RESUMO Contexto: A doença hepática alcoólica (DHA) e a doença hepática esteatótica associada à disfunção metabólica (MASLD) são comuns, e a microbiota intestinal (MI) está envolvida em ambas. Aqui, comparamos a composição da MI em modelos animais de MASLD e DHA para avaliar se existem padrões específicos para cada doença. Métodos: Modelo de MASLD - ratos machos adultos da linhagem Sprague Dawley, randomizados em dois grupos: MASLD-controle (n=10) alimentados com uma dieta padrão; grupo MASLD (n=10) alimentados com uma dieta rica em gordura e deficiente em colina por 16 semanas. Modelo de DHA - ratos machos adultos da linhagem Wistar randomizados: DHA-controle (n=8) alimentados com uma dieta padrão e água+0,05% de sacarina; grupos DHA alimentados com semente de girassol e 10% de etanol+0,05% de sacarina por 4 ou 8 semanas (DHA4, n=8; DHA8, n=8). DHA 4/8 no último dia receberam binge alcoólico (5 g/kg de etanol). Posteriormente, os animais foram sacrificados, e as fezes foram coletadas para análise da MI. Resultados: Ambos os modelos experimentais induziram características histopatológicas típicas das doenças. A diversidade alfa foi menor na MASLD em comparação com a DHA (P<0,001), e o padrão estrutural foi diferente entre elas (P<0,001). Bacteroidetes (55,7%), Firmicutes (40,6%) e Proteobactérias (1,4%) foram os filos mais prevalentes em todas as amostras, embora com abundâncias diferenciadas entre os grupos. DHA8 teve uma maior abundância dos filos Cyanobacteria (5,3%) e Verrucomicrobiota (3,2%) em relação aos outros. A análise de abundância diferencial identificou Lactobacillaceae_unclassified, Lachnospiraceae_NK4A136 e Turicibacter associados ao grupo DHA4, e os gêneros Clostridia_UCG_014_ge e Gastranaerophilales_ge associados ao DHA8. Conclusão: Neste estudo, demonstramos que o padrão estrutural da MI difere significativamente entre os modelos de MASLD e DHA. Estudos são necessários para caracterizar a microbiota e os metabólitos ativos em ambas as condições clínicas, a fim de encontrar novas estratégias terapêuticas. Contexto (DHA (MASLD comuns (MI Aqui Métodos Dawley MASLDcontrole controle n=10 n10 n 10 (n=10 1 DHAcontrole n=8 n8 (n=8 água005 água 0 05 água+0,05 etanol005 etanol etanol+0,05 DHA4 (DHA4 n=8. . n=8) 48 4/ 5 ( gkg g kg etanol. etanol) Posteriormente sacrificados Resultados doenças P<0,001, P0001 P P<0,001 , 001 (P<0,001) P<0,001. 55,7%, 557 55,7% 55 7 (55,7%) 40,6% 406 40 6 (40,6% 1,4% 14 (1,4% amostras 5,3% 53 3 (5,3% 3,2% 32 2 (3,2% outros Lactobacillaceaeunclassified Lactobacillaceae unclassified Lactobacillaceae_unclassified LachnospiraceaeNK4A136 LachnospiraceaeNKA Lachnospiraceae NK4A136 NK Lachnospiraceae_NK4A13 ClostridiaUCG014ge ClostridiaUCGge Clostridia UCG 014 ge Gastranaerophilalesge Gastranaerophilales Conclusão estudo clínicas terapêuticas n=1 n1 (n=1 n= (n= água00 água+0,0 etanol00 etanol+0,0 P000 P<0,00 00 (P<0,001 55,7 (55,7% 40,6 (40,6 1,4 (1,4 5,3 (5,3 3,2 (3,2 LachnospiraceaeNK LachnospiraceaeNK4A13 NKA NK4A13 Lachnospiraceae_NK4A1 ClostridiaUCG 01 (n água0 água+0, etanol0 etanol+0, P00 P<0,0 (P<0,00 55, (55,7 40, (40, 1, (1, 5, (5, 3, (3, LachnospiraceaeNK4A1 NK4A1 Lachnospiraceae_NK4A água+0 etanol+0 P0 P<0, (P<0,0 (55, (40 (1 (3 LachnospiraceaeNK4A NK4A água+ etanol+ P<0 (P<0, (55 (4 P< (P<0 (P< (P

