Ultrasound shear wave elastography for liver disease. A critical appraisal of the many actors on the stage

In the last 12\u200a-\u200a18 months nearly all ultrasound manufacturers have arrived to implement ultrasound shear wave elastography modality in their equipment for the assessment of chronic liver disease; the few remaining players are expected to follow in 2016.When all manufacturers rush to a new technology at the same time, it is evident that the clinical demand for this information is of utmost value. Around 1990, there was similar demand for color Doppler ultrasound; high demand for contrast-enhanced ultrasonography was evident at the beginning of this century, and around 2010 demand increased for strain elastography. However, some issues regarding the new shear wave ultrasound technologies must be noted to avoid misuse of the resulting information for clinical decisions. As new articles are expected to appear in 2016 reporting the findings of the new technologies from various companies, we felt that the beginning of this year was the right time to present an appraisal of these issues. We likewise expect that in the meantime EFSUMB will release a new update of the existing guidelines 1 2.The first ultrasound elastography method became available 13 years ago in the form of transient elastography with Fibroscan(\uae) 3. It was the first technique providing non-invasive quantitive information about the stiffness of the liver and hence regarding the amount of fibrosis in chronic liver disease 3. The innovation was enormous, since a non-invasive modality was finally available to provide findings otherwise achievable only by liver biopsy. In fact, prior to ultrasound elastography, a combination of conventional and Doppler ultrasound parameters were utilized to inform the physician about the presence of cirrhosis and portal hypertension 4. However, skilled operators were required, reproducibility and diagnostic accuracy were suboptimal, and it was not possible to differentiate the pre-cirrhotic stages of fibrosis. All these limitations were substantially improved by transient elastography, performed with Fibroscan(\uae), a technology dedicated exclusively to liver elastography. Since then, more than 1300 articles dealing with transient elastography have been listed in PubMed, some describing results with more than 10,000 patients 5. The technique has been tested in nearly all liver disease etiologies, with histology as the reference standard. Meta-analysis of data, available in many etiologies 6, showed good performance and reproducibility as well as some situations limiting reliability 5. Thresholds for the different fibrosis stages (F0 to F4) have been provided by many large-scale studies utilizing histology as the reference standard 7. Transient elastography tracks the velocity of shear waves generated by the gentle hit of a piston on the skin, with the resulting compression wave traveling in the liver along its longitudinal axis. The measurement is made in a 4\u200acm long section of the liver, thus able to average slightly inhomogeneous fibrotic deposition.In 2008 a new modality became available, Acoustic Radiation Force Impulse (ARFI) quantification, and classified by EFSUMB 1 as point shear wave elastography (pSWE), since the speed of the shear wave (perpendicular to the longitudinal axis) is measured in a small region (a "point", few millimeters) at a freely-choosen depth within 8\u200acm from the skin. This technology was the first to be implemented in a conventional ultrasound scanner by Siemens(\uae) 8. Several articles have been published regarding this technology, most with the best reference standards 9, some including findings on more than 1000 hepatitis C patients 10 or reporting meta-analysis of data 11. Although the correlation between Siemens pSWE and transient elastography appeared high 12 13, the calculated thresholds for the different fibrosis stages and the stiffness ranges between the two techniques are not superimposable.Interestingly, pSWE appears to provide greater applicability than transient elastography for measuring both liver 13 and spleen stiffness, which is a new application of elastography 14, of interest for the prediction of the degree of portal hypertension 15 16.Nowadays other companies have started producing equipment with pSWE technology, but only very few articles have been published so far, for instance describing the use of Philips(\uae) equipment, which was the second to provide pSWE. These articles show preliminary good results also in comparison with TE 17 18. Not enough evidence is currently available in the literature about the elastographic performance of the products most recently introduced to the market. Furthermore, with some products the shear wave velocities generated by a single ultrasound acoustic push pulse can be measured in a bidimensional area (a box in the range of 2\u200a-\u200a3\u200acm per side) rather than in a single small point, producing a so-called bidimensional 2D-SWE 1. The stiffness is depicted in color within the area and refreshing of the measurement occurs every 1\u200a-\u200a2 seconds. Once the best image is acquired, the operator chooses a Region Of Interest (ROI) within the color box, where the mean stiffness is then calculated. 