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Introduction and Objectives: Public health policies in metabolic dysfunction-associated steatotic liver disease (MASLD) are still lacking. This study aims to estimate the prevalence and severity of MASLD in primary health care (PHC) through non-invasive markers. Patients and Methods: Two-phase study, including a retrospective (RETR) and a prospective (PROS) one, was carried out in PHC in Brazil. In RETR, metabolic and hepatic profiles of 12,054 patients, including FIB-4, were evaluated. In PROS, 350 patients were randomly selected and submitted to a clinical and nutritional assessment. Results: RETR (65.4 % women, mean age 55.3 years old): dyslipidemia, hypertension, and type 2 diabetes mellitus (T2DM) present in 40.8 %, 34.3 %, and 12.2 % of the electronic health records, respectively. Fasting glucose >100 mg/dL in 34.5 %, and glycated hemoglobin higher than 5.7 % in 51.5 %, total cholesterol >200 mg/dL and triglycerides >150 mg/dL in 40.8 % and 32.1 %, respectively. Median FIB-4 was of 1.33, 5 % >2.67. No one had MASLD as a diagnostic hypothesis; PROS (71.8 % women, mean age 58 years old): body mass index (BMI) ≥30 kg/m² in 31.8 %. MASLD prevalence (FLI≥ 30 + cardiometabolic features) of 62.1 %; 39.4 % of patients had FLI ≥60, with higher BMI, waist circumference, fasting glucose, triglycerides, AST, ALT and GGT, as well as lower HDL-cholesterol (p < 0.001). FIB-4>1.3 in 40 % and NAFLD Fibrosis Score (NFS)>-1.45 in 59.2 % of steatotic patients. Conclusions: There is a high prevalence of MASLD in PHC, with a significant risk of liver fibrosis. These findings reinforce we need to develop public policies to defeat MASLD epidemics.

Background and aimConsidering the increasing prevalence of non-alcoholic steatohepatitis (NASH) and treatment gaps, this study aimed to evaluate the effect of probiotic supplementation on liver function markers, nutritional status, and clinical parameters.MethodsThis double-blind, randomized clinical trial (ClinicalTrials.gov ID: NCT0346782) included adult outpatients with biopsy-proven NASH. The intervention consisted of 24 weeks of supplementation with the probiotic mix Lactobacillus acidophilus (1 × 109 CFU) + Lactobacillus rhamnosus (1 × 109 CFU) + Lactobacillus paracasei (1 × 109 CFU) + Bifidobacterium lactis (1 × 109 CFU), or placebo, twice a day. The following parameters were evaluated: demographic and clinical data, transient elastography (FibroScan), liver enzymes, NAFLD fibrosis score, fatty liver index, laboratory assessment, serum concentration of toll-like receptor-4 (sTLR-4) and cytokeratin 18 (CK-18), anthropometric data, dietary intake, and physical activity. Regarding data analysis, the comparison between the groups was based on the delta of the difference of each variable analyzed (value at the end of treatment minus the baseline value) using the t-test for independent samples or the Mann–Whitney U-test.ResultsForty-four patients with NASH completed the trial (51.4 ± 11.6 years). At baseline, 87% of participants had a mild liver fibrosis degree on biopsy, normal values of liver enzymes, transient elastography values consistent with grade 1 fibrosis in both groups, increased waist circumference (WC), a BMI of 30.97 kg/m2, and 76% presented with metabolic syndrome (MetS). After the intervention, no differences were observed between the probiotic and placebo groups in terms of MetS, WC, BMI scores, or liver enzyme levels (p > 0.05 for all). The elastography values remained consistent with grade 1 fibrosis in both groups. Although CK-18 was reduced in both groups, a larger effect size was noted in the probiotic group (D = 1.336). sTLR-4 was also reduced in both groups, with no difference between groups (p = 0.885).ConclusionIntervention with probiotics in the early stages of NASH demonstrated no significant change in hepatic and clinical parameters.Clinical trial registrationClinicalTrials.gov, identifier NCT0346782.

Chlorella vulgaris and Tetradesmus obliquus were tested as biocontrol agents against the phytopathogenic fungus Fusarium oxysporum. This evaluation was conducted through in vitro and in vivo trials with spinach (Spinacia oleracea L.). The in vitro trials showed that C. vulgaris and T. obliquus were able to inhibit the phytopathogen, showing a similar inhibitory effect to that of the positive controls (Rovral, BASF® and Biocontrol T34, Biocontrol Technologies® S.L.). C. vulgaris aqueous suspensions at 3.0 g L−1 led to a hyphal growth of 0.55 cm, each corresponding to a reduction of 63% of fungal growth. With T. obliquus, the hyphal growth was 0.53 cm when applied at a concentration of 0.75 g L−1, having an inhibition of fungus growth of 64%. Thereafter, these results were validated in an in vivo trial on spinach using the same controls. The results revealed a lower severity and disease incidence and a reduction in the disease’s AUDPC (area under the disease progress curve) when spinach was treated with the microalgae suspensions. Overall, these findings highlight the potential of C. vulgaris and T. obliquus suspensions as promising biocontrol agents against F. oxysporum in spinach when applied through irrigation.

