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BACKGROUND: The burden of non-alcoholic fatty liver disease (NAFLD) in South America is among the highest in the world. However, the epidemiology and risk factors for NAFLD are insufficiently described in the region. AIM: To explore the associations between clinical characteristics and histopathological features of NAFLD METHODS: This was a descriptive study of 2722 patients with NAFLD from 8 medical centres across 5 South American countries. We collected clinical, biochemical and histopathological data using a templated chart. Fibrosis was assessed by elastography or fibrosis scores and confirmed with biopsy when available. We examined associations between histopathological features and clinical characteristics with logistic regression models. Models were adjusted for country, age and sex. RESULTS: The median age was 53 years (IQR: 41-62), and 63% were women. Subjects from Brazil had the highest body mass index at 42 kg/m2 . Sixty-seven percent had dyslipidemia, 46% had obesity, 30% had hypertension, 17% had type 2 diabetes mellitus (T2DM) and 34% had metabolic syndrome. Biopsy reports were available for 948 (35%), of which 58% showed fibrosis, 91% steatosis and 65% inflammation; 25% showed significant fibrosis and 27% severe steatosis. Metabolic syndrome, T2DM and hypertension were significantly associated with significant fibrosis (OR = 1.94, p < 0.001; OR = 2.93, p < 0.001 and OR = 1.60, p = 0.003, respectively), severe steatosis (OR = 2.05, p < 0.001; OR = 1.91, p = 0.001 and OR = 2.17, p < 0.001, respectively) and liver inflammation (OR = 1.66, p = 0.007; OR = 2.00, p = 0.002; OR = 1.62, p = 0.001, respectively). CONCLUSIONS: In the largest NAFLD cohort study to date from South America, metabolic syndrome, hypertension and T2DM were independently associated with significant fibrosis, severe steatosis, and inflammation. The prevalence of T2DM was lower than the reported global prevalence.

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BACKGROUND & AIMS: Genetic ancestry or racial differences in health outcomes exist in diseases associated with systemic inflammation (eg, COVID-19). This study aimed to investigate the association of genetic ancestry and race with acute-on-chronic liver failure (ACLF), which is characterized by acute systemic inflammation, multi-organ failure, and high risk of short-term death. METHODS: This prospective cohort study analyzed a comprehensive set of data, including genetic ancestry and race among several others, in 1274 patients with acutely decompensated cirrhosis who were nonelectively admitted to 44 hospitals from 7 Latin American countries. RESULTS: Three hundred ninety-five patients (31.0%) had ACLF of any grade at enrollment. Patients with ACLF had a higher median percentage of Native American genetic ancestry and lower median percentage of European ancestry than patients without ACLF (22.6% vs 12.9% and 53.4% vs 59.6%, respectively). The median percentage of African genetic ancestry was low among patients with ACLF and among those without ACLF. In terms of race, a higher percentage of patients with ACLF than patients without ACLF were Native American and a lower percentage of patients with ACLF than patients without ACLF were European American or African American. In multivariable analyses that adjusted for differences in sociodemographic and clinical characteristics, the odds ratio for ACLF at enrollment was 1.08 (95% CI, 1.03-1.13) with Native American genetic ancestry and 2.57 (95% CI, 1.84-3.58) for Native American race vs European American race CONCLUSIONS: In a large cohort of Latin American patients with acutely decompensated cirrhosis, increasing percentages of Native American ancestry and Native American race were factors independently associated with ACLF at enrollment.

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Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2020 the updated recommendations for the diagnosis and treatment of HCC. Since then, new data have emerged in the literature, including new drugs approved for the systemic treatment of HCC that were not available at the time. The SBH board conducted an online single-topic meeting to discuss and review the recommendations on the systemic treatment of HCC. The invited experts were asked to conduct a systematic review of the literature on each topic related to systemic treatment and to present the summary data and recommendations during the meeting. All panelists gathered together for discussion of the topics and elaboration of the updated recommendations. The present document is the final version of the reviewed manuscript containing the recommendations of SBH and its aim is to assist healthcare professionals, policy-makers, and planners in Brazil and Latin America with systemic treatment decision-making of patients with HCC.

