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Background: The search for prognostic markers in hepatocellular carcinoma (HCC) is essential for clinical decisions. In addition to established variables such as liver function and tumor extent, cancer-associated inflammation can impact clinical outcomes. Evolutionary variation in inflammatory indexes, such as the neutrophil-to-lymphocyte ratio (NLR) or platelet-to-lymphocyte ratio (PLR), may correlate with therapeutic benefit. Our aim is to assess the prognostic role of immune cell counts and inflammation indexes in HCC patients treated with systemic therapy and the evolutionary behavior of these variables within the first month of treatment. Methods: We analyzed a cohort of patients consecutively treated with first-line sorafenib from 2009 to 2021. Subgroups were divided based on the median value of each variable/index in “low” or “high”. Survival was estimated using the Kaplan-Meier method and compared using log-rank. Hazard Ratio (HR) with 95% confidence interval (CI) were estimated using Cox regression models and Harrell´s C indexes were calculated to define their accuracy. Results: 373 patients were included, most of them male (75.6%), Child-Pugh A (83.1%) and BCLC C (74%). Median survival was 9.7 months (95%CI: 8.7-10.8 months). The following factors were independently associated with a better prognosis: Child-Pugh A (p=0.011), ECOG-PS 0 (pConclusion: Evolutionary variation of NLR has a prognostic role in HCC patients under systemic therapy. This finding suggests that systemic inflammation and early modulation of the immune environment during treatment may correlate with survival.

BACKGROUND: The aim of the study was to evaluate the feasibility and safety of stereotactic body radiotherapy (SBRT) for the treatment of hepatocellular carcinoma in Brazil. SBRT is an evolving treatment in HCC patients not candidates to other local therapies. Its adoption in clinical practice has been heterogeneous, with lack of data on its generalizability in the Brazilian population. MATERIALS AND METHODS: We conducted a prospective pilot study involving HCC patients after failure or ineligibility for transarterial chemoembolization. Patients received SBRT 30 to 50 Gy in 5 fractions using an isotoxic prescription approach. This study is registered at clinicaltrials.gov NCT02221778. RESULTS: From Nov 2014 through Aug 2019, 26 patients received SBRT with 40 Gy median dose. Underlying liver disease was hepatitis C, hepatitis B and alcohol-related in, respectively, 50%, 23% and 19% of patients. Median lesion size was 3.8 cm (range, 1.5–10 cm), and 46% had multiple lesions. Thirty-two percent had tumor vascular thrombosis; median pretreatment alpha-fetoprotein (AFP) was 171.7 ng/mL (range, 4.2–5,494 ng/mL). 1y-local progression-free survival (PFS) was 86% (95% CI: 61% to 95%), with higher local control in doses ≥ 45Gy (p = 0.037; HR = 0.12). 1y-liver PFS, distant PFS and OS were, respectively, 52%, 77% and 79%. Objective response was seen in 89% of patients, with 3 months post-SBRT median AFP of 12 ng/mL (2.4–637 ng/mL). There were no grade 3 or 4 clinical toxicities. Grade 3 or 4 laboratory toxicities occurred in 27% of patients. CONCLUSION: SBRT is feasible and safe in patients unresponsive or ineligible for TACE in Brazil. Our study suggests doses > 45Gy yields better local control.

INTRODUCTION AND OBJECTIVES: Hepatocellular carcinoma (HCC) is the 6(th) cause of cancer and hepatitis C (HCV) and B (HBV) viruses are the most frequent risk factors for HCC. Patients co-infected with HCV or HBV and human immunodeficiency virus (HIV) present a faster progression to liver fibrosis and higher incidence of HCC. The aim of this study was to evaluate the survival and clinical outcomes of co-infected patients with HCC comparing with non-HIV patients. METHODS: We conducted a retrospective cohort study including 267 HCC patients with HCV or HBV infection with or without HIV. The primary endpoint was overall survival. A Kaplan-Meier curve was presented to assess survival function. Clinical and radiologic variables according to HIV status were compared by logistic regression. RESULTS: Among 267 HCC patients, 25 (9.3%) were HIV positive. In the co-infected group, patients were younger (49.8 vs 61.2 years, p

Background & Aims: Information on safety and efficacy of systemic treatment in patients with hepatocellular carcinoma (HCC) under dialysis are limited due to patient exclusion from clinical trials. Thus, we aimed to evaluate the rate, prevalence, tolerability, and outcome of sorafenib in this population. Methods: We report a multicenter study comprising patients from Latin America and Europe. Patients treated with sorafenib were enrolled; demographics, dose modifications, adverse events (AEs), treatment duration, and outcome of patients undergoing dialysis were recorded. Results: As of March 2018, 6156 HCC patients were treated in 44 centres and 22 patients were concomitantly under dialysis (0.36%). The median age was 65.5years, 40.9% had hepatitis C, 75% had Child-Pugh A, and 85% were Barcelona Clinic Liver Cancer-C. The median time to first dose modification, treatment duration and overall survival rate were 2.4months (interquartile ranges [IQR], 0.8-3.8), 10.8months (IQR, 4.5-16.9), and 17.5months (95% CI, 7.2-24.5), respectively. Seventeen patients required at least 1 dose modification. The main causes of first dose modification were asthenia/worsening of Eastern Cooperative Oncology Group-Performance Status and diarrhoea. At the time of death or last follow-up, four patients were still on treatment and 18 had discontinued sorafenib: 14 were due to tumour progression, 2 were sorafenib-related, and 2 were non-sorafenib-related AE. Conclusions: The outcomes observed in this cohort seem comparable to those in the non-dialysis population. Thus, to the best of our knowledge, this is the largest and most informative dataset regarding systemic treatment outcomes in HCC patients undergoing dialysis.

Objective: The aim of the present study was to evaluate the clinical features, Hepatocellular Carcinoma (HCC) screening, treatment modalities, and Overall Survival (OS) in a series of Non-Alcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma (NAFLD-HCC) Brazilian patients. Methods: This was a cross-sectional study at the Instituto do Cancer do Estado de São Paulo, at the Faculdade de Medicina da Universidade de São Paulo with the approval of the local research ethics committee. NAFLD patients with HCC diagnosed, from May 2010 to May 2019, were included. Results: A total of 131 patients were included. Risk factors for NAFLD were present in 94.7% of the patients. Only 29% of patients were in the HCC screening program before diagnosis. HCC treatment was performed in 84.7% of patients. Cumulative survival at the end of the first year was 72%, second-year 52%, and fifth-year 32%. HCC screening before diagnosis was not significantly associated with higher cumulative survival. The independent factors associated with shorter general survival were BCLC C-D, p < 0.001, and the size of the largest nodule > 42 mm, p = 0.039. Conclusions: Although the efficacy of screening in our population regarding overall survival was hampered due to the sample size (29% had screening), BCLC stages C‒D and the size of the largest nodule larger than 42 mm were identified as independent factors of worse prognosis.