ABSTRACT Background: Alcoholic liver disease (ALD) and metabolic-dysfunction associated steatotic liver disease (MASLD) are common, and gut microbiota (GM) is involved with both. Here we compared GM composition in animal models of MASLD and ALD to assess whether there are specific patterns for each disease. Methods: MASLD model- adult male Sprague Dawley rats, randomized into two groups: MASLD-control (n=10) fed a standard diet; MASLD-group (n=10) fed a high-fat-choline-deficient diet for 16 weeks. ALD model- adult male Wistar rats randomized: ALD-control (n=8) fed a standard diet and water+0.05% saccharin, ALD groups fed with sunflower seed and 10% ethanol+0.05% saccharin for 4 or 8 weeks (ALC4, n=8; ALC8, n=8). ALC4/8 on the last day received alcoholic binge (5g/kg of ethanol). Afterwards, animals were euthanized, and feces were collected for GM analysis. Results: Both experimental models induced typical histopathological features of the diseases. Alpha diversity was lower in MASLD compared with ALD (p<0.001), and structural pattern was different between them (P<0.001). Bacteroidetes (55.7%), Firmicutes (40.6%), and Proteobacteria (1.4%) were the most prevalent phyla in all samples, although differentially abundant among groups. ALC8 had a greater abundance of the phyla Cyanobacteria (5.3%) and Verrucomicrobiota (3.2%) in relation to the others. Differential abundance analysis identified Lactobacillaceae_unclassified, Lachnospiraceae_NK4A136_group, and Turicibacter associated with ALC4 and the Clostridia_UCG_014_ge and Gastranaerophilales_ge genera to ALC8. Conclusion: In this study, we demonstrated that the structural pattern of the GM differs significantly between MASLD and ALD models. Studies are needed to characterize the microbiota and metabolome in both clinical conditions to find new therapeutic strategies. Background (ALD metabolicdysfunction metabolic dysfunction (MASLD common (GM Methods model MASLDcontrol control n=10 n10 n 10 (n=10 MASLDgroup group highfatcholinedeficient high fat choline deficient 1 ALDcontrol n=8 n8 (n=8 water005 water 0 05 water+0.05 ethanol005 ethanol ethanol+0.05 ALC4, ALC (ALC4 n=8. . n=8) ALC48 ALC4/ 5g/kg 5gkg gkg 5g kg g ethanol. ethanol) Afterwards euthanized Results diseases p<0.001, p0001 p p<0.001 , 001 (p<0.001) P<0.001. P0001 P P<0.001 (P<0.001) 55.7%, 557 55.7% 55 7 (55.7%) 40.6%, 406 40.6% 40 6 (40.6%) 1.4% 14 (1.4% samples 5.3% 53 5 3 (5.3% 3.2% 32 2 (3.2% others Lactobacillaceaeunclassified Lactobacillaceae unclassified Lactobacillaceae_unclassified LachnospiraceaeNK4A136group LachnospiraceaeNKAgroup Lachnospiraceae NK4A136 NK A Lachnospiraceae_NK4A136_group ClostridiaUCG014ge ClostridiaUCGge Clostridia UCG 014 ge Gastranaerophilalesge Gastranaerophilales Conclusion study strategies n=1 n1 (n=1 n= (n= water00 water+0.0 ethanol00 ethanol+0.0 (ALC p000 p<0.00 00 (p<0.001 P000 P<0.00 (P<0.001 55.7 (55.7% 40.6 (40.6% 1.4 (1.4 5.3 (5.3 3.2 (3.2 LachnospiraceaeNK NKA NK4A13 ClostridiaUCG 01 (n water0 water+0. ethanol0 ethanol+0. p00 p<0.0 (p<0.00 P00 P<0.0 (P<0.00 55. (55.7 40. (40.6 1. (1. 5. (5. 3. (3. NK4A1 water+0 ethanol+0 p0 p<0. (p<0.0 P0 P<0. (P<0.0 (55. (40. (1 (5 (3 NK4A water+ ethanol+ p<0 (p<0. P<0 (P<0. (55 (40 ( p< (p<0 P< (P<0 (4 (p< (P< (p (P

