Gut-related molecules as potential biomarkers in patients with decompensated cirrhosis.

INTRODUCTION AND OBJECTIVES: Microbial translocation contributes to cirrhosis progression and complications. This study aims to investigate whether molecules related to intestinal permeability or microbial translocation can serve as prognostic biomarkers in patients with decompensated cirrhosis. MATERIALS AND METHODS: We prospectively evaluated hospitalized patients with decompensated cirrhosis for liver function, complications during hospitalization, in-hospital mortality, composite outcomes of in-hospital mortality and complications, 12-month mortality, and survival rates. Blood samples were collected upon admission, and 1,3 beta-d-glucan, zonulin, calprotectin, and lipopolysaccharide-binding protein were measured using commercial kits. RESULTS: Ninety-one patients with decompensated cirrhosis were enrolled. The mean age was 58 ±â€¯12 years; 57% were male. The three main cirrhosis etiologies were hepatitis C (35%), alcohol (25%), and non-alcoholic steatohepatitis (17%). In terms of liver function, 52% were Child C, and 68% had model for end-stage liver disease ≥15. The in-hospital and one-year mortality rates were 31% and 57%, respectively. Child-Pugh, 1,3 beta-glucan, and model for end-stage liver disease were positively correlated; zonulin was associated with complications during hospitalization (acute kidney injury) and composite outcomes, and calprotectin was associated with all outcomes except 12-month mortality. CONCLUSIONS: Serum calprotectin and zonulin levels emerge as noninvasive prognostic biomarkers for potentially unfavorable outcomes in patients with decompensated cirrhosis.

Hepatitis B Surface Antibody (Anti-HBs) Kinetics during Rituximab Chemotherapy and Performance of Hepatitis B Vaccine before Immunosuppression: Two Prospective Studies.

Rituximab promotes strong immunosuppression leading to a high risk of hepatitis B reactivation (HBV-R) and chronic infection. Current recommendations on HBV-R prevention are expensive and poorly individualized. In resolved hepatitis B patients, previous studies suggest that anti-HBs titers before immunosuppression can predict HBV-R risk. However, guidelines claim that additional data are necessary before recommending spare drug prophylaxis in patients with high anti-HBs titers. On the other hand, in patients with no previous contact with HBV, guidelines recommend vaccine before immunosuppression despite minimal evidence available. To shed light on these knowledge gaps, two prospective studies were conducted to evaluate anti-HBs in hematological cancer patients treated with rituximab. In the first study, anti-HBs-positive patients were referred for following up antibody titers before and during immunosuppression. Patients with anti-HBs ≥ 100 mIU/mL before immunosuppression had no negative seroconversion (anti-HBs loss), in contrast to 18% of those with anti-HBs < 100 mIU/mL. In the second study, patients with no previous contact with HBV were invited to receive HBV vaccine before rituximab chemotherapy. None seroconverted with anti-HBs. In conclusion, both studies reinforce the need to review concepts about HBV prevention during immunosuppression on current guidelines. Narrowing the use of drug prophylaxis and improving vaccine indications are recommended.

Noninvasive predictors of esophageal varices in patients with hepatosplenic schistosomiasis mansoni.