Background: Liver transplantation (LT) is the treatment of choice for unresectable early hepatocellular carcinoma (HCC). Previous studies demonstrated that Alpha-fetoprotein (AFP) is an important biomarker of prognosis and tumor recurrence. Aims: The aim of our study was to analyze the role of AFP in the post-transplant outcomes of HCC patients undergoing LT. Methods: We conducted a multicenter, retrospective cohort study, analyzing medical records of 1,119 liver transplant recipients with HCC in Brazil. Survival curves were presented using the Kaplan-Meier and compared using the log-rank test. Univariate cox regression analysis was fitted. We performed an evaluation of the effect of the continuous variable on the risk ratio, to define the best ''cutoff point'' of AFP level at HCC diagnosis and pre-transplantation capable of differentiating patients from risk of recurrence and survival. Results: Among 1,119 cases, 81% of patients were male, with a mean age at transplantation of 58 years. At HCC diagnosis, 85% were within Milan Criteria (MC). Median pre-LT AFP was 9.7 ng/ml (0-40,800 ng/ml) and 51% of patients had pre-LT AFP ≤ 10 ng/ml. The overall survival was 63% in 5 years and post-LT HCC recurrence was observed in 8% of patients. We found AFP > 400ng/ml at HCC diagnosis and AFP pre-LT > 200ng/ml as the better “cutoff points” for both overall survival and recurrence risk. Patients with AFP pre-LT ≤ 200 ng/ml had a better overall survival and recurrence-free survival compared with patients with AFP > 200 ng/ml, respectively, 76% and 92% versus 67% and 66% in 5-years (p 200ng/ml and being outside MC at diagnosis were also independent risk factors for post-LT HCC recurrence and poor survival in multivariate analysis. Conclusions: Our study demonstrated role of AFP as a main pre-transplant prognostic factor, both to predict post-LT tumor recurrence and survival.

Backgrounds: Down-staging (DS) is used to convert hepatocellular carcinoma (HCC) patients outside the criteria for liver transplantation (LT) into patients within the criteria. However, LT after DS remains controversial in the literature. Aims: Compare the post-LT survival and recurrence risk of HCC patients transplanted after DS with patients transplanted within the Brazilian selection criteria. Methods: We conducted a multicenter, retrospective cohort study, analyzing medical records of 1,119 liver transplant recipients with HCC in Brazil. HCC treatment prior to LT and whether or not the patient was enrolled after down-staging was analyzed. Survival curves were presented using the Kaplan-Meier and compared using the log-rank test. Univariate and multiple cox regression analysis was fitted. Results: 1,119 patients were included. 81% were males and mean age in the time of LT was 58 ± 8.2 years. In the majority of patients (91%) HCC was the reason for inclusion in transplant list and 8% of patients were listed after successful DS. At HCC diagnosis, 85% of patients were within Milan Criteria. TACE was the most frequent treatment performed. The overall survival (OS) of the entire series was 63% in 5 years, with an average follow-up time of 28 months and post-LT HCC recurrence was 8%. Relapse-free survival and OS, respectively, over 5 years, were 78% and 83% in DS patients and 75% and 89% in patients transplanted within criteria, with no statistical difference in the two analyzes. Evaluation of prognostic factors using simple and multiple Cox Regression did not show that DS was a risk factor for a worse survival or post-LT tumor recurrence. Conclusions: In our study, patients underwent DS show good post-transplant evolution, similar to those transplanted within criteria, suggesting that response to treatment is a good selection parameter for tumors with favorable tumor biology.

Background and Aims: Hepatocellular carcinoma (HCC) occurrence is rare in autoimmune hepatitis (AIH) and data about its characteristics are still scarce. The aims of this study were to describe HCC prevalence and risks factors in AIH patients in a tertiary referral hospital. Methods: Retrospective cohort of AIH patients followed from 2003 to 2019. The hazard ratios (HR) and their respective 95% confidence intervals (95%CI) were estimated using simple Cox regression. A multivariate regression model was fitted using relevant covariates for HCC occurrence. Results: Among 355 AIH patients, 84.5% were female, 85% AIH-1, 65% with cirrhosis and mean age at AIH diagnosis of 27±18yr. Sixteen cases of HCC were diagnosed (4.5%), all of them in cirrhotic patients, 81.3% female, mean age of 49±20yr, 83% overweight (BMI 34±5kg/m2) and 3 with associated steatohepatitis. The pooled incidence rate for HCC was 3.2 per 100 patient-years. The pooled incidence of HCC in patients with cirrhosis at AIH diagnosis was 4.5 per 100 patient-years. The median time between AIH diagnosis and HCC was 9 years (1-42). At univariate analysis the factors associated with HCC risk were age at diagnosis of AIH (HR,1.05; 95%CI,1.02-1.08; p

Background Liver transplantation (LT) is the treatment of choice for patients with unresectable early hepatocellular carcinoma (HCC). Post-LT HCC recurrence rates range from 8 to 20% and still impact on overall survival (OS). The aim of our study was to evaluate the impact of HCC recurrence on post-LT survival and analyze prognostic factors among those patients with recurrence. Patients and methods We carried out a national, multicenter, retrospective cohort study in Brazil. Medical records of 1119 LT recipients with HCC were collected. Data from patients with post-LT HCC recurrence were analyzed and correlated with post-relapse survival. Results OS of the 1119 patients included in the study was 63% over 5 years. Post-LT HCC recurrence occurred in 86 (8%) patients. The mean time to recurrence was 12 months. Sites of recurrence were extrahepatic in 55%, hepatic in 27%, and both hepatic and extrahepatic in 18%. Recurrence treatment was performed in 50 (64%) cases, mostly with sorafenib. Post-relapse survival rates were 34% at 1 year and 13% at 5 years. Univariable analysis identified α-fetoprotein more than 1000 ng/ml at relapse, recurrence treatment, extrahepatic location, and time to recurrence more than 2 years as prognostic factors. In multivariable analysis, recurrence treatment, extrahepatic location, and time to recurrence more than 2 years were independent predictors of better survival. Conclusion In a large Brazilian cohort of LT recipients with HCC, post-LT HCC recurrence occurred in 8% and impacted significantly on the OS. Patients with early recurrence presented a worse prognosis. However, treatment of recurrence improved outcomes, highlighting the importance of early diagnosis.

