A large cohort of hepatocellular carcinoma (HCC) patients from several collaborating Turkish institutions were examined for the tumor parameters of maximum diameter (MTD), portal vein thrombosis (PVT), and α-fetoprotein (AFP) levels. A relationship was found between MTD and blood platelet levels. Patients with large ≥5 cm tumors who had normal platelet levels had significantly larger tumors, higher percent of PVT, and significantly lower blood total bilirubin and liver cirrhosis than similar ≥5 cm tumor patients having thrombocytopenia. A comparison of patients with and without PVT showed significantly larger tumors, greater multifocality, blood AFP, and C-reactive protein levels, and, interestingly, lower HDL levels in the patients with PVT. Fifty-eight percent of the total cohort had AFP levels ≤100 IU/mL (and 42.1% had values ≤20 IU/mL). These patients had significantly smaller tumors, less tumor multifocality and percent PVT, lower total bilirubin, and less cirrhosis. There was considerable geographic heterogeneity within Turkey in the patterns of HCC presentation, with areas of higher and lower hepatitis B virus, hepatitis D virus, cirrhosis, and tumor aggressiveness parameters. Turkish patients thus have distinct patterns of presentation, but the biological relationships between MTD and both platelets and bilirubin levels are similar to the relationships that have been reported in other ethnic patient groups.

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A large database of 1773 HCC patients in Turkey was examined. 41.9% had alpha-fetoprotein (AFP) levels <20 IU/ml and an additional 16.123% had values between 20-100 IU/ml. This 58% of the cohort (<100 IU/ml AFP levels) was examined in detail. 66% of patients with small (<5 cm) HCCs had low AFP, compared to 49% of patients with larger (>5 cm) HCCs. The mean diameter (MTD) of larger MTD, low AFP tumors was 8.4cm. Therefore, factors other than AFP must contribute to HCC tumor growth. Larger tumors in low AFP patients had both higher platelet levels and increased PVT percent. Linear regression analysis for both MTD and multifocality showed that platelet numbers and presence of PVT were significant variables; whereas for PVT, significant variables were albumin, alkaline phosphatase and MTD. Comparisons between patients with AFP levels <20, 20-<100, 100-<1000 and >1000 IU/ml showed the most significant tumor finding was an increase in PVT percent between each group, and to a lesser extent, MTD. Thus, low-or normal-AFP HCCs constitute the majority of patients and have slightly lower MTD and much lower PVT percent than HCCs associated with elevated blood AFP levels. New, non-AFP markers are thus needed, especially for small HCCs

Macroscopic portal vein invasion (PVT) by hepatocellular carcinoma (HCC) in the liver is one of the most important negative prognostic factors for HCC patients. The characteristics of a large cohort of such patients were examined. We found that the percent of patients with PVT significantly increased with increasing maximum tumor diameter (MTD), from 13.7% with tumors of MTD <5cm to 56.4% with tumors of MTD >10cm. There were similar numbers of HCC patients with very large tumors with and without PVT. Thus, MTD alone was insufficient to explain the presence of PVT, as were high AFP levels, since less than 50% of high AFP patients had PVT. However, the percent of patients with PVT was also found to significantly increase with increasing blood alpha-fetoprotein (AFP) levels and tumor multifocality. A logistic regression model that included these 3 factors together showed an odds ratio of 17.9 for the combination of MTD>5.0cm plus tumor multifocality plus elevated AFP, compared to low levels of these 3 parameters. The presence or absence of macroscopic PVT may therefore represent different HCC aggressiveness phenotypes, as judged by a significant increase in tumor multifocality and AFP levels in the PVT positive patients. Factors in addition to MTD and AFP must also contribute to PVT development.

Introduction Hepatocellular carcinoma is associated with several chronic inflammatory conditions. It is increasingly understood that the inflammation may be part of the carcinogenic process and prognostically important. Objective To evaluate the serum levels of three inflammation markers in relation to survival in HCC patients. Methods We retrospectively examined the serum levels of CRP, albumin and ESR, both singly and in combination, in relation to patient survival. Results Survival worsened with increase in CRP or ESR or decrease in albumin levels. Combinations of CRP plus albumin or CRP plus ESR were associated with an even greater range of survival (3‐fold), together with significant differences in maximum tumor diameter (PVT) and percent of patients with portal vein thrombosis (PVT). The triplet of CRP plus albumin plus ESR was associated with a sevenfold difference in survival, comparing low vs high parameter levels. These significant differences were found in patients with small or large tumors. Conclusions Combinations of CRP with albumin or ESR or all three parameters together significantly related to differences in survival and to differences in MTD and percent PVT, in patients with both small and large size HCCs.