis, alpha-fetoprotein (AFP) and also with patient survival. RESULTS: We found that both low HDL (p=0.0002) and high LDL (p=0.003) levels were significantly associated with increased MTD, as well as in a final multiple linear regression model on MTD. The combination of low HDL combined with high HDL levels were significant in a regression model on MTD, PVT and an HCC Aggressiveness Index (Odds Ratio 12.91 compared to an Odds Ratio of 1 for the reference). Furthermore, in a Cox regression model on death, the HDL plus LDL combination had a significantly higher Hazard Ratio than the reference category. CONCLUSIONS: Low plasma HDL, high plasma LDL and especially the combination, were significantly related to more aggressive HCC phenotype and the combination was significantly related to a higher Hazard Ratio for death.

Portal Vein Thrombosis and Markers of Inflammation in Hepatocellular Carcinoma.

BACKGROUND: Macroscopic portal vein thrombosis (PVT) is a major poor prognosis factor in patients with hepatocellular carcinoma (HCC). Inflammation is increasingly recognized to be part of the hepatocarcinogenic process and its markers are also prognostically useful. AIMS: To examine the relationship of inflammation biomarkers to the presence of PVT and to survival in PVT patients with HCC. METHODS: A large HCC cohort was examined for the presence of PVT and analyzed retrospectively. RESULTS: Blood levels of NLR, PLR, ESR, CRP, AFP and GGTP were significantly related to the presence of PVT, but not the Glasgow Index. For patients with low alpha-fetoprotein levels, blood ESR and GGTP levels were also significantly increased in patients with PVT compared with those in patients without PVT. In a Cox regression model, serum GGTP levels had a significantly increased hazard ratio on death (1.52, p = 0.008). Kaplan-Meier analysis showed that PVT patients with low serum GGTP levels had significantly longer survival than PVT patients with high GGTP levels (p = 0.0041). CONCLUSIONS: Indices of inflammation, especially serum GGTP levels, related significantly to the presence of PVT and to survival in HCC patients with PVT.

Trends in Tumor Indices in Relation to Increased Hepatocellular Carcinoma Size: Evidence for Tumor Evolution as a Function of Growth.

BACKGROUND: The prognosis of HCC depends in large measure on maximum tumor diameter (MTD). AIMS: To examine characteristics of tumor aggressiveness over an MTD range of < 2 to 8 cm. METHODS: A large HCC database was examined retrospectively for trends in serum alpha-fetoprotein (AFP), and percent of patients with macroscopic portal vein thrombosis (PVT) or tumor multifocality. RESULTS: There was a significant trend to increased serum AFP levels and percent of patients with PVT, for each, p < 0.001. Within those trends, there were clearly identifiable sub-trends for variations of AFP or percent PVT patients, associated with specific MTD ranges. Calculation of the fold increase for either AFP or percent PVT patients over distinct MTD ranges showed a greater increase of AFP or percent PVT patients compared with the related MTD increase. Interestingly, the increase in percent PVT was mainly independent of AFP. CONCLUSIONS: Patterns of AFP and PVT increase can be discerned with increasing MTD, which are nonlinear. The greater fold increase in tumor aggressiveness factors compared with MTD suggests that HCCs may change with increasing size to a more aggressive phenotype. Baseline HCC biopsies might therefore be insufficient in future rational HCC management, and repeated liquid biopsies have potential in following HCC evolution and thus choices of therapies.