OBJECTIVES: To investigate whether quantitative textural features, extracted from pretreatment MRI, can predict sustained complete response to radiofrequency ablation (RFA) in patients with hepatocellular carcinoma (HCC). METHODS: In this IRB-approved study, patients were selected from a maintained six-year database of consecutive patients who underwent both pretreatment MRI imaging with a probable or definitive imaging diagnosis of HCC (LI-RADS 4 or 5) and loco-regional treatment with RFA. An experienced radiologist manually segmented the hepatic nodules in MRI arterial and equilibrium phases to obtain the volume of interest (VOI) for extraction of 107 quantitative textural features, including shape and first- and second-order features. Statistical analysis was performed to evaluate associations between textural features and complete response. RESULTS: The study consisted of 34 patients with 51 treated hepatic nodules. Sustained complete response was achieved by 6 patients (4 with single nodule and 2 with multiple nodules). Of the 107 features from the arterial and equilibrium phases, 20 (18%) and 25 (23%) achieved AUC >0.7, respectively. The three best performing features were found in the equilibrium phase: Dependence Non-Uniformity Normalized and Dependence Variance (both GLDM class, with AUC of 0.78 and 0.76, respectively) and Maximum Probability (GLCM class, AUC of 0.76). CONCLUSIONS: This pilot study demonstrates that a radiomic analysis of pre-treatment MRI might be useful in identifying patients with HCC who are most likely to have a sustained complete response to RFA. Second-order features (GLDM and GLCM) extracted from equilibrium phase obtained highest discriminatory performance.

Introduction and objectives: Hepatocellular carcinoma (HCC) is one of the main indications for orthotopic liver transplantation (OLT). In Brazil, selection criteria for HCC is an expanded version of the Milan Criteria (MC), the so-called ''Brazilian Milan Criteria'' (BMC). Our aims were to evaluate post-OLT outcomes in patients with HCC and analyze the BMC performance. Materials and Methods: We conducted a multicenter, retrospective cohort study, analyzing medical records of 1,059 liver transplant recipients with HCC. Tumor was staged according to MC and BMC and correlated with overall survival (OS) and disease-free survival (DFS). We compared the ability of MC and BMC to predict OS and DFS using Delta C-statistic. Results: Post-OLT OS were 63% in five years and HCC recurrence was observed in 8% of patients. At diagnosis, 85% of patients were within MC. Patients within MC at diagnosis and in the explant showed a higher OS and DFS than patients outside MC and within BMC and patients outside both criteria (p

More than 18 million people in 188 countries have been diagnosed as having coronavirus disease (COVID-19), and COVID-19 has been responsible for more than 600,000 deaths worldwide. Brazil is now the second most affected country globally. Faced with this scenario, various public health measures and changes in the daily routines of hospitals were implemented to stop the pandemic. Patients with hepatocellular carcinoma (HCC) are at an increased risk for severe COVID-19 as they present with two major diseases: cancer and concomitant chronic liver disease. The COVID-19 pandemic can significantly impact the management of HCC patients from diagnosis to treatment strategies. These patients need special attention and assistance at this time, especially since treatment for tumors cannot be delayed in most cases. The aim of this guideline was to standardize the management of HCC patients during the COVID-19 pandemic. This document was developed, on the basis of the best evidence available, by a multidisciplinary team from Instituto do Caˆncer do Estado de Sa˜o Paulo (ICESP), and Instituto Central of the Hospital das Clı´nicas da Universidade de Sa˜o Paulo (HC-FMUSP), which are members of the Sa˜o Paulo Clı´nicas Liver Cancer Group.

This study aimed to compare liver transplantation (LT) outcomes and evaluate the potential rise in numbers of LT candidates with hepatocellular carcinoma (HCC) of different allocation policies in a high waitlist mortality region. Three policies were applied in two Latin American cohorts (1085 HCC transplanted patients and 917 listed patients for HCC): (i) Milan criteria with expansion according to UCSF downstaging (UCSF-DS), (ii) the AFP score, and (iii) restrictive policy or Double Eligibility Criteria (DEC; within Milan + AFP score ≤2). Increase in HCC patient numbers was evaluated in an Argentinian prospective validation set (INCUCAI; NCT03775863). Expansion criteria in policy A showed that UCSF-DS [28.4% (CI 12.8-56.2)] or "all-comers" [32.9% (CI 11.9-71.3)] had higher 5-year recurrence rates compared to Milan, with 10.9% increase in HCC patients for LT. The policy B showed lower recurrence rates for AFP scores ≤2 points, even expanding beyond Milan criteria, with a 3.3% increase. Patients within DEC had lower 5-year recurrence rates compared with those beyond DEC [13.3% (CI 10.1-17.3) vs 24.2% (CI 17.4-33.1; P = 0.0006], without significant HCC expansion. In conclusion, although the application of a stricter policy may optimize the selection process, this restrictive policy may lead to ethical concerns in organ allocation (NCT03775863).

Background Before the targeted therapies era, cytotoxic chemotherapy (CCT) was an option for advanced hepatocellular carcinoma (HCC), even with the lack of supporting evidence. Since the last decade, sorafenib has been established as the first-line therapy. Although new agents are being incorporated, CCT is still considered in regions where new drugs are not available or for patients who progressed through the approved therapies and remain in good clinical condition. We aimed to describe our experience regarding the use of CCT as second-line treatment after sorafenib. Methods A database of 273 patients was evaluated. Patients that received CCT after sorafenib progression were selected for the analysis. Descriptive statistics was used for categorical and continue variables. Median survival was estimated with Kaplan-Meier curves. Variables were found to be significant if the two-sided p value was ≤ 0.05 on multivariate testing using the Cox regression model. Results Forty-five patients received CCT; 33 (73.3%) had Child-Pugh classification A, and 34 (75.6%) had stage C according to the Barcelona Clinic Liver Cancer (BCLC) staging system. The most used regimen was doxorubicin in 25 patients (55.6%). Median overall survival (OS) was 8.05 months (95% confidence interval [CI] 2.73 – 9.88 months). The 6-month and 1-year survival probability was 52.4% and 27.36%, respectively. Eastern Cooperative Oncology Group performance status (ECOG PS) 0–1 and disease control with sorafenib was independently associated with better OS in patients treated with CCT. Any-grade toxicities were observed in 82.2% and grade 3–4 in 44.4% of the patients. Conclusion In accordance with previous studies, CCT had a notable rate of adverse events. The poor prognosis of this cohort suggests that CCT may not alter the natural history of HCC after sorafenib progression.