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 and Objectives: Cardiovascular disease (CVD) is the major cause of death in non-alcoholic fatty liver disease (NAFLD), a clinical condition without any approved pharmacological therapy. Probiotics are often indicated for the disease, but their results are controversial in part due to the poor quality of studies. Thus, we investigated the impact of 24-week probiotics supplementation on cardiovascular risk (CVR) in biopsy-proven non-alcoholic steatohepatitis (NASH) patients. Patients and Methods: Double-blind, placebo-controlled, single-center study (NCT03467282), adult NASH, randomized for 24 weeks daily sachets of probiotic mix (109CFU of Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus paracasei and Bifidobacterium lactis) or placebo. Clinical scores (atherogenic indexes, atherosclerotic cardiovascular disease-ASCVD and systematic coronary risk evaluation-SCORE), biochemistry, miR-122, miR-33a, plasminogen activator inhibitor-1 (PAI-1), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), were determined before and after the intervention. Results: Forty-six patients were enrolled (23 received probiotics and 23 placebo), with a mean age of 51.7 years, most of them females and whites. Clinical and demographic features were similar between the groups at the baseline. The Median NAFLD activity score was 4.13 in both groups. Fibrosis was mild in most patients (15.2% and 65.2% F0 and F1, respectively). Treatment did not promote any clinically significant changes in body mass index or laboratory, including lipid and glucose profile. High CVR patients through atherogenic indexes decreased from baseline in both groups, as well as PAI-1 and miR-122 levels, although there was no difference between probiotics and placebo. Conclusions: A 24-week probiotic mix administration was not superior to placebo in reducing CVR markers in patients with NASH.

Introduction and Objectives: Liver fibrosis is an important prognosis marker in non-alcoholic fatty liver disease (NAFLD). Biopsy has been considered the gold-standard method for measuring liver fibrosis; however, it is an invasive procedure. Non-invasive diagnostic tools have been developed, such as clinical scores and magnetic resonance elastography (MRE), which is the most accurate non-invasive method to determine liver fibrosis. Thus, the aim was to determine the NAFLD Fibrosis Score (NFS) and the Fibrosis-4 Score (FIB-4) cut-off points that best identify NAFLD patients at risk for developing liver fibrosis. Patients and Methods: Single-center cross-sectional study with prospective recruitment of NAFLD (training-cohort) and MAFLD (validation-cohort) patients undergoing MRE. The NFS and the FIB-4 cut-off points that best-differentiated patients with fibrosis, using the MRE as the standard method, were determined. Results: Two cohorts were analyzed, a training cohort that included the initial 183 patients with NAFLD and a validation cohort that included 289 patients. In the training cohort, 60.1% had mild steatosis and 11.5% had liver fibrosis ≥ F1 by MRE. ROC curves were developed for FIB-4 and NFS, and the cut-off points chosen were 1.505 (sensitivity=85% and specificity=86%) for FIB-4 and -0.835 (sensitivity=100% and specificity=70%) for NFS, showing greater specificity than the cut-off points currently used (51% and 76%, respectively). The two cohorts exhibited similar characteristics and similar sensitivity and specificity results for the chosen cut-off points. Conclusions: This study has shown cut-off points with greater specificity and excellent sensitivity to guide the indication for further liver evaluation by MRE in NAFLD patients.

Introdução: O tacrolimo é um dos imunossupressores mais utilizados em pacientes após transplante hepático e com frequência se observa uma grande variação no seu nível sanguíneo (NS). Avaliar o tempo médio para se alcançar o NS alvo de tacrolimo pós-transplante hepático é fundamental, pois níveis muito baixos aumentam as chances de rejeição ao enxerto, e níveis muito altos estão associados a toxicidade. Método: Estudo de coorte observacional, retrospectivo, conduzido no Hospital de Clínicas de Porto Alegre. Foram incluídos pacientes transplantados hepáticos entre dezembro de 2012 e dezembro de 2017 em uso de tacrolimo via oral. Foram considerados com NS alvo pacientes que atingiram NS entre 6–8 ng/mL durante o primeiro mês pós-transplante. Resultados: 78% (67/87) dos pacientes atingiram o NS alvo em até 10 dias após o transplante hepático. Pacientes que apresentaram rejeição ao longo de 1 ano após o transplante demoraram em torno de 9 dias para atingir o NS alvo durante a internação-índice versus 7 dias em pacientes que não apresentaram rejeição. Conclusão: Nosso trabalho, ao considerar alvo terapêutico valores entre 6–8 ng/mL em pacientes pós-transplante imediato de fígado, demonstrou que essa população teve um tempo médio que parece determinar bom prognóstico, uma vez que, em menos de 2 semanas, 78% dos pacientes atingiram NS alvo perto do preconizado.

