BACKGROUNDDespite being the world’s most widely used system for staging and therapeutic guidance in hepatocellular carcinoma (HCC) treatment, the Barcelona clinic liver cancer (BCLC) system has limitations, especially regarding intermediate-grade (BCLC-B) tumors. The recently proposed Hong Kong liver cancer (HKLC) staging system appears useful but requires validation in Western populations.AIMTo evaluate the agreement between BCLC and HKLC staging on the management of HCC in a Western population, estimating the overall patient survival.METHODSThis was a retrospective study of HCC patients treated at a university hospital in southern Brazil between 2011 and 2016. Demographic, clinical, and laboratory data were collected. HCC staging was carried out according to the HKLC and BCLC systems to assess treatment agreement. Overall survival was estimated based on the treatment proposed in each system.RESULTSA total of 519 HCC patients were assessed. Of these, 178 (34.3%) were HKLC-I; 95 (18.3%) HKLC-IIA; 47 (9.1%) HKLC-IIB; 29 (5.6%) HKLC-IIIA; 30 (5.8%) HKLC-IIIB; 75 (14.4%) HKLC-IV; and 65 (12.5%) HKLC-V. According to the BCLC, 25 (4.9%) were BCLC-0; 246 (47.4%) BCLC-A; 107 (20.6%) BCLC-B; 76 (14.6%) BCLC-C; and 65 (12.5%) BCLC-D. The general agreement between the two systems was 80.0% - BCLC-0 and HKLC-I (100%); BCLC-A and HKLC-I/HKLC-II (96.7%); BCLC-B and HKLC-III (46.7%); BCLC-C and HKLC-IV (98.7%); BCLC-D and HKLC-V (41.5%). When sub-classifying BCLC-A, HKLC-IIB, HKLC-IIIA and HKLC-IIIB stages according to the up-to-7 in/out criterion, 13.4, 66.0, 100 and 36.7%, respectively, of the cases were classified as up-to-7 out.CONCLUSIONIn a Western population, the general agreement between the two systems was 80.0%, although in BCLC-B cases the agreement was low, suggesting that some individuals could be candidates for the curative treatment recommended by the HKLC. The authors suggest that the BCLC system should be routinely employed, although for BCLC-B cases it should be associated with the HKLC system.

Introduction: Sorafenib (SOR) has proved to be effective in patients with advanced hepatocellular carcinoma (HCC), since overall survival was higher in phase III clinical trials; however, disease progression can occur. Objectives: The study aimed to describe real-life experience in advanced HCC treatment with SOR at a university hospital in Brazil and to estimate the number of patients with indication of second-line therapy. Methods: This is a retrospective study that included cases of HCC with prescription of SOR based on real-life practice between 2011 and 2016. Demographic, clinical, and laboratory data were collected. Results: From 572 patients with HCC, SOR was prescribed in 103 cases. From them, 62.1% were classified as Child-Pugh (CP)-A, 54.4% as Barcelona Clinic Liver Cancer (BCLC)-C, and 74 (71.8%) started treatment. Overall survival was 25.5 (95% CI 17.0–34.1) months and 1-year survival was greater in patients who received SOR than in non-treated (88.7 vs. 44.4%, p < 0.001). There was no difference in survival between BCLC-B and C (p = 0.405), as well as CP-A and B (p = 0.919). In 21.6% of the patients, a second-line therapy with regorafenib was indicated. Conclusion: In this real-life study, SOR significantly increased the survival rate by 1 year in patients with advanced HCC regardless of BCLC staging and CP score. Second-line therapy would be indicated in 21.6% of cases.

The valorisation of agro-industrial residues presents a challenge in obtaining economically sustainable and environmentally friendly industrial processes. Olive pomace is a by-product generated in large quantities, from olive oil extraction. This residue mostly consists of lignocellulosic materials. The aim of this study was to evaluate the potential use of extracted olive pomaces (EOP) obtained from olives with different ripening indexes (RI) and from different cultivars (Cobrançosa; RI = 2.5; 3.3 and 4.7; and Galega Vulgar; RI = 1.8; 2.9 and 4.8), to produce bioactive oligosaccharides from hemicelluloses by autohydrolysis. The hydrothermal treatment conditions were optimized by Response Surface Methodology, following a central composite rotatable design (CCRD), as a function of temperature (T: 142–198 °C) and time (t: 48–132 min), corresponding to severity factor (SF) values from 3.2 to 4.9. For all pomace samples, soluble sugar production was described by concave surfaces as a function of temperature and time. Autohydrolysis with SF equal or higher than 4.0 produced higher sugar yields, with maximum values around 180 g glucose equivalent/kg EOP for SF of 4.7 (190 °C/120 min) or 4.9 (198 °C/90 min). These values were similar for both cultivars and were not dependent on the ripening stage of the olives. Maximum oligosaccharide (OS) yields of 98% were obtained by autohydrolysis with SF of 4.0. The increase in SF to 4.9 resulted in a decrease in OS yield to 86–92%, due to the release of monomeric sugars. The monosaccharides were mostly xylose (55.8–67.7% in Galega; 50.4–69.0% in Cobrançosa liquid phases), and glucose, galactose, arabinose and rhamnose, in smaller quantities. Therefore, the production of bioactive xylo-oligosaccharides (XOS) from olive pomaces mainly depends on the hydrothermal conditions used.

