A new and simple score to predict adequate and deep response to ursodeoxycholic acid in patients with primary biliary cholangitis: the ALP-A score.

BACKGROUND: Ursodeoxycholic acid (UDCA) is the standard treatment for primary biliary cholangitis (PBC), but a significant proportion of patients do not respond adequately, leading to increased risk of adverse outcomes. This study aims to develop a new and straightforward predictive score to identify PBC patients likely to achieve a complete response to UDCA. METHODS: A logistic regression analysis was conducted using a derivation cohort of PBC patients to identify pre-treatment variables associated with response to UDCA. This analysis led to the development of the ALP-A score, calculated as: Age at diagnosis divided by (alkaline phosphatase at diagnosis/upper limit of normal). ALP-A score accuracy was evaluated using the area under the ROC curve, validated with a large external cohort from Brazil. Additionally, the correlation between the ALP-A score and the previously validated UDCA response score (URS) was assessed. RESULTS: ALP-A score had good predictive power for adequate (AUC 0.794; 95% CI, 0.737-0.852) and deep (0.76; 95% CI, 0.69-0.83) UDCA response at 1 year of treatment. A cutoff score of 17 and 23 points was determined to be the optimal threshold for distinguishing adequate and deep responders, respectively, from non-responders. ALP-A score demonstrated a sensitivity of 73%, specificity of 71%, positive predictive value of 65%, negative predictive value of 78%, and overall accuracy of 72% for biochemical response. The URS displayed similar discriminative ability (AUC 0.798; 95% CI, 0.741-0.855). CONCLUSION: ALP-A score performs comparably to URS but offers the great advantage of simplicity for routine clinical use. It serves as a valuable tool to identify PBC patients less likely to respond to UDCA treatment, facilitating early consideration of alternative therapeutic approaches.

BRAZILIAN SOCIETY OF HEPATOLOGY UPDATED RECOMMENDATIONS FOR SYSTEMIC TREATMENT OF HEPATOCELLULAR CARCINOMA.

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.

Risk factors for cancer in patients with primary biliary cholangitis and autoimmune hepatitis and primary biliary cholangitis overlap syndrome.

INTRODUCTION AND OBJECTIVES: Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) and PBC overlap syndrome (AIH/PBC) have been associated with a higher risk of hepatocellular carcinoma (HCC) and extra-hepatic malignancy (EHM). This study aims to assess potential risk factors associated with cancer development in PBC and AIH/PBC. MATERIALS AND METHODS: The Brazilian Cholestasis Study Group database was reviewed to compare clinical and laboratory features of PBC patients with HCC and EHM with those without cancer. RESULTS: Among the 752 PBC patients enrolled, 64 of them with AIH/PBC, 87 cancers were identified in 72 patients, including 20 cases of HCC and 67 of EHM. Patients with HCC had a higher prevalence of cirrhosis (95% vs. 32.5% of those subjects without cancer, p≤0.001), smoking (55% vs. 12.3%, p≤0.001), CREST syndrome (30% vs 7.6%, p=0.003) and prior azathioprine (30% vs 8%, p= 0.005) and prednisone (35% vs 14%, p= 0.018) use, whereas patients with EHM had a higher prevalence of smoking (42.3% vs 12.4% of those subjects without cancer, p= <0.001), AMA positivity (96.6% vs 80.1%, p≤0.001), azathioprine therapy (21% vs 7.9%, p= 0.01) and concurrent other autoimmune diseases. In multivariate analysis, cirrhosis, obesity and prior azathioprine therapy were independent risk factors for HCC, while Sjogren syndrome and psoriasis were associated with EHM. Fibrates reduced EHM risk. CONCLUSIONS: The prevalence of EHM is higher when compared to HCC in PBC patients. Cirrhosis, obesity, prior azathioprine use, and concurrent autoimmune diseases were significantly associated with cancer in PBC.

Atualização das Recomendações da Sociedade Brasileira de Hepatologia para o Tratamento Sistêmico do Carcinoma Hepatocelular / Brazilian society of hepatology updated recommendations for systemic treatment of hepatocellular carcinoma

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.