Summary: The muscle fiber morphometric analysis (MusMA) is a protocol to segment and characterize the morphometry of individual cross-sectioned striated muscle fibers. Using a semi-automated Excel spreadsheet, the protocol allows the objective measurement of muscle fibers’ subpopulations, aiming to characterize physiopathological conditions related to muscle tissue. The main limitation of MusMA is the need for high-quality tissue slides and images and control samples to set up the analyses. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Obesity is key to liver steatosis development and progression. Transcranial direct current stimulation (tDCS) is a promising tool for eating disorders management but was not yet evaluated in steatosis. This study investigated tDCS’ effects on liver steatosis and inflammation in an experimental obesity model. Male Wistar rats (60 days-old) were randomly allocated (n = 10/group) as follows: standard-diet/sham tDCS (SDS), standard-diet/tDCS (SDT), hypercaloric-cafeteria-diet/sham tDCS (HDS), and hypercaloric-cafeteria-diet/tDCS (HDT). After 40 days of diet, animals received active or sham tDCS for eight days and were euthanized for liver fat deposition and inflammation analysis. HDS and HDT animals showed cumulative food consumption, total liver lipid deposits, IL-1β, TNF-α levels, IL-1β/IL-10 and TNF-α/IL-10 ratios significantly higher than the SDS and SDT groups (p

Abstract The prevalence of anti-hepatitis E virus (HEV) antibodies has a high heterogeneity worldwide. South American data are still scarce. The aim of this study was to evaluate the prevalence of HEV in populations at risk in comparison to blood donors (BD). A cross-sectional study was carried out in adults of different risk populations including crack users (CK), residents in a low income area (LIA), cirrhotic (CIR) and liver transplant patients (LT) compared with BD. The WANTAI HEV ELISA test was used and real-time PCR (in-house for screening and ALTONA as confirmatory test) for HEV RNA screening. A total of 400 participants were included. Anti-HEV IgG was positive in 19.5% of the total sample, reaching the highest rate in the CIR group, 22.5%, followed by CK, LT, and LIA (20%, 18.7%, and 17.5%, respectively). The prevalence found in BD individuals was of 18.7% (p = NS). Anti-HEV IgM was positive in only 1.5% of the sample (6/400). No blood or stools samples were positive for HEV RNA. The seroprevalence reported is among the highest rates ever found in Brazil. Considering the intense diagnostic investigation, data show that HEV circulation is more common that might be expected in our country.

ABSTRACT Over the last years, there is growing evidence that microorganisms are involved in the maintenance of our health and are related to various diseases, both intestinal and extraintestinal. Changes in the gut microbiota appears to be a key element in the pathogenesis of hepatic and gastrointestinal disorders, including non-alcoholic fatty liver disease, alcoholic liver disease, liver cirrhosis, inflammatory bowel disease, irritable bowel syndrome, and Clostridium difficile - associated diarrhea. In 2019, the Brazilian Society of Hepatology (SBH) in cooperation with the Brazilian Nucleus for the Study of Helicobacter Pylori and Microbiota (NBEHPM), and Brazilian Federation of Gastroenterology (FBG) sponsored a joint meeting on gut microbiota and the use of prebiotics, probiotics, and synbiotics in gastrointestinal and liver diseases. This paper summarizes the proceedings of the aforementioned meeting. It is intended to provide practical information about this topic, addressing the latest discoveries and indicating areas for future studies.

Non-alcoholic fatty liver disease (NAFLD) currently represents an epidemic worldwide. NAFLD is the most frequently diagnosed chronic liver disease, affecting 20–30% of the general population. Furthermore, its prevalence is predicted to increase exponentially in the next decades, concomitantly with the global epidemic of obesity, type 2 diabetes mellitus (T2DM), and sedentary lifestyle. NAFLD is a clinical syndrome that encompasses a wide spectrum of associated diseases and hepatic complications such as hepatocellular carcinoma (HCC). Moreover, this disease is believed to become the main indication for liver transplantation in the near future. Since NAFLD management represents a growing challenge for primary care physicians, the Asociación Latinoamericana para el Estudio del Hígado (ALEH) has decided to organize this Practice Guidance for the Diagnosis and Treatment of Non-Alcoholic Fatty Liver Disease, written by Latin-American specialists in different clinical areas, and destined to general practitioners, internal medicine specialists, endocrinologists, diabetologists, gastroenterologists, and hepatologists. The main purpose of this document is to improve patient care and awareness of NAFLD. The information provided in this guidance may also be useful in assisting stakeholders in the decision-making process related to NAFLD. Since new evidence is constantly emerging on different aspects of the disease, updates to this guideline will be required in future.

