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.

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.

Serum Ferritin and NAFLD in Patients Undergoing Bariatric Surgery.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become a challenge in public health, as the prevalence of obesity and overweight has been increasing. It has been observed that serum ferritin (SF) levels are commonly elevated in NAFLD patients. PURPOSE: To assess the relationship between SF levels and NAFLD, exploring the role of SF as a non-invasive marker of NAFLD. METHODS: Clinical, anthropometric, laboratory, and histological data of patients with obesity who underwent bariatric surgery in a reference center in Brazil were retrospectively evaluated. Data were collected in the preoperative period up to the first year postoperatively. RESULTS: A total of 431 patients were analyzed. The prevalence of hyperferritinemia was 18% in the preoperative period and 14% 1 year after the surgery. After multiple regression analysis, elevated SF was not an independent predictor of steatosis, non-alcoholic steatohepatitis (NASH), or liver fibrosis. CONCLUSIONS: Increased SF levels are common in patients with NAFLD; however, SF was not considered an independent predictor of steatosis, NASH, or fibrosis.

Fibromax and inflamatory markers cannot replace liver biopsy in the evaluation of non-alcoholic fatty liver disease.

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.

The prognostic impact of different stages of acute kidney injury in patients with decompensated cirrhosis: a prospective cohort study.

AIM: To assess the impact of the different stages of acute kidney injury (AKI) on the prognosis of patients hospitalized with decompensated cirrhosis. METHODS: This was a prospective cohort study of consecutive patients admitted in two tertiary hospitals in southern Brazil. Participants were considered eligible if they were admitted for acute decompensation of cirrhosis. The main exposure factor was the onset of AKI. AKI stages were defined according the European recommendations. The outcomes evaluated were survival time and death rates at 28 and 90 days from hospital admission. A χ2 test was used to compare mortality between groups. Kaplan-Meier survival analyses were undertaken assessing time to event as days from AKI diagnosis to death or liver transplant. RESULTS: Two hundred and five patients were included in the study, and 121 met the criteria for AKI. Patients with AKI 1b, AKI 2 and AKI 3 had higher 90-day mortality than patients without AKI (P = 0.008, P < 0.001 and P < 0.001, respectively). However, there was no difference in 90-day mortality when patients with AKI 1a were compared with those without AKI (P = 0.742). The mean survival of patients without AKI was higher than that of patients with AKI 1b (591.4 and 305.4 days, respectively, P = 0.015), while there was no significant difference between the mean survival of patients without AKI and that of patients with AKI 1a (591.4 and 373.6 days, respectively, P = 0.198). CONCLUSION: Only AKI ≥1b seems to substantially impact mortality of patients hospitalized for acute decompensation of cirrhosis.

Obstructive sleep apnea and severity of nonalcoholic fatty liver disease.

BACKGROUND: Mechanisms involving obstructive sleep apnea (OSA) and nonalcoholic fatty liver disease (NAFLD) are under increasing assessment. This study evaluated the correlation of OSA with the severity of NAFLD. MATERIALS AND METHODS: Prospective study in which patients with at least one of metabolic syndrome (MS) criteria were initially assessed by the NAFLD fibrosis score and according to the outcome (intermediate or high risk of advanced fibrosis) underwent liver biopsy (exception of patients with clinical, ultrasound or endoscopic diagnosis of cirrhosis). All patients performed polysomnography. For statistical analysis, the patients were assembled into two groups: (1) without apnea or mild apnea and (2) moderate or severe apnea. In the correlation of OSA with the severity of NAFLD, the risk factors evaluated were: degree of steatosis, presence and severity of nonalcoholic steatohepatitis (NASH) and fibrosis. RESULTS: Fifty-one patients were evaluated, 80.4% had systemic arterial hypertension (SAH), 68.6% type 2 diabetes mellitus, 62.7% dyslipidemia and 96.1% MS. Regarding the histological evaluation (n = 48), all had steatosis, 95.8% steatohepatitis and 83.3% fibrosis. In polysomnography, 80.4% were group 1 and 19.6% group 2. In univariate analysis, no correlation was found between steatosis severity, NASH and presence or severity of fibrosis with OSA. A multivariate analysis adjusted for obesity level, found that patients with moderate to severe OSA had an increased risk of hepatic fibrosis (odds ratio 1.22, 95% confidence interval: 1.02-1.45, P = 0.027). CONCLUSION: The present study demonstrated an association between fibrosis and moderate to severe OSA, regardless of obesity.