Response to Ursodeoxycholic Acid May Be Assessed Earlier to Allow Second-Line Therapy in Patients with Unresponsive Primary Biliary Cholangitis.

BACKGROUND: Response to ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) has been traditionally assessed 1 to 2 years after treatment initiation. With the development of new drugs, some patients may benefit from an earlier introduction of second-line therapies. AIMS: This study aims to identify whether well-validated response criteria could correctly identify individuals likely to benefit from add-on second-line therapy at 6 months. METHODS: Analysis of a multicenter retrospective cohort which included only patients with clear-cut PBC. RESULTS: 206 patients with PBC (96.6% women; mean age 54 ± 12 years) were included. Kappa concordance was substantial for Toronto (0.67), Rotterdam (0.65), Paris 1 (0.63) and 2 (0.63) criteria at 6 and 12 months, whereas Barcelona (0.47) and POISE trial (0.59) criteria exhibited moderate agreement. Non-response rates to UDCA was not statistically different when assessed either at 6 or 12 months using Toronto, Rotterdam or Paris 2 criteria. Those differences were even smaller or absent in those subjects with advanced PBC. Mean baseline alkaline phosphatase was 2.73 ± 1.95 times the upper limit of normal (× ULN) among responders versus 5.05 ± 3.08 × ULN in non-responders (p < 0.001). CONCLUSIONS: After 6 months of treatment with UDCA, the absence of response by different criteria could properly identify patients who could benefit from early addition of second-line therapies, especially in patients with advanced disease or high baseline liver enzymes levels.

RISK FACTORS ASSOCIATED WITH FRACTURE OF THE LUMBOSACRAL SPINE AND ITS COMPROMISE IN THE QUALITY OF LIFE OF CIRRHOTICS.

BACKGROUND: Chronic hepatic disease is associated with osteoporosis, osteopenia or osteomalacia. Osteoporosis and fractures due to bone fragility present high prevalences and are more frequent in patients with liver cirrhosis than in the general population. The search for a diagnosis of osteopenia and osteoporosis in this population may allow early intervention and modify unfavorable outcomes. OBJECTIVE: To know the prevalence of osteopenia or osteoporosis and of fracture due to bone fragility in individuals with liver cirrhosis, the associated risk factors, and its compromise in their quality of life (QoL). METHODS: Observational, transversal study performed with 71 liver cirrhosis patients of the Hepatology Service of the Hospital de Base do Distrito Federal, Brasília, DF, Brazil, between July 2017 and December 2018. The patients were submitted to bone densitometry (DXA) of the lumbar spine and of the femoral neck, to x-ray of the lumbosacral spine and to the Chronic Liver Disease Questionnaire (CLDQ) for the evaluation of quality of life (QoL). The Fracture Risk Assessment (FRAX) major was calculated for patients >50 years old. The analyses were performed for the evaluation of the risk factors associated with lumbosacral spine fracture. RESULTS: The majority (62%) of the 71 evaluated patients was diagnosed with osteoporosis or osteopenia on DXA. Of the 44 patients with osteopenia or osteoporosis, 52.3% were female, with a mean age of 62.6±9.51 years old, with the majority (72.7%) being Child A, cirrhotics of alcoholic etiology (36.4%), and with an intermediate QoL according to the CLDQ (3.3). Regarding the patients with lumbosacral spine fracture, the mean age was 61.6±11.1 years old, 60% were female, most of them Child A (66.7%), of alcoholic etiology (46.7%), and with an intermediary QoL according to the CLDQ (3.5). The presence of osteopenia and/or osteoporosis was associated with lumbosacral fracture (P<0.001), without correlation with the other analyzed variables: age, body mass index, gender, presence and absence of ascites, Child-Pugh classification, vitamin D, calcium, and phosphorus serum concentration, cirrhosis etiology and FRAX major. CONCLUSION: The prevalence of hepatic osteodystrophy was high, and the occurrence of lumbosacral spine fracture was more associated with osteoporosis and/or osteopenia among the cirrhotic patients studied. The QoL was intermediate and with no differences between cirrhotics with and without fracture.