Abstract Background Elastic fibers deposition is triggered during liver fibrosis and is related to worse clinical prognosis in chronic hepatitis C patients. This study aimed to verify if a new method for elastic fiber quantification can be used to discriminate between different degrees of fibrosis in liver biopsies of patients with hepatitis C. Methods Individuals presenting with different degrees of fibrosis in liver biopsy were included. Slides of liver samples were stained with orcein with and without prior oxidation. Morphometric analysis was proceeded, and quantification accomplished by corrected integrated density. Results Twenty-seven patients, mean age 52 years-old, 59% women, were included. Elastic fibers density was higher in advanced fibrosis patients and there was a positive correlation with Metavir score (Spearman r = 0.609, p

Metabolic dysfunction-associated fatty liver disease (MAFLD) has gained worldwide attention as a public health problem. Nonetheless, lack of enough mechanistic knowledge restrains effective treatments. It is known that thyroid hormone triiodothyronine (T3) regulates hepatic lipid metabolism, and mitochondrial function. Liver dysfunction of type 3 deiodinase (D3) contributes to MAFLD, but its role is not fully understood. Objective: To evaluate the role of D3 in the progression of MAFLD in an animal model. Methodology: Male/adult Sprague Dawley rats (n = 20) were allocated to a control group (2.93 kcal/g) and high-fat diet group (4.3 kcal/g). Euthanasia took place on the 28th week. D3 activity and expression, Uncoupling Protein 2 (UCP2) and type 1 deiodinase (D1) expression, oxidative stress status, mitochondrial, Krebs cycle and endoplasmic reticulum homeostasis in liver tissue were measured. Results: We observed an increase in D3 activity/expression (p < 0.001) related to increased thiobarbituric acid reactive substances (TBARS) and carbonyls and diminished reduced glutathione (GSH) in the MAFLD group (p < 0.05). There was a D3-dependent decrease in UCP2 expression (p = 0.01), mitochondrial capacity, respiratory activity with increased endoplasmic reticulum stress in the MAFLD group (p < 0.001). Surprisingly, in an environment with lower T3 levels due to high D3 activity, we observed an augmented alpha-ketoglutarate dehydrogenase (KGDH) and glutamate dehydrogenase (GDH) enzymes activity (p < 0.05). Conclusion: Induced D3, triggered by changes in the REDOX state, decreases T3 availability and hepatic mitochondrial capacity. The Krebs cycle enzymes were altered as well as endoplasmic reticulum stress. Taken together, these results shed new light on the role of D3 metabolism in MAFLD.

Cardiovascular (CV) disease is the main cause of death in nonalcoholic fatty liver disease (NAFLD), a clinical condition without any approved pharmacological therapy. Thus, we investigated the effects of ornithine aspartate (LOLA) and/or Vitamin E (VitE) on CV parameters in a steatohepatitis experimental model. Adult Sprague Dawley rats were randomly assigned (10 animals each) and treated from 16 to 28 weeks with gavage as follows: controls (standard diet plus distilled water (DW)), NAFLD (high-fat choline-deficient diet (HFCD) plus DW), NAFLD+LOLA (HFCD plus LOLA (200 mg/kg/day)), NAFLD+VitE (HFCD plus VitE (150 mg twice a week)) or NAFLD+LOLA+VitE in the same doses. Atherogenic ratios were higher in NAFLD when compared with NAFLD+LOLA+VitE and controls (p < 0.05). Serum concentration of IL-1β, IL-6, TNF-α, MCP-1, e-selectin, ICAM-1, and PAI-1 were not different in intervention groups and controls (p > 0.05). NAFLD+LOLA decreased miR-122, miR-33a, and miR-186 (p < 0.05, for all) in relation to NAFLD. NAFLD+LOLA+VitE decreased miR-122, miR-33a and miR-186, and increased miR-126 (p < 0.05, for all) in comparison to NAFLD and NAFLD+VitE. NAFLD+LOLA and NAFLD+LOLA+VitE prevented liver collagen deposition (p = 0.006) in comparison to NAFLD. Normal cardiac fibers (size and shape) were lower in NAFLD in relation to the others; and the inverse was reported for the percentage of regular hypertrophic cardiomyocytes. NAFLD+LOLA+VitE promoted a significant improvement in atherogenic dyslipidemia, liver fibrosis, and paracrine signaling of lipid metabolism and endothelial dysfunction. This association should be further explored in the treatment of NAFLD-associated CV risk factors.

Introduction: Calculation of the Tacrolimus variation index by using the MLVI (Medication Level Variability Index) is set in pediatric liver transplant patients, and it is useful in controlling treatment adherence by associating MLVI values > 2.5 to acute graft liver rejection. Purpose: To verify the association between MLVI values and rejection in adult liver transplant patients. Methods: A retrospective cohort study including liver transplant patients over 18 years of age from December 2012 to December 2017 using orally tacrolimus. For MLVI calculation, tacrolimus serum level outpatient samples were used after 1 year of transplantation. Results: A total of 125 patients were transplanted, of which 86 met criteria for inclusion in the study. The most frequent reason for transplantation was C virus infection (55.8%, n = 48). Rejection was identified in 18.6% of patients (n = 16). The mean MLVI among rejection and nonrejection patients was 2.5 and 2.1 respectively (RR = 0.95, CI: 0.4-2.1, p = 0.57). The frequency of non-immunological complications was 56.2% (n = 9) in patients with rejection versus 62.8% (n = 44) in patients without rejection, most of them with recurrence of virus C (56,8%, n = 25). Conclusion: Although the mean value of MLVI was higher in patients with rejection, our data showed no statistical difference between both groups, which differs from previous studies in pediatric patients. A higher number of nonimmune complications were observed in patients without rejection. The findings suggest that new MLVI cutoffs should be explored in the adult population.

