Risk predictors of advanced hepatic fibrosis in patients with nonalcoholic fatty liver disease - a survey in a university hospital in Brazil

ABSTRACT Objective: Describe the clinical profile of patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD) and analyze the risk predictors of hepatic fibrosis in outpatient follow-up at a university hospital. Subjects and methods: Demographic, clinical and laboratory data of a cohort of 143 patients with biopsy-proven NAFLD were retrospectively analysed under univariate analyses. Diagnostic accuracy, determined by AUROC, was evaluated for variables that showed a significant difference in univariate comparison analysis and diagnostic performances were determined by sensitivity and specificity. Results: The mean age of studied patients were 48 years, 66.4% of them were women. Age, presence of diabetes mellitus, hypertension, metabolic syndrome and laboratory variables such as AST/ALT ratio, GGT, platelet count and fasting glucose were significantly associated with advanced fibrosis. FIB-4 and NAFLD fibrosis score (AUROC 0.82 and 0.89, respectively) outperformed APRI (AUROC 0.73) for advanced liver fibrosis and cirrhosis (P of 0.04). Conclusion: In our study, metabolic syndrome, diabetes, hypertension, AST/ALT ratio, GGT, platelet count and fasting glucose were associated with hepatic fibrosis in patients with NAFLD. The non-invasive tests FIB-4 and NAFLD fibrosis score showed the best accuracy to stratify disease severity.

Risk predictors of advanced hepatic fibrosis in patients with nonalcoholic fatty liver disease - a survey in a university hospital in Brazil.

Objective: Describe the clinical profile of patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD) and analyze the risk predictors of hepatic fibrosis in outpatient follow-up at a university hospital. Methods: Demographic, clinical and laboratory data of a cohort of 143 patients with biopsy-proven NAFLD were retrospectively analysed under univariate analyses. Diagnostic accuracy, determined by AUROC, was evaluated for variables that showed a significant difference in univariate comparison analysis and diagnostic performances were determined by sensitivity and specificity. Results: The mean age of studied patients were 48 years, 66.4% of them were women. Age, presence of diabetes mellitus, hypertension, metabolic syndrome and laboratory variables such as AST/ALT ratio, GGT, platelet count and fasting glucose were significantly associated with advanced fibrosis. FIB-4 and NAFLD fibrosis score (AUROC 0.82 and 0.89, respectively) outperformed APRI (AUROC 0.73) for advanced liver fibrosis and cirrhosis (P of 0.04). Conclusion: In our study, metabolic syndrome, diabetes, hypertension, AST/ALT ratio, GGT, platelet count and fasting glucose were associated with hepatic fibrosis in patients with NAFLD. The non-invasive tests FIB-4 and NAFLD fibrosis score showed the best accuracy to stratify disease severity.

Histoplasmosis Related to Immunosuppression in a Patient with Crohn's Disease: A Diagnostic Challenge.

BACKGROUND Infliximab, a monoclonal antibody against tumor necrosis factor (TNF) alpha with proven efficacy and known safety profile, is currently widely used in the treatment of inflammatory bowel diseases. Increased risk for serious infections and malignant neoplasms secondary to immunosuppression is a major concern during therapy with this medication. Histoplasmosis is a granulomatous disease caused by the fungus Histoplasma capsulatum. Disseminated forms of the disease have immunodepression as a major risk factor. CASE REPORT A 39-years-old man had been followed with refractory fistulizing ileocolonic Crohn's disease using combination therapy (infliximab plus azathioprine) and also receiving short courses of steroids. After 2 years of this immunosuppressive therapy, the patient presented with high fever (39.5ºC) for 5 days, associated with profuse sweating, and moderate pain in the left hypochondrium. The patient was hospitalized. Diagnoses of tuberculosis, malignancy, autoimmune diseases, and bacterial and viral infections were rapidly discarded after investigation. Clinical, laboratory, and image signs of liver involvement prompted a guided percutaneous biopsy, which revealed granulomatous hepatitis, with the presence of fungal structures suggestive of Histoplasma capsulatum. Upon treatment with liposomal amphotericin followed by itraconazole, the patient showed an impressively positive clinical response. CONCLUSIONS TNF blockers, particularly when associated with other immunosuppressors, are a serious risk factor for opportunistic infections. This unusual case of disseminated histoplasmosis in a patient with Crohn's disease using infliximab in combination with azathioprine and steroids emphasizes the need for surveillance of this uncommon but potentially lethal complication before starting TNF blockers therapy.

