OBJECTIVES:Although liver biopsy is the gold standard for determining the degree of liver fibrosis, issues regarding its invasiveness and the small amount of liver tissue evaluated can limit its applicability and interpretation in clinical practice. Non-invasive evaluation methods for liver fibrosis can address some of these limitations. The aim of this study was to evaluate the accuracy of transient elastography-FibroScan®, acoustic radiation force impulse (ARFI), enhanced liver fibrosis (ELF), the aspartate aminotransferase-to-platelet ratio index (APRI), and the FIB-4 index compared with liver biopsy in hepatitis C.METHODS:We evaluated chronic hepatitis C patients who were followed at the Division of Clinical Gastroenterology and Hepatology, Hospital das Clínicas, Department of Gastroenterology of University of São Paulo School of Medicine, São Paulo, Brazil, and who underwent liver biopsy. The accuracy of each method was determined by a receiver operating characteristic (ROC) curve analysis, and fibrosis was classified as significant fibrosis (≥F2), advanced fibrosis (≥F3), or cirrhosis (F4). The Obuchowski method was also used to determine the diagnostic accuracy of each method at the various stages of fibrosis. In total, 107 FibroScan®, 51 ARFI, 68 ELF, 106 APRI, and 106 FIB-4 analyses were performed.RESULTS:A total of 107 patients were included in the study. The areas under the ROC curve (AUROCs) according to fibrosis degree were as follows: significant fibrosis (≥F2): FibroScan®: 0.83, FIB-4: 0.76, ELF: 0.70, APRI: 0.69, and ARFI: 0.67; advanced fibrosis (≥F3): FibroScan®: 0.85, ELF: 0.82, FIB-4: 0.77, ARFI: 0.74, and APRI: 0.71; and cirrhosis (F4): APRI: 1, FIB-4: 1, FibroScan®: 0.99, ARFI: 0.96, and ELF: 0.94. The accuracies of transient elastography, ARFI, ELF, APRI and FIB-4 determined by the Obuchowski method were F0-F1: 0.81, 0.78, 0.44, 0.72 and 0.67, respectively; F1-F2: 0.73, 0.53, 0.62, 0.60, and 0.68, respectively; F2-F3: 0.70, 0.64, 0.77, 0.60, and 0.67, respectively; and F3-F4: 0.98, 0.96, 0.82, 1, and 1, respectively.CONCLUSION:Transient elastography remained the most effective method for evaluating all degrees of fibrosis. The accuracy of all methodologies was best at F4.

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Based on the biochemical and histological evidence in this pilot study, NAC in combination with MTF appears to ameliorate several aspects of NASH, including fibrosis. Further studies of this form of combination therapy are warranted to assess its potential efficacy.

ResumoNa maioria dos mamíferos a atividade da enzima lactase diminui na parede intestinal após o desmame, caracterizando a hipolactasia primária que provoca sintomas de intolerância à lactose. A intensidade dos sintomas de distensão, flatulência, dor abdominal e diarreia variam, dependendo da quantidade de lactose ingerida, e aumentam com o passar da idade. A hipolactasia é determinada geneticamente, porém uma mutação ocorreu para que fizesse parte da humanidade tolerar o leite na idade adulta. O diagnóstico é feito por teste de tolerância, empregando a lactose como desafio. Com a descoberta dos finlandeses do polimorfismo associado com a persistência da lactase, principalmente no norte da Europa, o exame genético passou a ser outra ferramenta diagnóstica mais confortável para o intolerante. No Brasil, 43% dos brancos e dos mulatos têm alelo de persistência da lactase, sendo a hipolactasia mais frequente entre os negros e japoneses. Entretanto, na prática clínica indivíduos com hipolactasia podem ser orientados a consumir alguns derivados do leite e alimentos contendo lactose sem apresentar sintomas de intolerância, enquanto que outros terão que fazer restrição de lactose na dieta. ConceitoMá absorção ou má digestão de lactose é a diminuição na capacidade de hidrolisar a lactose, que é resultante da hipolactasia. A hipolactasia significa diminuição da atividade de enzima lactase na mucosa do intestino delgado 1 , também denominada recentemente de "lactase não persistente" 2 . O aparecimento de sintomas abdominais por má absorção de lactose caracteriza a intolerância à lactose. A má absorção de lactose nem sempre provoca sintomas de intolerância à lactose 1 . Após o desmame, ocorre uma redução geneticamente programada e irreversível da atividade da lactase na maioria das populações do mundo, cujo mecanismo é desconhecido, resultando em má absorção primária de lactose 3 . Porém, a hipolactasia também pode ser secundária a doenças que causem dano na borda em escova da mucosa do intestino delgado ou que aumentem significativamente o tempo de trânsito intestinal, como nas enterites infecciosas, giardíase 4 , doença celíaca 5 , doença inflamatória intestinal (especialmente doença de Crohn), enterites induzidas por drogas ou radiação, doença diverticular do cólon 6 e anemia (estudo em ratos, mostrando diminuição na expressão gênica) 7 . Diferentemente da hipolactasia primária do adulto, a hipolactasia secundária é transitória e reversível 8 . Enzima lactase-florizina hidrolase da família 1 das glicosil hidrolasesA estrutura primária traduzida da enzima lactase-florizina hidrolase foi deduzida a partir de sequências de cDNA, apresentando 1927 aminoácidos (NP_002290.2-número de acesso no NCBI), sendo que as duas atividades de lactase e florizina hidrolase (glicosilceramidase) se localizam no mesmo polipeptídeo 9 . A estrutura inicial tem peso molecular de 215000 e, após ser processada provavelmente no complexo de Golgi, o peso molecular cai para 160000, se ancorando na membrana da borda em escova do enterócito 10 , poré...