Fatores de risco associados à fratura de coluna lombossacra e seu comprometimento na qualidade de vida em cirróticos / Risk factors associated with fracture of the lumbosacral spine and its compromise in the quality of life of cirrhotics

ABSTRACT Background Chronic hepatic disease is associated with osteoporosis, osteopenia or osteomalacia. Osteoporosis and fractures due to bone fragility present high prevalences and are more frequent in patients with liver cirrhosis than in the general population. The search for a diagnosis of osteopenia and osteoporosis in this population may allow early intervention and modify unfavorable outcomes. Objective To know the prevalence of osteopenia or osteoporosis and of fracture due to bone fragility in individuals with liver cirrhosis, the associated risk factors, and its compromise in their quality of life (QoL). Methods Observational, transversal study performed with 71 liver cirrhosis patients of the Hepatology Service of the Hospital de Base do Distrito Federal, Brasília, DF, Brazil, between July 2017 and December 2018. The patients were submitted to bone densitometry (DXA) of the lumbar spine and of the femoral neck, to x-ray of the lumbosacral spine and to the Chronic Liver Disease Questionnaire (CLDQ) for the evaluation of quality of life (QoL). The Fracture Risk Assessment (FRAX) major was calculated for patients >50 years old. The analyses were performed for the evaluation of the risk factors associated with lumbosacral spine fracture. Results The majority (62%) of the 71 evaluated patients was diagnosed with osteoporosis or osteopenia on DXA. Of the 44 patients with osteopenia or osteoporosis, 52.3% were female, with a mean age of 62.6±9.51 years old, with the majority (72.7%) being Child A, cirrhotics of alcoholic etiology (36.4%), and with an intermediate QoL according to the CLDQ (3.3). Regarding the patients with lumbosacral spine fracture, the mean age was 61.6±11.1 years old, 60% were female, most of them Child A (66.7%), of alcoholic etiology (46.7%), and with an intermediary QoL according to the CLDQ (3.5). The presence of osteopenia and/or osteoporosis was associated with lumbosacral fracture (P<0.001), without correlation with the other analyzed variables: age, body mass index, gender, presence and absence of ascites, Child-Pugh classification, vitamin D, calcium, and phosphorus serum concentration, cirrhosis etiology and FRAX major. Conclusion The prevalence of hepatic osteodystrophy was high, and the occurrence of lumbosacral spine fracture was more associated with osteoporosis and/or osteopenia among the cirrhotic patients studied. The QoL was intermediate and with no differences between cirrhotics with and without fracture.

RESUMO Contexto A doença hepática crônica associa-se com osteoporose, osteopenia ou osteomalácia. A osteoporose e as fraturas por fragilidade óssea têm altas prevalências e são mais frequentes em pacientes com cirrose hepática do que na população geral. A busca por osteopenia e osteoporose nesta população pode permitir a intervenção precoce e modificar os desfechos desfavoráveis. Objetivo Conhecer a prevalência de osteopenia ou osteoporose e de fraturas por fragilidade óssea em portadores de cirrose hepática, fatores de risco associados e seu comprometimento na qualidade de vida. Métodos Estudo observacional e transversal realizado com 71 pacientes portadores de cirrose hepática do Serviço de Hepatologia do Hospital de Base do Distrito Federal, Brasília, DF, Brasil, no período de julho de 2017 a dezembro de 2018. Os pacientes foram submetidos à densitometria óssea de coluna lombar e colo de fêmur, raio-x de coluna lombo sacra e ao questionário Chronic Liver Disease Questionnaire (CLDQ, na sigla em inglês) para avaliação de qualidade de vida. Foi calculado o escore de Fracture Risk Assessment Tool "FRAX Maior" nos pacientes >50 anos. As análises foram realizadas para a avaliação dos fatores de risco associados à fratura de coluna lombo sacra. Resultados Dos 71 pacientes avaliados, a maioria (62%) foi diagnosticada com osteoporose ou osteopenia à densitometria. Dos 44 portadores de osteopenia ou osteoporose, 52,3% eram do sexo feminino, com idade média de 62,6±9,51 anos, sendo a maioria (72,7%) Child A, cirróticos de etiologia alcoólica (36,4%) e com qualidade de vida intermediária ao CLDQ (3,3). Dos pacientes com fratura de coluna lombo sacra, a média de idade foi de 61,6±11,1 anos, 60% eram do sexo feminino, a maioria Child A (66,7%), de etiologia alcoólica (46,7%), e apresentaram qualidade de vida intermediária ao CLDQ (3,5). A presença de osteopenia e/ou osteoporose esteve associada à fratura lombo sacra (P<0,001), sem correlação com as demais variáveis analisadas: idade, índice de massa corporal (IMC), gênero, presença e ausência de ascite, classificação de Child-Pugh, concentrações séricas de vitamina D, cálcio e fósforo, etiologia da cirrose e "FRAX maior". Conclusão A prevalência de osteodistrofia hepática foi elevada, e a ocorrência de fratura de coluna lombo sacra esteve mais associada à osteoporose e/ou osteopenia entre cirróticos estudados. A qualidade de vida se mostrou intermediária e sem diferença entre cirróticos com e sem fratura.