HLA-E gene polymorphisms in chronic hepatitis C: Impact on HLA-E liver expression and disease severity.

Hepatitis C virus usually produces chronic infection and liver damage. Considering that: i) the human leukocyte antigen-E (HLA-E) molecule may modulate the immune response, and ii) little is known about the role of HLA-E gene variability on chronic hepatitis C, we studied the impact of HLA-E polymorphisms on the magnitude of HLA-E liver expression and severity of hepatitis C. HLA-E variability was evaluated in terms of: i) single nucleotide polymorphism (SNP) alleles and genotypes along the gene (beginning of the promoter region, coding region and 3'UTR), and ii) ensemble of SNPs that defines the coding region alleles, considered individually or as genotypes. The comparisons of the HLA-E variation sites between patients and controls revealed no significant results. The HLA-E + 424 T > C (rs1059510), +756 G > A (rs1264457) and + 3777 G > A (rs1059655) variation sites and the HLA-E*01:01:01:01 and HLA-E*01:03:02:01 alleles, considered at single or double doses, were associated with the magnitude of HLA-E liver expression in Kupfer cell, steatosis, inflammatory activity and liver fibrosis. Although these associations were lost after corrections for multiple comparisons, these variable sites may propitiate biological clues for the understanding of the mechanisms associated with hepatitis C severity.

HLA-G liver expression and HLA-G extended haplotypes are associated with chronic hepatitis C in HIV-negative and HIV-coinfected patients.

Chronic hepatitis C virus (HCV) infection induces liver damage and the HCV/Human Immunodeficiency Virus (HIV)-coinfection may further contribute to its progression. The HLA-G molecule inhibits innate and adaptive immunity and may be deleterious for chronically virus-infected cells. Thus we studied 204 HCV-mono-infected patients, 142 HCV/HIV-coinfected patients, 104 HIV-mono-infected patients and 163 healthy subjects. HLA-G liver expression was similarly induced in HCV and HCV/HIV specimens, increasing with advanced fibrosis and necroinflammatory activity, and with increased levels of liver function-related enzymes. Plasma soluble HLA-G (sHLA-G) levels were higher in HCV/HIV patients compared to HCV, HIV and to healthy individuals. sHLA-G continued to be higher in coinfected patients even after stratification of samples according to degree of liver fibrosis and necroinflammatory activity when compared to mono-infected patients. Some HLA-G gene haplotypes differentiated patient groups and presented few associations with liver and plasma HLA-G expression. HLA-G thus may help to distinguish patient groups.

Phase angle as a severity indicator for liver diseases.

OBJECTIVE: The aim of this study was to evaluate the applicability of phase angle (PhA) as a severity indicator of chronic liver diseases. METHODS: We examined the medical records of 54 patients-27 with hepatocellular carcinoma (HCC) and 27 with non-alcoholic fatty liver disease (NAFLD). The patients were ≥18 y of age. Clinical data, such as Child-Pugh and Barcelona Clinic Liver Cancer (HCC), aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis (FIB)-4 (NAFLD), nutritional parameters (body mass index [BMI], handgrip strength [HGS], and bioelectrical impedance [BIA] data) were collected. Nutritional Risk Index (NRI) was calculated. Analysis was performed using Mann-Whitney test and analysis of variance. Simple multiple linear regression for predictions (Child-Pugh in HCC, APRI and FIB-4 in NAFLD). Receiver operating characteristic curve was estimated to search a cutoff for PhA. For survival, we used the Kaplan-Meier estimator. To verify whether PhA affected patients' survival, we used the Mantel-Haenszel. RESULTS: The prevalence of cirrhosis was high in HCC (n = 25) and low in the NAFLD (n = 4). No patient was classified as undernourished based on BMI; however, NRI showed that 74.1% of patients with HCC had nutritional risk. Child-Pugh was positively correlated with the edema index (extracellular water/total body water [ECW/TBW]) and negatively correlated with PhA and HGS. Higher Child-Pugh and BCLC scores were associated with worse NRI. APRI and FIB-4 were positively correlated with weight and BMI. A significant difference between groups was found for the median values of R, ECW/TBW, PhA, HGS, and albumin. There was a trend toward lower survival in patients with HCC, according to the cutoff point of 5.1 degrees for PhA. CONCLUSION: PhA was shown to be an independent prognostic indicator for cirrhosis and may be related to survival in these patients.