El conjunto rupestre al aire libre del Arroyo de las Almas (La Fregeneda, Salamanca), situado junto al encuentro de los ríos Águeda y Duero, tiene, al menos, 600 motivos grabados con una amplia secuencia temporal que transcurre desde el Paleolítico Superior hasta nuestros días. Mostramos aquí, por primera vez, los 21 motivos paleolíticos, grabados todos ellos por incisión, e integrables en el Magdaleniense.

Introduction and objectives: Glecaprevir/pibrentasvir is a highly effective and well tolerated treatment for hepatitis C infection. Brazilian patients were not included in the original development studies for glecaprevir/pibrentasvir. This study aimed to assess safety and efficacy of glecaprevir/pibrentasvir in treatment-naïve Brazilian adults without cirrhosis or with compensated cirrhosis. Patients and methods: EXPEDITION-3 was a Phase 3, open-label, multicenter study in treatment-naïve Brazilian adults with hepatitis C infection genotype 1–6. Patients without cirrhosis (F2 or F3) or with compensated cirrhosis (F4) received 8 or 12 weeks of glecaprevir/pibrentasvir, respectively. The primary efficacy endpoint was the rate of sustained virologic response at post-treatment Week 12. Secondary endpoints were on-treatment virologic failure and relapse rates. Baseline polymorphisms were assessed in NS3 and NS5A. Adverse events and laboratory abnormalities were monitored. Results: 100 patients were enrolled, 75 received 8 weeks of treatment and 25 received 12 weeks; all patients completed treatment. Overall sustained virologic response at post-treatment Week 12 rate was high (98.0%; 98/100; 95% confidence interval: 93.0–99.4) and remained high regardless of baseline viral or host factors, including demographics, hepatitis C virus RNA levels, polymorphisms in NS3 and/or NS5A, genotype, and relevant comorbidities. 55% of patients reported ≥1 adverse event, the most common being headache (18.0%). Four patients reported serious adverse events; none were considered drug related or led to study drug discontinuation. No hepatic decompensations were observed. Conclusions: Glecaprevir/pibrentasvir was effective and well tolerated in treatment-naïve Brazilian patients with hepatitis C infection without cirrhosis and with compensated cirrhosis. Trial Registration: ClinicalTrials.gov NCT03219216.

Hepatic sinusoidal obstruction syndrome (HSOS) is a hepatic vascular disease histologically characterized by edema, necrosis, detachment of endothelial cells in small sinusoidal hepatic and interlobular veins and intrahepatic congestion, which leads to portal hypertension and liver dysfunction. In the Western world, most HSOS cases are associated with myeloablative pretreatment in a hematopoietic stem cell transplantation setting. Here we report a case of a 54 years old female patient, otherwise healthy, with no history of alcoholic ingestion, who presented with jaundice and signs of portal hypertension, including ascites and bilateral pleural effusion. She had no history of liver disease and denied any other risk factor for liver injury, except Senecio brasiliensis ingestion as a tea, prescribed as a therapy for menopause. Acute viral hepatitis and thrombosis of the portal system were excluded in complementary investigation, as well as sepsis, metastatic malignancy and other liver diseases, setting a RUCAM score of 6. Computed tomography demonstrated a diffuse liver parenchymal heterogeneity (in mosaic) and an extensive portosystemic collateral venous circulation, in the absence of any noticeable venous obstruction. HSOS diagnosis was confirmed through a liver biopsy. During the following-up period, patient developed refractory pleural effusion, requiring hemodialysis. Right before starting anticoagulation, she presented with abdominal pain and distention, with findings compatible of mesenteric ischemia by computed tomography. A laparotomy was performed, showing an 80 cm segment of small bowel ischemia, and resection was done. She died one day after as a result from a septic shock refractory to treatment. The presented case was related to oral intake of S. brasiliensis, a plant containing pyrrolidine alkaloids, which are one of the main causes of HSOS in the East, highlighting the risk of liver injury with herbs intake.

Radon (222Rn) and thoron (220Rn) are radioactive gases emanating from geological materials. Inhalation of these gases is closely related to an increase in the probability of lung cancer if the levels are high. The majority of studies focus on radon, and the thoron is normally ignored because of its short half-life (55.6 s). However, thoron decay products can also cause a significant increase in dose. In buildings with high radon levels, the main mechanism for entry of radon is pressure-driven flow of soil gas through cracks in the floor. Both radon and thoron can also be released from building materials to the indoor atmosphere. In this work, we study the radon and thoron exhalation and emanation properties of an extended variety of common building materials manufactured in the Iberian Peninsula (Portugal and Spain) but exported and used in all countries of the world. Radon and thoron emission from samples collected in the closed chamber was measured by an active method that uses a continuous radon/thoron monitor. The correlations between exhalation rates of these gases and their parent nuclide exhalation (radium/thorium) concentrations were examined. Finally, indoor radon and thoron and the annual effective dose were calculated from radon/thoron concentrations in the closed chamber. Zircon is the material with the highest concentration values of 226Ra and 232Th and the exhalation and emanation rates. Also in the case of zircon and some granites, the annual effective dose was higher than the annual exposure limit for the general public of 1 mSv y−1, recommended by the European regulations.