MALNUTRITION IN CIRRHOSIS: ASSOCIATION WITH ETIOLOGY AND HEPATOCELLULAR DYSFUNCTION.

BACKGROUND: The protein-energy malnutrition alters the prognosis of patients with cirrhosis. Its prevalence may vary according to the etiology of liver disease, it´s severity and the evaluation of the method applied. The infection by the hepatitis C virus (HCV) and alcoholism are the main etiologies of cirrhosis and result in a significant morbidity and mortality. OBJECTIVE: To evaluate the nutritional status of patients with cirrhosis according the liver disease etiology and severity. METHODS: It is a prospective study, in which the sample was for convenience and consisted of patients with cirrhosis, infected by HCV or alcoholic etiology. The nutritional status evaluation was carried out through anthropometry, food consumption, bioelectrical impedance (BIA) and subjective global assessment (SGA). The anthropometric data evaluated were weight, height, body mass index (BMI), triceps skinfold (TSF), circumference of the arm (CA), non-dominant handshake strength (FAM) and the adductor pollicis muscle thickness (APM). Patients were classified according to the severity of liver disease, using the Child-Pugh and Model for End-stage Liver Diseases (MELD) scores. RESULTS: Ninety patients with cirrhosis were evaluated, 47 with HCV and 43 with alcoholic etiology. The prevalence of protein-calorie malnutrition ranged from 10.9% to 54.3% in the HCV group and from 4.7% to 20.9% in the alcoholic group, depending on the method used for evaluation. The group with HCV infection presented a higher malnutrition prevalence in comparison to the alcoholic in the following evaluations: TSF (P<0.001), phase angle (PA) (P=0.016) and SGA (P=0.010). PA values were lower in patients with viral cirrhosis (5.68±1.05) when compared to those with alcoholic etiology (6.61±2.31) (P=0.016). When all patients were analyzed, regardless of etiology, an inversely correlation was observed among Child-Pugh score and PA values (P=0.018). CONCLUSION: HCV cirrhosis showed worse nutritional parameters in comparison to alcoholic etiology; however, the PA was associated with worse liver function in both etiologies.

Avaliação de pacientes com hepatite autoimune atendidos em ambulatório de referência do sul do Brasil / Evaluation of patients with autoimmune hepatitis in a specialized outpatient clinic in southern brazil

ABSTRACT BACKGROUND: Autoimmune hepatitis (AIH) is a chronic liver disease, characterized by necroinflammation and autoimmune etiology. Studies evaluating the characteristics of patients with AIH are scarce in Brazil. OBJECTIVE: Our objective was to evaluate the profile of patients with AIH in a specialized center in Southern Brazil and to verify factors related to treatment response. METHODS: this was a retrospective cohort study, which analyzed demographic, epidemiological, clinical, laboratory, and histologic data. Patients with AIH diagnosed according to the criteria of the International Autoimmune Hepatitis Group (IAIHG) were included. In liver biopsies, the degree of fibrosis, histological activity, presence of hepatocyte rosettes, plasma cell infiltrates, and confluent necrosis were evaluated. In the statistical analysis, the significance level was 5%. RESULTS: Forty adults patients diagnosed with AIH were included. The evaluated population predominantly consisted of women (75.0%) and the average age at diagnosis was 44.2 years. The association with extrahepatic autoimmune diseases occurred in 20.0% of cases. Clinically, 35.0% of patients presented with acute onset hepatitis, 37.5% with cirrhosis, and 27.5% with other forms of presentation. The most common clinical manifestation was jaundice (47.5%). Thirty-five patients were treated, and of these, 97.1% used prednisone combined with azathioprine. The average treatment time was 2.7 years. Response to treatment was complete or partial in 30 (85.7%) and absent in 5 (14.3%) patients. There was no statistically significant difference when evaluating response to treatment in relation to forms of presentation, histological findings, and the presence of autoantibodies. Regarding fibrosis, regression was observed in 18.75% of the cases. CONCLUSION: Most patients with AIH were young at presentation and of female sex. The association with extrahepatic autoimmune diseases and cirrhosis at presentation was seen in a considerable proportion of patients. Treatment was effective, but there were no clinical, histological or serological parameters capable of predicting treatment response.