Heart failure (HF) is, after cirrhosis, the second-most common cause of ascites. Serum B-type natriuretic peptide (BNP) plays an important role in the diagnosis of HF. Therefore, we hypothesized that BNP would be useful in the differential diagnosis of ascites. Consecutive patients with new onset ascites were prospectively enrolled in this crosssectional study. All patients had measurements of serum-ascites albumin gradient (SAAG), total protein concentration in ascitic fluid, serum, and ascites BNP. We enrolled 218 consecutive patients with ascites resulting from HF (n 5 44), cirrhosis (n 5 162), peritoneal disease (n 5 10), and constrictive pericarditis (n 5 2). Compared to SAAG and/or total protein concentration in ascites, the test that best discriminated HF-related ascites from other causes of ascites was serum BNP. A cutoff of >364 pg/mL (sensitivity 98%, specificity 99%, and diagnostic accuracy 99%) had the highest positive likelihood ratio (168.1); that is, it was the best to rule in HF-related ascites. Conversely, a cutoff £ 182 pg/mL had the lowest negative likelihood ratio (0.0) and was the best to rule out HF-related ascites. These findings were confirmed in a 60-patient validation cohort. Conclusions: Serum BNP is more accurate than ascites analyses in the diagnosis of HFrelated ascites. The workup of patients with new onset ascites could be streamlined by obtaining serum BNP as an initial test and could forego the need for diagnostic paracentesis, particularly in cases where the cause of ascites is uncertain and/or could be the result of HF. (HEPATOLOGY 2014;59:1043-1051 See Editorial on Page 751A scites secondary to heart failure (HF) is, after cirrhosis, the second-most common cause of ascites. 1 The pathophysiology of ascites in both HF and cirrhosis is hepatic sinusoidal hypertension, and therefore the serum-ascites albumin gradient (SAAG) is greater than 1.1 g/dL in both conditions. 2 Because the hepatic sinusoids are normal (leaky, i.e., without significant collagen deposition in the space of Disse) in HF and are abnormal in cirrhosis (less leaky as a result of capillarization of sinusoids), 3 ascites total protein content is higher in HF-related ascites than in cirrhotic ascites and has been used to help in the differential diagnosis between these two entities, with a ascites protein level of >2.5 mg/dL suggesting the presence of ascites related to HF. However, a significant number of cases are still misclassified. 2,4 Even the Abbreviations: ASE, American Society of Echocardiography; BNP, B-type natriuretic peptide; CLD, chronic liver disease; HF, heart failure; HVPG, hepatic venous pressure gradient; INR, international normalized ratio; IQR, interquartile range; LR, likelihood ratio; NPV, negative predictive value; NT-proBNP, N-terminal proBNP; PH, portal hypertension; PPV, positive predictive value; SAAG, serum-ascites albumin gradient; STARD, Standards for reporting Studies of Diagnostic Accuracy; US, ultrasound.From the

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-O b j e c t i v e:To determine CASI-S accuracy in the diagnosis of dementia. M e t h o d: The Cognitive Abilities Screening Instrument -Short Form (CASI-S) was applied in 43 Alzheimer's disease (AD) patients and 74 normal controls. AD diagnosis was based on DSM-IV, NINCDS-ADRDA, and CAMDEX. CASI-S includes: registration, temporal orientation, verbal fluency (4-legged animals in 30s), and recall (3 words). Its maximum score is 33 points. A copy of 2 pentagons was added. Results: ROC curve showed an accuracy of 0.87, with standard error of 0.032, and 95% confidence intervall between 0.795 and 0.925. The cut-off score for cognitive deficit was 23, with sensitivity of 76.7%, specificity 86.5%, positive likelihood ratio (LR) 5.68, and negative LR 0.27. The cut-off score for subjects 70 years or older was 20, with sensitivity of 71.4% and specificity 97.1%. C o n c l u s i o n: CASI-S is a practical test, with high specificity, particularly in individuals above 70 years of age. The adding of the drawing test did not improve its accuracy.

Several new direct-acting antiviral (DAA) drugs are in development for chronic hepatitis C viral (HCV) infection, and NS3-NS4A serine protease and the NS5B RNA-dependent RNA polymerase have been the major targets. HCV variants displaying drug-resistant phenotypes have been observed both in vitro and during clinical trials. Our aim was to characterize amino acid changes at positions previously associated with resistance in protease (NS3) and polymerase (NS5B) regions from treatment-naïve HCV patients infected with genotypes 1a, 1b and 3a. All 1383 NS3 protease sequences (genotype 1a = 680, 1b = 498 and 3a = 205) and 806 NS5B polymerase sequences (genotypes 1a = 471, 1b = 329, 3a = 6) were collected from Los Alamos databank. Genotype 3a protease sequences showed the typical low-level resistance mutation V36L. NS3 sequences from other genotypes presented mutations on positions 36, 39, 41, 43, 54, 80, 109, 155 and 168 in a frequency lower than 2%, except for the mutation Q80R found in 35% of genotype 1a isolates. Polymerase sequences from genotype 3a patients showed five typical mutations: L419I, I424V, I482L, V499A and S556G. Two positions presented high polymorphism in the NS5B region from genotype 1a (V499A) and genotype 1b (C316N) subjects. Our results demonstrated a natural profile of genotype 3a that can be associated with the pre-existence of HCV variants resistant to first-generation protease inhibitors and to non-nucleoside polymerase inhibitors. Likewise, genotype 1b isolates and genotype 1a sequences exhibited pre-existing mutations associated with resistance to Palm II and Thumb I polymerase inhibitors, respectively.