Serum Inflammation Parameters and Survival in Hepatocellular Carcinoma Patients: Importance of Albumin and Gamma-Glutamyltranspeptidase.

INTRODUCTION: Many single and combination blood tests that reflect local or systemic inflammation have been shown to be useful prognosticators in patients with a variety of tumor types. To try to clarify, this issue in patients with nonsurgically treatable hepatocellular carcinoma, multiple serum parameters were evaluated for their relationship to survival. METHODS: A prospectively collected database was interrogated of 487 patients with known hepatocellular carcinoma and documented survival and having all the inflammation parameters of interest in this study, together with baseline tumor characteristics from CT scans. Serum parameters included NLR, PLR, CRP, ESR, albumin, and GGT. RESULTS: All the parameters had significant hazard ratios on Cox regression model. Combination double parameters with hazard ratios >2.0 were: ESR plus GGT, albumin plus GGT, albumin plus ESR. The triplet combination of albumin plus GGT plus ESR had a hazard ratio of 6.33. Using Harrell's concordance index (C-index), the highest inflammation-based 2-parameter prognostic score was for albumin plus GGT. When clinical characteristics of patients with high values for albumin plus low values for GGT were compared to low values for albumin plus high values for GGT (worse prognosis), statistically significant differences were found for tumor size, tumor focality, macroscopic portal vein invasion, and serum alpha-fetoprotein levels. Addition of ESR did not provide additional tumor information. CONCLUSION: The combination of serum albumin plus GGT levels was the most prognostically useful among the inflammation parameters that were tested, and reflected significant differences in tumor aggressiveness characteristics.

Dietary profiling of physical frailty in older age phenotypes using a machine learning approach: the Salus in Apulia Study.

PURPOSE: Growing awareness of the biological and clinical value of nutrition in frailty settings calls for further efforts to investigate dietary gaps to act sooner to achieve focused management of aging populations. We cross-sectionally examined the eating habits of an older Mediterranean population to profile dietary features most associated with physical frailty. METHODS: Clinical and physical examination, routine biomarkers, medical history, and anthropometry were analyzed in 1502 older adults (65 +). CHS criteria were applied to classify physical frailty, and a validated Food Frequency Questionnaire to assess diet. The population was subdivided by physical frailty status (frail or non-frail). Raw and adjusted logistic regression models were applied to three clusters of dietary variables (food groups, macronutrients, and micronutrients), previously selected by a LASSO approach to better predict diet-related frailty determinants. RESULTS: A lower consumption of wine (OR 0.998, 95% CI 0.997-0.999) and coffee (OR 0.994, 95% CI 0.989-0.999), as well as a cluster of macro and micronutrients led by PUFAs (OR 0.939, 95% CI 0.896-0.991), zinc (OR 0.977, 95% CI 0.952-0.998), and coumarins (OR 0.631, 95% CI 0.431-0.971), was predictive of non-frailty, but higher legumes intake (OR 1.005, 95%CI 1.000-1.009) of physical frailty, regardless of age, gender, and education level. CONCLUSIONS: Higher consumption of coffee and wine, as well as PUFAs, zinc, and coumarins, as opposed to legumes, may work well in protecting against a physical frailty profile of aging in a Mediterranean setting. Longitudinal investigations are needed to better understand the causal potential of diet as a modifiable contributor to frailty during aging.

90K/Mac-2 BP Is a New Predictive Biomarker of Response to Infliximab Therapy in IBD Patients.

Inflammatory bowel diseases (IBD), comprising Crohn's disease (CD) and Ulcerative Colitis (UC), are multifactorial disorders characterized by a chronic inflammatory status with the secretion of cytokines and immune mediators. Biologic drugs targeting pro-inflammatory cytokines, such as infliximab, are broadly used in the treatment of IBD patients, but some patients lose responsiveness after an initial success. The research into new biomarkers is crucial for advancing personalized therapies and monitoring the response to biologics. The aim of this single center, observational study is to analyze the relationship between serum levels of 90K/Mac-2 BP and the response to infliximab, in a cohort of 48 IBD patients (30 CD and 18 UC), enrolled from February 2017 to December 2018. In our IBD cohort, high 90K serum levels were found at baseline in patients who then developed anti-infliximab antibodies at the fifth infusion (22 weeks after the first), becoming non-responders (9.76 ± 4.65 µg/mL compared to 6.53 ± 3.29 µg/mL in responder patients, p = 0.005). This difference was significant in the total cohort and in CD, but not significant in UC. We then analyzed the relationship between serum levels of 90K, C-reactive protein (CRP), and Fecal calprotectin. A significant positive correlation was found at baseline between 90K and CRP, the most common serum inflammation marker (R = 0.42, p = 0.0032). We concluded that circulating 90K could be considered a new non-invasive biomarker for monitoring the response to infliximab. Furthermore, 90K serum level determination, before the first infliximab infusion, in association with other inflammatory markers such as CRP, could assist in the choice of biologics for the treatment of IBD patients, thereby obviating the need for a drug switch due to loss of response, and so improving clinical practice and patient care.