RESUMO CONTEXTO: A hepatite autoimune (HAI) é uma doença hepática crônica, de caráter necroinflamatório e etiologia autoimune. Os estudos que avaliam as características de pacientes com HAI são escassos no Brasil. OBJETIVO: Nosso objetivo foi avaliar o perfil dos pacientes com HAI atendidos em um centro de referência do sul do Brasil e verificar fatores relacionados à resposta ao tratamento. MÉTODOS: Este foi um estudo de coorte retrospectivo, que analisou dados demográficos, epidemiológicos e clínicos. Nas biópsias hepáticas, foram avaliados o grau de fibrose, a atividade histológica, a presença de rosetas, de infiltrado plasmocitário e de necrose confluente. Na análise estatística, o nível de significância foi de 5%. RESULTADOS: Foram incluídos 40 pacientes adultos com diagnóstico de HAI. Houve predomínio do sexo feminino (75,0%), e a média de idade no diagnóstico foi de 44,2 anos. A associação com doenças autoimunes extra-hepáticas ocorreu em 20,0% dos casos. Clinicamente, 35,0% dos pacientes se apresentaram sob forma de hepatite aguda, 37,5% com cirrose e 27,5% com outras formas de apresentação. A manifestação clínica mais comum na apresentação foi a icterícia (47,5%). Trinta e cinco pacientes foram tratados, sendo que destes, 97,1% utilizaram prednisona associada com azatioprina. A média do tempo de tratamento foi 2,7 anos. A resposta ao tratamento foi completa ou parcial em 30 (85,7%) e ausente em 5 (14,3%) pacientes. Não houve diferença estatisticamente significativa quando avaliada a resposta ao tratamento em relação à forma de apresentação, aos achados histológicos e à presença de autoanticorpos. Em relação à fibrose, foi observada regressão em 18,75% dos casos. CONCLUSÃO: A maioria dos pacientes era jovem no momento do diagnóstico e do sexo feminino. A associação com doenças autoimunes extra-hepáticas e com cirrose na apresentação foi vista em uma parcela considerável dos casos. O tratamento foi eficaz, mas não houve parâmetros clínicos, histológicos ou sorológicos capazes de prever a resposta ao tratamento.

Desnutrição na cirrose: associação com a etiologia e disfunção hepatocelular / Malnutrition in cirrhosis: association with etiology and hepatocellular dysfunction

ABSTRACT BACKGROUND: The protein-energy malnutrition alters the prognosis of patients with cirrhosis. Its prevalence may vary according to the etiology of liver disease, it´s severity and the evaluation of the method applied. The infection by the hepatitis C virus (HCV) and alcoholism are the main etiologies of cirrhosis and result in a significant morbidity and mortality. OBJECTIVE: To evaluate the nutritional status of patients with cirrhosis according the liver disease etiology and severity. METHODS: It is a prospective study, in which the sample was for convenience and consisted of patients with cirrhosis, infected by HCV or alcoholic etiology. The nutritional status evaluation was carried out through anthropometry, food consumption, bioelectrical impedance (BIA) and subjective global assessment (SGA). The anthropometric data evaluated were weight, height, body mass index (BMI), triceps skinfold (TSF), circumference of the arm (CA), non-dominant handshake strength (FAM) and the adductor pollicis muscle thickness (APM). Patients were classified according to the severity of liver disease, using the Child-Pugh and Model for End-stage Liver Diseases (MELD) scores. RESULTS: Ninety patients with cirrhosis were evaluated, 47 with HCV and 43 with alcoholic etiology. The prevalence of protein-calorie malnutrition ranged from 10.9% to 54.3% in the HCV group and from 4.7% to 20.9% in the alcoholic group, depending on the method used for evaluation. The group with HCV infection presented a higher malnutrition prevalence in comparison to the alcoholic in the following evaluations: TSF (P<0.001), phase angle (PA) (P=0.016) and SGA (P=0.010). PA values were lower in patients with viral cirrhosis (5.68±1.05) when compared to those with alcoholic etiology (6.61±2.31) (P=0.016). When all patients were analyzed, regardless of etiology, an inversely correlation was observed among Child-Pugh score and PA values (P=0.018). CONCLUSION: HCV cirrhosis showed worse nutritional parameters in comparison to alcoholic etiology; however, the PA was associated with worse liver function in both etiologies.