2D-SWE can be performed as a "one shot" technique or as a semi-"real-time" technique for a few seconds (at about 1 frame per second) in order to obtain a stable elastogram. With either technique, there should be no motion/breathing during image acquisition. A bidimensional averaged area should overcome the limitation of pSWE to inadvertently investigate small regions of greater or lesser stiffness than average. A shear wave quality indicator could be useful to provide real-time feedback and optimize placement of the sampling ROIs, a technology recently presented by Toshiba(\uae), but which is still awaiting validation in the literature.Supersonic Imagine by Aixplorer(\uae) which works with a different modality of insonation and video analysis compared to the the previously-mentioned three techniques (i.\u200ae., transient elastography, pSWE and 2D-SWE), leading to a bidimensional assessment of liver stiffness in real time up to 5\u200aHz and in larger regions; thus this technique is also termed real-time 2\u200aD SWE. It has been available on the market for a few years 19 20, and many articles have been published showing stiffness values quite similar to those of Fibroscan(\uae) 21; likewise, defined thresholds based on histological findings have appeared in several articles 19 20 21.After this brief summary of the technological state of the art we would like to mention the following critical issues that we believe every user should note prior to providing liver stiffness reports. \ub7 The thresholds obtained from the "oldest" techniques for the various fibrosis stages based on hundreds of patients with histology as reference standard cannot be straightforwardly applied to the new ultrasound elastography techniques, even if based on the same principle (e.\u200ag. pSWE). In fact, the different manufacturers apply proprietary patented calculation modes, which might result in slightly to moderately different values. It should be kept in mind that the range for intermediate fibrosis stages (F1 to F3) is quite narrow, in the order of 2\u200a-\u200a3 kilopascal (over a total range spanning 2 to 75 kPa with Fibroscan), so that slightly different differences in outputs could shift the assessment of patients from one stage to another. Comparative studies using phantoms and healthy volunteers, as well as patients, are eagerly awaited. In fact, the equipment might not produce linear correlations of measurements at different degrees of severity of fibrosis. As a theoretical example, some equipment might well correlate in their values with an older technique, such as transient elastography, at low levels of liver fibrosis, but not as well in cases of more advanced fibrosis or vice versa. Consequentely, when elastography data are included in a report, the equipment utilized for the measurement should be clearly specified, and conclusions about the fibrosis stage should be withheld if an insufficient number of comparative studies with solid reference standards are available for that specific equipment.. \ub7 Future studies using histology as a reference might be biased in comparison to previous studies, since nowadays fewer patients with chronic hepatitis C or hepatitis B undergo biopsy. In fact, due to wide availability of effective drugs as well as the use of established elastography methods for patients with viral hepatitis, most cases submitted to biopsy today have uncertain etiology or inconsistent and inconclusive clinical data. Therefore, extrapolated thresholds from such inhomogeneous populations applied to more ordinary patients with viral hepatitis might become problematic in the future, although no better solution is currently anticipated. This situation might lead to the adoption of a standard validated elastographic method as reference, but this has to be agreed-upon at an international level.. \ub7 Ultrasound elastography embedded in conventional scanners usually allows the choice of where to place the ROI within the color stiffness box and whether to confirm or exclude each single measurement when determining the final value. Thus, the operator has a greater potential to influence the final findings than with Fibroscan\uae, where these choices are not available. This has to be kept in mind to avoid the possibility that an operator could, even inadvertently, tend to confirm an assumption about that specific patient or to confirm the patient's expectations.. \ub7 Quality criteria for the new technologies following transient elastography are absent (depending on the manufacturer) or have not been satisfactorily defined, so that the information potentially inserted in a report cannot currently be judged for its reliability by the clinician.. (ABSTRACT TRUNCATED