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Cirrhosis is an emerging major cause of the development of hepatocellular carcinoma (HCC), but in non-alcoholic fatty liver disease (NAFLD), up to 50% of patients with HCC had no clinical or histological evidence of cirrhosis. It is currently challenging to propose general recommendations for screening patients with NAFLD without cirrhosis, and each patient should be evaluated on a case-by-case basis based on the profile of specific risk factors identified. For HCC screening in NAFLD, a valid precision-based screening is needed. Currently, when evaluating this population of patients, the use of non-invasive methods can guide the selection of those who should undergo a screening and surveillance program. Hence, the objective of the present study is to review the epidemiology, the pathophysiology, the histopathological aspects, the current recommendations, and novel perspectives in the surveillance of non-cirrhotic NAFLD-related HCC.

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ABSTRACT Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2020 the updated recommendations for the diagnosis and treatment of HCC. Since then, new data have emerged in the literature, including new drugs approved for the systemic treatment of HCC that were not available at the time. The SBH board conducted an online single-topic meeting to discuss and review the recommendations on the systemic treatment of HCC. The invited experts were asked to conduct a systematic review of the literature on each topic related to systemic treatment and to present the summary data and recommendations during the meeting. All panelists gathered together for discussion of the topics and elaboration of the updated recommendations. The present document is the final version of the reviewed manuscript containing the recommendations of SBH and its aim is to assist healthcare professionals, policy-makers, and planners in Brazil and Latin America with systemic treatment decision-making of patients with HCC.

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 2020 a atualização das recomendações da SBH para o diagnóstico e tratamento do CHC. Desde então, novas evidências científicas sobre o tratamento sistêmico do CHC foram relatadas na literatura médica, incluindo novos medicamentos aprovados que não estavam disponíveis na época do último consenso, levando a diretoria da SBH a promover uma reunião monotemática on-line para discutir e rever as recomendações sobre o tratamento sistêmico do CHC. Um grupo de experts foi convidado para realizar uma revisão sistemática da literatura e apresentar uma atualização, baseada em evidências científicas, sobre cada tópico relacionado ao tratamento sistêmico e a apresentar os dados e recomendações resumidas durante a reunião. Todos os painelistas se reuniram para discutir os tópicos e elaborar as recomendações atualizadas. O presente documento é a versão final do manuscrito revisado, contendo as recomendações da SBH, e seu objetivo é auxiliar os profissionais de saúde, formuladores de políticas e planejadores no Brasil e na América Latina na tomada de decisões sobre o tratamento sistêmico de pacientes com CHC.

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Hepatocellular carcinoma (HCC) is among the most common cancers and it is a major cause of cancer-related deaths. Non-alcoholic fatty liver disease (NAFLD) affects approximately one fourth of individuals worldwide and it is becoming one of the most important causes of HCC. The pathogenic mechanisms leading to NAFLD-related HCC are complex and not completely understood. However, metabolic, fibrogenic, oncogenic, inflammatory and immunological pathways seem to be involved. First-line therapy of advanced HCC has recently undergone major changes, since the combination of atezolizumab and bevacizumab was proven to increase survival when compared to sorafenib. Other immune-oncology drugs are also demonstrating promising results in patients with advanced HCC when compared to traditional systemic therapy. However, initial studies raised concerns that the advantages of immunotherapy might depend on the underlying liver disease, which seems to be particularly important in NAFLD-related HCC, as these tumors might not benefit from it. This article will review the mechanisms of NAFLD-related hepatocarcinogenesis, with an emphasis on its immune aspects, the efficacy of traditional systemic therapy for advanced NAFLD-related HCC, and the most recent data on the role of immunotherapy for this specific group of patients, showing that the management of this condition should be individualized and that a general recommendation cannot be made at this time.

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BACKGROUND: Malnutrition, lipodystrophy, and dyslipidemia are prevalent characteristics in patients with human immunodeficiency virus (HIV) infection with or without previous treatment. Such a clinical condition can lead to the hypothesis of the presence of hepatic steatosis with possible progression to fibrosis and the risk of hepatocellular carcinoma. Notably, a low phase angle (PA), evaluated by bioelectrical impedance analysis (BIA), is an independent prognostic marker of clinical progression and survival in HIV-infected patients. AIM: To evaluate the relationship between PA and body composition with steatosis and hepatic fibrosis in HIV/hepatitis C virus (HCV)-coinfected patients. METHODS: A retrospective observational study by convenience sampling of coinfected HIV/HCV patients, in which all patients underwent transient elastography (Fibroscan) and BIA evaluation. Student's t test was used for group comparisons, and Spearman's or Pearson's correlation test was used when appropriate. The significance level was set at 5%, and analyses were performed using SPSS version 21.0. RESULTS: Forty-three patients who received antiretroviral therapy met the inclusion criteria, and 23 (53.5%) were under treatment with protease inhibitors (PIs). There was no difference in PA between those who used PIs and those who did not (P = 0.635). There was no correlation between fibrosis grade and PA (P = 0.355) or lean mass (P = 0.378). There was a significant inverse correlation between the controlled attenuation parameter (CAP) and lean mass (P = 0.378), positive correlation between PA and lean mass (P = 0.378), and negative correlation between PA and fatty mass (P = 0.378), although the CAP and PA were not correlated. When evaluated by sex, no significant correlations were found. CONCLUSION: PA determines the muscle function of HIV/HCV-coinfected patients, and the CAP values reinforce the association with lean mass, suggesting that patients require early nutritional interventions.