RESUMO CONTEXTO: A desnutrição proteico-calórica altera o prognóstico dos pacientes com cirrose. Sua prevalência pode variar de acordo com a etiologia da hepatopatia, gravidade da doença e o método de avaliação empregado. A infeção pelo vírus da hepatite C (VHC) e o alcoolismo, estão entre as principais etiologias da cirrose e acarretam significativa morbidade e mortalidade. OBJETIVO: Avaliar o estado nutricional do paciente com cirrose de acordo com a etiologia e gravidade da hepatopatia. MÉTODOS: Estudo prospectivo, em que a amostra foi por conveniência constituída de pacientes com cirrose, infectados pelo vírus da hepatite C (VHC) ou etiologia alcoólica. A avaliação do estado nutricional foi realizada através da antropometria, consumo alimentar, bioimpedância elétrica (BIA) e da avaliação subjetiva global (ASG). Os dados antropométricos avaliados foram: peso, altura, índice de massa corporal (IMC), prega cutânea triciptal (PCT), circunferências do braço (CB), força do aperto de mão não dominante (FAM) e a espessura do músculo adutor do polegar (MAP). Os pacientes foram classificados de acordo com a gravidade da hepatopatia, através do escore Child-Pugh e Model for End-stage Liver Diseases (MELD). RESULTADOS: Foram avaliados 90 pacientes com cirrose, 47 com etiologia pelo VHC e 43 com etiologia alcoólica. A prevalência de desnutrição proteico-calórica variou de 10,9% a 54,3% no grupo do VHC e de 4,7% a 20,9% no grupo dos alcoolistas, dependendo do método utilizado para avaliação. O grupo com infecção pelo VHC apresentou maior prevalência de desnutrição em relação ao de etiologia alcoólica nas seguintes avaliações: PCT (P<0,001), ângulo de fase (AF) (P=0,016) e ASG (P=0,010). Os valores do AF foram menores nos pacientes com cirrose viral (5,68±1,05) quando comparados aos com etiologia alcoólica (6,61±2,31) (P=0,016). Quando analisados todos os pacientes, independente da etiologia da hepatopatia, observou-se uma correlação inversamente proporcional entre a classificação de Child-Pugh e os valores de AF (P=0,018). CONCLUSÃO: A cirrose pelo VHC demonstrou piores parâmetros nutricionais em relação à etiologia alcoólica; entretanto, em ambas etiologias o AF foi associado com pior função hepática em ambas etiologias.

EVALUATION OF PATIENTS WITH AUTOIMMUNE HEPATITIS IN A SPECIALIZED OUTPATIENT CLINIC IN SOUTHERN BRAZIL.

BACKGROUND: Autoimmune hepatitis (AIH) is a chronic liver disease, characterized by necroinflammation and autoimmune etiology. Studies evaluating the characteristics of patients with AIH are scarce in Brazil. OBJECTIVE: Our objective was to evaluate the profile of patients with AIH in a specialized center in Southern Brazil and to verify factors related to treatment response. METHODS: this was a retrospective cohort study, which analyzed demographic, epidemiological, clinical, laboratory, and histologic data. Patients with AIH diagnosed according to the criteria of the International Autoimmune Hepatitis Group (IAIHG) were included. In liver biopsies, the degree of fibrosis, histological activity, presence of hepatocyte rosettes, plasma cell infiltrates, and confluent necrosis were evaluated. In the statistical analysis, the significance level was 5%. RESULTS: Forty adults patients diagnosed with AIH were included. The evaluated population predominantly consisted of women (75.0%) and the average age at diagnosis was 44.2 years. The association with extrahepatic autoimmune diseases occurred in 20.0% of cases. Clinically, 35.0% of patients presented with acute onset hepatitis, 37.5% with cirrhosis, and 27.5% with other forms of presentation. The most common clinical manifestation was jaundice (47.5%). Thirty-five patients were treated, and of these, 97.1% used prednisone combined with azathioprine. The average treatment time was 2.7 years. Response to treatment was complete or partial in 30 (85.7%) and absent in 5 (14.3%) patients. There was no statistically significant difference when evaluating response to treatment in relation to forms of presentation, histological findings, and the presence of autoantibodies. Regarding fibrosis, regression was observed in 18.75% of the cases. CONCLUSION: Most patients with AIH were young at presentation and of female sex. The association with extrahepatic autoimmune diseases and cirrhosis at presentation was seen in a considerable proportion of patients. Treatment was effective, but there were no clinical, histological or serological parameters capable of predicting treatment response.

IMPACT OF ACUTE KIDNEY INJURY STAGING ON PROGNOSIS OF PATIENTS WITH CIRRHOSIS.