Expressão e distribuição da conexina 32 em fígados de ratos com fibrose induzida experimentalmente

The connexin 32 (Cx32) is a protein that forms the channels that promote the gap junction intercellular communication (GJIC) in the liver, allowing the diffusion of small molecules through cytosol from cell-to-cell. Hepatic fibrosis is characterized by a disruption of normal tissue architeture by cellular lesions, and may alter the GJIC. This work aimed to study the expression and distribution of Cx32 in liver fibrosis induced by the oral administration of dimethylnitrosamine in female Wistar rats. The necropsy of the rats was carried out after five weeks of drug administration. They presented a hepatic fibrosis state. Sections from livers with fibrosis and from control livers were submitted to immunohistochemical, Real Time-PCR and Western-Blot analysis to Cx32. In fibrotic livers the Cxs were diffusely scattered in the cytoplasm, contrasting with the control livers, where the Cx32 formed junction plaques at the cell membrane. Also it was found a decrease in the gene expression of Cx32 without reduction in the protein quantity when compared with controls. These results suggest that there the mechanism of intercellular communication between hepatocytes was reduced by the fibrotic process, which may predispose to the occurrence of a neoplastic process, taken in account that connexins are considered tumor suppressing genes.A conexina 32 (Cx32) é uma proteína que constitui os canais que promovem as comunicações intercelulares via junções comunicantes (CIJC) no fígado, permitindo difusão de pequenas moléculas citoplasmáticas de uma célula à outra. A fibrose hepática caracteriza-se pela alteração da arquitetura normal do fígado e podem alterar as CIJCs. O objetivo deste trabalho foi estudar a expressão e distribuição de Cx32 na fibrose hepática. O objetivo do presente trabalho foi estudar a expressão e distribuição da Cx32 em fígados com fibrose induzida pela administração oral de dimetilnitrosamina em fêmeas de ratos Wistar. A necropsia foi realizada após cinco semanas da última administração da droga e observou-se um quadro de fibrose hepática. Amostras dos fígados com fibrose e de animais controle foram submetidas à análise imunoistoquímica, por Real Time-PCR e por Western-Blot verificando-se a presença de Cx32 difusa e dispersa no citoplasma dos fígados com fibrose. No grupo controle a Cx32 localizou-se na membrana citoplasmática com a formação de placas juncionais. O fígado com fibrose também revelou diminuição da expressão gênica de Cx32, embora sem a redução da quantidade do produto protéico, quando comparado ao grupo controle. Estes resultados sugerem que o mecanismo de comunicação intercelular entre os hepatócitos reduziu-se durante o processo fibrótico, o que pode predispor a ocorrência de processos neoplásicos, uma vez que as conexinas são consideradas genes supressores de tumores.FAPESPCNP

Histological features and survival in idiopathic pulmonary fibrosis

BACKGROUND: Idiopathic pulmonary fibrosis was recently redefined as usual interstitial pneumonia of unknown etiology. Consequently, the prognostic value of histological findings needs to be reassessed. OBJECTIVE: To correlate clinical, functional and histological findings with survival in patients with idiopathic pulmonary fibrosis. METHOD: Patients (n = 51; mean age: 66 ± 8 years; gender: 21 females/30 males) were evaluated. Of the 51, 26 were smokers or ex-smokers. Duration of symptoms, forced vital capacity and smoking habits were recorded. All patients presented usual interstitial pneumonia verified through histology. Degree of honeycombing, established fibrosis, desquamation, cellularity, myointimal thickening of blood vessels and number of fibroblastic foci were graded according to the semiquantitative method. RESULTS: Median duration of symptoms was 12 months and initial forced vital capacity was 72 ± 21%. Cox multivariate analysis revealed that survival correlated inversely and significantly (p < 0.05) with duration of symptoms and fibroblastic foci score, as well as with myointimal thickening of blood vessels. Limited numbers of fibroblastic foci, as well as myointimal thickening involving less than 50% of blood vessels, were predictive of greater survival. No correlation with survival was found for gender, age, forced vital capacity, inflammation or degree of cellularity. CONCLUSION: Semiquantitative analysis of lung biopsies yields relevant prognostic information regarding patients with usual interstitial pneumonia.INTRODUÇÃO: A fibrose pulmonar idiopática foi recentemente redefinida como pneumonia intersticial usual de etiologia desconhecida. O valor prognóstico dos achados histológicos deve ser reavaliado. OBJETIVO: Neste estudo foram correlacionados os achados histológicos e alguns dados clínicos e funcionais (duração dos sintomas, capacidade vital forçada, idade, sexo, hábito de fumar) com a sobrevida. MÉTODO: Foram estudados 51 pacientes portadores de fibrose pulmonar idiopática. A média de idade foi de 66 ± 8 anos. Vinte e um pacientes eram do sexo feminino; 26 eram fumantes ou ex-fumantes. Todos apresentavam quadro de pneumonia intersticial usual na histologia. Grau de faveolamento, fibrose estabelecida, descamação, celularidade, espessamento vascular miointimal e focos fibroblásticos foram graduados por método semiquantitativo. RESULTADOS: A mediana do tempo de sintomas foi de 12 meses e a capacidade vital forçada inicial foi de 72 ± 21%. Por análise de risco proporcional de Cox, a sobrevida correlacionou-se, de maneira significativa (p < 0,05) e inversa, com o tempo de história, com a extensão dos focos fibroblásticos e com o espessamento miointimal da parede dos vasos. Focos fibroblásticos esparsos e espessamento miointimal envolvendo menos de 50% dos vasos foram preditivos de maior sobrevida. Sexo, idade, capacidade vital forçada, grau de inflamação e celularidade não se correlacionaram com a sobrevida. CONCLUSÃO: A análise semiquantitativa da biópsia pulmonar em portadores de fibrose pulmonar idiopática fornece informações prognósticas relevantes.UNIFESP Departamento de PatologiaHSPE Departamento de PatologiaHSPE Departamento de Doenças do Aparelho RespiratórioSociedade Brasileira de Pneumologia e TisiologiaSanta Casa Pavilhão Pereira FilhoUNIFESP, Depto. de PatologiaSciEL