Anti-mitochondrial Antibody-Negative Primary Biliary Cholangitis Is Part of the Same Spectrum of Classical Primary Biliary Cholangitis.

BACKGROUND: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease in which anti-mitochondrial antibodies (AMA) are the diagnostic hallmark. Whether AMA-negative PBC patients represent a different phenotype of disease is highly debated. AIMS: The purpose of our study was to compare AMA-positive and AMA-negative PBC patients in a large non-white admixed Brazilian cohort. METHODS: The Brazilian Cholestasis Study Group multicentre database was reviewed to assess demographics, clinical features and treatment outcomes of Brazilian PBC patients, stratifying data according to AMA status. RESULTS: A total of 464 subjects (95.4% females, mean age 56 ± 5 years) with PBC were included. Three hundred and eighty-four (83%) subjects were AMA-positive, whereas 80 (17%) had AMA-negative PBC. Subjects with AMA-negative PBC were significantly younger (52.2 ± 14 vs. 59.6 ± 11 years, p = 0.001) and had their first symptom at an earlier age (43.2 ± 13 vs. 49.5 ± 12 years, p = 0.005). Frequency of type 2 diabetes was significantly increased in subjects with AMA-negative PBC (22.5% vs. 12.2%, p = 0.03). Lower IgM (272.2 ± 183 vs. 383.2 ± 378 mg/dL, p = 0.01) and triglycerides (107.6 ± 59.8 vs.129.3 ± 75.7 mg/dL, p = 0.025) and higher bilirubin (3.8 ± 13.5 vs. 1.8 ± 3.4 mg/dL, p = 0.02) levels were also observed in this subgroup. Response to ursodeoxycholic acid varied from 40.5 to 63.3% in AMA-positive and 34 to 62.3% in AMA-negative individuals, according to different response criteria. Outcomes such as development of liver-related complications, death and requirement for liver transplantation were similar in both groups. CONCLUSIONS: AMA-negative PBC patients are similar to their AMA-positive counterparts with subtle differences observed in clinical and laboratory features.

Clinical features and treatment outcomes of primary biliary cholangitis in a highly admixed population.