Introduction and aim. Despite the emergence of new treatments for genotype 3 HCV (G3 HCV), there is still a lack of data about this particular subgroup in Brazil. We aimed to describe clinical and sociodemographic variables and treatment profile of G3 HCV Brazilian patients. Methods. This was a descriptive, retrospective study, performed in a specialized center for HCV treatment in Brazilian South Region. Medical charts of patients diagnosed with G3 HCV were reviewed to collect clinical, sociodemographic and treatment information. Results. 564 subjects were enrolled, with mean age of 59.3 years (SD=10.5). Cirrhosis was present in 54.4% of patients. Most common co-existent conditions were systemic arterial hypertension (36.6%) and diabetes mellitus (30.0%). Regarding treatment, 25.2% of patients were treatment-naïve and 74.8% were currently treating (11.6%) or had received a previous treatment (87.0%). The most frequent ongoing treatment was sofosbuvir+daclatasvir(± ribavirin) (87.8%). Of the 388 patients who had at least one previous treatment, 67.0% achieved sustained virologic response in the last treatment. Caucasian/white, non-obese, transplanted patients, those with longer time since diagnosis and with cirrhosis were more likely to receive treatment, according to multivariate analysis. Patients with hepatocellular carcinoma had 64.1% less chance to be on treatment during the study period than those without this condition; patients with chronic kidney disease presents were 2.91-fold more likely to have a treatment interruption than those without. Conclusion. This study describes a large sample of Brazilian patients with G3 HCV. Treatment patterns were mainly influenced by presence of HCV complications and comorbidities.

Introduction: Penile cancer is rare, accounting for less than 1% of all male cancers in industrialized countries. It is most common in areas of high prevalence of HPV, being a third of cases attributed to the carcinogenic effect of HPV. Tumour cells infected with HPV overexpress p16INK4a, as such p16INK4a has been used as a surrogate of HPV infections. Objective: To evaluate the prognostic factor of p16INK4a overexpression in penile cancer. Methods: Retrospective analysis of patients diagnosed with penile cancer, submitted to surgery in a Portuguese Oncological Institution in the last 20 years (n = 35). Histological review of surgical pieces and immunohistochemical identification of p16INK4a. Relation between p16INK4a and the following factors were studied: age, histological subtype, tumour dimensions, grade, TNM stage, perineural invasion, perivascular invasion, disease free survival (DFS) and cancer specific survival (CSS). Results: p16INK4a was positive in 8 patients (22.9%). Identification of p16INK4a did not correlate with none of the histopathological factors. In this work we identified a better DFS and CSS in patients positive for p16INK4a (DFS at 36 months was 100.0% vs. 66.7%; CSS at 36 months was 100.0% vs. 70.4%), although without statistical significance (p > 0.05). In multivariate analysis of histopathological factors studied, only N staging correlated with DFS and CSS (p = 0.017 and p = 0.014, respectively). Discussion: the percentage of cases positive for p16INK4a is smaller than the one found in literature, which can suggest a less relevant part of HPV infection in the oncogenesis of penile cancer in the studied population. Identification of p16INK4a did not relate with other clinicopathological factors. Tendency for a more favourable prognosis in patients with p16INK4a agrees with results found in literature. The most relevant factor for prognosis is nodal staging. Conclusions: penile cancer positive for p16INK4a shows a trend for better survival, although the most relevant factor is nodal staging.

Introduction: Patients with localized prostate cancer (PCa) are active participants in the choice of treatment. Objectives: To access the effects of social and demographic factors in the choice of treatment in cases of localized PCa, in a Portuguese population. Methods: Identification of all patients with the diagnosis of localized PCa in the last four years in an oncological centre. Evaluation of the effects of sociodemographic factors (age, profession, literacy, marital status, district and number of inhabitants of the place of residence) in the choice of treatment. Results: 300 patients with localized PCa were evaluated: 17.3% (n = 52) opted for radical prostatectomy (RP); 39,3% had (n = 118) external radiotherapy; brachytherapy in 29.3% (n = 88) and other options (active surveillance, cryotherapy and hormonal therapy) in 14.1% (n = 42). In relation to surgical treatment (RP) the following results were obtained: a) > 70 years: 3.9% (n = 5); ≤ 70 years: 27.5% (n = 47), p < 0.001; b) primary sector: 10.3% (n = 3); secondary sector: 16.2% (n = 27); tertiary sector: 24.1% (n = 21); quaternary sector: 8.3% (n = 1), p = 0.296; c) marital status married: 17.9% (n = 47); single: 0% (n = 0); divorced: 25.0% (n = 5); widow: 0% (n = 0), p = 0.734; d) residency in a city: 14.1% (n = 13); city > 4000 habitants: 22.7% (n = 15); city ≤ 4000 habitants: 16.9% (n = 24), p = 0.701. Using multinomial regression with age (p = 0.001), district (p = 0.035), marital status (p = 0.027) and profession (0.179), this model explained 17.2%-28.4% of therapeutic choices (p < 0.001). Conclusions: The main socioeconomical factor that influence treatment choice was age. Unmarried patients over 70 years choose less radical prostatectomy. Other sociodemographic factors have minor influence in the choice of the treatment.