Etude du profil d'activation des macrophages alvéolaires chez le transplanté pulmonaire

La transplantation pulmonaire est une option thérapeutique d'ultime recours pour les patients souffrant de maladies pulmonaires telles que la broncho-pneumopathie chronique obstructive (BPCO), la mucoviscidose, l'hypertension artérielle pulmonaire sévère et la fibrose pulmonaire. Bien que devenue une intervention établie, elle est associée chez 30 à 50% des patients à cinq ans post-greffe au développement d'une dysfonction chronique du greffon, principalement liée à une inflammation chronique et un remodelage tissulaire à l'origine d'une fibrose

Avaliação histopatológica hepática em pacientes obesos mórbidos submetidos à cirurgia bariátrica

Trabalho de Conclusão de Curso - Universidade Federal de Santa Catarina. Curso de Medicina. Dapartamento de Clínica Cirúrgica

Biópsia hepática em cunha ou com agulha em cirurgia bariátrica convencional

Background: Morbidly obese patients, despite normal laboratory tests and no clinical evidence of disease, present high prevalence of hepatic histological changes. Hepatic biopsy is able to define diagnosis, staging and to assess the evolution (follow-up) of hepatic disease, thus helping to define clinical management. There is no agreement on which biopsy technique provides better material for analysis. Considering that subcapsular fibrosis is a common finding, sampling from more profound sites is necessary in order to achieve an adequate histological assessment. Methods: This is a transversal study of 264 consecutive morbidly obese patients, submitted to open Roux and Y gastric bypass between July 2001 and September 2004, in which a transoperatory liver biopsy was taken. The first 107 were wedge biopsies and the last 157 were needle biopsies. The histological degree of steatosis, presence of fibrosis and adequacy of material from the different biopsy techniques were compared. Results: The degree of steatosis of both sampling techniques showed no statistical difference (p=0. 132). The presence of fibrosis in wedge biopsies (46. 1% fibrosis, n: 41) was significantly higher than in needle biopsies (13. 7% fibrosis, n: 20), p<0. 001. As expected, sample size of needle biopsies was smaller than the obtained by the wedge technique (p < 0. 001), but there was no difference in the quality of material obtained (p=0. 95). Conclusion: Needle biopsies were as effective as wedge biopsies to assess the degree of steatosis in morbidly obese patients. The presence of subcapsular fibrosis in needle biopsies was lower than in wedge biopsies, suggesting an adequate tissue sampling through a less invasive technique.Introdução: Pacientes obesos mórbidos, mesmo na presença de provas laboratoriais normais e sem evidência clínica de doença, apresentam alta prevalência de alterações na histologia hepática. A biópsia hepática é indicada para definir diagnóstico, graduação, estadiamento e evolução de doenças hepáticas, ajudando a definir o manejo clínico. Discute-se qual a melhor técnica para coleta de tecido hepático, que costuma apresentar fibrose na região sub-capsular, exigindo coleta de material mais profundo. Método: Estudo transversal, envolvendo 264 pacientes obesos mórbidos, submetidos à redução gástrica, com derivação em Y de Roux convencional de julho 2001 a setembro de 2004, nos quais a biópsia hepática foi realizada como procedimento de rotina no transoperatório. As primeiras 107 biópsias foram realizadas em cunha e as 157 seguintes por agulha. Foram avaliados os resultados histológicos nas duas técnicas baseando-se no grau de esteatose hepática, presença de fibrose e adequabilidade do material. Resultados: Não houve diferença significativa quanto ao grau de esteatose entre as duas técnicas (p=0,132). A presença de fibrose foi significativamente maior nos casos em que a biópsia foi realizada em cunha (41 = 46,1%), quando comparados à técnica por agulha (20 = 13,7%): p<0,001. As biópsias por agulha foram significativamente menores que as em cunha: p<0,001, mas não houve diferença quanto à adequabilidade das amostras: p=0,95, nas diferentes técnicas. Conclusão: A biópsia por agulha mostrou os mesmos resultados obtidos com a biópsia em cunha em relação ao grau de esteatose. A presença de fibrose foi significativamente menor na técnica por agulha

Comment modéliser les événements de la fibrose cutanée ?