INTRODUCTION AND OBJECTIVES: Little is known about primary biliary cholangitis (PBC) in non-whites. The purpose of this study was to evaluate clinical features and outcomes of PBC in a highly admixed population. MATERIAL AND METHODS: The Brazilian Cholestasis Study Group multicentre database was reviewed to assess demographics, clinical features and treatment outcomes of Brazilian patients with PBC. RESULTS: 562 patients (95% females, mean age 51 ± 11 years) with PBC were included. Concurrent autoimmune diseases and overlap with autoimmune hepatitis (AIH) occurred, respectively, in 18.9% and 14%. After a mean follow-up was 6.2 ± 5.3 years, 32% had cirrhosis, 7% underwent liver transplantation and 3% died of liver-related causes. 96% were treated with ursodeoxycholic acid (UDCA) and 12% required add-on therapy with fibrates, either bezafibrate, fenofibrate or ciprofibrate. Response to UDCA and to UDCA/fibrates therapy varied from 39%-67% and 42-61%, respectively, according to different validated criteria. Advanced histological stages and non-adherence to treatment were associated with primary non-response to UDCA, while lower baseline alkaline phosphatase (ALP) and aspartate aminotransferase (AST) levels correlated with better responses to both UDCA and UDCA/fibrates. CONCLUSIONS: Clinical features of PBC in highly admixed Brazilians were similar to those reported in Caucasians and Asians, but with inferior rates of overlap syndrome with AIH. Response to UDCA was lower than expected and inversely associated with histological stage and baseline AST and ALP levels. Most of patients benefited from add-on fibrates, including ciprofibrate. A huge heterogeneity in response to UDCA therapy according to available international criteria was observed and reinforces the need of global standardization.

Fibrates for the Treatment of Primary Biliary Cholangitis Unresponsive to Ursodeoxycholic Acid: An Exploratory Study.

Aim: Up to 40% of patients with primary biliary cholangitis (PBC) will have a suboptimal biochemical response to ursodeoxycholic acid (UDCA), which can be improved by the addition of fibrates. This exploratory study aims to evaluate the long-term real-life biochemical response of different fibrates, including ciprofibrate, in subjects with UDCA-unresponsive PBC. Methods: The Brazilian Cholestasis Study Group multicenter database was reviewed to assess the response rates to UDCA plus fibrates in patients with UDCA-unresponsive PBC 1 and 2 years after treatment initiation by different validated criteria. Results: In total, 27 patients (100% women, mean age 48.9 ± 9.2 years) with PBC were included. Overall response rates to fibrates by each validated criterion varied from 39 to 60% and 39-76% at 12 and 24 months after treatment combination, respectively. Combination therapy resulted in a significant decrease in ALT and ALP only after 2 years, while GGT significantly improved in the first year of treatment. Treatment response rates at 1 and 2 years appear to be comparable between ciprofibrate and bezafibrate using all available criteria. Conclusion: Our findings endorse the efficacy of fibrate add-on treatment in PBC patients with suboptimal response to UDCA. Ciprofibrate appears to be at least as effective as bezafibrate and should be assessed in large clinical trials as a possibly new, cheaper, and promising option for treatment of UDCA-unresponsive PBC patients.

Correlation between hepatopulmonary syndrome and oxygen saturation pulse oximetry in cirrhotic patients.

OBJECTIVE: Hepatopulmonary Syndrome (HPS) is a complication of cirrhosis that worsens the disease's prognosis, pre and post liver transplant. The objective of this study is to analyze the prevalence of HPS in cirrhotic patients at our service and to correlate it with oxygen saturation (SatO2) using a pulse oximeter to evaluate if this is useful as a screening test for HPS. A prospective study was conducted in patients with hepatic cirrhosis conventionally selected from 2014 to 2016. All the patients underwent an echocardiogram with microbubbles and oxygen saturation measurement by pulse oximetry. Those with intrapulmonary shunt were submitted to arterial blood gas analysis. The relationship between oxygen saturation and HPS was assessed by the multivariate model of binary logistic regression. We analyzed 77 patients, and 23.3% (18 patients) had all criteria for HPS. The relationship between HPS and SatO2 did not show statistical significance, even after the variables were adjusted for sex, age, and smoking. Oxygen saturation alone was not able to detect HPS in the sample of cirrhotic patients. More accurate methods for screening and diagnosis of the syndrome should be used.