Abstract Background: Some evidence suggests an association between gut dysbiosis and cirrhosis progression. The authors investigated Gut Microbiome (GM) influence on 90-day mortality and hospitalization/rehospitalization rates in cirrhotic patients. Methods: Compensated/decompensated outpatients and decompensated inpatients were prospectively included and compared to healthy controls. Clinical, laboratory, GM, and two ratios between phyla were evaluated. Patients were followed up for 90 days for hospitalization/rehospitalization and mortality. Results: 165 individuals were included (50 compensated, 49 decompensated outpatients; 36 decompensated inpatients; 30 healthy), 48.5 % female, mean age was 61, main cirrhosis etiology was hepatitis C (27.3 %), and mostly Child-Pugh (CP) B patients, median MELD of 13. As liver disease progressed, microbiota diversity decreased between the groups (p = 0.05; p < 0.004). There were 9 deaths and 22 hospitalizations or rehospitalizations. GM composition had correlation with norfloxacin (p = 0.36, p = 0.04), encephalopathy (p = 0.31, p = 0.01), lactulose (p = 0.26, p = 0.01), 90-day mortality (p = 0.22, p = 0.04), CP (p = 0.17, p = 0.01), previous 6-month antibiotic use (p = 0.16, p = 0.01), MELD (p = 0.145, p = 0.01), ALBI (p = 0.1, p = 0.04) and 90-day hospitalization/rehospitalization (p = 0.08, p = 0.03). Firmicutes/Bacteroidetes (F/B) and Firmicutes/Proteobacteria (F/P) ratios were progressively lower and more significant and had an association with 90-day mortality (p < 0.001). Three MELD set-points (≥ 15, 18 and 20) were significantly associated with both ratios, with similar accuracies. Conclusions: GM dysbiosis was associated with higher CP, MELD, 90-day mortality and hospitalization/rehospitalization. F/B and F/P ratios were associated with 90-day mortality. Background progression (GM 90day day hospitalizationrehospitalization hospitalization rehospitalization patients Methods Compensateddecompensated Compensated controls Clinical laboratory evaluated Results 16 50 (5 compensated 4 3 healthy, , healthy) 485 48 5 48. female 61 27.3 273 27 (27. %, %) ChildPugh Child Pugh (CP 13 progressed 0.05 005 0 05 0.004. 0004 0.004 . 004 0.004) 2 rehospitalizations 036 0.36 0.04, 0.04 04 031 31 0.31 0.01, 001 0.01 01 0.01) 026 26 0.26 022 0.22 017 17 0.17 6month month 6 016 0.16 0145 145 0.145 1 0.1 008 08 0.08 0.03. 003 0.03 03 0.03) FirmicutesBacteroidetes Firmicutes Bacteroidetes FB F (F/B FirmicutesProteobacteria Proteobacteria FP P (F/P 0.001. 0001 0.001 0.001) setpoints set points ≥ ( 15 20 accuracies Conclusions 27. (27 0.0 00 000 0.00 0.3 02 0.2 014 14 0.14 0. (2

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. (CHC mundo (SBH 202 então médica consenso online on line atualizadas revisado saúde 20 2

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. (HCC cancerrelated cancer worldwide (SBH 202 then time singletopic single professionals policymakers, policymakers policy makers, makers policy-makers decisionmaking decision making 20 2

ABSTRACT Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as Nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in individuals with overweight or obesity. In this context, a panel of experts from three medical societies was organized to develop an evidence-based guideline on the screening, diagnosis, treatment, and follow-up of MASLD. Material and methods: A MEDLINE search was performed to identify randomized clinical trials, meta-analyses, cohort studies, observational studies, and other relevant studies on NAFLD. In the absence of studies on a certain topic or when the quality of the study was not adequate, the opinion of experts was adopted. Classes of Recommendation and Levels of Evidence were determined using prespecified criteria. Results: Based on the literature review, 48 specific recommendations were elaborated, including 11 on screening and diagnosis, 9 on follow-up, 14 on nonpharmacologic treatment, and 14 on pharmacologic and surgical treatment. Conclusions: A literature search allowed the development of evidence-based guidelines on the screening, diagnosis, treatment, and follow-up of MASLD in individuals with overweight or obesity. Introduction dysfunctionassociated dysfunction associated MASLD, , (MASLD) NAFLD, NAFLD (NAFLD) obesity context evidencebased evidence based diagnosis treatment followup follow up methods trials metaanalyses, metaanalyses meta analyses, analyses meta-analyses adequate adopted criteria Results review 4 elaborated 1 followup, up, Conclusions (MASLD (NAFLD

RESUMO 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.

ABSTRACT 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.

OBJECTIVE: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%, p<0.001) and a higher incidence of serious adverse events (50.7% vs. 34.8%, p<0.001). Multivariate analysis revealed that sustained viral response was associated with the absence of cirrhosis, viral recurrence after previous treatment, pretreatment platelet count greater than 100,000/mm3, and achievement of a rapid viral response. Female gender, age>65 years, diagnosis of cirrhosis, and abnormal hemoglobin levels/platelet counts prior to treatment were associated with serious adverse events. CONCLUSION: Although serious adverse events rates were higher in this infected population, sustained viral response rates were similar to those reported for other patient cohorts.