Background & aims: Gaucher disease (GD) is a multisystemic disease. Liver involvement in GD is not well characterised and ranges from hepatomegaly to cirrhosis and hepatocellular carcinoma. We aim to describe, and assess the effect of treatment, on the hepatic phenotype of a cohort of patients with GD types I and II. Methods: Retrospective study based on the review of the medical files of the Gaucher Reference Centre of the Hospital de Clínicas de Porto Alegre, Brazil. Data from all GD types I and III patients seen at the centre since 2003 were analysed. Variables were compared as pre- (“baseline”) and post-treatment (“follow-up”). Results: Forty-two patients (types I: 39, III: 3; female: 22; median age: 35 y; enzyme replacement therapy: 37; substrate reduction therapy: 2; non-treated: 3; median time on treatment-MTT: 124 months) were included. Liver enzyme abnormalities, hepatomegaly, and steatosis at baseline were seen in 19/28 (68%), 28/42 (67%), and 3/38 patients (8%), respectively; at follow-up, 21/38 (55%), 15/38 (39%) and 15/38 (39%). MRI iron quantification showed overload in 7/8 patients (treated: 7; MTT: 55 months), being severe in 2/7 (treated: 2/2; MTT: 44.5 months). Eight patients had liver biopsy (treated: 6; MTT: 58 months), with fibrosis in 3 (treated: 1; time on treatment: 108 months) and steatohepatitis in 2 (treated: 2; time on treatment: 69 and 185 months). One patient developed hepatocellular carcinoma. Conclusions: GD is a heterogeneous disease that causes different patterns of liver damage even during treatment. Although treatment improves the hepatocellular damage, it is associated with an increased rate of steatosis. This study highlights the importance of a follow-up of liver integrity in these patients. Keywords: Gaucher disease, Enzyme replacement therapy, Liver steatosis, Hemosiderosis, Biopsy, large-core needle, Cholelithiasis

A 63-year-old female patient with recent diagnosis of hepatitis C and cirrhosis and no other comorbidities, on no medications, was found to have Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma and began systemic therapy with sorafenib 400 mg twice daily. Five days after starting treatment, the patient went to an emergency department with pruritic, target-shaped, erythematous papules compatible with erythema multiforme, painful oral aphthous ulcers, and fever. Sorafenib was suspended and the patient underwent oral corticosteroid treatment for 5 days, showing significant improvement of the lesions. One month after discharge, the patient was reassessed at an outpatient clinic. As she was asymptomatic and had no skin lesions, sorafenib was resumed at a lower dose (200 mg daily). Three hours after ingesting a single dose of sorafenib, the patient experienced chills, fever, rash, angioedema and stridor. She immediately sought the emergency department and was diagnosed with anaphylaxis. The patient received intravenous corticosteroid therapy, which improved her respiratory and cutaneous symptoms in 72 h. Sorafenib was permanently suspended, and regorafenib could not be prescribed as second-line therapy. This is the first description of anaphylaxis to sorafenib.

On the northern fringes of Serra do Extremo, overlooking the valley of the river Minho, the hills of Monte Faro and Monte dos Fortes revealed an exceptional collection of prehistoric rock carvings belonging to the Iberian Atlantic Art tradition. In the late 1970s and early 1980s, A. Leite da Cunha e E. J. Silva studied here the well-known sites of Monte da Laje, Tapada do Ozão e Monte dos Fortes. Between 2013 and 2015, a new research project amplified the numbers to over one hundred carved rocks, amongst which 91 are dated to Late Prehistory. This allows us to acknowledge that this is the largest assemblage of Atlantic Art identified, so far, in Portugal. This paper, which inaugurates the dissemination of the research outcomes, reveals how the project was structured, the methodology adopted and offers a preliminary description of the archaeological sites.