BACKGROUND: Acute kidney injury (AKI) is a common and severe complication of cirrhosis. OBJECTIVE: To evaluate the impact of AKI staging on 30-day mortality of patients with cirrhosis. METHODS: We performed a retrospective cohort study of hospitalized patients with cirrhosis. Acute kidney injury (AKI) was diagnosed according to the International Club of Ascites recommendations and staged according to the European Association for the Study of the Liver guidelines. Comparisons between groups were made by one-way analysis of variance and Tukey test. Chi-square was calculated for dichotomous variables. Comparisons of renal impairment status among patients were performed using Kaplan-Meier statistics and differences between groups were analyzed using the log-rank test. A P-value <0.05 was considered to be statistically significant. RESULTS: Two hundred and thirty-two patients were included in the study. The diagnosis of AKI was performed in 98 (42.2%) of them. The overall 30-day mortality was 19.8% (46/232). Mortality increased as the degree of AKI progressed. Among patients who did not have AKI, mortality was 5.2% (7/134). When compared to patients without AKI, patients diagnosed with AKI stage 1a had mortality of 12.1% (4/33, P=0.152); patients with AKI stage 1b had mortality of 45% (18/40, P<0.001); and patients with AKI stages 2 or 3 had mortality of 68% (17/25, P<0.001). Moreover, it is noteworthy that full response to treatment was associated to a decreased mortality when compared to patients who did not show complete recovery of renal function (14.3% vs 57.9%, P<0.001). CONCLUSION: AKI stages 1b or greater, but not AKI stage 1a, are associated to higher 30-day mortality of patients with cirrhosis.

Avaliação prognóstica de lesão renal aguda em pacientes cirróticos / Impact of acute kidney injury staging on prognosis of patients with cirrhosis

ABSTRACT BACKGROUND: Acute kidney injury (AKI) is a common and severe complication of cirrhosis. OBJECTIVE: To evaluate the impact of AKI staging on 30-day mortality of patients with cirrhosis. METHODS: We performed a retrospective cohort study of hospitalized patients with cirrhosis. Acute kidney injury (AKI) was diagnosed according to the International Club of Ascites recommendations and staged according to the European Association for the Study of the Liver guidelines. Comparisons between groups were made by one-way analysis of variance and Tukey test. Chi-square was calculated for dichotomous variables. Comparisons of renal impairment status among patients were performed using Kaplan-Meier statistics and differences between groups were analyzed using the log-rank test. A P-value <0.05 was considered to be statistically significant. RESULTS: Two hundred and thirty-two patients were included in the study. The diagnosis of AKI was performed in 98 (42.2%) of them. The overall 30-day mortality was 19.8% (46/232). Mortality increased as the degree of AKI progressed. Among patients who did not have AKI, mortality was 5.2% (7/134). When compared to patients without AKI, patients diagnosed with AKI stage 1a had mortality of 12.1% (4/33, P=0.152); patients with AKI stage 1b had mortality of 45% (18/40, P<0.001); and patients with AKI stages 2 or 3 had mortality of 68% (17/25, P<0.001). Moreover, it is noteworthy that full response to treatment was associated to a decreased mortality when compared to patients who did not show complete recovery of renal function (14.3% vs 57.9%, P<0.001). CONCLUSION: AKI stages 1b or greater, but not AKI stage 1a, are associated to higher 30-day mortality of patients with cirrhosis.

RESUMO CONTEXTO: A lesão renal aguda (LRA) é uma complicação comum e grave na cirrose. OBJETIVO: Avaliar o impacto dos estágios da LRA na mortalidade em 30 dias de pacientes com cirrose. MÉTODOS: Realizou-se um estudo de coorte retrospectivo com pacientes com cirrose hospitalizados. LRA foi diagnosticada de acordo com as recomendações do International Club of Ascites e o estadiamento foi feito de acordo com as recomendações da European Association for the Study of the Liver. Comparações entre os grupos foram feitas por análise de variância unidirecional e teste de Tukey. O teste do qui-quadrado foi calculado para variáveis categóricas. Comparações quanto à lesão renal entre os pacientes foram realizadas com estatísticas de Kaplan-Meier, e diferenças entre os grupos foram analisadas pelo teste de log-rank. Um P-valor <0,05 foi considerado estatisticamente significativo. RESULTADOS: Duzentos e trinta e dois pacientes foram incluídos no estudo. O diagnóstico de LRA foi realizado em 98 (42,2%) deles. A mortalidade geral em 30 dias foi de 19,8% (46/232). A mortalidade aumentou de acordo com a progressão dos estágios de LRA. Entre pacientes sem LRA, a mortalidade foi de 5,2% (7/134). Quando comparados aos pacientes sem LRA, pacientes diagnosticados com LRA estágio 1a tiveram mortalidade de 12,1% (4/33, P=0,152); pacientes com LRA estágio 1b tiveram mortalidade de 45% (18/40, P<0,001); e pacientes com LRA estágios 2 ou 3 tiveram mortalidade de 68% (17/25, P<0,001). Além disso, é importante ressaltar que a resposta completa ao tratamento associou-se à menor mortalidade quando comparada à ausência de recuperação completa da função renal (14,3% vs 57,9%, P<0,001). CONCLUSÃO: LRA estágios 1b ou superior, mas não estágio 1a, estão associadas à maior mortalidade em 30 dias de pacientes com cirrose.