Background: Hepatocellular carcinoma (HCC) is one of the main indications for liver transplantation (LT). Bridge therapy (BT) is recommended when waiting time on transplant list is longer than six months to avoid tumor progression and dropout. Response to locoregional treatment has been considered as a good prognostic parameter in post-LT, however, its role still needs to be defined. Aims: To evaluate the role of BT for HCC on survival and post-LT tumor recurrence. Methods: Brazilian multicenter retrospective cohort study in HCC patients submitted to LT with clinical and radiological data analysis. Data related to HCC pre-LT treatment, type of treatment and the final response according to mRECIST criteria in the last pre-LT image exam were analyzed. Survival curves were presented using the Kaplan-Meier and compared using the log-rank test. Results: 1,119 patients were included. 81% were males and mean age at LT was 58 ± 8.2 years. At HCC diagnosis, 85% were within Milan criteria (MC) by imaging studies and 67%, underwent BT prior to LT. TACE/TAE were performed in 80%, PEI 9%, RFA 3%, surgery 1% and combined therapy 7%. According to mRECIST, 37% showed complete response (CR), 38% partial response (PR), 12% stable disease (SD) and 13% progressive disease (PD) after BT. The overall survival (OS) was 63% in 5 years, with a mean follow-up of 28 months. The post-LT tumor recurrence was 8%. There was no difference in the risk of post-LT tumor recurrence or survival among patients who underwent BT or not or between the various types of treatment performed. However, patients who have CR to BT had a higher recurrence-free survival compared to patients with PR, SD or PD (p = 0.019). Conclusions: This study demonstrated the role of BT in LT, since patients with complete response, had a lower risk of post-transplant tumor recurrence.

Aims The scirrhous variant of hepatocellular carcinoma (S-HCC) and fibrolamellar HCC (FL-HCC) are less common subtypes of HCC that are characterized by abundant fibrous stroma. Here, we aimed to investigate differences in the tumour microenvironment and the tumour epithelial cell characteristics of S-HCC and FL-HCC. Methods and results Whole tissue sections of 17 S-HCCs and 9 FL-HCCs were subjected to immunohistochemical stains for keratin 7 (K7), K19, EpCAM, CD56/NCAM, CD163, CD68, pSTAT3, FAP, CCN2 and Ki-67. FL-HCC patients were younger than S-HCC patients (P < 0.001), and chronic liver disease was seen in the background of 88.2% of S-HCC and in none of the FL-HCC. CD68 and CD163-positive tumour-infiltrating macrophages, and FAP-positive cancer-associated fibroblasts (CAFs) were more abundant in the stroma of S-HCCs compared to FL-HCCs (all P < 0.05). Tumour epithelial K19 expression was more frequent in S-HCCs compared to FL-HCCs (P = 0.023). Significant positive correlations were seen between pSTAT3 expression status in tumour epithelial cells and CAFs, the extent of stromal CAF and macrophage infiltration and K19 expression status. No significant differences were seen for K7, EpCAM, CD56/NCAM, CCN2 expression and Ki-67 labelling index between S-HCCs and FL-HCCs. Conclusion S-HCC and FL-HCC are subtypes of HCC with extensive fibrosis, and the nature of the fibrous stroma differs between them. While the stroma of FL-HCC is composed of dense lamellated collagenous bands with sparse cellular components, S-HCC demonstrates more abundant CAF and tumour-infiltrating macrophages and stemness-related marker expression, suggesting the presence of a complex tumour microenvironment that may influence the aggressive behaviour of S-HCCs.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2015 its first recommendations about the management of HCC. Since then, new data have emerged in the literature, prompting the governing board of SBH to sponsor a single-topic meeting in August 2018 in São Paulo. All the invited experts were asked to make a systematic review of the literature reviewing the management of HCC in subjects with cirrhosis. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of updated recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present manuscript is the final version of the reviewed manuscript containing the recommendations of SBH. RESUMO O carcinoma hepatocelular (CHC) é uma das principais causas de mortalidade relacionada a câncer no Brasil e no mundo. A Sociedade Brasileira de Hepatologia (SBH) publicou em 2015 suas primeiras recomendações sobre a abordagem do CHC. Desde então, novas evidências sobre o diagnóstico e tratamento do CHC foram relatadas na literatura médica, levando a diretoria da SBH a promover uma reunião monotemática sobre câncer primário de fígado em agosto de 2018 com o intuito de atualizar as recomendações sobre o manejo da neoplasia. Um grupo de experts foi convidado para realizar uma revisão sistemática da literatura e apresentar uma atualização baseada em evidências científicas visando que pudesse nortear a prática clínica multidisciplinar do CHC. O texto resultante foi submetido a avaliação e aprovação de todos membros da SBH através de sua homepage. O documento atual é a versão final que contêm as recomendações atualizadas e revisadas da SBH.

Over 38,000 cases of hepatocellular carcinoma (HCC) are estimated to occur in Latin America annually. The region is characterized by sociocultural heterogeneity and economic disparities, which impose barriers in addressing this major health issue. A significant proportion of patients are still diagnosed in the later stages of the disease, although efforts to implement effective screening programs have been reported by referral centers. While viral hepatitis remains the predominant etiology of liver disease among HCC cases in Latin America, a high prevalence of fatty liver disease in the region is a matter of concern, reflecting the current scenario in many Western countries. In addition, other risk factors such as alcohol, aflatoxin, and early-onset HCC in hepatitis B virus infection contribute to the burden of HCC in Latin America. Interventions to increase screening coverage, expand healthcare access, and implement continuing medical training are key challenges to be overcome.

As doenças do fígado e das vias biliares são causas comuns de morbidade e mortalidade. Procedimentos invasivos com finalidade diagnóstica e terapêutica são frequentemente recomendados nos casos de doenças hepatobiliares. O reconhecimento das indicações e limitações das técnicas comumente empregadas é crucial para uma adequada seleção dos pacientes, maximizando os resultados positivos e reduzindo o risco de complicações. Em 2018, a Sociedade Brasileira de Hepatologia (SBH), em colaboração com a Sociedade Brasileira de Radiologia Intervencionista e Cirurgia Endovascular (SOBRICE) e a Sociedade Brasileira de Endoscopia Digestiva (SOBED) realizaram um encontro exclusivamente voltado para a discussão dos procedimentos invasivos nas doenças hepatobiliares. Este texto resume as principais recomendações discutidas durante o evento, e tem a intenção de auxiliar clínicos, gastroenterologistas, hepatologistas, radiologistas e endoscopistas no uso adequado dos procedimentos invasivos para manejo de pacientes com doenças hepatobiliares. Liver and biliary tract diseases are common causes of morbidity and mortality worldwide. Invasive procedures are usually performed in those patients with hepatobiliary diseases for both diagnostic and therapeutic purposes. Defining proper indications and restraints of commonly used techniques is crucial for proper patient selection, maximizing positive results and limiting complications. In 2018, the Brazilian Society of Hepato­logy (SBH) in cooperation with the Brazilian Society of Interventional Radiology and Endovascular surgery (SOBRICE) and the Brazilian Society of Digestive Endoscopy (SOBED) sponsored a joint single-topic meeting on invasive procedures in patients with hepatobiliary diseases. This paper summarizes the proceedings of the aforementioned meeting. It is intended to guide clinicians, gastroenterologists, hepatologists, radiologists, and endoscopists for the proper use of invasive procedures for management of patients with hepatobiliary diseases.