BACKGROUND: No previous study have evaluated transient elastography for predicting esophageal varices in hepatosplenic schistosomiasis. AIM: To investigate noninvasive methods of predicting esophageal varices in patients with hepatosplenic schistosomiasis mansoni. METHODS: Cross-sectional multicentric study included 51 patients with hepatosplenic schistosomiasis. Patients underwent ultrasonography-dopplerfluxometry, upper endoscopy, complete blood cell count and transient elastography (Fibroscan®) for liver and spleen stiffness measurement (LSM and SSM). Noninvasive scores previously established for cirrhotic population were studied: platelet count to spleen diameter ratio (PSR), LSM-spleen diameter to platelet ratio score (LSPS) and varices risk score (VRS). We proposed a version of LSPS and VRS by replacing LSM with SSM and named them SSPS and modified-VRS, respectively. RESULTS: Esophageal varices were detected in 42 (82.4%) subjects. Individuals with varices presented higher SSM (73.5 vs 36.3 Kpa, p = 0.001), splenic vein diameter (10.8 vs 8.0 mm, p = 0.017), SSPS (18.7 vs 6.7, p = 0.003) and modified-VRS (4.0 vs 1.4, p = 0.013), besides lower PSR (332 vs 542, p = 0.038), than those without varices. SSPS was independently associated with varices presence (OR=1.19, 95%CI 1.03-1.37, p = 0.020) after multivariate analysis. In a model excluding noninvasive scores, SSM was independently associated with varices diagnosis (OR=1.09, 95%CI 1.03-1.16, p = 0.004). AUROC was 0.856 (95%CI 0.752-0.961, p = 0.001) for SSM and 0.816 (95%CI 0.699-0.932, p = 0.003) for SSPS (p = 0.551). CONCLUSIONS: Spleen-related variables were predictors of esophageal varices: SSM, splenic vein diameter, SSPS, modified-VRS and PSR. Multivariate models indicated that SSM and SSPS are useful tools for predicting varices in non-cirrhotic portal hypertension by hepatosplenic schistosomiasis and may be used in clinical practice.

Can gadoxetic acid-enhanced magnetic resonance imaging be used to avoid liver biopsy in patients with nonalcoholic fatty liver disease?

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver disease worldwide. The diagnosis of nonalcoholic steatohepatitis (NASH), the most severe form of NAFLD, is crucial and has prognostic and therapeutic implications. However, currently this diagnosis is based on liver biopsy and has several limitations. AIM: To evaluate the performance of gadoxetic acid-enhanced magnetic resonance imaging (GA-MRI) in differentiating isolated steatosis from NASH in patients with NAFLD. METHODS: In this prospective study, 56 patients with NAFLD (18 with isolated steatosis and 38 with NASH) underwent GA-MRI. The contrast enhancement index (CEI) was calculated as the rate of increase of the liver-to-muscle signal intensity ratio from before and 20 min after intravenous GA administration. Between-group differences in mean CEI were examined using Student's t test. The area under the receiver operator characteristic curve and the diagnostic performance of gadoxetic acid-enhanced magnetic resonance imaging were evaluated. RESULTS: The mean CEI for all subjects was 1.82 ± 0.19. The mean CEI was significantly lower in patients with NASH than in those with isolated steatosis (P = 0.008). Two CEI cut-off points were used: < 1.66 (94% specificity) to characterize NASH and > 2.00 (89% sensitivity) to characterize isolated steatosis. CEI values between 1.66 and 2.00 indicated liver biopsy, and the procedure could be avoided in 40% of patients with NAFLD. CONCLUSION: GA-MRI is an effective noninvasive method that may be useful for the differentiation of NASH from isolated steatosis, and could help to avoid liver biopsy in patients with NAFLD.

Métodos de imagem no diagnóstico de esquistossomose hepatoesplânica / Imaging techniques in the diagnosis of hepatosplenic schistosomiasis

A esquistossomose constitui grave problema de saúde pública, com mais de 200 milhões de infectados no mundo. Deste total, cerca de 10% desenvolvem a forma hepatoesplênica da doença caracterizada por fibrose periportal e hipertensão porta. No passado, o diagnóstico da esquistossomose hepatoesplênica (EHE) era realizado por métodos invasivos como esplenoportografia e biópsia hepática. O estudo das alterações no sistema porta e da morfologia hepática e esplênica com métodos de imagem representou um avanço significativo no diagnóstico da doença. Os métodos mais utilizados atualmente são a ultrassonografia abdominal, a ressonância nuclear magnética e a tomografia computadorizada de abdomen. O objetivo do presente artigo é abordar as principais contribuições de cada método no diagnóstico da EHE.