First-wave protease inhibitors for hepatitis C genotype 1 treatment: a real-life experience in Brazilian patients.

INTRODUCTION: Licensed for chronic hepatitis C treatment in 2011, the protease inhibitors (PIs) telaprevir (TVR) and boceprevir (BOC), which have high sustained viral responses (SVR), ushered a new era characterized by the development of direct-action drugs against the hepatitis C virus (HCV). The aim of this study was to analyze the effectiveness and safety of BOC and TVR administered with pegylated interferon and ribavirin and to share the experience of a Brazilian reference center. METHODS: A retrospective descriptive study was conducted in patients with HCV genotype 1 infection who started treatment between July 2013 and December 2015. Data were collected using a computerized system. RESULTS: A total of 115 subjects were included, of which 58 (50.4 %) had liver cirrhosis and 103 (89.6 %) used TVR. The overall SVR rate was 61.7 % (62.1 % for TVR and 58.3 % for BOC). The presence of cirrhosis was associated with a lower SVR rate, whereas patients who relapsed after prior therapy had a greater chance of showing SVR than did non-responders. The incidence of adverse drug reactions (ADRs) was high. Almost all patients (~100 %) presented with hematologic events. Furthermore, treatment had to be discontinued in 15 subjects (13 %) due to severe ADRs. CONCLUSIONS: In conclusion, the SVR rates in our study were lower than those reported in pre-marketing studies but were comparable to real-life data. ADRs, particularly hematological ADRs, were more common compared to those in previous studies and resulted in a high rate of treatment discontinuity.

First-wave protease inhibitors for hepatitis C genotype 1 treatment: a real-life experience in Brazilian patients

Abstract INTRODUCTION: Licensed for chronic hepatitis C treatment in 2011, the protease inhibitors (PIs) telaprevir (TVR) and boceprevir (BOC), which have high sustained viral responses (SVR), ushered a new era characterized by the development of direct-action drugs against the hepatitis C virus (HCV). The aim of this study was to analyze the effectiveness and safety of BOC and TVR administered with pegylated interferon and ribavirin and to share the experience of a Brazilian reference center. METHODS: A retrospective descriptive study was conducted in patients with HCV genotype 1 infection who started treatment between July 2013 and December 2015. Data were collected using a computerized system. RESULTS: A total of 115 subjects were included, of which 58 (50.4 %) had liver cirrhosis and 103 (89.6 %) used TVR. The overall SVR rate was 61.7 % (62.1 % for TVR and 58.3 % for BOC). The presence of cirrhosis was associated with a lower SVR rate, whereas patients who relapsed after prior therapy had a greater chance of showing SVR than did non-responders. The incidence of adverse drug reactions (ADRs) was high. Almost all patients (~100 %) presented with hematologic events. Furthermore, treatment had to be discontinued in 15 subjects (13 %) due to severe ADRs. CONCLUSIONS: In conclusion, the SVR rates in our study were lower than those reported in pre-marketing studies but were comparable to real-life data. ADRs, particularly hematological ADRs, were more common compared to those in previous studies and resulted in a high rate of treatment discontinuity.

Usefulness of a new prognostic index for alcoholic hepatitis.