RESUMO Contexto A hepatite C é uma doença hepática que provoca alterações importantes no metabolismo e também tem impacto no estado nutricional. Objetivo Avaliar o estado nutricional e o risco cardiovascular em pacientes com hepatite C crônica. Métodos Este estudo transversal investigou 58 pacientes com hepatite C crônica, não cirróticos e que não estavam sob tratamento farmacológico ativo. Pacientes com consumo de álcool significativo (maior de 10 g de etanol/dia) foram excluídos. Os pacientes realizaram avaliação nutricional, através de medidas antropométricas, e avaliação funcional, através da medida da força do aperto de mão pela dinamometria. A prática de atividade física foi avaliada através do Questionário Internacional de Atividade Física. Os pacientes também passaram por avaliação clínica e laboratorial. O risco cardiovascular foi calculado pelo escore de Framingham. Resultados A média de idade dos pacientes foi 51,6±9,7 anos, 55,2% eram do sexo feminino, e 79,3% apresentavam genótipo 1. O grau de fibrose mais prevalente foi F1 (37,9%), seguido por F2 (27,6%) e F3 (1,7%). A prevalência de sobrepeso/obesidade considerando o índice de massa corporal foi de 70,7%. No entanto, 57,7% dos homens e 68,8% das mulheres foram considerados desnutridos de acordo com a força do aperto de mão. Estes pacientes também apresentaram circunferência da cintura (93,5±10,7 cm) e circunferência do pescoço (37,0±3,6 cm) elevados. Quase 60% dos pacientes foram considerados sedentários ou irregularmente ativos. Em relação ao risco cardiovascular, 50% dos pacientes apresentou elevado risco de sofrer evento cardiovascular em 10 anos. Conclusão Apesar de grande parte dos pacientes com hepatite C apresentarem excesso de peso, associado a alto risco cardiovascular, os mesmos também apresentaram diminuição da capacidade funcional, indicativa de comprometimento proteico-calórico. Portanto, o índice de massa corporal não pode ser considerado o único método de avaliação para diagnóstico nutricional de pacientes com doença hepática. Adotar métodos como a força do aperto de mão pode ser importante para uma melhor compreensão do estado nutricional destes pacientes.

ABSTRACT Background Hepatitis C is a liver disease that causes significant changes in metabolism, and also has an impact on nutritional status. Objective To evaluate the nutritional status and cardiovascular risk in patients with chronic hepatitis C. Methods This cross-sectional study investigated 58 patients with chronic hepatitis C, non-cirrhotic and were not under active pharmacological treatment. Patients with significant alcohol consumption (greater than 10 g ethanol/day) were excluded. Patients underwent nutritional assessment through anthropometric measurements and functional assessment using hand grip strength by dynamometry. The physical activity was assessed using the International Physical Activity Questionnaire. Patients also underwent clinical and laboratory evaluation. Cardiovascular risk was calculated by the Framingham score. Results The mean age of patients was 51.6±9.7 years, 55.2% were female, and 79.3% had genotype 1. The most prevalent degree of fibrosis was F1 (37.9%) followed by F2 (27.6%) and F3 (1.7%). The prevalence of overweight/obesity considering the body mass index was 70.7%. However, 57.7% of men and 68.8% of women were considered malnourished according to hand grip strength. These patients also had waist circumference (93.5±10.7 cm) and neck circumference (37.0±3.6 cm) high. Almost 60% of patients were considered sedentary or irregularly active. In relation to cardiovascular risk, 50% of patients had high risk of suffering a cardiovascular event within 10 years. Conclusion Although most patients with hepatitis C presented overweight, associated with high cardiovascular risk, they also have reduced functional capacity, indicative of protein-caloric commitment. Therefore, body mass index can not be considered the only method of assessment for nutritional diagnosis of patients with liver disease. Adopting methods such as hand grip strength can be important for a better understanding of nutritional status of these patients.

Protein-calorie malnutrition (PCM) is a prognostic factor increasing complications and mortality in chronic liver diseases. Objectives: To quantify the dietary intake and compare different methods of nutritional assessment in patients with chronic liver diseases. Ninety seven outpatients of Hospital de Clínicas de Porto Alegre, with chronic hepatits (CH) and cirrhosis (CIR), were assessed from April 2009 to January 2010. The CH patients presented higher calorie and protein intake (p<0.05) than the CIR patients. Malnutrition prevalence in CH and CIR groups by the Royal Free Hospital-Global Assessment (RFH) was 51.2 vs 84%, Hand Grip Strength 61 vs 82.1%, Subjective Global Assessment 14.6 vs 32.1%, Adductor Pollices Muscle 7.3 vs 14.3%, Arm Muscle Circumference 4.9 vs 14.3% and Body Mass Index2.4 vs 3.6% (p<0.05), respectively. HGS and RFH were the best methods to identify malnutrition and present concordance with each other.