Performance of noninvasive scores for the diagnosis of advanced liver fibrosis in morbidly obese with nonalcoholic fatty liver disease.

OBJECTIVES: Liver fibrosis is one of the most important predictors of mortality related to nonalcoholic fatty liver disease (NAFLD). The use of noninvasive markers has the advantage of a simple and low-cost evaluation. The aim of this study was to evaluate the performance of six noninvasive scores for the diagnosis of advanced liver fibrosis in morbidly obese patients. MATERIAL AND METHODS: A retrospective study validation included 323 morbidly obese patients undergoing bariatric surgery. Advance fibrosis was defined as stage 3 and 4 (septal fibrosis or cirrhosis). Accuracy, sensitivity, specificity, positive (PPV) or negative (NPV) predictive value, and positive (PLR) or negative (NLR) likelihood ratio test of the following noninvasive liver fibrosis scores were evaluated: aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR); AST to platelet ratio index (APRI); BARD; FIB4, NAFLD fibrosis score (NFS) and BAAT, which were compared with the histological findings of the intraoperative liver biopsy. The cutoff points established in the validation studies were used: AAR > 1; APRL > 0.98; BARD ≥ 2; FIB4 > 2.67; NFS > 0.676 and BAAT > 1. RESULTS: Twenty-nine patients (8.97%) presented advanced fibrosis. APRI presented the higher specificity (99.61%), PPV (85.71%), PLR (62.5) and accuracy (0.93). FIB4 was the second test in accuracy (0.9) and in PLR (10.53). BAAT presented the highest sensitivity (73.08%) and NPV (94.78%); NFS the lowest sensitivity (12,5%), and BARD the lowest accuracy (0.44). CONCLUSION: APRI and FIB-4 were the tests with best performance to predict advanced fibrosis.

Evaluation of thrombocytopenia in patients with non-alcoholic fatty liver disease without cirrhosis.

INTRODUCTION AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in western countries. It is often related to metabolic syndrome, presenting an increased risk of advanced liver disease and cardiovascular-related death. In some etiologies of chronic liver disease, thrombocytopenia has been associated not only with advanced stages of fibrosis but also with autoimmune disease. In NAFLD, however, its prevalence and related factors are still unknown. The aim of this study is to evaluate the prevalence of thrombocytopenia in NAFLD patients without cirrhosis and to investigate its related risk factors. PATIENTS AND METHODS: This was a retrospective study carried out in two tertiary hospitals in the South and Southeast regions of Brazil. Patients diagnosed with NAFLD by liver biopsy were included. Those with other causes of liver disease and/or cirrhosis were excluded. For analysis, patients were divided into two groups, with and without thrombocytopenia. Data was analyzed using a significance level of 5%. RESULTS: 441 non-cirrhotic patients with NAFLD (evaluated by liver biopsy) were included in the study. The prevalence of thrombocytopenia was 3.2% (14/441 patients). In the comparative analysis between groups, thrombocytopenia was associated with male sex (p=0.007) and level of hemoglobin (p=0.023). CONCLUSION: Thrombocytopenia is an infrequent event in NAFLD patients without cirrhosis and is related with male sex and higher hemoglobin levels.

Transient hepatic elastography has the best performance to evaluate liver fibrosis in non-alcoholic fatty liver disease (NAFLD).