Schistosomiasis is a serious public health problem with over 200 million infected worldwide. Nearly 10% of infected individuals develop the hepatosplenic form of the disease characterized by periportal fi brosis and portal hypertension. In the past, the diagnosis of hepatosplenic schistosomiasis (HHS) was performed by invasive methods such as liver biopsy and splenoportography. The study of changes in portal system and morphological aspects of liver and spleen with imaging techniques represented a significant advance in the diagnosis of the disease. The most widely used techniques are abdominal ultrasonography, magnetic resonance imaging and computed tomography of the abdomen. The aim of this article is to discuss the main contribution of each technique in the diagnosis of HHS.

ELF (Enhanced Liver Fibrosis) como marcador não invasivo de fibrose hepática na hepatite C crônica / ELF (Enhanced Liver Fibrosis) as a non invasive predictor of liver fibrosis in hepatitis C

A fibrose hepática é o aspecto mais relevante e o mais importante determinante de morbimortalidade na hepatite C crônica (HCC). Historicamente, a biópsia hepática é o método de referência para avaliação da fibrose causada pela HCC, apesar de apresentar limitações. O estudo de marcadores não invasivos, que possam obviar a necessidade da biópsia, é uma área de constante interesse na hepatologia. Idealmente, a avaliação da fibrose hepática deveria ser acurada, simples, prontamente disponível, de baixo custo e informar sobre o prognóstico da patologia. Os marcadores não invasivos mais estudados são a elastografia hepática transitória (EHT) e os laboratoriais. A EHT já foi extensamente validada na HCC e está inserida na rotina de avaliação destes pacientes. Dentre os laboratoriais, existem diversos testes em continua experimentação e, até o momento, nenhum foi integrado à prática clínica no Brasil, embora já aplicados rotineiramente em outros países. O Enhanced Liver Fibrosis (ELF), um teste que dosa no soro ácido hialurônico, pró-peptídeo amino-terminal do colágeno tipo III e inibidor tissular da metaloproteinase 1, tem se mostrado bastante eficaz na detecção de fibrose hepática significativa e de cirrose na HCC. Neste estudo o ELF teve o seu desempenho avaliado em relação a biópsia hepática e demonstrou apresentar boa acurácia na detecção tanto de fibrose significativa quanto de cirrose. Na comparação com a EHT apresentou acurácia semelhante para estes mesmos desfechos, com significância estatística. No entanto, foi observada uma superestimação da fibrose com a utilização dos pontos de corte propostos pelo fabricante. Este achado está em acordo com a literatura, onde não há consenso sobre o melhor ponto de corte a ser empregado na prática clínica. Com a ampliação da casuística foi possível propor novos pontos de corte, através da análise clássica, com a biópsia hepática como padrão ouro...

Liver fibrosis is the most relevant issue concerning chronic hepatitis C (CHC) and determines its prognosis. Historically, liver biopsy has been the reference method for evaluating fibrosis related to CHC, though it presents many drawbacks. There is a continuing interest in the development of non invasive markers capable of replacing liver biopsy. The ideal surrogate for fibrosis evaluation should be accurate, simple, low cost and yield prognostic information. So far, the most well known non invasive methods are transient hepatic elastography (TE) and laboratory panels. TE has already been extensively validated and is integrated in patients routine. There is plenty of laboratory panels in continuing evaluation and some are already integrated in daily practice abroad. In Brasil, until the present moment, it is not a reality. Enhanced Liver Fibrosis (ELF) panel comprises the serum concentration of hyaluronic acid, tissue inhibitor of matrix metalloproteinases-1, and aminoterminal propeptide of type III procollagen and has demonstrated good performance in detecting significant fibrosis and cirrhosis in CHC patients. In the present study ELF had it’s performance evaluated against liver biopsy and obtained satisfactory accuracy in detecting significant fibrosis and cirrhosis. In comparison to TE no statistically significant diference was observed, for the same endpoints mentioned before. However, the application of manufacturer’s cutoff points produced overestimation of fibrosis stages. These findings are in accordance with other author’s results, in that there is no consensus so far on the most adequate cutoff points for main clinical end points. Enlarging the data permited calculating new cutoff points, through the classical statistical approach, using liver biopsy as the gold standard...