Processed meat consumption and the risk of incident late-onset depression: a 12-year follow-up of the Salus in Apulia Study.

BACKGROUND: the possible relationship between dietary habits and the incidence of late-onset depression (LOD), defined as first depression onset at later age, is unclear. OBJECTIVE: to investigate the relationship between consumption of different food groups and incident LOD. DESIGN: longitudinal population-based study with a 12-year follow-up. SETTING: Castellana Grotte, Bari, Italy. SUBJECTS: five hundred and forty-six older subjects from the Salus in Apulia Study. METHODS: baseline data were recorded in 2003-06, and diagnostic data were recorded in 2013-18 at follow-up. Dietary intake was assessed with a food frequency questionnaire. Depressive disorders were assessed with the Structured Clinical Interview for DSM-IV Axis I Disorders. Subjects who already suffered from depression or other psychiatric disorders at baseline were excluded from the analysis. The association between LOD and single dietary determinants was examined by Cox regression analysis and then applying the hazard ratio (HR). RESULTS: subjects with incident LOD (n = 34) had lower global cognition and total cholesterol levels and a higher body mass index (BMI) at baseline. Only processed meat significantly increased the risk of incident LOD of about 10% by 5 g/day intake (HR adjusted for age, sex, education, multimorbidity and BMI: 1.13, 95% confidence intervals: 1.04-1.22). A similar relationship was found for single foods in the processed meat food group such as sausages, salami and mortadella and baked ham, but not for raw ham. CONCLUSIONS: in midlife, a higher intake of processed meat was not only associated with an increased risk of cardiovascular- and metabolic-related chronic diseases in older age but also with an increased risk of developing LOD.

Role of plant-based diet in late-life cognitive decline: results from the Salus in Apulia Study.

OBJECTIVES: Consistency among population-based studies investigating the relationship between diet and cognition in older inhabitants in the Mediterranean area is poor. The present study investigated whether diet changes over 12 years were associated with cognitive function in older people in Southern-Italy. METHODS: From the 'Salus in Apulia Study', that includes the MICOL and GreatAGE Studies, 584 participants were selected, firstly enrolled in MICOL3 (M3) and later in the GreatAGE Study (MICOL4, M4). Foods and micronutrients intake were recorded in both studies, and global cognitive function in M4, assessed with the Mini Mental State Examination. RESULTS: Plant-based foods, particularly coffee and vegetables, as well as vitamin A sources, were inversely associated to age-related cognitive impairment. Alcohol consumption showed a detrimental role on cognition, while red meat appeared to be beneficial in the present study, although its role is traditionally considered harmful for cognitive function. DISCUSSION: Our study confirmed that a traditional Mediterranean dietary pattern based on agricultural products and low alcohol consumption may help to prevent/delay age-related cognitive impairment.

Fibrosis-4 Index vs Nonalcoholic Fatty Liver Disease Fibrosis Score in Identifying Advanced Fibrosis in Subjects With Nonalcoholic Fatty Liver Disease: A Meta-Analysis.

INTRODUCTION: In subjects with nonalcoholic fatty liver disease (NAFLD), advanced fibrosis (AF) carries the highest risk of adverse liver-related events. To reduce the number of unnecessary biopsies, several noninvasive tools (NITs) for the risk stratification of fibrosis have been developed. We conducted this meta-analysis to assess the performance of the fibrosis-4 index (FIB-4) and NAFLD fibrosis scores (NFS), the 2 most common NITs, for the appropriate selection of subjects with AF for biopsy. METHODS: Four databases were searched until December 2020 (CRD42021224766). Original articles reporting data on the performance of FIB-4 and NFS, interpreted according to standard cutoffs in subjects with biopsy-proven NAFLD, were included. Separate data extractions were performed according to the lower cutoff, the higher cutoff, and the dual threshold approach. The numbers of subjects classified as true-negative, true-positive, false-negative, and false-positive were extracted. Summary operating points were estimated using a random-effects model. RESULTS: Eighteen studies evaluating 12,604 subjects were included. Participants were adult outpatients with biopsy-proven NAFLD or nonalcoholic steatohepatitis. Overall, a weak-to-moderate performance was found for both scores. The head-to-head comparison showed FIB-4 to be associated with a higher performance in ruling in and NFS in ruling out AF in the single threshold approach, whereas, with the dual threshold approach, a lower prevalence of indeterminate findings was found for FIB-4. DISCUSSION: This meta-analysis suggested that currently available NITs have a limited performance in identifying AF among subjects with NAFLD. Further studies are needed to optimize existing thresholds or develop new NITs.