INTRODUCTION AND AIM: The gold-standard for fibrosis diagnosis in non-alcoholic fatty liver disease (NAFLD) is liver biopsy, despite its invasive approach, sampling limitations and variability among observers. The objective was to validate the performance of non-invasive methods (Fibroscan™; APRI, FIB4 and NAFLD score) comparing with liver biopsy in the evaluation of liver fibrosis in patients with NAFLD. MATERIAL AND METHODS: NAFLD patients ≥18 years of age who were submitted to liver biopsy were included and evaluated at two reference tertiary hospitals in Brazil with transient hepatic elastography (THE) assessment through Fibroscan™, APRI, FIB4 and NAFLD scores were determined. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values for the diagnosis of advanced fibrosis were calculated to evaluate the performance of these non-invasive methods in NAFLD patients, adopting liver biopsy as the gold standard. RESULTS: A total of 104 patients were studied. At three different cutoff values (7.9, 8.7 and 9.6kPa) THE presented the highest sensitivity values (95%, 90% and 85% respectively), and the highest NPV (98%, 96.4% and 95.1% respectively) for the diagnosis of advanced fibrosis. It also presented the highest AUROC (0.87; CI 95% 0.78-0.97). CONCLUSION: When compared to the gold standard, transient hepatic elastography presented the best performance for the diagnosis and exclusion of advanced fibrosis in patients with NAFLD, overcoming APRI, FIB4 and NAFLD score.

Prevalence and characteristics of hepatopulmonary syndrome in children with cirrhosis in southern Brazil.

BACKGROUND: Hepatopulmonary syndrome (HPS) is defined as a triad characterized by arterial deoxygenation, intrapulmonary vascular dilatations (IPVDs), and liver disorder. The aims of this study were to assess the prevalence of HPS in children with cirrhosis, the clinical characteristics of patients with HPS, and the tests used for the diagnosis of IPVD. PATIENTS AND METHODS: This was a prospective, cross-sectional study of 40 children with cirrhosis (median age: 44 months). Investigations of HPS included arterial blood gas analysis, contrast-enhanced transthoracic echocardiography (CE-TTE), and perfusion lung scanning using technetium-99m-labeled macroaggregated albumin (Tc-MMA). Patients' clinical characteristics (age, etiology of cirrhosis, and severity of hepatopathy) were assessed. HPS was defined as liver disease; alveolar-arterial oxygen gradient of at least 15 mmHg and/or partial pressure of arterial oxygen less than 80 mmHg; and detection of IPVD by CE-TTE or Tc-MMA scanning. Statistical significance was indicated by a P value less than 0.05. RESULTS: The prevalence of HPS was 42.5% (17/40). Eight patients had moderate HPS (47%) and two patients had severe HPS (12%). In bivariate analysis, biliary atresia (P=0.033) and median age (10 months; P=0.005) were associated with HPS. In multivariate analysis, only age remained statistically significant (prevalence ratio=0.99; 95% confidence interval=0.98-0.99; P=0.010). Sixteen patients with HPS had IPVD detected by CE-TTE (94.1%) and six patients had IPVD detected by Tc-MMA scanning (35.3%), with no significant agreement between these methods (κ=-0.12; P=0.163). CONCLUSION: HPS is a common complication of cirrhosis in children. A combination of clinical and imaging criteria should be used to diagnose HPS.

Impact of Diabetes Mellitus and Insulin on Nonalcoholic Fatty Liver Disease in the Morbidly Obese.

INTRODUCTION AND AIM: The prevalence of obesity, type 2 diabetes mellitus and non-alcoholic fatty liver disease are increasing. Type 2 diabetes mellitus may aggravate non-alcoholic fatty liver disease, increasing the risk of developing cirrhosis and hepatocellular carcinoma. This study aims to determine the effect of type 2 diabetes mellitus and insulin therapy on non-alcoholic fatty liver disease in the patients with morbid obesity. MATERIAL AND METHODS: Clinical, anthropometric and laboratory data were analyzed together with intraoperative liver biopsies from morbidly obese patients undergoing bariatric surgery. RESULTS: 219 patients with morbid obesity were evaluated. Systemic arterial hypertension (55.9% vs. 33.8%, p = 0.004) and dyslipidemia (67.1% vs. 39.0%, p < 0.001) were more prevalent in patients with diabetes when compared to patients without diabetes. In multivariate analysis, type 2 diabetes mellitus was an independent risk factor for severe steatosis (RR = 2.04, p = 0.023) and severe fibrosis (RR = 4.57, p = 0.013). Insulin therapy was significantly associated with non-alcoholic steatohepatitis (RR = 1.89, p = 0.001) and fibrosis (RR = 1.75, p = 0.050) when all patients were analysed, but when only patients with diabetes were analysed, insulin therapy was not associated with non-alcoholic steatohepatitis or fibrosis. CONCLUSION: Type 2 diabetes mellitus plays an important role in the progression of non-alcoholic fatty liver disease as an independent risk factor for severe fibrosis.