Fatores prognósticos e associados à efetividade do tratamento da hepatite C crônica / Prognostic and associated factors to the effectiveness of chronic hepatitis C treatment

A hepatite C é uma doença recentemente reconhecida cujo tratamento é de eficácia aquém da desejável. O objetivo deste estudo é conhecer os fatores prognósticos de resposta virológica sustentada (RVS) e de efetividade do tratamento da hepatite C crônica e propor um modelo teórico que contenha as principais relações identificadas. A prevalência do HCV no Brasil é estimada entre 0,94% a1,89%, com tendência a aumentar. Há populações especificamente sob maior risco como detentos, usuários de drogas e renais crônicos em diálise. Devido ao seu caráter crônico e progressivo estima-se que as complicações relacionadas aumentem nas próximas décadas caso não haja tratamento efetivo. O tratamento é caro, com efeitos colaterais importantes e promove RVS apenas em uma parcelados indivíduos, mesmo sob condições ideais. São descritos como fatoresprognósticos para RVS: genótipo, carga viral pré-tratamento, cinética viral,transaminases, estágio de fibrose, sexo, idade, peso, raça, esteatose e aderência ao tratamento. Dispensado de acordo com critérios do Ministério da Saúde, otratamento utiliza interferon peguilado para o genótipo 1 e interferon convencional para os genótipos 2 e 3, associado à ribavirina. Associados a RVS, além do custo, outros fatores concorrem para a efetividade do tratamento: diagnóstico precoce doscasos, implementação de pólos de aplicação, qualidade e disponibilidade damedicação, critérios e interrupção precoce através da cinética viral, redução da necessidade de re-tratamento e de transplante hepático. Para aumentar a efetividade do tratamento concluímos ser necessário melhor rastreamento dos casosde infecção pelo VHC, disseminação de pólos de aplicação dos medicamentos eviabilizar exames para cinética viral.

Chronic C hepatitis is a recently recognized entity which treatment efficacy is not definitely established. The aim of this study is to know the prognostic factors for sustained virologic response and effectiveness of the treatment, as well as propose atheoretical model concerning its main issues. Brazilian prevalence of hepatitis C is around 0,94% to 1,89%, with an increasing tendency. Prisoners, drug addicts and patients in dialysis are at greater risk of infection. Related complications tend to increase in the next decades due to the chronic and progressive disease’s character.Only part of treated patients obtain virologic sustained response even in optimal conditions. VHC genotype, pretreatment viral load, viral kinetic, aminotransferases levels, fibrosis, gender, age, body weight, race, steatosis and treatment adherenceare prognostic factors associated with a sustained virologic response. According to the Brazilian control strategy peguilated interferon is used for treatment of genotype 1 and conventional interferon for genotypes 2 and 3. Other factors act along virologicsustained response for treatment effectiveness, such as related costs, early diagnosis, quality and availability of medication, “pólos de aplicação”, early stop criteria implementation, reduced number of retreatments and liver transplantations. In conclusion, to improve hepatitis C treatment effectiveness is necessary to optimizescreening programs, implement more “pólos de aplicação” and make viral kinetic viable.

Diagnóstico morfológico da cyclospora cayetanensis: um parasito emergente / Morphological diagnosis of cyclospora cayetanensis: an amergent pathogen

Criptosporidiose e isosporose säo causas bem estabelecidas de diarréia crônica em pacientes com a Sindrome de Imunodeficiência Adquirida (SIDA) e outros estados de imunodeficiência, sendo algumas vezes fatal. Recentemente, um novo coccideo morfologicamente semelhantes ao Cryptosporidium, foi descoberto em fezes de indivíduos imunocompetentes e imunocomprometidos com diarréia. Visto que o quadro clínico da infecçäo pela cyclospora cayetanenesis é similar ao da criptosporidiose, este novo organismo poderia facilmente ser confundido com o Cryptosporidium. No entanto neste artigo apresentamos características morfológicas e de coloraçäo da Cyclospora cayetanensis que nos permitem distingui-la do Cryptosporidium