La malnutrición se asocia con un peor pronóstico y mortalidad en pacientes con enfermedades crónicas del hígado. Objetivos: Cuantificar la ingesta alimentaria, y comparar diferentes métodos de evaluación nutricional en pacientes con hepatitis y cirrosis. Fueran estudiados 97 pacientes del ambulatorio del Hospital de Clínicas de Porto Alegre con hepatitis crónica (HC) y cirrosis (CIR), desde abril 2009 hasta enero 2010. Los pacientes con HC presentaron mayor consumo de calorías y proteínas por kilogramo de peso corporal (p<0,05) que los pacientes del grupo CIR. La prevalencia de desnutrición en los grupos HC y CIR fué: Royal Free Hospital-global assessment (RFH) 51,2 vs 84%, hand grip streght (HGS) 61 vs 82,1%, evaluación subjetiva global 14,6 vs 32,1%, músculo aductor del pulgar 7,3 vs 14,3%, circunferencia muscular del brazo 4,9 vs 14,3% y el indice de masa corporal 2,4 vs 3,6% (p<0,05). HFH y HGS fueron los métodos que mejor evidenciaron la malnutrición habiendo concordancia entre ellos.

CONTEXTO: Dados da literatura atual sugerem piores resultados quando os transplantes hepáticos são realizados com enxertos provenientes de doadores idosos. O uso da solução Universidade de Wisconsin (UW) é universal; entretanto alternativas como a fructose-1,6-bisfosfato (FBP) vêm sendo estudadas. OBJETIVOS: Determinar o impacto do envelhecimento do doador no dano de isquemia a frio em fígados de ratos, comparando as soluções de FBP e UW. MÉTODOS: Vinte ratos Wistar foram estudados - 10 com 20 semanas: 5 preservados com UW (C-UW) e 5 com FBP (C-FBP); e outros 10, com 50 semanas: 5 com UW (E-UW) e 5 com FBP (E-FBP). A preservação durou 8 horas. Foram dosadas AST e LDH nas alíquotas do líquido de preservação a cada 2 horas. RESULTADOS: Os níveis de AST e LDH foram superiores no grupo (C-UW) (P<0.05). Quando comparadas UW x FBP no grupo de idosos houve diferença quanto à LDH, mas não com a AST. CONCLUSÃO: A preservação dos fígados de ratos idosos foi similar aos dos controles, quando preservados com FBP. Quando utilizada UW, a lesão de preservação foi menor no grupo de ratos idosos. A FBP minimizou a isquemia a frio nos controles, quando comparada a UW. Houve tendência de a FBP ser superior a UW no grupo idosos.

CONTEXT: There are consistent clues of worse results with grafts from older donors, especially in hepatitis C. University of Wisconsin (UW) solution is adopted for liver preservation, but other solutions are being studied, as fructose-1,6-bisphosphate (FBP). OBJECTIVE: To determinate the impact of aging of the donor on the cold ischemia injury in rat livers and compare UW and FBP. METHODS: Twenty male Wistar rats were studied - 10, aging 20 weeks: 5 to preservation with UW (C-UW) and 5, FBP (C-FBP); and other 10, aging 50 weeks: 5 to UW (E-UW) and 5 to FBP (E-FBP). Rats were anesthesized, submitted to hepatectomy, and graft was kept under 2-4ºC for 8 hours. Liquid samples were taken at 2, 4, 6, and 8 hours, to determine AST and LDH. At the end, in the liver tissue thiobarbituric acid reactive substances and catalase were determined. RESULTS: Average liver weight was similar between controls and the others (12.5 g ± 1.8 and 13.4 g ± 2.0). AST and LDH levels were higher in C-UW group (P<0.05). In the older group, there was a difference between UW and FBP preserved livers related to LDH, but not to AST. Thiobarbituric acid reactive substances were superior in control group than in the older one (P = 0.001). Catalase activity was similar between these groups (P = 0.11), but it was superior in UW preserved animals (P = 0.02). CONCLUSION: Livers from older rats were similar to the controls regarding cold ischemia injury in FBP group. Surprisingly, with UW solution there was less cold ischemia injury in the elderly group. When comparing both solutions, FBP provided significantly more protection than UW in the controls. There was a trend to FBP to being better than UW in the elderly group. Further studies with liver from older donors and ischemia and reperfusion are needed.

