Clinical and epidemiological aspects of hepatocellular carcinoma in Brazil

OBJECTIVES: We performed a national survey to update hepatocellular carcinoma (HCC) epidemiology in Brazil and determined the clinical and epidemiological profiles of patients with HCC in different Brazilian regions. METHODS: Data from 29 centers included 1,405 patients diagnosed with HCC from 2004 to 2009. RESULTS: The median age was 59 (1-92 years old; 78% male). At diagnosis, females were older than males (median age: 62 vs. 59 years old respectively; p<0.0001). Ninety-eight percent of the patients had cirrhosis (1279/1308). Hepatitis C virus was the main etiology (54%), followed by hepatitis B virus (16%) and alcohol (14%). In Southeastern and Southern Brazil, hepatitis C virus accounted for over 55% of cases. In the Northeast and North, hepatitis C virus accounted for less than 50%, and hepatitis B virus accounted for 22-25% of cases; hepatitis B was more prevalent in the Northern than in the Southern regions. Some 43%, 35%, and 22% of patients were in early, intermediate, and advanced stages respectively. Initial therapies for HCC included chemoembolization or embolization (36%), percutaneous ablation (13%), liver resection (7%), and sorafenib (1%). Liver transplantation was performed in 242 patients (19%), but it was the initial therapy for only 56 patients (4%). CONCLUSION: The epidemiology, classification, and therapy selection for HCC varied among Brazilian regions. Hepatitis C infection was the most common etiology of liver cirrhosis; chemoembolization was the most common therapy employed. Liver cirrhosis was the main risk factor for HCC development in Brazil

Adherence to BCLC recommendations for the treatment of hepatocellular carcinoma: impact on survival according to stage

OBJECTIVES: This study sought to assess the adherence of newly diagnosed hepatocellular carcinoma patients to the Barcelona Clinic Liver Cancer system treatment guidelines and to examine the impact of adherence on the survival of patients in different stages of the disease. METHODS: This study included all patients referred for the treatment of hepatocellular carcinoma between 2010 and 2012. Patients (n=364) were classified according to the Barcelona Clinic Liver Cancer guidelines. Deviations from the recommended guidelines were discussed, and treatment was determined by a multidisciplinary team. The overall survival curves were estimated with the Kaplan-Meier method and were compared using the log-rank test. RESULTS: The overall rate of adherence to the guidelines was 52%. The rate of adherence of patients in each scoring group varied as follows: stage 0, 33%; stage A, 45%; stage B, 78%; stage C, 35%; and stage D, 67%. In stage 0/A, adherent patients had a significantly better overall survival than non-adherent patients (hazard ratio=0.19, 95% confidence interval (CI): 0.09-0.42;

Clinical and pathological evaluation of fibrolamellar hepatocellular carcinoma: a single center study of 21 cases

OBJECTIVES: Fibrolamellar hepatocellular carcinoma is a rare primary malignant liver tumor that differs from conventional hepatocellular carcinoma in several aspects. The aim of this study was to describe the clinical, surgical and histopathological features of fibrolamellar hepatocellular carcinoma and to analyze the factors associated with survival. METHODS: We identified 21 patients with histopathologically diagnosed fibrolamellar hepatocellular carcinoma over a 22-year period. Clinical information was collected from medical records and biopsies, and surgical specimens were reviewed. RESULTS: The median age at diagnosis was 20 years. Most patients were female (67%) and did not have associated chronic liver disease. Most patients had a single nodule, and the median tumor size was 120 mm. Vascular invasion was present in 31% of patients, and extra-hepatic metastases were present in 53%. Fourteen patients underwent surgery as the first-line therapy, three received chemotherapy, and four received palliative care. Eighteen patients had “pure fibrolamellar hepatocellular carcinoma,” whereas three had a distinct area of conventional hepatocellular carcinoma and were classified as having “mixed fibrolamellar hepatocellular carcinoma.” The median overall survival was 36 months. The presence of “mixed fibrolamellar hepatocellular carcinoma” and macrovascular invasion were predictors of poor survival. Vascular invasion was associated with an increased risk of recurrence in patients who underwent surgery. CONCLUSION: Fibrolamellar hepatocellular carcinoma was more common in young female patients without chronic liver disease. Surgery was the first therapeutic option to achieve disease control, even in advanced cases. Vascular invasion was a risk factor for tumor recurrence. The presence of macrovascular invasion and areas of conventional hepatocellular carcinoma were directly related to poor survival

INGESTÃO PROLONGADA DE CHÁ BRANCO NOS PARÂMETROS HEMATOLÓGICOS DE RATAS WISTAR

O chá branco é uma bebida saudável, porém este chá pode interferir em vários fatores de crescimento envolvidos no metabolismo. Portanto, este trabalho teve como objetivo verificar o efeito do consumo prolongado de chá branco nos parâmetros hematológicos de ratas Wistar. Foram utilizados dois grupos de ratas: controle (n=30) que recebeu água e o grupo que recebeu apenas chá branco para beber (n=30). O experimento teve duração de 3 meses, ao final de cada mês, 10 ratas de cada grupo eram eutanasiadas e o sangue dos animais colhido para hemograma e bioquímica sérica. A análise estatística foi a ANOVA seguida do teste de Tukey e Teste T, foram consideradas diferenças estatísticas quando

Serum lipidomic profiling as a useful tool for screening potential biomarkers of hepatitis B-related hepatocellular carcinoma by ultraperformance liquid chromatography–mass spectrometry