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BACKGROUND: To evaluate the performance of a non-invasive test (Fibromax™, Ferring Pharmaceutical, Saint-Prex, Switzerland) and inflamatory markers (IL-1ß, IL-6, IL-8, TNF-α, MCP-1) in the diagnosis and staging of patients with non-alcoholic fatty liver disease. METHODS: Patients older than 18 years with steatosis were prospectively evaluated at a tertiary hospital in southern Brazil. Liver biopsy, Fibromax™ test and inflamatory markers (IL-1ß, IL-6, IL-8, TNF-α, MCP-1) were performed. Measures of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were used, considering liver biopsy as the gold standard. RESULTS: Seventy-three Fibromax™ tests were analyzed. SteatoTest presented a sensitivity of 95.5% and PPV of 97.0% for the diagnosis of steatosis. NashTest obtained a sensitivity of 83.3%, specificity of 37.5%, PPV of 90.9% and NPV of 23.1% for the diagnosis of non-alcoholic steatohepatitis (NASH). FibroTest presented a sensitivity of 38.9%, specificity of 92.7%, PPV of 63.6% and NPV of 82.3% to evaluate advanced fibrosis. In the evaluation of patients with grade 2 and 3 steatosis, ROC analyses showed an area under the curve (AUROC) for SteatoTest of 0.68 (P=0.015). NashTest AUROC was 0.59 (P=0.417) for the evaluation of NASH. FibroTest AUROC was 0.79 (P<0.001) for advanced fibrosis. Kappa coefficient values for SteatoTest, NashTest and FibroTest were not statistically significant. Thirty-seven patients performed also analysis of the inflamatory markers, showing that patients with inflammatory activity grade 2-3 on liver biopsy had significantly higher levels of IL6 (P=0.016) and lower TNF-α (P=0.034), but there was no other difference when analysed fibrosis or steatosis. CONCLUSIONS: The Fibromax™ test and the inflamatory markers (IL-1ß, IL-6, IL-8, TNF-α, MCP-1) did not present a satisfactory performance to be considered a good alternative to replace liver biopsy in the evaluation of non-alcoholic fatty liver disease.

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Introduction and objectives It has been suggested that albumin administration could alter the natural history of cirrhosis, and also, that long-term treatment with albumin might be associated with improvement in survival, control of ascites, reduction in the incidence bacterial infections, renal dysfunction, hepatic encephalopathy (HE) and hyponatremia, as well as reduction in length of hospitalization in patients with cirrhosis and ascites. The objective of the present study is to evaluate the role of albumin in the management of HE. Materiales and methods:: This is a systematic review of randomized controlled trials that evaluated the use of albumin in adult patients with cirrhosis and HE. The search for eligible studies was performed in MEDLINE, EMBASE, and Cochrane CENTRAL databases until June 2020. The outcomes of interest were the complete reversal of HE and mortality. Meta-analysis was performed using the random effects model, through the Mantel-Haenszel method. Results: This systematic review was registered at the PROSPERO platform (CRD42020194181). The search strategy retrieved 1,118 articles. After reviewing titles and abstracts, 24 studies were considered potentially eligible, but 22 were excluded after full-text analysis. Finally, 2 studies were included. In the meta-analysis, albumin was associated to significant lower risks of persistent HE (risk ratio - RR = 0.60; 95% confidence interval - CI = 0.38-0.95, p = 0.03) and mortality (RR = 0.54; 95% CI = 0.33-0.90, p = 0.02). Conclusion: Albumin administration improves HE and reduces mortality in patients with cirrhosis and HE.

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