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BACKGROUND: Nonalcoholic fatty liver disease comprises a spectrum of lesions ranging from steatosis to cirrhosis, with nonalcoholic steatohepatitis being the progressive form of the disease. Alcohol intake, viral hepatitis and other liver diseases must be excluded. Liver biopsy is the gold standard for diagnosis of the disease and is the only method able to differentiate nonalcoholic steatohepatitis from simple steatosis, to grade inflammation and to stage fibrosis. AIMS: To analyze the histopathological findings and evaluate interobserver agreement in biopsies previously diagnosed as steatosis or steatohepatitis. METHODS: Seventy needle biopsies were analyzed according to Brunt et al.(4), with modifications in the grading and staging components. Clinical data of patients were collected. Interobserver agreement was calculated based on histopathological findings. RESULTS: Mild nonalcoholic steatohepatitis (grade 1) was the most common form. If fibrosis was detected, stage 1 was the most frequent. Interobserver agreement was very good for macrovesicular steatosis (K W = 0,82) and good for lobular inflammation (K W = 0,68) and fibrosis (K W = 0,73). CONCLUSIONS: The classification of Brunt et al., with modifications, can be applied to diagnosis not only of nonalcoholic steatohepatitis but also of nonalcoholic fatty liver disease, representing a reliable method for use in the daily practice of pathologists.

INTRODUÇÃO: A doença hepática gordurosa não-alcoólica compreende um espectro de lesões que variam da esteatose à cirrose, sendo a esteatoepatite não-alcoólica a forma progressiva da doença. Uso de álcool, hepatites virais e outras doenças hepáticas devem ser excluídos. A biópsia hepática é o padrão-ouro para o diagnóstico da doença, sendo o único método capaz de diferenciar a esteatoepatite da esteatose, graduar a inflamação e estadiar a fibrose. OBJETIVOS: Analisar os achados histopatológicos e avaliar a concordância interobservador em biópsias previamente diagnosticadas como esteatose ou esteatoepatite. MATERIAIS E MÉTODOS: Setenta biópsias por agulha foram analisadas segundo Brunt et al.(4), com modificações nos componentes determinantes da atividade e no estadiamento. Os informes clínicos dos pacientes foram coletados. A concordância interobservador foi calculada com base nos achados histopatológicos. RESULTADOS: Esteatoepatite não-alcoólica discreta (grau 1) foi a forma mais comum. Se havia fibrose, o estágio 1 foi o mais freqüente. Concordância interobservador foi muito boa para esteatose macrovacuolar (KW = 0,82) e boa para inflamação lobular (KW = 0,68) e fibrose (KW = 0,73). CONCLUSÕES: A classificação de Brunt et al., com modificações, pode ser usada para o diagnóstico não somente da esteatoepatite não-alcoólica, mas também da doença hepática gordurosa não-alcoólica, representando método confiável para uso na rotina diária dos patologistas.

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BACKGROUND: The aim of this study was to investigate the HCV genotypes, hepatic siderosis, inflammatory activity and fibrosis of the liver in patients with chronic renal failure (CRF) on haemodialysis in Brazil. METHODS: A cohort of 72 CRF patients was compared with a group of 65 candidates for blood donation (CBD). For the subjects selected, who tested positive for anti-HCV antibodies and were HCV-PCR positive, a protocol with epidemiological, clinical and laboratory information was completed. An ultrasound-guided liver biopsy was performed and histological analysis of liver fragments was carried out. The presence of HCV-RNA in plasma was established by nested-RT-PCR. The genotype was determined by Restriction Fragment Length Polymorphism (RFLP) analysis of the PCR product. RESULTS: HCV genotype 1 was predominant in both groups, but genotype 2 was the second most common amongst CRF patients, and there was a significant difference when compared with the CBD group (P=0.016). Regarding inflammation and fibrosis, no significant difference was observed in the histology of the liver between the study groups. Siderosis of the liver was more prevalent in the CRF group (P=0.000). Severe complications of liver biopsies were reported in 10 CRF patients (13.2%). CONCLUSIONS: Genotype 2 was observed more frequently in the haemodialysis group. No statistically significant difference was detected between the CRF and CBD groups with regard to both inflammatory response and liver fibrosis. Hepatic siderosis has been attributed to excessive iron administration. As percutaneous liver biopsy resulted in severe complications, we suggest that other procedures of evaluating liver damage in CRF patients should be looked at thoughtfully.