BACKGROUND: Alcoholic liver disease is a major cause of end-stage liver disease worldwide and severe forms of alcoholic hepatitis are associated with a high short-term mortality. Objectives To analyze the importance of age-bilirubin-INR-creatinine (ABIC) score as an index of mortality and predictor for complications in patients with alcoholic hepatitis. To evaluate its correlation with those complications, with risk of death, as well as the scores model for end stage liver disease (MELD) and Maddrey's discriminat function. METHODS: A total of 46 medical records of patients who had been hospitalized with alcoholic hepatitis were assessed retrospectively with lab tests on admission and after seven days. Score calculations were carried out and analyzed as well. RESULTS: The scores showed positive reciprocal correlation and were associated with both hepatic encephalopathy and ascites. ABIC index, which was classified as high risk, presented as a risk factor for these complications and for death. In univariate logistic regression analysis of mortality, the ABIC index at hospital admission odds ratio was 19.27, whereas after 7 days, it was 41.29. The average survival of patients with ABIC of low and intermediate risk was 61.1 days, and for those with high risk, 26.2 days. CONCLUSIONS: ABIC index is a predictor factor for complications such as ascites and hepatic encephalopathy, as well as for risk of death. Thus, it is a useful tool for clinical practice.

Usefulness of annew prognostic index for alcoholic hepatitis / Utilidade de um novo índice prognóstico na hepatite alcoólica

Background Alcoholic liver disease is a major cause of end-stage liver disease worldwide and severe forms of alcoholic hepatitis are associated with a high short-term mortality. Objectives To analyze the importance of age-bilirubin-INR-creatinine (ABIC) score as an index of mortality and predictor for complications in patients with alcoholic hepatitis. To evaluate its correlation with those complications, with risk of death, as well as the scores model for end stage liver disease (MELD) and Maddrey’s discriminat function. Methods A total of 46 medical records of patients who had been hospitalized with alcoholic hepatitis were assessed retrospectively with lab tests on admission and after seven days. Score calculations were carried out and analyzed as well. Results The scores showed positive reciprocal correlation and were associated with both hepatic encephalopathy and ascites. ABIC index, which was classified as high risk, presented as a risk factor for these complications and for death. In univariate logistic regression analysis of mortality, the ABIC index at hospital admission odds ratio was 19.27, whereas after 7 days, it was 41.29. The average survival of patients with ABIC of low and intermediate risk was 61.1 days, and for those with high risk, 26.2 days. Conclusions ABIC index is a predictor factor for complications such as ascites and hepatic encephalopathy, as well as for risk of death. Thus, it is a useful tool for clinical practice. .

Contexto A doença hepática alcoólica é uma das maiores causas de doença hepática avançada no mundo, sendo que as formas graves de hepatite alcoólica estão associadas a alta mortalidade a curto prazo. Objetivos Avaliar a importância do índice age-bilirrubin-INR-creatinine (ABIC) como fator prognóstico na hepatite alcoólica e sua correlação com as complicações dessa doença, com o risco de óbito e com os escores Model for End stage Liver Disease (MELD) e Função Discriminante de Maddrey. Métodos Um total de 46 prontuários de pacientes internados por hepatite alcoólica foram avaliados de forma retrospectiva. Foi realizado levantamento de exames laboratoriais do primeiro dia de internação e 7 dias após, além de cálculo dos escores estudados. Resultados Os índices ABIC, Maddrey e MELD apresentaram correlação positiva entre si e associaram-se a encefalopatia hepática e a ascite (P<0,05). O índice ABIC, classificado de alto risco, foi fator de risco para essas complicações e para óbito. Em análise de regressão logística univariada para óbito, a razão de risco do ABIC de entrada no hospital foi de 19,27 (P=0,012) e após 7 dias de 41,29 (P=0,002). A sobrevida acumulada daqueles com ABIC de alto risco foi de 93,3% em 7 dias e de apenas 26,9% em 60 dias. Conclusões O índice prognóstico ABIC é fator de predição para complicações como ascite e encefalopatia hepática, assim como para risco de óbito, sendo ferramenta útil na prática clínica. .

