Low alpha-fetoprotein HCC and the role of GGTP

BACKGROUND: HCC patients are heterogeneous in terms of both tumor and liver factors. Alpha-fetoprotein (AFP) is an important prognostic tumor marker for those patients with elevated AFP levels. AIMS: To examine the differences in HCC patients with high or low AFP levels in blood and evaluate the prognostic parameters in low AFP patients. METHODS: A cohort of 2,440 HCC patients from 11 Italian medical centers was studied. AFP-positive patients were compared to AFP-negative ones, and the blood and tumor parameters of AFP-negative patients were examined. RESULTS: Low blood AFP levels were found in 58% of the total cohort, in 64% of patients with small HCCs, and in 51% of patients with large HCCs. In patients with large tumors, platelet and gamma glutamyl transpeptidase (GGTP) levels, tumor multifocality and portal vein thrombosis (PVT) incidence were all greater than in patients with small tumors, regardless of AFP status. Patients with higher AFP levels had worse survival rates than those with low AFP in each tumor size group. In patients with small tumors, the elevated AFP was associated with significantly increased PVT and worse survival. In patients with large tumors, the elevated AFP was associated with significantly higher GGTP, ALKP, and bilirubin levels, as well as with increased PVT and multifocality, and worse survival. Low-AFP patients with high GGTP levels had worse survival than patients with low GGTP levels. CONCLUSION: Patients with low AFP were the majority in this cohort, and patients with elevated GGTP had worse prognosis than those with low GGTP. GGTP may be a useful tumor and prognosis marker in low-AFP patients. AFP-negative patients are important to identify due to their enhanced survival

Significance of platelet and AFP levels and liver function parameters for HCC size and survival

BACKGROUND: Hepatocellular carcinoma (HCC) is a heterogeneous disease with both tumor and liver factors being involved. AIMS: To investigate HCC clinical phenotypes and factors related to HCC size. METHODS: Prospectively-collected HCC patients' data from a large Italian database were arranged according to the maximum tumor diameter (MTD) and divided into tumor size terciles, which were then compared in terms of several common clinical parameters and patients' survival. RESULTS: An higer MTD tercile was significantly associated with increased blood alpha-fetoprotein (AFP), gamma-glutamyl transpeptidase (GGTP), and platelet levels. Patients with higher platelet levels had larger tumors and higher GGTP levels, with lower bilirubin levels. However, patients with the highest AFP levels had larger tumors and higher bilirubin levels, reflecting an aggressive biology. AFP correlation analysis revealed the existence of 2 different groups of patients: those with higher and with lower AFP levels, each with different patient and tumor characteristics. The Cox proportional-hazard model showed that a higher risk of death was correlated with GGTP and bilirubin levels, tumor size and number, and portal vein thrombosis (PVT), but not with AFP or platelet levels. CONCLUSIONS: An increased tumor size was associated with increased blood platelet counts, AFP and GGTP levels. Platelet and AFP levels were important indicators of tumor size, but not of survival

Alpha-fetoprotein has no prognostic role in small hepatocellular carcinoma identified during surveillance in compensated cirrhosis.

none14Alpha-fetoprotein is a tumor marker that has been used for surveillance and diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis. The prognostic capability of this marker in patients with HCC has not been clearly defined. In this study our aim was to evaluate the prognostic usefulness of serum alpha-fetoprotein in patients with well-compensated cirrhosis, optimal performance status, and small HCC identified during periodic surveillance ultrasound who were treated with curative intent. Among the 3,027 patients included in the Italian Liver Cancer study group database, we selected 205 Child-Pugh class A and Eastern Cooperative Group Performance Status 0 patients with cirrhosis with a single HCC ≤ 3 cm of diameter diagnosed during surveillance who were treated with curative intent (hepatic resection, liver transplantation, percutaneous ethanol injection, radiofrequency thermal ablation). Patients were subdivided according to alpha-fetoprotein serum levels (i.e., normal ≤ 20 ng/mL; mildly elevated 21-200 ng/mL; markedly elevated >200 ng/mL). Patient survival, as assessed by the Kaplan-Meier method, was not significantly different among the three alpha-fetoprotein classes (P = 0.493). The same result was obtained in the subgroup of patients with a single HCC ≤ 2 cm (P = 0.714). An alpha-fetoprotein serum level of 100 ng/mL identified by receiver operating characteristic curve had inadequate accuracy (area under the curve = 0.536, 95% confidence interval = 0.465-0.606) to discriminate between survivors and deceased patients. CONCLUSION: Alpha-fetoprotein serum levels have no prognostic meaning in well-compensated cirrhosis patients with single, small HCC treated with curative intent.Giannini, Eg; Marenco, S; Borgonovo, G; Savarino, V; Farinati, F; Del Poggio, P; Rapaccini, Gl; Di Nolfo, Ma; Benvegnù, L; Zoli, M; Borzio, F; Caturelli, E; Chiaramonte, M; Trevisani, F.Giannini, EDOARDO GIOVANNI; Marenco, Simona; Borgonovo, Giacomo; Savarino, Vincenzo; Farinati, F; Del Poggio, P; Rapaccini, Gl; Di Nolfo, Ma; Benvegnù, L; Zoli, M; Borzio, F; Caturelli, E; Chiaramonte, M; Trevisani, F

Liver cell apoptosis in chronic hepatitis C correlates with histological but not biochemical activity or serum HCV-RNA levels

In hepatitis C virus (HCV) infection, mechanisms responsible for liver cell damage are still poorly understood and both necrosis and apoptosis may be operative. By using terminal deoxynucleotydil transferase-mediated d-UTP-biotin nick-end labeling (TUNEL) we have evaluated and quantified apoptosis in liver biopsy specimens from 61 patients with chronic hepatitis C. All patients had detectable apoptotic cells in the liver. Presence of increased apoptotic activity was confirmed in selected cases by electron microscopy and by DNA gel electrophoresis. The amount of liver cell apoptosis expressed as apoptotic index, ranged between 0.01% to 0.54% and showed a positive correlation with histological activity grading (P <.0005) and with the amount of infiltrating CD8-positive cells (P =. 01). Apoptosis did not correlate with transaminase levels or with HCV load and genotype. These results support the concept that immune-mediated apoptosis may play a role in the pathogenesis of chronic hepatitis C and indicate that this type of reaction may occur in the absence of significant alanine transaminase (ALT) elevation, thus explaining the lack of correlation between biochemical activity and liver histological damag

Patients with advanced hepatocellular carcinoma need a personalized management: A lesson from clinical practice

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