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) has emerged as an important cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC). The Barcelona Clinic Liver Cancer (BCLC) system is the preferred staging system to evaluate patients with HCC and links prognosis assessment with treatment recommendation. The aim of this retrospective study was to evaluate whether the BCLC staging system and its treatment algorithm are suitable for patients with HCC arising from NAFLD. Methods: Forty-two patients with HCC related to either to NAFLD or cryptogenic cirrhosis were retrieved retrospectively from 2 centers in Brazil. Patients were classified according to BCLC staging system. If the proposed HCC therapy could not be applied, the case was considered to represent deviations from the recommended BCLC guideline. Causes of treatment deviations were investigated. Results: There were 4 patients without evidence of cirrhosis according to liver biopsy and/or clinical evaluation. One (2%), 21 (50%), 10 (24%), 5 (12%), and 5 patients (12%) were classified initially to the very early (0), early (A), intermediate (B), advanced (C), and terminal (D) BCLC stages, respectively. Thirty-five patients (83%) were treated according to BCLC recommendations. There were 3 cases (of 5) of protocol deviation in BCLC C patients. The 1- and 2-year overall survival rates were 81% and 66%, respectively. Conclusions: The BCLC system is applied in most cases of NAFLDrelated HCC cases. Deviation of BCLC is found more frequently in BCLC C stage patients.

Background Hepatitis C virus (HCV) infection is often persistent and gradually advances from chronic hepatitis to liver cirrhosis and hepatocellular carcinoma (HCC). Worldwide, hepatocellular carcinoma is the fifth most common neoplasm. Method of study the Interferon lambda (IFNL) polymorphisms genotypes (rs8099917, rs12979860 and rs12980275) and the presence of mutations in HCV core protein were analyzed in 59 patients with HCC, and also in 50 cirrhotic patients (without HCC). Results the rs12980275-AG genotype was associated with HCC on age-adjusted analysis (OR 2.42, 95% CI 1.03-5.69, P=0.043). Core substitutions R70Q and L91M were mainly found in genotype 1b isolates. Furthermore, a borderline level of statistical significance association was found among the presence of amino acid Glutamine (Q) in the position 70 and IFNL3 genotype AG (P=0.054). Conclusions the screening of these polymorphisms and functional studies would be useful in clinical practice for identifying groups at high risk of HCC development.

The original version of this article unfortunately contained a mistake in the author group section.

Currently, there is no consensus in the literature regarding the screening of hepatic nodules in patients who have undergone the Fontan procedure. The objectives of this study are to evaluate in this population the frequency of hepatic nodules at ultrasound (US), CT, and MRI; to measure liver stiffness using acoustic radiation force impulse (ARFI) elastography; and to investigate predictive factors for hepatic nodules.In this cross-sectional study, 49 patients who underwent the Fontan procedure were prospectively recruited from August 2014 through June 2016. These patients underwent clinical evaluation for hepatic disorders, ARFI elastography, US, CT, and MRI.Most of the patients had no symptoms, and hepatic nodules were detected in three of 49 (6.1%) patients at US, 14 of 44 (31.8%) patients at CT, and 19 of 48 (39.6%) patients at MRI. Liver stiffness at ARFI elastography was significantly higher in patients with hepatic nodules than in patients without such nodules (2.64 ± 0.81 m/s vs 1.94 ± 0.49 m/s; p = 0.002) and was a significant predictor of hepatic nodule (AUC, 0.767; p = 0.002). No clinical or laboratory data had any significant correlation with the existence of hepatic nodules, including time since Fontan procedure.In our study, more than one-third of patients had hepatic nodules at CT or MRI, but US did not detect most hepatic nodules. Liver stiffness at ARFI elastography was significantly higher in patients with hepatic nodules, and it may help guiding which patient should be further imaged with CT or MRI.