Associations between nutritional frailty and 8-year all-cause mortality in older adults: The Salus in Apulia Study.

INTRODUCTION: Preventive nutritional management of frailty, a multidimensional intermediate status in the ageing process, may reduce the risk of adverse health-related outcomes. We investigated the ability of a measure combining physical frailty with nutritional imbalance, defined as nutritional frailty, to predict all-cause mortality over a period of up to 8 years. METHODS: We analysed data on 1,943 older adults from the population-based 'Salus in Apulia Study'. Physical frailty was operationalized using Cardiovascular Health Study criteria and cognitive frailty by combining physical frailty with cognitive impairment. A novel five-item construct was built to assess the extent of nutritional imbalance identified with a machine learning algorithm. Cox models and Kaplan-Meier survival probability analyses of physical frailty, nutritional imbalance (two or more of the following: low body mass index, low skeletal muscle index, ≥2.3 g/day sodium intake, <3.35 g/day potassium intake and <9.9 g/day iron intake), cognitive frailty and the novel nutritional frailty phenotype (physical frailty plus nutritional imbalance) were applied to assess all-cause mortality risk, adjusted for age, sex, education and multimorbidity. RESULTS: The overall prevalence of nutritional frailty was 4.52% (95% confidence interval, CI:3.55-5.44), being more frequent in males. Subjects with nutritional frailty were at higher risk for all-cause mortality [hazard ratio (HR):2.31; 95%CI:1.41-3.79] than those with physical frailty (HR:1.45,95% CI:1.0-2.02), nutritional imbalance (HR:1.39; 95%CI:1.05-1.83) and cognitive frailty (HR:1.06; 95%CI:0.56-2.01). CONCLUSIONS: Efforts to identify, manage and prevent frailty should include the nutritional domain. The nutritional frailty phenotype may highlight major nutritional determinants that could drive survival and health trajectories in older adults.

Trends in adherence to the Mediterranean diet in South Italy: A cross sectional study.

BACKGROUND AND AIMS: Increasing literature data show that adherence to the Mediterranean diet is undergoing profound changes in recent years, albeit with marked differences across nations. In Italy, one of the cradles of the Mediterranean diet, the literature regarding the trend for Mediterranean diet adherence is conflicting. Thus, we aimed to explore the trends of adherence to the Mediterranean diet in a large cohort of participants living in South Italy, over 20 years from 1985-86 to 2005-06. METHODS AND RESULTS: Cross-sectional study with two evaluations, one made in 1985-86 and another in 2005-06; all participants were adults aged 30-70 years of age. The adherence to the Mediterranean diet was evaluated using the score proposed by Panagiotakos et al. This score features values ranging from 0 to 55, higher scores reflecting a greater adherence. The data are reported by age (30-49 vs. 50-69 years). Overall, 2451 subjects were included in 1985-86 and 2375 in 2005-06. A significant reduction was observed in the adherence to the Mediterranean diet (age 30-49 years: 31.82 ± 4.18 in 1985-86 vs. 29.20 ± 4.48 in 2005-06, reduction by 8.2%, p < 0.0001; age 50-69: 32.20 ± 4.09 in 1985-86 vs.30.15 ± 4.27 in 2005-06, reduction by 6.3%, p < 0.0001). Among all these items, the most dramatic change was observed for olive oil consumption, that decreased by 2.35 points in younger and 0.89 in older people. CONCLUSION: The adherence to the Mediterranean diet decreased from 1985-86 to 2005-06 in South Italy, particularly in younger people, above all due to a decreased olive oil consumption.

Remnant cholesterol as a risk factor for cardiovascular, cancer or other causes mortality: A competing risks analysis.

