Monofocal hepatocellular carcinoma: How much does size matter?

BACKGROUND & AIMS: According to the Barcelona Clinic Liver Cancer (BCLC) staging system, monofocal hepatocellular carcinoma (HCC) is classified as early (BCLC A) irrespective of its size, even though controversies still exist regarding staging and treatment of large tumours. We aimed at evaluating the appropriate staging and treatment for large (>5 cm) monofocal (HCC). METHODS: From the Italian Liver Cancer database, we selected 924 patients with small early monofocal HCC (2-5 cm; SEM-HCC), 163 patients with larger tumours (>5 cm; LEM-HCC) and 1048 intermediate stage patients (BCLC B). RESULTS: LEM-HCC patients had a worse overall survival (OS) than SEM-HCC (31.0 vs 49.0 months; P < .0001), and this was confirmed at multivariate analysis (HR 1.63, 95% CI 1.29-2.05; P < .0001). The small difference in OS between LEM-HCC and BCLC B patients (31.0 vs 27.0 months; P = .03) disappeared in the multivariate model (HR 0.98, 95% CI 0.77-1.25; P = .89). In all monofocal tumours, treatment was the strongest independent predictor of survival, with a progressively decreasing survival benefit moving from "curative" to "palliative" therapies. The survival of resected patients with LEM-HCC was significantly shorter than that of SEM-HCC (44.0 vs 78.0 months; P = .002), but liver resection provided the highest survival benefit in both groups compared to other treatments. CONCLUSIONS: Monofocal HCC larger than 5 cm should not be staged as BCLC A and either a different staging system or a different subgrouping of patients (e.g. BCLC AB) should be used. Liver resection, if feasible, remains the recommended treatment for all these patients.

Association of abnormal plasma bilirubin with aggressive hepatocellular carcinoma phenotype.

Cirrhosis-related abnormal liver function is associated with predisposition to hepatocellular carcinoma (HCC). It features in several HCC classification systems and is an HCC prognostic factor. The aim of the present study was to examine the phenotypic tumor differences in HCC patients with normal or abnormal plasma bilirubin levels. A 2,416-patient HCC cohort was studied and dichotomized into normal and abnormal plasma bilirubin groups. Their HCC characteristics were compared for tumor aggressiveness features, namely, blood alpha-fetoprotein (AFP) levels, tumor size, presence of portal vein thrombosis (PVT) and tumor multifocality. In the total cohort, elevated bilirubin levels were associated with higher AFP levels, increased PVT and multifocality, and lower survival, despite similar tumor sizes. When different tumor size terciles were compared, similar results were found, even among patients with small tumors. A multiple logistic regression model for PVT or tumor multifocality showed increased odds ratios for elevated levels of gamma glutamyl transpeptidase (GGTP), bilirubin, and AFP and for larger tumor sizes. We conclude that HCC patients with abnormal bilirubin levels had worse prognosis than patients with normal bilirubin. They also had an increased incidence of PVT and tumor multifocality, and higher AFP levels, in patients with both small and larger tumors. The results show an association between bilirubin levels and indices of HCC aggressiveness.

Prevalence and prognostic significance of the presence of esophageal varices in patients with hepatocellular carcinoma.

BACKGROUND & AIMS: It has been suggested that clinically relevant portal hypertension may affect the therapeutic management and prognosis of cirrhotic patients with hepatocellular carcinoma (HCC). Nevertheless, the importance of the presence of esophageal varices in these patients has not yet been addressed formally. In this study our aim was to evaluate the prevalence and prognostic relevance of the presence of esophageal varices in a large series of patients with HCC. METHODS: The prevalence of esophageal varices was evaluated in 1153 HCC patients who were consecutively referred to 10 Italian centers (the Italian Liver Cancer group). Survival was calculated from the time of HCC diagnosis until death or until the most recent follow-up visit, and was evaluated according to the presence or absence of esophageal varices. The independent prognostic meaning of the presence of esophageal varices was evaluated further in a multivariate regression analysis. RESULTS: Esophageal varices were found in 730 patients (63.3%). Patients with varices showed significantly shorter survival times (P < .0001) as compared with patients without varices. Death as a result of bleeding was more common in patients with varices (P = .0127). In multivariate analysis, the presence of esophageal varices was associated independently with poorer survival (adjusted relative risk, 1.25; 95% confidence interval, 1.06-1.48; P = .0095). CONCLUSIONS: More than half of the patients with HCC have esophageal varices. The presence of esophageal varices is associated with a higher risk of death from bleeding, and is an independent determinant of the patient's prognosis. This variable should be taken into account in the diagnostic and therapeutic work-up of HCC patients.