Neste ensaio avaliou-se o efeito de diferentes misturas de substrato comercial e vermicomposto na produção de biomassa, composição química e rendimento dos óleos essenciais de Thymus zygis. Utilizaram-se 5 substratos resultantes da mistura de um vermicomposto (V) com um substrato orgânico comercial (O), em cinco proporções diferentes (v/v): V100 (100%V); VO75-25 (75%V+25%O); VO50 -50 (50%V+50%O); VO 25-75 (25%V + 75%O) e O100 (100%O). A inclusão do vermicomposto no substrato não melhorou a produção de biomassa. Na modalidade O100 produziu-se mais biomassa, tendo sido na modalidade VO25-75 onde se obteve o valor mais baixo. Na modalidade V100 todas as plantas secaram tendo-se ainda apresentado nesta modalidade o valor mais elevado de pH e de densidade real e inversamente o menor valor de espaço poroso total. Os monoterpenos oxigenados predominaram nos óleos extraídos das plantas nas modalidades O100 e VO25-75, contrariamente ao que se verificou para os monoterpenos não oxigenados tendo estes predominado nas modalidades VO75-25 e VO50-50. A concentração de timol foi elevada nas misturas testadas, em particular na modalidade VO25-75.In this trial we evaluated the effect of different mixtures of organic growing media substratum and vermicompost and their physical properties on biomass, chemical composition and yield of essential oils of Thymus zygis. Five treatments were established based on two types of organic materials (O, commercial growing media, and V, vermicompost). The following proportions were studied (v/v): V100 (100%V); VO75-25 (75%V+25%O); VO50-50 (50%V+50%O); VO 25-75 (25%V+75%O) and O100 (100%O). The inclusion of vermicompost did not improve biomass production. The treatment O100 produced more biomass and the lowest was obtained in VO25-75. On V100 treatment all plants were dead and also have showed the highest pH and particle density and conversely presented the lowest value of total pore space. Oxygenated monoterpenes predominated in the oils extracted from plants in O100 and VO25-75, contrary to what was found for non-oxygenated monoterpenes having these prevailed in VO75-25 and VO50-50. The concentration of thymol was high in the mixtures tested, particularly in VO25-75.

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 (PCONTEXTO: 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

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.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.

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: 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.

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.

Aims. To determine lymphocyte IRS (IRS1 cells) in HCV patients, correlating it to liver IRS (IRS 1liver) and HOMA-IR. This study tested the hypothesis that IRS1 cells expression can be used as insulin resistance (IR) marker in HCV-infected patients. IRS1 cells were not studied before in HCV infection. Materials and Methods. HCV chronically infected patients, naïve, nonobese, noncirrhotic, and nondiabetic were prospectively included and compared to controls (blood donors). Blood was taken, and leukocytes were separated. IRS1 was determined by real-time PCR. Liver tissue was obtained from transplant donors as controls. Results. 41 HCV-positive patients were included, 26 males (60.5%); mean age of 45 (±7.9); 33 (80.5%) from genotype 1. 6 out of 12 controls were males (50%); mean age was 26.7 (±3.2). There was expression of IRS1 in leukocytes. The median IRS1 cells (HCV) were 0.061 (0.004 to 0.469); the median IRS 1liver (HCV) was 0.0003 (0.00002 to 0.0186)—lower than in controls (resp., 𝑃=0.005 and 𝑃=0.018). HOMA-IR had an inverse correlation with IRS 1liver (𝑃=0.04). There was no correlation between IRS1 liver and IRS1 cells (𝑃=0.930). Conclusions. There was expression of IRS1 in leukocytes. IRS1 cells and IRS1 liver were lower in HCV patients than in controls.

Introduction. There is an association between HCV and insulin resistance (IR), which is currently assessed by HOMA-IR. There is evidence that HOMA-adiponectin (HOMA-AD) is more accurate, but its role in HCV patients is unknown. The purpose of this study was to evaluate IR in an HCV sample and controls, in order to compare the accuracy of HOMA-IR and HOMA-AD. Methods. Ninety-four HCV outpatients aged

To analyze retrospectively 19 patients with positive pelvic lymph node disease obtained with a radical prostatectomy. To discuss the actual role of pelvic lymphadenectomy and evaluate the results obtained using one treatment protocol.Between January 1993 and December 2001 450 patients underwent radical prostatectomy for localized prostate cancer. Nineteen patients were identified as having positive ganglionar disease (4.2%). The mean PSA value of the 450 patients was 11.8 ng/ml (ranging 1.9 - 40 ng/ml). We analyzed the survival curves using the method of Kaplan-Meier, based on non recurrence of elevated biochemical total PSA values. The mean follow up time was 37.7 months. The recurrence of disease was defined by two consecutive determinations of PSA values greater than 0.2 ng/ml. Results: the mean age of the nineteen patients was 66 years, varying between 56 and 74. The specific survival curve for these patients shows a survival probability of 60.9%, after 5 years. The survival curve of biochemical free recurrence shows a probability of 37.5%, after 5 years.A progressive decrease in the incidence of patients with ganglionar disease was observed after radical prostatectomy. It is therefore disputable the role of routine lymphadenectomy, its advantages, disadvantages and indications. The scientific analysis have permited great controversy regarding treatment. Our results with a treatment protocol which utilizes preventive adjuvant radiotherapy together with hormone treatment, initially differed and actually systematic, shows a survival rate similar to other studies.The actual indication of lymphadenectomy is maintained in radical retropubic prostatectomy and in patients with a risk of extracapsular disease in perineal prostatectomy or laparoscopy prostatectomy. The monotherapy offers a limited potential of cure. An extensive disease needs an aggressive therapy. A combination of adjuvant radiation therapy and simultaneous hormone treatment is indicated until there exists a randomized study, with an adequate follow up time, to determine which treatment strategy is the best.

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%, p65 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.

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.