BACKGROUND AND AIMS: Cardiovascular diseases (CVDis) are leading causes of morbidity and mortality. Even after the introduction of pharmacological therapy to lower Cholesterol, there is still a residual risk that may be ascribed to remnant cholesterol (RC). We aimed, by analyzing two prospective cohort studies, to estimate the effect of RC on risk and hazard of cardiovascular deaths (CVDs), while accounting for competing risks such as cancer (CDs) and other-causes deaths (OCDs). METHODS AND RESULTS: Cohorts were enrolled in 1992 and 2005. Personal data history was recorded. A fasting venous blood sample was obtained, and RC was calculated at baseline. Cause of Death was coded by using ICD-10th version. Follow-up ended on December 31, 2017. Flexible parametric competing-risks models were applied, with age at death as time-axis. In total, 5729 subjects were enrolled. There were 861 (15.1%) deaths: 234 CVDs (27.2%), 245 CDs (28.5%), 271 OCDs (31.5%) and 111 unknown causes of death (12.8%). RC exposure was a strong risk factor only for CVDs (Risk 2.54, 95% Confidence Interval 1.21; 5.34; Trend 1.26 (1.00; 1.58) for ≥1.29 mmol/L). CONCLUSIONS: RC is a strong independent risk factor for cardiovascular mortality. Competing risk analysis is demonstrably a useful tool to disentangle associations among different competing events with a common risk factor.

Characteristics of Hepatocellular Carcinoma Aggressiveness Factors in Turkish Patients.

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.

Differential Tissue Fatty Acids Profiling between Colorectal Cancer Patients with and without Synchronous Metastasis.

The early detection of colorectal cancer and determination of its metastatic potential are important factors to set up more efficacious therapeutic strategies. In the present study, we hypothesize that fatty acids analysis in colorectal cancer patients can discriminate between metastatic and non-metastatic patients. Fifty-one consecutive patients with histologically proven colorectal cancer were enrolled in the study and the presence of synchronous metastasis was detected in 25 of these 51 patients. Fatty acid profile analysis in red blood cell membranes was not able to discriminate the metastatic colorectal cancer patients from those without metastasis. However, significant differences in the tumor tissue fatty acid profile were found in metastatic cancer patients when compared to patients without metastasis. Metastatic patients showed significantly lower percentages of Eicosapentaenoic acid (EPA) and higher levels of γ-linolenic acid (GLA), a n-3- and n-6-Polyunsaturated fatty acid (PUFA), respectively. Our findings, suggesting that membrane lipid rearrangement could influence the cellular function and make the cell more prone to metastasis, offer the opportunity to develop nutritional strategies that may be helpful in the prevention and treatment of colorectal cancer.

The ALBI grade provides objective hepatic reserve estimation across each BCLC stage of hepatocellular carcinoma.

BACKGROUND & AIMS: Overall survival (OS) is a composite clinical endpoint in hepatocellular carcinoma (HCC) due to the mutual influence of cirrhosis and active malignancy in dictating patient's mortality. The ALBI grade is a recently described index of liver dysfunction in hepatocellular carcinoma, based solely on albumin and bilirubin levels. Whilst accurate, this score lacks cross-validation, especially in intermediate stage HCC, where OS is highly heterogeneous. METHODS: We evaluated the prognostic accuracy of the ALBI grade in estimating OS in a large, multi-centre study of 2426 patients, including a large proportion of intermediate stage patients treated with chemoembolization (n=1461) accrued from Europe, the United States and Asia. RESULTS: Analysis of survival by primary treatment modality confirmed the ALBI grade as a significant predictor of patient OS after surgical resection (p<0.001), transarterial chemoembolization (p<0.001) and sorafenib (p<0.001). Stratification by Barcelona Clinic Liver Cancer stage confirmed the independent prognostic value of the ALBI across the diverse stages of the disease, geographical regions of origin and time of recruitment to the study (p<0.001). CONCLUSIONS: In this large, multi-centre retrospective study, the ALBI grade satisfied the criteria for accuracy and reproducibility following statistical validation in Eastern and Western HCC patients, including those treated with chemoembolization. Consideration should be given to the ALBI grade as a stratifying biomarker of liver reserve in routine clinical practice. LAY SUMMARY: Liver failure is a key determinant influencing the natural history of hepatocellular carcinoma (HCC). In this large multi-centre study we externally validate a novel biomarker of liver functional reserve, the ALBI grade, across all the stages of HCC.

Role of Albumin in Growth Inhibition in Hepatocellular Carcinoma.