Abstract\ud \ud Background\ud Chronic hepatitis B (CHB) virus infection is a major cause of hepatocellular carcinoma (HCC), as late diagnosis is the main factor for the poor survival of patients. There is an urgent need for accurate biomarkers for early diagnosis of HCC. The aim of the study was to explore the serum lipidome profiles of hepatitis B-related HCC to identify potential diagnostic biomarkers.\ud \ud \ud Methods\ud An ultraperformance liquid chromatography mass spectrometry (UPLC-MS) lipidomic method was used to characterize serum profiles from HCC (n = 32), liver cirrhosis (LC) (n = 30), CHB (n = 25), and healthy subjects (n = 34). Patients were diagnosed by clinical laboratory and imaging evidence and all presented with CHB while healthy controls had normal liver function and no infectious diseases.\ud \ud \ud Results\ud The UPLC-MS-based serum lipidomic profile provided more accurate diagnosis for LC patients than conventional alpha-fetoprotein (AFP) detection. HCC patients were discriminated from LC with 78 % sensitivity and 64 % specificity. In comparison, AFP showed sensitivity and specificity of 38 % and 93 %, respectively. HCC was differentiated from CHB with 100 % sensitivity and specificity using the UPLC-MS approach. Identified lipids comprised glycerophosphocolines, glycerophosphoserines and glycerophosphoinositols.\ud \ud \ud Conclusions\ud UPLC-MS lipid profiling proved to be an efficient and convenient tool for diagnosis and screening of HCC in a high-risk population.The Fleury SA Group supported this work and AMPC received a doctorate\ud scholarship from Fundação de Amparo à Pesquisa do Estado de São Paulo –\ud FAPESP (no. 2013/03701-0). The funding agencies did not interfere in the\ud scientific aspects of the study

The influence of HIV infection on the natural history of hepatocellular carcinoma: results from a global multi-cohort study

Purpose. Conflicting evidence indicates HIV-seropositivity to influence the outcome of patients with hepatocellular carcinoma (HCC), a leading cause of mortality in people with HIV. We aimed to verify whether HIV affected the overall survival (OS) of patients with HCC independent of treatment and geographic origin. Patients and Methods: We designed an international multi-cohort study of HCC patients who did not receive any anticancer treatment accrued from four continents. We estimated the effect of HIV-seropositivity on patients’ OS while accounting for common prognostic factors and demographic characteristics in uni- and multi-variable models. Results: A total of 1588 patients were recruited, 132 of whom were HIV-positive. Most patients clustered within Barcelona Clinic Liver Cancer (BCLC) C/D criteria (n=1168, 74%), Child-Turcotte-Pugh (CTP) Class B (median score 7, IQR 3). At HCC diagnosis the majority of HIV-positive patients (n=65, 64%) had been on anti-retrovirals for a median duration of 8.3 years (IQR 8.59) and had median CD4+ cell counts of 256 (IQR 284) with undetectable HIV RNA (n=68, 52%). OS significantly reduced throughout BCLC stages 0-D (16, 12, 7.5, 3.1 and 3 months, p<0.001). Median OS of HIV-positive patients was half that of HIV-uninfected counterparts: 2.2 months, (bootstrap 95%CI 1.2-3.1) versus 4.1 months (95%CI 3.6-4.4). In adjusted analyses HIV-seropositivity increased the hazard of death by 24% (p=0.0333) independent of BCLC (p<0.0001), CTP (p<0.0001), alpha-fetoprotein (AFP) (p<0.0001), geographical origin (p<0.0001) and male gender (p=0.0016). Predictors of worse OS in HIV-positive patients included CTP (p=0.0071) and AFP (p<0.0001). Conclusions. Despite adequate antiretroviral treatment, HIV-seropositivity is associated with decreased survival in HCC independent of stage, anti-cancer treatment and geographical origin. Mechanistic studies investigating the immuno-biology of HIV-associated HCC are urgently required

Repertoire, Genealogy and Genomic Organization of Cruzipain and Homologous Genes in Trypanosoma cruzi, T. cruzi-Like and Other Trypanosome Species

Trypanosoma cruzi, the agent of Chagas disease, is a complex of genetically diverse isolates highly phylogenetically related to T. cruzi-like species, Trypanosoma cruzi marinkellei and Trypanosoma dionisii, all sharing morphology of blood and culture forms and development within cells. However, they differ in hosts, vectors and pathogenicity: T. cruzi is a human pathogen infective to virtually all mammals whilst the other two species are non-pathogenic and bat restricted. Previous studies suggest that variations in expression levels and genetic diversity of cruzipain, the major isoform of cathepsin L-like (CATL) enzymes of T. cruzi, correlate with levels of cellular invasion, differentiation, virulence and pathogenicity of distinct strains. In this study, we compared 80 sequences of genes encoding cruzipain from 25 T. cruzi isolates representative of all discrete typing units (DTUs TcI-TcVI) and the new genotype Tcbat and 10 sequences of homologous genes from other species. The catalytic domain repertoires diverged according to DTUs and trypanosome species. Relatively homogeneous sequences are found within and among isolates of the same DTU except TcV and TcVI, which displayed sequences unique or identical to those of TcII and TcIII, supporting their origin from the hybridization between these two DTUs. In network genealogies, sequences from T. cruzi clustered tightly together and closer to T. c. marinkellei than to T. dionisii and largely differed from homologues of T. rangeli and T. b. brucei. Here, analysis of isolates representative of the overall biological and genetic diversity of T. cruzi and closest T. cruzi-like species evidenced DTU- and species-specific polymorphisms corroborating phylogenetic relationships inferred with other genes. Comparison of both phylogenetically close and distant trypanosomes is valuable to understand host-parasite interactions, virulence and pathogenicity. Our findings corroborate cruzipain as valuable target for drugs, vaccine, diagnostic and genotyping approaches