CONTEXTO: Cirrose, diabetes mellitus, intolerância à glicose e resistência insulínica é uma associação que vem sendo discutida, bem como a desnutrição nesta população, pelo risco de pior evolução de hepatopatia. OBJETIVO: Determinar a prevalência de diabetes mellitus, intolerância à glicose e resistência insulínica e desnutrição protéico-calórica em cirróticos (vírus C+ ou -) candidatos a transplante hepático e avaliar a capacidade diagnóstica dos testes de diabetes mellitus e seu impacto na evolução em 3 meses. MÉTODOS: Estudo transversal prospectivo de pacientes consecutivos, com avaliação de diabetes mellitus por glicemia de jejum e/ou teste de tolerância oral à glicose, cálculo dos índices HOMA-IR e avaliação nutricional através da avaliação subjetiva global, antropometria e força do aperto de mão não-dominante. RESULTADOS: Sessenta e quatro virgula cinco por cento tinham diabetes mellitus, 9 (22,5%) deles foram diagnosticados por glicemia de jejum e 31 (77,5%) por tolerância oral à glicose. A resistência insulínica foi encontrada em 40 pacientes (69%). Não houve relação com a causa da cirrose. A desnutrição protéico-calórica foi encontrada em 3,22% dos pacientes através do índice de massa corporal, 45,2% por antropometria, 58,1% pela avaliação subjetiva global e 88,7% pela força do aperto de mão não-dominante. Houve associação entre diabetes mellitus diagnosticado pelo teste de tolerância oral à glicose e a maior prevalência de complicações infecciosas e/ou morte em 3 meses (P = 0,017). CONCLUSÃO: A prevalência de diabetes mellitus, intolerância à glicose, resistência insulínica e desnutrição protéico-calórica é alta em cirróticos em lista de transplante hepático. A evolução em 3 meses é pior quando há diabetes mellitus. O teste de tolerância oral à glicose teve rendimento superior à glicemia de jejum no diagnóstico de diabetes mellitus. Sugere-se o emprego rotineiro de teste de tolerância oral à glicose nesta população.

CONTEXT: Cirrhosis, diabetes mellitus, impaired glucose tolerance, insulin resistance, and protein calorie malnutrition are important issues in cirrhotic patients because they can increase the progression of liver disease and worsen its prognosis. OBJECTIVE:To determine the prevalence of diabetes mellitus, impaired glucose tolerance and insulin resistance in cirrhotic patients being evaluated for liver transplantation and their impacts on a 3-month follow-up, and to compare fasting glycemia and oral glucose tolerance test. METHODS: A cross-sectional study was performed in consecutively included adult patients. Diabetes mellitus was established through fasting glycemia and oral glucose tolerance test in diagnosing diabetes mellitus in this population. HOMA-IR and HOMA-β indexes were calculated, and nutritional assessment was performed by subjective global assessment, anthropometry and handgrip strength through dynamometry. RESULTS: Diabetes mellitus was found in 40 patients (64.5%), 9 (22.5%) of them by fasting glycemia and 31 (77.5%) of them by oral glucose tolerance test. Insulin resistance was found in 40 (69%) of the patients. There was no relationship between diabetes mellitus and the etiology of cirrhosis. Protein calorie malnutrition was diagnosed in a range from 3.22% to 45.2% by anthropometry, 58.1% by subjective global assessment and 88.7% by handgrip strength. Diabetes mellitus identified by oral glucose tolerance test was related significantly to a higher prevalence of infectious complications and deaths in a 3-month period (P = 0.017). CONCLUSION: The prevalence of diabetes mellitus, impaired glucose tolerance, insulin resistance and protein calorie malnutrition is high in cirrhotic patients on the waiting list for liver transplantation. There were more infectious complications and/or deaths in a 3-month follow-up period in patients with diabetes mellitus diagnosed by oral glucose tolerance test. Oral glucose tolerance test seems to be indicated as a routine practice in this population.