Classiquement, les fibroses cutanées sont considérées comme l’étape ultime d’un processus inflammatoire chronique et persistant, qui pérennise l’hyperplasie et la différenciation fibroblastique ainsi que l’accumulation de matrice extracellulaire. Le retentissement clinique de ces fibroses s’exprime tant au niveau esthétique que fonctionnel, et se révèle d’autant plus problématique qu’il n’existe à ce jour ni régression spontanée, ni thérapeutique antifibrosante efficace et sûre. Le développement et le maintien de la fibrose cutanée impliquent les différents composants cellulaires de la peau ainsi que plusieurs médiateurs paracrines, qui activent différentes voies de signalisation intracellulaires : ce réseau d’interaction est complexe et difficile à modéliser. Cette revue présente les modèles cellulaires et expérimentaux permettant de modéliser la fibrose cutanée, et expose leurs apports dans la compréhension des mécanismes physiopathologiques de fibrogenèse cutanée. Ces modèles constituent des outils performants pour tester de nouvelles hypothèses mécanistiques et thérapeutiques.Skin fibrosis is classically seen as the consequence of chronic inflammation and altered healing response that is characterized by the differentiation of fibroblasts into secretory myofibroblasts and accumulation of connective tissue. Although fibrosis severely affects organ function and causes esthetic defects, no effective therapy is currently available to attenuate the fibrogenic process probably because the fibrogenic process is more complex than previously thought. Indeed, it might involve several interacting and mutually dependent cell types (fibroblasts, keratinocytes, endothelial cells, inflammatory cells), numerous paracrine factors, bio-active molecules and micro-environmental stimuli (growth factors, vasoactive peptides, balance between pro- and anti-inflammatory cytokines, coagulation system, reactive oxygen species, extracellular matrix…). In this perspective, the traditional approach that model individual cell response in simple cell culture system is probably inadequate and too simplistic. This article reviews the new models used to study skin fibrosis in vitro, in organotypic culture systems and in vivo and examines how these different models might be used to identify new molecular pathways involved in fibrogenesis. The monolayer cultures allow the study of fibrogenic signals induced by a single factor on a single cell type. Isolation of cells from fibrotic tissue allows to define the fibrogenic differentiation acquired in vivo. The organotypic models allow cell to cell and cell to matrix interaction and the experimental models in pigs and mice allowed studies in integrated physiological systems. These various and complementary models would also provide new tools to develop and test new drugs and treatments

Evaluation of the histological parameters in usual interstitial pneumonia (idiopathic pulmonary fibrosis)

Idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) is a progressive interstitial pulmonary disease of unknown etiology. Since Hamman's and Rich's (1944) reports, many studies have tried to find a histological marker for the correlation between prognosis and response to therapy. However, there are many doubts regarding pathogenesis. In addition, it is generally accepted that response to therapy is related to the relative degree of cellularity and fibrosis. The purpose of this study is to describe the results of inflammatory/exudative changes, fibrotic/reparative changes, and airway alterations, using a semi-quantitative method by independent evaluation of two pathologists, in 24 open lung biopsies with the diagnosis of idiopathic pulmonary fibrosis. Fourteen histological features were analyzed using the 0 to 5 scale for interstitial alterations and the 0 to 2 scale for the airway changes. There was significant interobserver agreement for all histological features with Kw (Kappa) variations between 0.47 and 0.92. There was significant disagreement only for septal inflammatory intensity analysis, suggesting that these features must be discussed by the pathologists. The semi-quantitative method assessment was effective.A fibrose pulmonar idiopática (alveolite fibrosante criptogênica) é uma doença pulmonar intersticial progressiva de etiologia desconhecida, morfologicamente reconhecida como pneumonia intersticial usual. Desde a publicação de Hamman e Rich (1944) até os dias atuais, uma das grandes preocupações foi a tentativa de encontrar um marcador histológico para correlacionar com prognóstico e resposta terapêutica. A busca desta situação não tem sido muito alentadora, pois existem vários pontos duvidosos na patogênese desta doença. Admite-se que a resposta terapêutica desta entidade se relaciona com a celularidade e fibrose presentes no tecido. A proposta deste estudo é descrever os resultados de método semiquantitativo segundo a avaliação independente de dois patologistas, das alterações exsudativo-inflamatórias, reparativo-fibróticas e de vias aéreas, em 24 pacientes com diagnóstico de fibrose pulmonar idiopática, submetidos à biópsia a céu aberto. Foram analisados 14 parâmetros histológicos segundo escala de 0 a 5 para as alterações intersticiais e de 0 a 2 para o comprometimento de vias aéreas e de espaços aéreos. Da análise independente realizada pelos dois observadores constatou-se concordância significante em todas as variáveis histológicas com Kw (teste de Kappa) indo de 0,47 a 0,92. Apenas na análise da intensidade da inflamação septal as discordâncias também foram significantes, sugerindo que para este parâmetro a percentagem de comprometimento tecidual deve ser previamente discutida entre os observadores. O método utilizado demonstrou ser rápido e eficiente.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PatologiaUNIFESP, EPM, Depto. de PatologiaSciEL