INTRODUÇÃO: O transplante (TX) de fígado corresponde ao tratamento de escolha em pacientes com cirrose e carcinoma hepatocelular (CHC) precoce irressecável. A recidiva do CHC pós-transplante, entretanto, ainda apresenta impacto na sobrevida dos pacientes transplantados com este tumor. As taxas de recidiva, nos estudos mais recentes, variam de 8 a 20%. O tamanho e número de nódulos, a presença de invasão vascular e de nódulos satélites no explante, são fatores de risco relacionados à recidiva tumoral pós-transplante. No Brasil, observamos um crescimento importante do número de transplantes de fígado, inclusive por CHC. Entretanto, existem poucos estudos nacionais analisando os resultados do transplante hepático por CHC. Os objetivos do nosso estudo foram analisar as características demográficas, clínicas e a evolução dos pacientes submetidos a transplante hepático com CHC no Brasil, avaliando os fatores prognósticos relacionados com a recidiva do CHC pós-transplante e sobrevida e estudar o desempenho dos critérios de seleção para transplante utilizados no nosso país, os \"Critérios de Milão Brasil\" (CMB). MÉTODOS: Estudo de coorte retrospectivo, multicêntrico, para analisar os resultados do transplante de fígado em pacientes com CHC, após a implantação do sistema MELD. Foram incluídos 1.119 pacientes transplantados com CHC, de 07/2006 até 07/2015, em 13 centros de transplante, no Brasil. Características clínicas, demográficas, exames laboratoriais e de imagem e dados anatomopatológicos, foram retrospectivamente analisados e correlacionados com a sobrevida e recidiva do CHC pós-transplante. RESULTADOS: A maioria dos pacientes era do sexo masculino (81%), com uma idade média no TX de 58 anos. A etiologia mais associada ao tumor foi a Hepatite C (VHC), presente em 60% dos casos. O tempo médio de espera em lista foi de 9,8 meses. Setenta e oito pacientes (8%) foram incluídos por \"Down-staging\". Nos exames de imagem do diagnóstico, a maioria dos casos (67%) apresentava um nódulo, com tamanho médio de 30 mm; 85% estavam dentro dos Critérios de Milão (CM), 8% fora dos CM, mas dentro dos \"Critérios de Milão Brasil\" (CMB) e 7% fora de ambos os critérios. O tratamento do CHC em lista foi realizado em 67% dos pacientes. Na análise do explante, 44% apresentavam tumor uninodular, com tamanho médio de 26 mm e a maioria (71%) tinha CHC moderadamente diferenciado. A invasão vascular foi observada em 26% dos casos e nódulos satélites em 22%. No explante, 70% dos pacientes estavam dentro dos CM, 20,5% fora dos CM, mas dentro dos CMB e 9,5%fora de ambos os critérios. A sobrevida global foi de 79% em 1 ano, 72,5% em 3 anos e 63%, em 5 anos, com um tempo médio de seguimento de 28 meses. Excluindo os pacientes que foram a óbito no pós-operatório ( < 30 dias pós-transplante), a sobrevida global foi de 89% em 1 ano e 75%, em 5 anos. A recidiva do CHC pós-TX ocorreu em 8% (86/1.119) dos casos, em um tempo médio de 12 meses. A sobrevida livre de recidiva (SLR) foi de 94,4% em 1 ano e 88,3%, em 5 anos. A recidiva do CHC foi extra-hepática em 55% dos casos, hepática em 27% e hepática e extra-hepática em 18%. Os pacientes transplantados que evoluíram com recidiva tumoral apresentaram alta mortalidade, com uma sobrevida em 1 ano de 34% e em 5 anos de 13%. Em relação aos fatores prognósticos, os pacientes transplantados dentro dos Critérios de Milão apresentaram melhor sobrevida e SLR quando comparados aos pacientes transplantados fora dos CM, mas dentro dos CMB, tanto quando analisamos os dados do diagnóstico, quanto através da análise do explante. Os pacientes transplantados após realização de \"Down-staging\" apresentaram taxas de recidiva e sobrevida semelhantes aos pacientes transplantados sem \"Down-staging\". Os níveis séricos elevados de alfa-fetoproteína (AFP) foram um fator prognóstico importante de sobrevida e recidiva tumoral. Os melhores pontos de corte de AFP encontrados para avaliação do risco de recidiva e sobrevida foram: AFP > 400 ng/ml, no momento do diagnóstico e AFP > 200 ng/ml pré-transplante. Realizamos, também, uma comparação dos \"Critérios de Milão Brasil\" com os Critérios de Milão, através do índice IDI (Integrated Discrimination Index) e os CMB apresentaram performance inferior aos CM, na capacidade de classificar corretamente os pacientes em relação ao risco de recidiva tumoral. Os níveis séricos elevados de AFP, o estádio fora dos Critérios de Milão no momento do diagnóstico e no explante e a presença e invasão vascular no explante, foram fatores de risco independentes de recidiva do CHC pós-transplante e pior sobrevida. A idade > 60 anos e a etiologia da hepatopatia (VHC), também foram fatores prognósticos negativos de sobrevida. CONCLUSÕES: A presença de recidiva tumoral teve grande impacto na sobrevida do paciente transplantado com CHC. O estadiamento tumoral no diagnóstico e no explante, avaliado através dos Critérios de Milão, os níveis séricos elevados de AFP e a presença de invasão vascular no explante foram fatores prognósticos importantes de recidiva do CHC pós-transplante e sobrevida. Os pacientes transplantados após \"Down-staging\" apresentaram evolução pós-transplante semelhante a dos pacientes transplantados sem \"Down-staging\". Os pacientes transplantados fora dos CM, mas dentro dos CMB, apresentaram pior sobrevida, quando comparados aos pacientes dentro dos CM. Os CMB apresentaram desempenho inferior aos CM na capacidade de classificar corretamente os pacientes em relação ao risco de recidiva tumoral INTRODUCTION: Liver transplantation (LT) is the treatment of choice for patients with cirrhosis and unresectable early hepatocellular carcinoma (HCC). HCC post-transplant recurrence, however, still has an impact on survival. In recent studies, the incidence of HCC recurrence after transplantation ranged from 8% to 20%. Tumor number, size, vascular invasion and satellite nodules have emerged as risk factors for HCC recurrence. In Brazil, in the last decade, we observed a significant increase in the number of liver transplants performed, including in patients with HCC. However, there are few national studies analyzing the results of liver transplantation for HCC. The aim of this multicentric study was to analyze the demographic characteristics, clinical features and outcomes of patients submitted to liver transplantation with HCC in Brazil, evaluate prognostic factors related to HCC post-transplant recurrence and survival, and study the performance of the national selection criteria for liver transplantation, the \"Brazilian Milan Criteria\" (BMC). METHODS: We conducted a national, multicentric, retrospective study to analyze the results of liver transplantation in patients with HCC, in \"MELD era\". Medical records of 1,119 transplanted patients with HCC between 07/2006 and 07/2015, from 13 transplant centers in Brazil, were collected. Patient and tumor characteristics, radiologic and pathologic data were retrospectively analyzed and correlated with post-transplant HCC recurrence and survival. RESULTS: Of the 1,119 HCC transplanted patients, median age was 57 years and 81% were male. Etiology of liver disease was HCV in 60%. Median time on transplant list was 9.8 months. Seventy-eight patients (8%) were included after \"Down-staging\". At diagnosis, most patients had uninodular HCC (67%) and median tumor burden was 30 mm. At diagnosis, in imaging studies, 85% of patients were within the Milan criteria (MC), 8% out of the MC but within the \"Brazilian Milan Criteria\" (BMC) and 6% out of both criteria. During the waiting list period, HCC treatment was performed in 67%. In explant analysis, tumor was uninodular in 46% and moderately differentiated in the majority of cases (71%). Median HCC size was 26 mm. Vascular invasion and satellite nodules were observed in 26% and 22% of patients, respectively. In explant, 70% of patients were within Milan Criteria, 20.5% outside MC but within BMC and 9.5% out of both criteria. Mean follow-up was 28 months, an overall survival was 79% in 1 year, 72.5% in 3 years and 63% in 5 years. Excluding patients who died within 30 days after surgery, overall survival was 89% in 1 year and 75% in 5 years. HCC post-transplant recurrence occurred in 86/1,119 (8%) cases, at a mean time of 12 months. Recurrence-free survival (RFS) was 94.4% in 1 year and 88.3% in 5 years. Sites of recurrence were extrahepatic in 55%, hepatic in 27% and both hepatic and extrahepatic in 18%. Transplanted patients with tumor recurrence presented high mortality, with 1-year survival rate of 34% and 5-year survival rate of 13%. Analyzing the prognostic factors, patients transplanted under Milan Criteria, in radiologic or explant analysis, presented better survival and RFS when compared to patients transplanted outside MC, but within BMC. Patients submitted to liver transplantation after \"Down-staging\" present long-term survival and RFS similar to patients transplanted without \"Down-staging\". Alpha-fetoprotein (AFP) levels were an important pre-transplant prognostic factor for tumor survival and recurrence. The best AFP cut off points found for relapse risk and survival assessment were: AFP at diagnosis > 400 ng / ml and AFP pre-transplant > 200 ng / ml. We also performed a comparison of the \"Brazilian Milan Criteria\" with the Milan Criteria through the Integrated Discrimination Index (IDI). The BMC presented a lower performance than the MC, in the ability to correctly classify patients in relation to the risk of relapse. Elevated AFP levels before liver transplantation, tumor outside Milan Criteria at diagnosis and in explant, and vascular invasion, were independent risk factors for post-transplant HCC recurrence and worse survival. Age > 60 years and etiology of liver disease (HCV), were also negative prognostic factors for survival. CONCLUSIONS: The presence of tumor recurrence had a major impact on survival of transplanted patients with HCC. Tumor staging, evaluated by Milan Criteria on imaging studies or explant analysis, high serum AFP levels and presence of vascular invasion in explant were important prognostic factors for post-transplant HCC recurrence and survival. Patients transplanted after Down-staging presented long-term outcomes similar to patients transplanted under conventional criteria. Patients transplanted outside Milan Criteria, but within \"Brazilian Milan Criteria\" presented worse survival, when compared to patients within MC. The BMC showed lower performance than MC in the ability to correctly classify patients in relation to the risk of tumor recurrence