OBJECTIVE: Levels of serum albumin have recently emerged, together with C-reactive protein, as an important prognostic indicator for hepatocellular carcinoma (HCC). It has recently been reported that larger HCCs are associated with lower albumin levels. However, the albumin-mediated growth decrease has yet to be determined. METHODS: We examined a large HCC cohort and then by direct exposure of HCC cells in vitro, the relationship of albumin levels to HCC growth. RESULTS: We found that patients with lower albumin levels had significantly larger maximum tumor diameters, more portal vein thrombosis, more tumor multifocality, higher α-fetoprotein levels, and a lower survival than patients with higher albumin levels. Direct addition of exogenous albumin at physiological concentrations resulted in decreased growth in several HCC cell lines in vitro. We found a decrease in MAP kinase levels and in levels of Cdk2 and Cdk4, cyclinE, as well as in α-fetoprotein. CONCLUSION: These results indicate that in addition to its role as a monitor of systemic inflammation, albumin may have a direct role in HCC growth inhibition, either through modulation of α-fetoprotein or through its actions on growth-controlling kinases.

A Hepatocellular Carcinoma Aggressiveness Index and Its Relationship to Liver Enzyme Levels.

BACKGROUND: Prognosis in hepatocellular carcinoma (HCC) is influenced by both liver and tumor factors, which have been considered independent influences. However, recent evidence has shown that the underlying liver also has prognostic information. AIMS: To investigate possible relationships between liver function parameters and HCC aggressiveness indices. METHODS: A large HCC patient database with baseline clinical information and survival data was retrospectively examined. RESULTS: Data on 756 HCC patients with normal bilirubin were examined for a relationship between serum liver enzymes and 4 HCC aggressiveness indices of maximum tumor diameter, portal vein invasion, tumor multifocality or serum alpha-fetoprotein levels. An association was found between elevated enzyme levels and increased HCC aggressiveness. An aggressiveness index was constructed from the 4 indices and expressed as a sum of their scores, which in turn reflected 3 survival groups. In a Cox model, the hazard ratios for each of the groups were significantly different. CONCLUSIONS: Statistically significant correlations were found between standard liver function parameters and HCC aggressiveness. A composite aggressiveness index was constructed, yielding 3 groups with different survival probabilities. These findings support the concept of the importance of the underlying liver in relation to HCC biology.

Hepatocellular Carcinoma Extrahepatic Metastasis in Relation to Tumor Size and Alkaline Phosphatase Levels.

BACKGROUND: Hepatocellular carcinoma (HCC) is known to metastasize. However, there are few reports on patients with metastasis at the time of HCC diagnosis. AIMS: To evaluate the incidence and characteristics of extrahepatic metastasis patients presenting at baseline with noncurable, advanced HCC. RESULTS: The total HCC cohort was initially dichotomized into 2 subcohorts, with (n = 214) and without (n = 719) extrahepatic metastasis ('metastasis'), and patient baseline characteristics were compared. The main findings for patients with metastasis (22.9% of total cohort) compared with other, nonmetastatic patients were: more advanced tumors, as judged by larger tumor diameters, more tumor multifocality and percent with portal vein thrombosis, higher blood α-fetoprotein and des x03B3;-carboxy prothrombin levels and alkaline phosphatase (ALKP), but not bilirubin levels, and a lower incidence of cirrhosis. There was a strong correlation between increases in tumor size and percent of patients with metastasis. A subset of patients with larger tumors was identified with low blood ALKP levels and better survival. Survival in the total metastasis cohort was lower than in the non-metastasis cohort, as expected, but only in patients with smaller tumors. In patients with larger tumors, survival with or without metastasis was similar and poor. CONCLUSIONS: There was a lower incidence of cirrhosis in HCC patients with metastasis, and they had larger and more aggressive primary tumors. Patients with smaller, but not larger, tumors and metastasis had worse prognosis than patients without metastasis. A distinct subset of metastatic patients was identified that had better prognosis and low ALKP levels.

Low Alpha-Fetoprotein Levels Are Associated with Improved Survival in Hepatocellular Carcinoma Patients with Portal Vein Thrombosis.

BACKGROUND: Macroscopic portal vein thrombosis (PVT) is a common and dire prognostic feature of patients with hepatocellular carcinoma (HCC) and often precludes many treatments as a result. Little is known about its causes or mechanisms or clinical associations. AIMS: To examine patients with PVT in order to possibly identify prognostically different subsets. METHODS: A large cohort of non-curable patients with advanced and biopsy-proven HCC in which survival was documented, were retrospectively examined. RESULTS: We analyzed a large HCC cohort containing 366 (63.3%) PVT-positive patients and found that PVT is associated with patients having larger tumors and higher levels of alpha-fetoprotein (AFP) and des-gamma carboxyprothrombin (DCP). We identified in patients with normal bilirubin levels (≤ 2.0 mg/dl) two PVT-positive patients, having higher and lower AFP levels, respectively. They differed in the significantly better prognosis of the low AFP patients, which may be useful for patient management decisions. CONCLUSIONS: Patients with PVT are heterogeneous with respect to AFP levels. AFP-negative patients have a significantly better survival than those who have elevated AFP.

Alpha-fetoprotein and albumin inversely relate to each other and to tumor parameters in patients with hepatocellular carcinoma.

Background and Aim: Alpha-fetoprotein (AFP), an oncofetal protein and biomarker in hepatocellular carcinoma (HCC), has unclear roles and actions.To evaluate the relationships between AFP, liver function tests, and HCC aggressiveness. Materials and Methods: A retrospective analysis of an HCC patient database was conducted to examine the relationships between baseline serum AFP values, liver function tests, and tumor characteristics. Results: Statistically significant positive trends were observed between AFP levels and both AST and bilirubin, along with negative trends between AFP and albumin. Significant correlations were also found between AFP and MTD, multifocality, and PVT. Increases in MTD, multifocality, and PVT were noted even at low AFP levels, indicating both AFP-independent and AFP-dependent processes. However, these parameter changes were minimal compared to the substantial changes in AFP levels. Relationships between AFP-related liver and tumor characteristics were found to be similar but inverse to those for albumin, with normal albumin levels associated with more favorable tumor characteristics. Additionally, serum levels of albumin and AFP were inversely related. Conclusion: AFP and albumin levels significantly, but inversely, correlate with tumor parameters, suggesting that albumin may suppress HCC functions and could serve as a potential prognostic marker.

Hepatocellular carcinoma size: platelets, γ-glutamyl transpeptidase, and alkaline phosphatase.

BACKGROUND: Thrombocytopenia is a cirrhosis surrogate which is associated with hepatocellular carcinoma (HCC) development. AIMS: To compare the clinical characteristics of HCC in the presence and absence of thrombocytopenia. METHODS: The baseline clinical data of a large cohort of randomly presenting, biopsy-proven HCC patients was examined for phenotypic patterns, after organizing the data by tumor size and subdivision into tumor size terciles. RESULTS: Small tumor size tercile I patients had the lowest platelet counts. Patients with higher platelets within each size tercile had the lowest bilirubin and prothrombin time and higher γ-glutamyl transpeptidase (GGTP) and alkaline phosphatase (ALKP) levels. When patients with similar platelet and bilirubin levels were compared, α-fetoprotein, GGTP, and ALKP were significantly increased in patients with larger tumors and in the presence of portal vein thrombus. Large tumor size tercile III patients without thrombocytopenia had larger tumors, higher GGTP and ALKP, and lower bilirubin levels than did patients with thrombocytopenia. CONCLUSIONS: Thrombocytopenia occurred in 40.7% of patients with smaller tumors but only in 11.3% of patients with larger tumors. Patients without thrombocytopenia had elevated GGTP and ALKP and lower bilirubin levels, regardless of tumor size, but they also had larger tumors within the large tumor tercile.

Thrombocytosis and hepatocellular carcinoma.

BACKGROUND: Thrombocytopenia has been reported to be both a risk factor for hepatocellular carcinoma (HCC) development as well as a prognostic factor. Many HCCs also occur in presence of normal platelets. AIM: To examine a cohort of HCC patients with associated thrombocytosis. METHODS: Records were examined of a cohort of 634 biopsy-proven and randomly presenting HCC patients without thrombocytopenia. RESULTS: In the total cohort, 52 patients were identified with thrombocytosis (platelet levels >400 × 10(9)/L) and compared with 582 patients with normal platelet values. The average tumor sizes were 13.1 versus 8.8 cm (p < 0.0001), and their total average bilirubin levels were 0.9 versus 1.5 (p = 0.02), comparing thrombocytosis patients versus normal platelet count HCC patients. These differences were even more pronounced in patients with HCC sizes >5 cm. Thrombocytosis patients were younger and had less cirrhosis, but similar percent with hepatitis B or C or alcohol consumption. CONCLUSION: Thrombocytosis in association with HCC occurs in patients with larger tumor sizes and better liver function.