RACIONAL: Infecções são a causa principal de morbimortalidade em pacientes submetidos a transplantes hepáticos. OBJETIVO: Avaliar as principais características destas infecções em pacientes de um hospital universitário do sul do Brasil. MÉTODO: Uma coorte retrospectiva foi conduzida com os 55 pacientes transplantados hepáticos adultos cuja cirurgia foi realizada entre 1996 e 2000 no Hospital de Clínicas de Porto Alegre, RS, todos aos eventos infecciosos que ocorreram nesta população foram registrados. RESULTADOS: Uma ou mais infecções (média 2,1 episódios) foram diagnosticadas em 47 pacientes, o período de maior ocorrência destas foi o primeiro mês após a cirurgia. As infecções mais comuns foram: bacteremias, infecções intra-abdominais e pneumonias, a etiologia mais freqüente foi bacteriana, sendo os germes mais comuns os estafilicocos (em particular o S. aureus) e a E. coli. A taxa de mortalidade associada a infecções foi elevada: 17 óbitos de todos observados na coorte (27 no total). Os fatores de risco para infecção estatisticamente significantes foram: reoperação, diabetes, estenose de via biliar e classificação de Child-Pugh elevada. CONCLUSÃO: As infecções continuam sendo grave ameaça aos pacientes transplantados hepáticos e intenso esforço, que envolve o conhecimento da epidemiologia microbiológica, pesquisa e acompanhamento dos pacientes deve ser empregado, para prevenir e tratar de forma adequada estas complicações.

BACKGROUND: Infections after liver transplantations are the most important cause of morbi-mortality. In this study, we assessed the main characteristics of these infections in a southern Brazilian university hospital. METHODS: We conducted a retrospective cohort with 55 patients who underwent orthotopic liver transplantation between 1996 and 2000 in the "Hospital de Clínicas de Porto Alegre", Porto Alegre, RS, Brazil, to characterize the infections that occurred in the group. RESULTS: One or more infections (average 2.10) were diagnosed in 47 patients, especially during the first month after transplantation. The most common were bacteremia, intra-abdominal infections and pneumonia, predominantly with bacteria, especially Staphylococcus sp (and particularly S. aureus) and E. coli. The mortality rate attributed to infections was high: 17 cases of all deaths (total 27 deaths). Significant risk factors for infections included reoperation, diabetes, biliary stenosis and higher Child-Pugh scores. CONCLUSION: Infections remain a severe threat in liver transplant patients, and special efforts should be made to prevent and manage them correctly.

RACIONAL: A desnutrição é freqüente em cirróticos, mas sua avaliação é difícil. A predição do gasto energético basal pela equação de Harris-Benedict não está validada neste grupo. A alternativa seria mensurá-la através da calorimetria indireta. OBJETIVOS: Realizar avaliação nutricional em cirróticos, aferir o gasto energético basal pela calorimetria indireta e compará-lo ao estimado pela equação de Harris-Benedict. MATERIAL E MÉTODOS: Estudaram-se 34 adultos com cirrose pelo vírus da hepatite C, em acompanhamento ambulatorial, classificados de acordo com Child-Pugh e escore "model of end-stage liver disease". O gasto energético basal foi estimado pela equação de Harris-Benedict e medido pela calorimetria indireta. Avaliação nutricional foi realizada por antropometria, avaliação nutricional subjetiva global, dinamometria e inquérito recordatório. RESULTADOS: Em relação à classificação de Child-Pugh, 15 (44,2%) eram A, 12 (35,3%) B e 7 (20,6%) C e 33 (97,1%) apresentaram valores inferiores a 20 no escore "model of end-stage liver disease". O gasto energético basal estimado foi maior do que o medido (Harris-Benedict 1404,5 ± 150,3 kcal; calorimetria indireta 1059,9 ± 309,6 kcal). A prevalência de desnutrição variou entre os métodos (índice de massa corpórea, circunferência muscular do braço, avaliação nutricional subjetiva global, prega cutânea do tríceps e dinamometria: 0%; 5,9%; 17,6%; 35,3% e 79,4%, respectivamente). A ingestão calórica e protéica foi de 80% e 85% do recomendado, com inadequação na ingestão de cálcio, magnésio, ferro e zinco. CONCLUSÕES: A desnutrição foi freqüente. A dinamometria parece ser o melhor método para o diagnóstico. A ingestão foi inadequada. Considerando que o gasto energético basal estimado foi superior ao medido e a necessidade de maior aporte calórico, a utilização da equação de predição talvez possa substituir a calorimetria indireta.