Alcohol Consumption Influences Clinical Outcome in Patients Admitted to a Referral Center for Liver Disease.

INTRODUCTION AND AIM: Excessive alcohol consumption is a public health concern worldwide and has been associated with high mortality rates. This study aimed to determine the prevalence of alcohol consumption and its influence on the prognosis of hospitalized cirrhotic patients in a tertiary care hospital. MATERIAL AND METHODS: We reviewed the medical records of all patients with hepatic cirrosis admitted between January 2009 and December 2014, in a referral center for liver disease in southern Brazil. Data on clinical outcomes, associated conditions, infections, and mortality were collected and compared between alcoholic and nonalcoholic patients. RESULTS: The sample consisted of 388 patients; 259 (66.7%) were men. One hundred fifty-two (39.2%) were classified as heavy use of alcohol. Most alcoholic patients were men (n = 144; 94.7%). Mean age was 55.6 ± 8.9 years. Hepatic decompensations and infections were more prevalent in alcoholic patient. Spontaneous bacterial peritonitis and respiratory tract infection accounted for most of the infections. Excessive alcohol consumption was associated with mortality (P = 0.009) in multivariate analysis. CONCLUSION: On the present study, the prevalence of heavy use of alcohol was high and associated with a poorer prognosis in hospitalized cirrhotic patients, increasing the risk of infection and death.

LIVER BIOPSY: IMPORTANCE OF SPECIMEN SIZE IN THE DIAGNOSIS AND STAGING OF CHRONIC VIRAL HEPATITIS.

UNLABELLED: Liver biopsy is the gold standard method for the grading and staging of chronic viral hepatitis, but optimal biopsy specimen size remains controversial. The aim of this study was to evaluate the quality of liver specimen (number of portal tracts) and to evaluate the impact of the number of portal tracts in the staging of chronic hepatitis. MATERIAL AND METHODS: 468 liver biopsies from consecutive patients with hepatitis C virus and hepatitis B virus infection from 2009 to 2010 were evaluated. RESULTS: The length of fragment was less than 10 mm in 43 cases (9.3%), between 10 and 14 mm in 114 (24.3%), and ≥ 15 mm in 311 (64.4%); of these, in 39 (8.3%) cases were ≥ 20 mm. The mean representation of portal tracts was 17.6 ± 2.1 (5-40); in specimens ≥ 15 mm the mean portal tract was 13.5 ± 4.7 and in cases ≤ 15 mm was 11.4 ± 5.0 (p = 0.002). Cases with less than 11 portal tracts were associated with F3, and cases with 11 or more portal tracts with F2 (p = 0.001). CONCLUSION: this study demonstrated the good quality of liver biopsy and a relationship between the macroscopic size of the fragment and the number of portal tracts.

LIVER BIOPSY: IMPORTANCE OF SPECIMEN SIZE IN THE DIAGNOSIS AND STAGING OF CHRONIC VIRAL HEPATITIS

Liver biopsy is the gold standard method for the grading and staging of chronic viral hepatitis, but optimal biopsy specimen size remains controversial. The aim of this study was to evaluate the quality of liver specimen (number of portal tracts) and to evaluate the impact of the number of portal tracts in the staging of chronic hepatitis. Material and Methods: 468 liver biopsies from consecutive patients with hepatitis C virus and hepatitis B virus infection from 2009 to 2010 were evaluated. Results: The length of fragment was less than 10 mm in 43 cases (9.3%), between 10 and 14 mm in 114 (24.3%), and ≥ 15 mm in 311 (64.4%); of these, in 39 (8.3%) cases were ≥ 20 mm. The mean representation of portal tracts was 17.6 ± 2.1 (5-40); in specimens ≥ 15 mm the mean portal tract was 13.5 ± 4.7 and in cases ≤ 15 mm was 11.4 ± 5.0 (p = 0.002). Cases with less than 11 portal tracts were associated with F3, and cases with 11 or more portal tracts with F2 (p = 0.001). Conclusion: this study demonstrated the good quality of liver biopsy and a relationship between the macroscopic size of the fragment and the number of portal tracts.