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Introduction: The intermediate stage of the Barcelona Clinic Liver Cancer (BCLC) classification includes a heterogenous population of patients with hepatocellular carcinoma (HCC), and palliative treatment with transarterial chemoembolization is recommended for all of them. In this regard, 2 other classifications could be useful, the subclassification BCLC-B (SUB) and the classification Hong Kong Liver Cancer (HKLC). Objective: To determine the indication of curative or palliative treatment between SUB and HKLC in BCLC-B patients. Patients and Methods: A retrospective study in HCC patients seen between 2011 and 2016 in southern Brazil. Demographic, clinical, and laboratory data were collected. HCC staging was performed with BCLC, SUB, and HKLC. Results: A total of 570 patients with HCC were assessed, of whom 95 were classified as BCLC-B: 25 (26.0%) B1, 48 (50.5%) B2, 9 (9.5%) B3, and 13 (13.7%) B4. Overall median survival was 21.1 (95% confidence interval, 14.2-28.0) months. Median survival was higher for BCLC-B1 patients than in subgroups B3 (P=0.046) and B4 (P=0.001), and this was also seen for B2 versus B4 (P=0.044). Regarding the HKLC classification, a significantly higher median survival was observed for HKLC-I and HKLC-IIB in relation to the categories HKLC-IIIA (P<0.001 and 0.004, respectively) and HKLC-IIIB (P<0.001 and 0.006, respectively). When HKLC was applied, the following were identified as candidates for curative treatment: BCLC-B1, 24 (96.0%); BCLC-B2, 26 (54.2%); BCLC-B3, 0 (0%); and BCLC-B4, 3 (23.1%). Conclusion: In intermediate HCC, SUB was able to identify a subset of patients with a higher overall survival. According to HKLC, 55.8% of BCLC-B patients could receive curative treatment.

Metabolic dysfunction associated fatty liver disease (MAFLD) has gained worldwide attention as a public health problem. Nonetheless, lack of enough mechanistic knowledge restrains effective treatments. It is known that T3 regulate hepatic lipid metabolism, and mitochondrial function. Liver dysfunction of T3 contributes to MAFLD, but its role is not fully understood. Objective: To evaluate the role of T3 dysfunction in the progression of MAFLD in an animal model. Method-ology: Male/adult Sprague Dawley rats (n=20) were allocated to a control group (standard di-et&ndash;2.93kcal/g) and diet group (CDHF&ndash;4.3kcal/g). Euthanasia took place in the 28th week. D3 ac-tivity and expression, UCP2 and D1 expression, REDOX status, mitochondrial, Krebs cycle and endoplasmic reticulum homeostasis in liver tissue were measured. Results: We observed an in-crease in D3 activity/expression (P&lt;0.001) related to increased TBARS and carbonyls and GSH reduction in the MAFLD group (P&lt;0.05). There was a T3-dependent decrease in UCP2 expression (P=0.01), mitochondrial capacity, respiratory activity with increased endoplasmic reticulum stress in the MAFLD group (P &lt; 0.001). Surprisingly, in and environment with lower T3 levels we observed an augmented alpha-ketoglutarate dehydrogenase (KGDH) and glutamate dehydro-genase (GDH) enzymes activity (P&lt;0.05). Conclusion: Induced D3, triggered by changes in the REDOX state, decreases T3 availability, and hepatic mitochondrial capacity. The Krebs cycle en-zymes were altered as well as reticulum stress. Taken together, these results shed new light on the role of T3 metabolism in MAFLD and new treatment opportunities.

A reestenose arterial é um processo inflamatório que pode ocorrer após colocação de stent por cateterismo. Os stents farmacológicos surgiram para reduzir esse problema e o inibidor multiquinase sorafenibe demonstrou ser um composto com ação efetiva. Este estudo in vitro avaliou os efeitos do sorafenibe sobre a citotoxicidade, migração celular e distribuição das células nas fases do ciclo celular. A linhagem celular de músculo liso de rato A7r5 foi tratada com sorafenibe em concentrações que variaram de 0 a 5 μM. Os efeitos citotóxicos foram avaliados por dois ensaios colorimétricos, MTT e SRB após 24 horas de tratamento. A distribuição das células nas fases do ciclo celular foi avaliada por citometria de fluxo e a capacidade de cicatrização/migração celular pelo ensaio scratch wound assay. Comparado com o controle positivo paclitaxel, o sorafenibe demonstrou um efeito 1,6 vezes maior na redução da proliferação celular. Na avaliação do ciclo celular, o sorafenibe mostrou um bloqueio na fase G0/G1. Além disso, o sorafenibe aumentou o número de A7r5 células na fase sub-G1, sugerindo morte celular. No entanto, no estudo de cicatrização/migração celular, não foi observado efeito quando comparado ao controle negativo. Assim, esses resultados in vitro sugerem que o sorafenibe é eficaz para uso em stents farmacológicos, sugerindo uma continuidade na investigação desse fármaco.

distribuição das células nas fases do ciclo celular. A linhagem celular de músculo liso de rato A7r5 foi tratada com sorafenibe em concentrações que variaram de 0 a 5 μM. Os efeitos citotóxicos foram avaliados por dois ensaios colorimétricos, MTT e SRB após 24 horas de tratamento. A distribuição das células nas fases do ciclo celular foi avaliada por citometria de fluxo e a capacidade de cicatrização/migração celular pelo ensaio scratch wound assay. Comparado com o controle positivo paclitaxel, o sorafenibe demonstrou um efeito 1,6 vezes maior na redução da proliferação celular. Na avaliação do ciclo celular, o sorafenibe mostrou um bloqueio na fase G0/G1. Além disso, o sorafenibe aumentou o número de A7r5 células na fase sub-G1, sugerindo morte celular. No entanto, no estudo de cicatrização/migração celular, não foi observado efeito quando comparado ao controle negativo. Assim, esses resultados in vitro sugerem que o sorafenibe é eficaz para uso em stents farmacológicos, sugerindo uma continuidade na investigação desse fármaco.