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BACKGROUND/AIMS: The circulating renin-angiotensin system (RAS) [plasma renin activity (PRA), Angiotensin (Ang) I, Ang II and Ang-(1-7)] was evaluated in a model of hepatic fibrosis in rats. To investigate the pathophysiological involvement of Ang-(1-7), animals were treated with the Ang-(1-7) Mas receptor antagonist, A-779. METHODS: RAS components, liver function and histology were examined in male Wistar rats (220-300 g). Animals were submitted to sham-surgery or ligature of the bile duct and evaluated 1, 2, 4 and 6 weeks later. Blood samples were obtained to determine biochemical parameters and RAS components. A second group was treated with A-779 or vehicle to measure liver hydroxyproline and total transforming growth factor beta-1 (TGFbeta1). RESULTS: PRA and Ang I were significantly elevated in rats at 4 and 6 weeks compared to sham-operated animals. Ang II and Ang-(1-7) progressively increased over the 6 weeks. Changes in RAS profile correlated with histological signs of fibrosis and deterioration in liver function. Pharmacological blockade of the Ang-(1-7) receptor aggravated liver fibrosis with a significant elevation in hydroxyproline and total TGFbeta(1). CONCLUSIONS: Hepatic fibrosis was associated with RAS activation in our model. Our data also suggested that Ang-(1-7) played a protective role in hepatic fibrosis.

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BACKGROUND: Hepatic steatosis and nonalcoholic steatohepatitis (NASH) have been increasingly implicated in the genesis of hepatic fibrosis and cirrhosis. However, no consensus exists about whether weight reduction may reverse this process. METHODS: To assess the effect of Roux-en-Y gastric bypass (RYGBP) on the histological evolution of NASH diagnosed in 64 patients by routine liver biopsy ("first" biopsy) performed during surgery, we performed a "second" biopsy after 23.5 +/- 8.4 months in 16 patients (14 female, 2 male). RESULTS: From the first to the second biopsy, BMI decreased from 53.4 +/- 8.8 kg/m2 to 31.1 +/- 4.7 kg/m2, arterial hypertension decreased from 75% to 43.8%, and type 2 diabetes decreased from 43.8% to zero. On the first biopsy, nonalcoholic fatty liver disease (NAFLD) type 3 was observed in 12 patients (75%) and type 4 in 4 (25%). The second biopsy revealed complete regression of NAFLD in 15 patients (93.7%) and only 1 (6.3%) had NAFLD type 1 (mild steatosis without inflammation). Complete regression of necroinflammatory activity was observed in all patients. Among the 4 patients presenting fibrosis in the first biopsy, complete remission was observed in 1 and improvement in 1. Two continued to show the same degree of fibrosis without evidence of disease activity. No worsening of steatosis, necroinflammatory activity or fibrosis was observed in any of the patients, and none progressed to cirrhosis. CONCLUSION: RYGBP improves steatosis, necroinflammatory activity and hepatic fibrosis in patients with morbid obesity and NASH.

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The detection of hepatic nodules by imaging techniques in cirrhotic patients has increased and the growing consensus that these lesions may be premalignant increases their clinical importance and demands precise diagnostic criteria. The prevalence of macroscopic suspect hepatic nodule (MSHN) in cirrhotic livers was analyzed to identify macroregenerative nodule (MRN), dysplastic nodule and hepatocellular carcinoma (HCC) and to evaluate an association between MSHN and HCC. Hepatic nodules larger than 1cm and different from the surrounding nodules of the cirrhosis in color and texture were considered MSHN. Sixty-one cirrhotic liver explants were serially sectioned into 0.5 to 0.7cm slices and MSHN and protocol samples were examined histologically. Ninety-four MSHN were identified in 26 livers (histologically 11 were cirrhotic nodules, 61 MRN, 12 dysplastic nodules, and ten HCC). HCC was identified macroscopically in one liver and by light microscopy within MSHN in six other livers. The relation between HCC and MSHN, specifically MRN, was statistically significant. These findings suggest an association between MRN and MSHN with HCC in cirrhotic livers and reinforce the practical importance of histological classification of hepatic nodules in cirrhosis in order to guide the management of patients who are waiting for liver transplant or surgical treatment.