Diagnóstico por imagem de Body Packers: relato de caso / Image diagnosis of Body Packers: case report

Introdução: o Brasil é atualmente a principal rota de tráfico de drogas da América Latina. Em aeroportos internacionais, passageiros com perfil considerado como suspeito pela Polícia Federal são conduzidos até serviços de pronto-atendimento para serem avaliados, ainda que assintomáticos e sem alterações visíveis. Objetivos: discutir, a partir de um relato de caso, os métodos de imagem diagnósticos para body packers mais utilizados na prática. Métodos: relato de caso de paciente atendido pelo Centro de Informações e Atendimento Toxicológico (CIAT) do Hospital Pronto-Socorro João XXIII em Belo Horizonte (MG). Resultados: um paciente trazido pela Polícia Federal, que negava ter ingerido pacotes de cocaína e estava assintomático com exame físico normal, foi submetido à propedêutica por imagem. Foi realizado uma tomografia computadorizada (TC) de abdome que evidenciou inúmeros corpos estranhos pelo trato gastrointestinal do paciente. Foi realizado também uma radiografia simples de abdome não foi útil em mostrar com precisão a localização e quantificação dos papelotes. Conclusões: tendo em vista o fato de que a ruptura de um único invólucro pode provocar intoxicação grave e muitas vezes fatal, a ausência de mensuração quantitativa e os falso-negativos da radiografia simples de abdome tornam esse método limitado. Sugerimos que a TC seja o método de imagem inicial, o que garante maior rapidez e precisão no manejo do caso, economia no tempo de estadia do paciente e maior segurança para o mesmo.(AU)

Introduction: Brazil is currently the main drug traffic route of Latin America. At international airports, passengers considered as suspect by the Federal Police are driven to emergency care services to be evaluated, even if asymptomatic and no visible abnormalities. Objectives: discuss, from a case report, the most used in practice diagnostic imaging methods. Methods: case report of patient assisted by the Center for Information and Toxicological Assistance (CIAT), Hospital Pronto-Socorro João XXIII in Belo Horizonte (MG). Results: a patient brought by the Federal Police, denied having ingested packets of cocaine and was asymptomatic with a normal physical examination, underwent imaging workup. A computed tomography (CT) was performed and revealed that many foreign bodies into the gastrointestinal tract of the patient. A plain abdominal x-ray was also made and wasn't helpful in showing the exact location and quantification of packets. Conclusions: considering the fact that the rupture of a single packet can cause severe intoxication, often fatal, the absence of quantitative measurement and the false-negative of plain abdominal x-ray make this method limited. We suggest that CT should be the initial imaging method, which provides greater speed and accuracy in handling the case, reducing the patient's length of stay and providing greater security.(AU)

Pesquisa de substâncias antagonistas tipo bacteriocinas produzidas por amostras de Staphylococcus aureus meticilina resistentes isoladas de pacientes inter-nados no Hospital Regional do Município de Barbacena, Minas Gerais / Research of antagonist substances bacteriocins produced by samples of methicillin-resistant staphylococcus aureus isolated from patients admitted to Regional Hospital of Barbacena-City, Minas Gerais

Objetivos: detectar a produção de bacteriocinas, determinar a suscetibilidade das amostras coletadas a essas substãncias e estabelecer possível correlação entre bacteriocinas e sua ação antimicrobiana. Métodos: foram coletadas 14 amostras isoladas de processos infecciosos causados por cepas de Staphylococcus aureus/Meticilina resistentes (MRSA),de pacientes do município de Barbacena-MG. Essas amostras foram previamente identificadas, caracterizadas com o MRSA , preservadas à temperatura de -80ºC em freezer, em meio apropriado de manutenção com crioprotetores, skim-milke, e submetidas a testes no laboratório. Resultados: foram realizados 196 testes, sendo que 100 por cento das amostras testadas mostraram -se produtoras de bacteriocinas. As cepas MRSAs eram, em 71,4 por cento dos casos, sensíveis à ação de bacteriocinas produzidas pelas bactérias testadas, tendo o seu crescimento inibido. O fenômeno de autoantagonismo foi também observado em 57,1 por cento das bactérias estudadas. Conclusão: os resultados demonstraram o alto potencial antimicrobiano das MRSAs isoladas. O autoantagonismo exerce marcante papel na manutenção do equilíbrio entre as com unidades microbianas que constituem a flora humana normal. Diante do aumento e da rápida disseminação de bactérias patógenas multirresistentes, encontradas em ambientes hospitalares e na comunidade, as bacteriocinas estudadas poderiam oferecer solução alternativa na terapêutica de infecções envolvendo esses patógenos.