BACKGROUND: Malnutrition is frequent in cirrhotic patients, and its assessment is difficult. Functional assessment through a dynamometer is a simple method and could minimize these drawbacks. Harris-Benedict prediction formulae estimates the resting energy expenditure but has not been validated for this population. One alternative is the use of indirect calorimetry. AIM: To assess nutritional status in cirrhotic patients and estimates the resting energy expenditure through indirect calorimetry and compares it to Harris-Benedict. PATIENTS AND METHODS: Thirty four adult hepatitis C cirrhotic outpatients were studied, classified by Child-Pugh and model of end-stage liver disease score. The resting energy expenditure was predicted through Harris-Benedict and measured by indirect calorimetry. Nutritional assessment was done through anthropometry, subjective global assessment, hand-grip strength and a 3-day recall. RESULTS: Fifteen (44.2%) were Child-Pug A, 12 (35.3%) B and 7 (20.6%) C, and 33 (97.1%) had model of end-stage liver disease scores less than 20. The resting energy expenditure predicted was higher than the measured (Harris-Benedict 1404.5 ± 150.3 kcal; indirect calorimetry 1059.9 ± 309.6 kcal). The prevalence of malnutrition varied between methods (body mass index, muscle arm circumference, subjective global assessment, triceps skinfold thickness and hand-grip strength: 0; 5.9; 17.6; 35.3 and 79.4%, accordingly). Calories and proteins intake were 80% and 85% of recommended amounts and there was inadequate intake of calcium, magnesium, iron and zinc. CONCLUSION: Malnutrition was frequent and hand-grip strength seemed to be the most sensitive method for its diagnosis. Calories and protein intakes were inadequate. Considering that the predicted resting energy expenditure was higher than the measured one and the need to offer higher caloric intake, the use of the predicting equation may replace indirect calorimetry.

RACIONAL: O transplante hepático é o tratamento de escolha para várias doenças hepáticas terminais. A desnutrição nesta população é freqüente. O uso de nutrição enteral precoce não é rotina nos grupos de transplante. OBJETIVO: Relatar a experiência do uso de nutrição enteral precoce em indivíduos transplantados hepáticos e avaliar sua segurança. PACIENTES/MÉTODOS: Foram estudados 35 adultos submetidos a transplante hepático. A avaliação do estado nutricional pré-transplante hepático foi realizada pela avaliação nutricional subjetiva global e força do aperto da mão não-dominante, aferida pela dinamometria. A dieta enteral foi iniciada em até 12 horas. A via oral foi iniciada assim que houvesse ruídos hidroaéreos. RESULTADOS: A média de idade dos indivíduos avaliados foi de 45,5 anos (± 8,93). De acordo com a avaliação nutricional subjetiva global, a prevalência de desnutrição pré-transplante foi de 77,1% e pela força do aperto da mão não-dominante de 100%. A nutrição enteral precoce foi iniciada em até 12 horas, moda de 10,9 horas e mantida exclusivamente por período médio de 2,6 dias (± 2,2). Via oral exclusiva foi obtida no período médio de 9,5 dias (± 9,7). A nutrição enteral precoce proveu o aporte calórico estimado em 97% dos casos. Intolerância à dieta enteral ocorreu em cinco indivíduos (14,2%), sendo que em quatro foi reinstituída com sucesso após intervalo de 12 horas. A prevalência de infecção respiratória foi de 28,6%. Em apenas dois pacientes (5,7%) houve broncopneumonia com aspecto aspirativo ao estudo radiológico do tórax. CONCLUSÕES: A nutrição enteral precoce foi um método eficaz na provisão de calorias e seguro em sua aplicação a pacientes transplantados hepáticos.

BACKGROUND: Orthotopic liver transplantation is the treatment of choice for end-stage liver disease. Malnutrition is common in this population. Early enteral nutrition is not routine in the transplant groups. AIM: To report our experience with the use of early enteral nutrition in patients undergoing orthotopic liver transplantation and also evaluate its safety. PATIENTS/METHODS: We studied 41 adults submitted to orthotopic liver transplantation. Pre- orthotopic liver transplantation nutritional assessment was accomplished by the subjective global assessment and grip strength. Enteral nutrition was begun in 12 hours. Oral feeding was initiate gradually as soon as possible. RESULTS: We studied 35 individuals, with an average of age of 45.5 years (8.93). The prevalence of malnutrition in orthotopic liver transplantation was of 77.1% determined by subjective global assessment, and 100% by grip strength. Early enteral nutrition was begun in all of the individuals in up to 12 hours, mode 10.9 hours, and maintained exclusively by medium period of 2.6 days (2.2). Oral feeding was obtained in the medium period of 9.5 days (9.7). Early enteral nutrition provided total caloric intake in 97% of the cases. Intolerance to the enteral feeding occurred in five individuals (14.2%), and in four of them it was resumed successfully after 12 hours. The prevalence of respiratory infection was of 28.6%. In only two patients (5.7%) there was aspirative bronchopneumonia. CONCLUSIONS: Early enteral nutrition is an effective method in the provision of calories and safe in application to patients undergoing orthotopic liver transplantation.