Introduction: Sorafenib is an orally active multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma (HCC) and is the only systemic treatment associated with a survival benefit in advanced stage. The aims of this study were to evaluate the tolerance and survival of sorafenib-treated patients, and to identify potential prognostic factors of survival. Methods: A total of 88 HCC patients treated with sorafenib from June 2010 to January 2014 were retrospectively reviewed. Tumour stage, liver function and adverse events to sorafenib were analyzed. Univariate and multivariate analysis were carried out to identify predictors of survival in patients with advanced HCC treated with sorafenib. Results: There were 64 (73%) males included in this study, with a median age of 61.16 years. Eight (91%) patients had Child-Pugh class A cirrhosis. Most patients were classified as BCLC C (82%). Hepatitis C virus was the predominant cause of HCC (68%). Sorafenib was the initial treatment modality in 43%. Median time of sorafenib therapy was 8.23 months. Overall survival in 1 year was 57.3% and 36.7% in 2 years. The median survival was 16.3 months. In the univariate analysis of the OS based on Child-Pugh score did not demonstrate a significant difference in our study (p = 0.62). The presence of dermatologic adverse event predicted a better overall survival in the multivariate analysis. Better survival was also observed in patients with AFP level Even in the presence of adverse events, the use of sorafenib should be continued because the longer usage time improves survival.

Background and Aims: Schistosomiasis is a major chronic disease of humans in endemic regions, and infected individuals may develop a spectrum of pathology, including hepatic fibrosis, hepatosplenomegaly, and portal hypertension. Hepatocellular carcinoma (HCC) is considered the fifth most common cancer in the world, and there is limited and controversial evidence suggesting that Schistosoma mansoni infection may be a possible risk factor for HCC. The aim of this study was to report a case series of patients with HCC and S. mansoni infection and to conduct a literature review on the topic. Methods: From January 2002 to January 2015, an institutional database was screened retrospectively to identify patients with HCC and S. mansoni infection at a single center in the Department of Gastroenterology of University of São Paulo School of Medicine and Hospital das Clínicas, Brazil. Results: Seven cases were included. The mean age of patients was 62.1±10.3 years; six (85.7%) were male and one (14.3%) was female. All cases had positive epidemiology, coming from endemic areas of S. mansoni infection in Brazil, and four (57.1%) had previous complications (upper gastrointestinal bleeding) related to portal hypertension or surgery intervention (splenectomy) performed more than 10 years before the HCC diagnosis. Nontumoral portal vein thrombosis was identified in five (71.4%) patients. All patients had negative serology for HCV, and four (57.1%) had positivity of HBVcore antibodies without evidence of viral replication. According to BCLC staging, one (14.3%) patient was BCLC A and received TACE instead of RFA because HCC size was >30 mm; three (42.8%) BCLC B patients received sorafenib instead of local regional treatment due to the presence of nontumoral TPV. During follow-up, all patients developed tumoral progression and died. Conclusions: It remains unclear if S. mansoni infection alone has carcinogenic potential. The available literature indicates that S. Mansoni, in the presence of HBV and HCV infections, likely acts as a cofactor for the hepatic lesion and potentiates injury.

Introduction: Transarterial chemoembolization (TACE) reduces tumor growth and increases survival in patients with hepatocellular carcinoma (HCC). Drug-eluting beads (DEB) deliver slow-release chemotherapy and reduce systemic toxicity during TACE. This study correlated initial tumor response according to modified RECIST (mRECIST) criteria and 1-year survival in patients with HCC treated with TACE-DEB, and identified predictors of tumor response. Methods: Fifty-two patients with HCC received TACE-DEB loaded with doxorubicin 75 mg during a 6-month period. Tumor response was evaluated 1 month after the procedure according to mRECIST criteria. Results: Most patients were cirrhotic and etiology of liver disease was hepatitis C in 26/52 (50%). Similar numbers of patients had Barcelona Clinic Liver Cancer (BCLC) A and BCLC B disease. Most patients had one nodule (66%). Complete response (CR) was achieved in 12/52 (23%), partial response in 19/52 (37%), stable disease in 4/52 (8%) and progressive disease in 17/52 (32%). Largest HCC ≤58 mm and BCLC stage A were associated with CR. The 1-year survival was 74%, with survival rates of 95% and 56% in the BCLC A and B groups, respectively. Variables reflecting tumor extension were associated with better survival. CR according to mRECIST criteria was a predictor of better 1-year survival (100% vs. 64%, P studies are needed to evaluate other predictors of survival and to determine if tumor response predicts long-term survival.

BACKGROUND Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare disease with an indolent behavior. Its prognosis is better than that of patients with hepatocellular carcinoma. The authors present their experience with resection of FLHCC. METHODS Twenty-one patients with FLHCC were treated at our institution between 1990 and 2012. Of these patients, 14 were subjected to resection of the tumor. Patient demographics, medical history, results of imaging studies and laboratory tests, surgical data, and pathologic findings were evaluated. RESULTS The median age of the patients at the diagnosis of the tumor was 20 years and 14 patients were female. None of the patients had tumor-associated chronic liver disease or cirrhosis. The mean tumor size was 12.8 cm (range 6-19) and 18 patients had a single liver nodule. Fourteen patients were subjected to hepatectomy and six of them had lymph node metastases resected. Pathologic evaluation revealed that 5 (35.7%) patients had major vascular invasion. Tumor recurrence was seen in 8 patients (66.7%), during a follow-up. The median survival time for patients who were subjected to resection was 36 months. The 5-year overall survival rate and disease free survival rate were 28.0% and 8.5%, respectively. Univariate analysis showed that vascular invasion was the only variable associated with the disease free survival rate. CONCLUSIONS Despite an aggressive treatment, patients with FLHCC presented unexpected low survival rates. It seems that an underestimated malignant behavior is attributed to this disease, and that the forms of adjuvant treatment should be urgently evaluated. (Hepatobiliary Pancreat Dis Int 2014;13:618-621)