Correlation between hepatopulmonary syndrome and oxygen saturation pulse oximetry in cirrhotic patients

SUMMARY Hepatopulmonary Syndrome (HPS) is a complication of cirrhosis that worsens the disease's prognosis, pre and post liver transplant. The objective of this study is to analyze the prevalence of HPS in cirrhotic patients at our service and to correlate it with oxygen saturation (SatO2) using a pulse oximeter to evaluate if this is useful as a screening test for HPS. A prospective study was conducted in patients with hepatic cirrhosis conventionally selected from 2014 to 2016. All the patients underwent an echocardiogram with microbubbles and oxygen saturation measurement by pulse oximetry. Those with intrapulmonary shunt were submitted to arterial blood gas analysis. The relationship between oxygen saturation and HPS was assessed by the multivariate model of binary logistic regression. We analyzed 77 patients, and 23.3% (18 patients) had all criteria for HPS. The relationship between HPS and SatO2 did not show statistical significance, even after the variables were adjusted for sex, age, and smoking. Oxygen saturation alone was not able to detect HPS in the sample of cirrhotic patients. More accurate methods for screening and diagnosis of the syndrome should be used.

RESUMO A Síndrome Hepatopulmonar (SHP) é uma complicação da cirrose que piora o prognóstico da doença pré e pós-transplante hepático. O objetivo do trabalho é analisar a prevalência de SHP em pacientes cirróticos de nosso serviço e correlacioná-la com a saturação de oxigênio (SatO2) pelo oxímetro de pulso, e avaliar se este seria útil como um exame de triagem no diagnóstico de SHP. Foi realizado um estudo prospectivo em pacientes portadores de cirrose hepática no período de 2014 a 2016. Todos os pacientes foram submetidos a um ecocardiogama com microbolhas e a saturação de oxigênio pela oximetria de pulso. Aqueles com shunt intrapulmonar foram submetidos a gasometria arterial. A relação entre a saturação de oxigênio e SHP foi avaliada pelo modelo multivariado de regressão logística binário. Foram analisados 77 pacientes, destes 23,3% (18 pacientes) apresentaram todos os critérios para SHP. A relação entre a SHP com a SatO2 não obteve significância estatística, mesmo após as variáveis terem sido ajustadas pelo sexo, idade e tabagismo atual ou passado. A saturação de oxigênio, de forma isolada, não foi capaz de distinguir a SHP na amostra de pacientes cirróticos em nosso estudo. Deve-se utilizar métodos mais acurados para a triagem e diagnóstico dessa síndrome.

Direct antiviral therapy for treatment of hepatitis C: A real-world study from Brazil.

INTRODUCTION AND OBJECTIVES: Direct antiviral agents (DAAs) including sofosbuvir (SOF), daclatasvir (DCV), simeprevir (SIM) and ombitasvir, paritaprevir and dasabuvir were introduced 2015 in Brazil for treatment of hepatitis C virus (HCV) infection. The aims of this study were to assess effectiveness and safety of HCV treatment with DAA in real-life world in a highly admixed population from Brazil. MATERIALS AND METHODS: All Brazilian reference centers for HCV treatment were invited to take part in a web-based registry, prospectively conducted by the Brazilian Society of Hepatology, to assess outcomes of HCV treatment in Brazil with DAAs. Data to be collected included demographics, disease severity and comorbidities, genotype (GT), viral load, DAA regimens, treatment side effects and sustained virological response (SVR). RESULTS: 3939 patients (60% males, mean age 58±10 years) throughout the country were evaluated. Most had advanced fibrosis or cirrhosis, GT1 and were treated with SOF/DCV or SOF/SIM. Overall SVR rates were higher than 95%. Subjects with decompensated cirrhosis, GT2 and GT3 have lower SVR rates of 85%, 90% and 91%, respectively. Cirrhosis and decompensated cirrhosis in GT1 and male sex and decompensated cirrhosis in GT3 were significantly associated with no SVR. Adverse events (AD) and serious AD occurred in 18% and 5% of those subjects, respectively, but less than 1% of patients required treatment discontinuation. CONCLUSION: SOF-based DAA regimens are effective and safe in the heterogeneous highly admixed Brazilian population and could remain an option for HCV treatment at least in low-income countries.