A detecção de nódulos hepáticos por técnicas de imagem em pacientes com cirrose tem aumentado, e o consenso de que essas lesões podem ser pré-malignas aumenta sua importância clínica e demanda critério diagnóstico preciso. A prevalência de nódulos hepáticos macroscopicamente suspeitos (NHMS) em fígados com cirrose foi analisada para identificar macronódulo regenerativo (MNR), nódulo displásico e carcinoma hepatocelular (CHC) e para avaliar a associação de NHMS e CHC. Nódulos hepáticos maiores que 1cm com cor e textura diferentes dos demais nódulos da cirrose em cada peça foram definidos como NHMS. Sessenta e um fígados explantados por cirrose foram seccionados em fatias de 0,5 a 0,7cm e NHMS e amostras de áreas aleatórias do fígado foram examinadas histologicamente. Noventa e quatro NHMS foram identificados em 26 fígados (à histologia 11 foram nódulos típicos da cirrose; 61, MNR; 12, nódulos displásicos; e dez, CHC). O CHC foi identificado macroscopicamente em um fígado e pela microscopia óptica em NHMS em seis outros. A relação entre CHC e NHMS, especificamente MNR, foi estatisticamente significante. Esses achados sugerem associação entre MNR e NHMS com o CHC em fígados com cirrose e reforçam a importância prática da classificação histológica dos nódulos na cirrose, com o propósito de orientar a conduta médica no manuseio de pacientes que estão à espera de transplante hepático ou de tratamento cirúrgico.

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We report the second case in literature of a boy with the association of large omphalocele, accessory hepatic lobe, and biliary atresia, and the first successful treatment. The patient was submitted to a surgical treatment at 44 days of life, including Kasai procedure, correction of the remnant abdominal wall defect, and removal of a hepatic accessory lobe. The boy evolved with normalization of hepatic function tests. After 15 years of follow-up, the patient is completely healthy, weights 45 kg, and is 1.64 m tall.

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BACKGROUND: The authors analyze and describe the hepatic histopathology of patients with morbid obesity submitted to gastric bypass. METHODS: A liver biopsy was performed in 112 patients at the beginning of gastric bypass, and clinical data (gender, age, BMI and associated diseases) were obtained from the patient records. RESULTS: Among the patients, 74.1% (n=83) were females and 25.9% (n=29) were males, age 39.59+/-10.12 years, with BMI 48.79+/-7.54. Regarding the diseases associated with morbid obesity, arterial hypertension was observed in 67.9% (n=76) of the patients, joint diseases in 55.4% (n=62), dyslipidemia in 40.2% (n=45), and diabetes type 2 in 27.7% (n=31). 111 patients (99.1%) showed different types of non-alcoholic fatty liver disease (NAFLD) (types 1, 2, 3 and 4), with types 3 and 4 accounting for 57.7% (n=64). A significant association was observed between NAFLD type 4 and diabetes type 2 (P=0.018). The presence of glycogen nuclei was significantly correlated with steatosis (P=0.000), lobular inflammation (P=0.019) and perisinusoidal fibrosis (P=0.000). CONCLUSION: 1) Liver biopsy taken at gastric bypass reveals different types of NAFLD; 2) Diabetes type 2 is associated with NAFLD type 4; 3) Glycogen nuclei are correlated with steatosis, lobular inflammation and perisinusoidal fibrosis; 4) Steatosis represents the basic injury in NAFLD and is associated with hepato-cellular ballooning. 5) In view of the frequency of hepatic alterations, a biopsy should be part of the surgical protocol of morbid obesity, this method being the only one able to determine the presence of lesions and to stage fibrosis.

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Este estudo retrospectivo investigou os aspectos clínicos de 295 pacientes com hepatite C crônica. A idade variou entre 13 e 81 anos (mediana=49 anos) sendo 55% entre 40 a 60 anos. O fator de risco principal foi hemotransfusão, seguido pelo uso de drogas injetáveis. A maioria dos casos era assintomática. Cinqüenta por cento dos pacientes apresentavam complicações da cirrose hepática ao diagnóstico. Não houve associação entre o genótipo e a gravidade da fibrose hepática. Os fenômenos auto-imunes foram diagnosticados em 10% dos pacientes. A ALT estava aumentada em 69% dos casos. Trinta e dois por cento tinham ALT normal e 8% destes eram cirróticos. Somente 26% dos pacientes tratados com interferon mais ribavirina por 48 semanas apresentaram resposta virológica sustentada. Os resultados deste estudo alertam para a alta morbidade da hepatite C no nosso meio.

Clinical aspects of chronic hepatitis C in a retrospective study including 295 patients were studied. The age ranged from 13 to 81 years (mean = 49 years); 55% were 40 to 60 years old. The mainly risk factor to infection was blood transfusion, followed by drug injection. Most patients were asymptomatic but 50% had cirrhosis by the time of diagnosis. Genotype was not related to worse status of fibrosis. Auto-immune events appeared in 10% of patients. High and normal levels of alanine-aminotransferase (ALT) were found in 69% and 32% of the patients, respectively. Eight per cent of the patients with normal levels of ALT were cirrhotic. Only 26% of treated patients had sustained response to virus after treatment with interferon and ribavirin for 48 weeks. The results show a high morbidity.

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