To evaluate outcomes of radiofrequency ablation (RFA) therapy for early hepatocellular carcinoma (HCC) and identify survival- and recurrence-related factors.Consecutive patients diagnosed with early HCC by computed tomography (CT) or magnetic resonance imaging (MRI) (single nodule of ≤ 5 cm, or multi- (up to 3) nodules of ≤ 3 cm each) and who underwent RFA treatment with curative intent between January 2010 and August 2011 at the Instituto do Câncer do Estado de São Paulo, Brazil were enrolled in the study. RFA of the liver tumors (with 1.0 cm ablative margin) was carried out under CT-fluoro scan and ultrasonic image guidance of the percutaneous ablation probes. Procedure-related complications were recorded. At 1-mo post-RFA and 3-mo intervals thereafter, CT and MRI were performed to assess outcomes of complete response (absence of enhancing tissue at the tumor site) or incomplete response (enhancing tissue remaining at the tumor site). Overall survival and disease-free survival rates were estimated by the Kaplan-Meier method and compared by the log rank test or simple Cox regression. The effect of risk factors on survival was assessed by the Cox proportional hazard model.A total of 38 RFA sessions were performed during the study period on 34 patients (age in years: mean, 63 and range, 49-84). The mean follow-up time was 22 mo (range, 1-33). The study population showed predominance of male sex (76%), less severe liver disease (Child-Pugh A, n = 26; Child-Pugh B, n = 8), and single tumor (65%). The maximum tumor diameters ranged from 10 to 50 mm (median, 26 mm). The initial (immediately post-procedure) rate of RFA-induced complete tumor necrosis was 90%. The probability of achieving complete response was significantly greater in patients with a single nodule (vs patients with multi-nodules, P = 0.04). Two patients experienced major complications, including acute pulmonary edema (resolved with intervention) and intestinal perforation (led to death). The 1- and 2-year overall survival rates were 82% and 71%, respectively. Sex, tumor size, initial response, and recurrence status influenced survival, but did not reach the threshold of statistical significance. Child-Pugh class and the model for end-stage liver disease score were identified as predictors of survival by simple Cox regression, but only Child-Pugh class showed a statistically significant association to survival in multiple Cox regression analysis (HR = 15; 95%CI: 3-76 mo; P = 0.001). The 1- and 2-year cumulative disease-free survival rates were 65% and 36%, respectively.RFA is an effective therapy for local tumor control of early HCC, and patients with preserved liver function are the best candidates.

Background and aim Transarterial chemoembolization (TACE) or sorafenib is recommended for hepatocellular carcinoma BCLC stages B and C respectively. We studied the role of combination of TACE and sorafenib in BCLC stages B/C. Material and methods We undertook an observational study on a cohort of cirrhotics with HCC from August 2010 through October 2014. Patients in BCLC stages B/C who had received TACE and/or sorafenib were included. mRECIST criteria were used to assess tumor response. The primary end point was overall survival. Results Out of 124 patients, 47.6% were in BCLC-B and 52.4% in BCLCC. Baseline characteristics were comparable. The predominant etiology was cryptogenic (37.2% and 38.5%, p = NS). 49.1% in BCLC-B and 56.9% in BCLC-C had received TACE+sorafenib. In BCLC-B, the overall survival improved from 9 months (95% CI 6.3-11.7) using TACE only to 16 months (95% CI 12.9-19.1) using TACE+sorafenib (p l 0.05). In BCLC-C, addition of TACE to sorafenib improved the overall survival from 4 months (95%CI 3-5) to 9 months (95%CI 6.8-11.2) (p l 0.0001). As per mRECIST criteria, patients on TACE+sorafenib had reduced progressive disease (37.8% vs. 83.3%), improved partial response (43.2% vs. 3.3%) and one had complete response compared to those on sorafenib alone (p l 0.0001) in BCLC-C but not in BCLC-B group. Hand foot syndrome was noted in 27.7% patients on sorafenib and post TACE syndrome in 80.2% patients, but both were reversible. No major adverse events were noted. Conclusion TACE+sorafenib was more effective than TACE or sorafenib alone in HCC BCLC stages B or C with a significant survival benefit and improved tumour regression especially in BCLC-C patients.

The global hepatocellular carcinoma (HCC) incidence is widely variable, depending on geographic region and the prevalence of major risk factors. In Brazil, two large multicentre retrospective studies were performed to investigate clinical and epidemiological aspects of HCC. In the first study, performed in 1997, HCC was found in cirrhotic livers in 71% of cases. Chronic alcoholism was present in 36% of cases, chronic hepatitis B in 35% and hepatitis C in 25%. In a 2010 survey, cirrhosis was present in 98% of cases and HCV was the main aetiology (54%). Differences in HBV prevalence were found among regions. Selection of HCC treatment depends on tumour burden, liver function and performance status. Liver transplantation (LT) is the best available curative treatment for HCC in its early stage and with compromised liver function. After modifications in priority policy, the number of patients with early HCC submitted for LT has increased in the past 5 years in Brazil. Chemoembolization is the most common initial HCC therapy in early and intermediate stages of HCC in Brazil.

The aims of this study were to analyze the overall survival of patients with cirrhosis and small hepatocellular carcinoma (HCC) and identify independent pretreatment predictors of survival in Brazil.Between 1998 and 2003, 74 patients with cirrhosis and small HCC were evaluated. Predictors of survival were identified using the Kaplan-Meier survival curves and the Cox model.The overall survival rates were 80%, 41%, and 17% at 12, 36, and 60 months, respectively. The mean length of follow-up after HCC diagnosis was 23 months (median 22 mo, range: 1 to 86 mo) for the entire group. Univariate analysis showed that model for endstage liver disease (MELD) score (P=0.016), Child-Pugh classification (P=0.007), alpha-fetoprotein level (P=0.006), number of nodules (P=0.041), tumor diameter (P=0.009), and vascular invasion (P0.0001) were significant predictors of survival. Cox regression analysis identified vascular invasion (relative risk=14.60, confidence interval 95%=3.3-64.56, P0.001) and tumor size20 mm (relative risk=2.14, confidence interval 95%=1.07-4.2, P=0.030) as independent predictors of decreased survival. Treatment of HCC was related to increased overall survival.Identification of HCC smaller than 20 mm is associated with longer survival. Presence of vascular invasion, even in small tumors, maybe associated with poor prognosis. Treatment of small tumors of up to 20 mm diameter is related to increased survival.