Predictive value of serum markers of hepatic fibrosis in patients with chronic hepatitis C

INTRODUCTION: Serum markers have been used in the assessment of liver fibrosis in patients with chronic hepatitis C (CHC). AIMS: We evaluated the capacity of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, gama-glutamyltransferase (GGT) levels, platelet count, the AST to platelet ratio index (APRI) and serum hyaluronic acid (HA) to predict the intensity of hepatic fibrosis in patients with CHC and the variation of these markers after therapy with interferon. PATIENTS AND METHODS: In 72 patients with hepatitis C, AST/ALT ratio, GGT levels, platelet count, the APRI index (calculated as the ratio of AST to platelets) and serum HA concentration were determined and compared to histological staging according to the scoring system of METAVIR. Sixty-five patients received interferon and ribavirin therapy. The individuals that completed the treatment (n = 33) underwent a new test for serum marker of fibrosis in order to compare it with pre-treatment levels. RESULTS: GGT levels, platelet count, the APRI index and serum HA were correlated with the stage of hepatic fibrosis (p < 0.01), except AST/ALT ratio. The analysis of the areas under the ROC curve (AUC) evidenced that APRI and HA levels were the markers with the best association with hepatic staging: AUC (APRI) = 0.85 and AUC (HA) = 0.86. After therapy with interferon, only GGT and the APRI showed reduction of their levels (p < 0.05). CONCLUSION: HA and the APRI index were the most accurate approaches to liver fibrosis staging and they may be used as alternative diagnostic methods in patients with CHC.INTRODUÇÃO: Os marcadores séricos têm sido empregados na avaliação da fibrose hepática em pacientes portadores de hepatite crônica C (HCC). OBJETIVOS: Avaliar a capacidade do índice aspartato aminotransferase (AST)/alanina aminotransferase (ALT), dos níveis séricos de gama-glutamiltransferase (GGT), contagem de plaquetas, do índice AST/plaquetas (APRI) e do ácido hialurônico (AH) em predizer a intensidade da fibrose hepática na HCC e a variação desses marcadores após tratamento com interferon. PACIENTES E MÉTODOS: Em 72 pacientes portadores de hepatite C determinamos no soro o índice AST/ALT, GGT, plaquetas, índice APRI (obtido pelo quociente AST/plaquetas) e o AH, que foram comparados ao estadiamento histológico, segundo os critérios de METAVIR. Receberam tratamento com interferon e ribavirina 65 pacientes. Os indivíduos que concluíram o tratamento (n = 33) realizaram nova dosagem dos marcadores séricos de fibrose para comparar com os níveis pré-tratamento. RESULTADOS: Observamos que a GGT, a contagem de plaquetas, o índice APRI e o AH se correlacionaram com estádio de doença hepática (p < 0,01), exceto o índice AST/ALT. A análise das áreas sob as curvas ROC (AUC) evidenciaram que a melhor associação com estadiamento hepático foi para o índice APRI e a dosagem sérica do AH: AUC (APRI) = 0,85 e AUC (AH) = 0,86. Na avaliação pós-terapia com interferon, apenas a GGT e o índice APRI apresentaram redução de seus níveis (p < 0,05). CONCLUSÃO: O AH e o índice APRI apresentaram maior acurácia no estadiamento da fibrose, podendo ser aplicados como métodos diagnósticos alternativos na HCC.Universidade Federal de São Paulo (UNIFESP)Universidade Federal de Alagoas Hospital UniversitárioUNIFESPFundação Universitária de Ciências da Saúde de Alagoas Governador Lamenha FilhoUFAL HUUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPMSciEL