Factors associated with spontaneous HBsAg clearance in chronic hepatitis B patients followed at a university hospital.

INTRODUCTION: Few studies have evaluated the factors involved in the spontaneous HBsAg seroclearance in patients with chronic hepatitis B (HBV) followed up on a long-term basis from areas with a low prevalence of HBV infection. We aimed to determine the rate of spontaneous HBsAg seroclearance and the factors related to it in patients with chronic HBV infection followed up at the Hepatitis Outpatient Clinic of HCFMRP from 1992-2008. MATERIALS AND METHODS: A total of 548 patients with chronic HBV infection (366 with chronic hepatitis B and 182 inactive carriers) were followed for 15 years and 9 months with an annual measurement of HBV-DNA, ALT, AST and GGT (average of 4 annual determinations) and serology (HBsAg, HBeAg, Anti-HBeAg and Anti-HBsAg). RESULTS: Spontaneous HBsAg seroclearance occurred in 40 patients (7.3%) with a mean age of 46.0 ± 14.4 years, corresponding to an annual rate of 0.7%.The factors related to spontaneous HBsAg seroclearance were inactive carrier status (67.5 vs. 32.5%, p = 0.000191) and age of more than 40 years (p = 0.0007). There was no difference in the rate of spontaneous HBsAg seroclearance when comparing males and females (p = 0.383). Patients with spontaneous HBsAg seroclearance did not progress to more severe forms of the disease during follow-up. CONCLUSION: Spontaneous HBsAg seroclearance has a favorable long-term prognosis in patients with chronic HBV infection. HBsAg seroclearance occurred at rates compatible with low prevalence areas and was associated with low serum HBV-DNA levels and an age older than 40 years.

Can the insulin sensitivity index (ISI) in association with insulin-like growth factor binding protein-1 identify insulin resistance early in overweight children?

UNLABELLED: Association between insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) has been reported. This prompted us to evaluate the power of the insulin sensitivity index (ISI) in association with IGFBP-1 to identify IR early in obese children/adolescents. OGTT was performed in 34 obese/overweight children/adolescents. Glucose, insulin and IGFBP-1 were measured in serum samples and ISI was calculated. Considering the presence of three or more risk factors for IR as a criterion for IR, ISI < 4.6 showed 87.5% sensitivity and 94.5% specificity in diagnosing IR. IGFBP-1 was lower in the group with ISI < 4.6 (p < 0.01). In this group, three patients had higher than expected IGFBP-1, suggesting hepatic IR, while three patients with ISI > 4.6 showed very low IGFBP-1 levels. CONCLUSION: ISI < 4.6 is a good indicator of early peripheral IR and, associated with IGFBP-1, can identify increased risk of hepatic IR. Low IGFBP-1 levels among non-IR children may indicate increased portal insulin levels.

The protective effect of CAPE on hepatic ischemia/reperfusion injury in rats.

BACKGROUND/AIMS: The transcription factor nuclear factor-kappa B (NF-kappaB) exerts a pivotal role in the pathogenesis of hepatic ischemia/reperfusion (I/R) injury. Caffeic acid phenyl ester (CAPE), a potent and specific NF-kappaB inhibitor, presents protective effects on I/R injury in some tissues. This study aimed to evaluate the effect of CAPE on hepatic I/R injury in rats. MATERIALS AND METHODS: Wistar rats were submitted to a sham operation, 60 min ischemia, or 60 min ischemia plus saline or CAPE treatment followed by 6 h reperfusion. Liver tissue injury was evaluated by alanine aminotransferase, aspartate aminotransferase, and tissue glutathione measurement, and histological damage score. Apoptotic hepatocytes were determined by the transferase-mediated dUTP-biotin nick-end labeling assay. Hepatic neutrophil accumulation was assessed by the naphthol method. Lipid peroxidation and NF-kappaB activation were evaluated by 4-hydroxynonenal and NF-kappaB p65 immunohistochemistry, respectively. RESULTS: Animals submitted to ischemia showed a marked increase of alanine aminotransferase and aspartate aminotransferase after reperfusion, but with lower levels in CAPE group. Tissue glutathione content declined gradually during ischemia to reperfusion and was partially recovered with CAPE treatment. The histological damage score, apoptosis index, and neutrophil infiltration, as well as 4-hydroxynonenal and NF-kappaB p65 nuclear labeling, were higher in the liver of animals submitted to I/R compared to the ischemia group. However, the CAPE treatment significantly reduced all of these alterations. CONCLUSIONS: CAPE was able to protect the liver against normothermic I/R injury in rats. This effect may be associated with the inhibition of the NF-kappaB signaling pathway and decrease of the acute inflammatory response following I/R in the liver.

Liver HLA-E Expression Is Associated with Severity of Liver Disease in Chronic Hepatitis C.

Hepatitis C virus (HCV) can escape from innate and adaptive immunity, making the immune response ineffective. Human leukocyte antigen E (HLA-E) might regulate the antiviral function of immune response and contribute to the persistence of HCV and the severity of liver disease. This study aimed to evaluate the expression of HLA-E in the liver and its association with the severity of liver disease in HCV patients. We performed a retrospective analysis of liver biopsies from 125 HCV patients and from 20 control subjects without liver disease. Liver biopsies were reviewed and classified according to severity of fibrosis and inflammatory activity. The pathologist assessed the magnitude of HLA-E expression in a semiquantitative way, attributing scores from 0 to 3. Immunohistochemistry showed positive for HLA-E in hepatocyte and Kupffer cells. The rate of HLA-E positivity in hepatocytes and Kupffer cells was significantly higher in HCV patients compared to controls. The liver samples classified as severe fibrosis and necroinflammatory activity presented greater expression of HLA-E on Kupffer cells and hepatocytes, with a significant linear association. It indicates that HLA-E expression may have an immunomodulatory effect and a possible role in the severity of liver disease in chronic hepatitis C.

Telomere biology and telomerase mutations in cirrhotic patients with hepatocellular carcinoma.

Telomeres are repetitive DNA sequences at linear chromosome termini, protecting chromosomes against end-to-end fusion and damage, providing chromosomal stability. Telomeres shorten with mitotic cellular division, but are maintained in cells with high proliferative capacity by telomerase. Loss-of-function mutations in telomere-maintenance genes are genetic risk factors for cirrhosis development in humans and murine models. Telomerase deficiency provokes accelerated telomere shortening and dysfunction, facilitating genomic instability and oncogenesis. Here we examined whether telomerase mutations and telomere shortening were associated with hepatocellular carcinoma (HCC) secondary to cirrhosis. Telomere length of peripheral blood leukocytes was measured by Southern blot and qPCR in 120 patients with HCC associated with cirrhosis and 261 healthy subjects. HCC patients were screened for telomerase gene variants (in TERT and TERC) by Sanger sequencing. Age-adjusted telomere length was comparable between HCC patients and healthy subjects by both Southern blot and qPCR. Four non-synonymous TERT heterozygous variants were identified in four unrelated patients, resulting in a significantly higher mutation carrier frequency (3.3%) in patients as compared to controls (p = 0.02). Three of the four variants (T726M, A1062T, and V1090M) were previously observed in patients with other telomere diseases (severe aplastic anemia, acute myeloid leukemia, and cirrhosis). A novel TERT variant, A243V, was identified in a 65-year-old male with advanced HCC and cirrhosis secondary to chronic hepatitis C virus (HCV) and alcohol ingestion, but direct assay measurements in vitro did not detect modulation of telomerase enzymatic activity or processivity. In summary, constitutional variants resulting in amino acid changes in the telomerase reverse transcriptase were found in a small proportion of patients with cirrhosis-associated HCC.

Hepatic stellate cells in human schistosomiasis mansoni: a comparative immunohistochemical study with liver cirrhosis.

This study compares the populations of liver mesenchymal cells (LMCs) and their proliferative activity in schistosomal periportal fibrosis and in hepatitis C virus-induced cirrhosis. LMCs were evaluated by immunohistochemical double staining for proliferating cell nuclear antigen (PCNA) and alpha-smooth muscle actin (alpha-SMA) or glial fibrillary acid protein (GFAP) in liver biopsies from humans with schistosomal fibrosis (n=40), hepatitis C virus-induced cirrhosis (n=20), and normal controls (n=20). The number of LMCs was found to be higher in schistosomal fibrosis than in the normal liver, but lower than in cirrhosis. alpha-SMA- and GFAP-positive cells were increased in both diseases, but more so in cirrhosis. In cirrhotic liver, alpha-SMA-positive cells were highly predominant in relation to GFAP-positive cells. However, there was an inverted ratio between these cells in schistosomiasis as compared to cirrhosis. The PCNA labeling index was higher in alpha-SMA-positive cells than in GFAP-positive cells, and did not differ between pipe-stem fibrosis and liver cirrhosis regarding alpha-SMA- or GFAP-positive cells. The predominance of GFAP-positive cells observed in schistosomiasis suggests that hepatic stellate cells (HSCs) have a major role in connective tissue deposition in the human schistosomal liver. On the other hand, the smaller number of LMCs in schistosomal fibrosis in comparison to liver cirrhosis may be related to mild and limited injury due to the schistosomal egg-induced inflammatory response. The granulomatous inflammation around Schistosoma mansoni eggs appears to mobilize and activate a reduced number of mesenchymal cells in comparison to the scattered necro-inflammatory reaction produced by the hepatitis C virus.

The precore mutation is associated with severity of liver damage in Brazilian patients with chronic hepatitis B.

BACKGROUND: The clinical relevance of the G1896A precore mutation in chronic hepatitis B is still poorly understood. OBJECTIVES: To assess the frequency of G1896A precore mutation in Brazilian patients with chronic hepatitis B, as well as its relation to the viral genotype, serum HBV-DNA levels and liver damage. STUDY DESIGN: Fifty chronic hepatitis B patients (29 HBeAg-negative and 21 HBeAg-positive) were studied. HBV-DNA was quantified by the Amplicor HBV Monitor test and precore region and S gene were amplified and submitted to automatic sequencing. The histological activity index (HAI), degrees of hepatic fibrosis and distribution of core antigen (HBcAg) in hepatocytes were determined. RESULTS: Precore mutation occurred in 1/21 (4.8%) HBeAg-positive patients and in 17/29 (58.6%) HBeAg-negative (p < 0.0001). Genotype D was identified in 56.5%, genotype A in 41.3%, and genotype F in 2.2%. The frequency of genotypes D and A, as well as serum levels of ALT and HBV-DNA were similar in patients infected with wild type and with precore mutant. Patients infected with precore mutant presented a higher frequency of moderate/severe HAI (p: 0.03) and moderate/severe fibrosis and cirrhosis (p: 0.03) than those infected with wild type. There was no association between G1896A mutation and cytoplasmic expression of HBcAg. CONCLUSIONS: Precore mutation was frequent among Brazilian subjects with chronic hepatitis B and its presence was associated with greater severity of liver disease.

Hereditary hemochromatosis in a Brazilian university hospital in São Paulo State (1990-2000).

Hereditary hemochromatosis (HH) is the most common genetic disease among individuals of European descent. Two mutations (845G-->A, C282Y and 187C-->G, H63D) in the hemochromatosis gene (HFE gene) are associated with HH. About 85-90% of patients of northern European descent with HH are C282Y homozygous. The prevalence of HH in the Brazilian population, which has a very high level of racial admixture, is unknown. The aims of the present study were to identify individuals with diagnostic criteria for HH among patients with a body iron overload attended at the university hospital of the Faculty of Medicine of Ribeirao Preto from 1990 to 2000, and to evaluate the prevalence of HFE mutations. We screened first-degree relatives for HFE mutations. Four of 72 patients (three men and one woman, mean age 47 years) fulfilled the criteria for HH. HFE mutations were studied in three patients [two C282Y homozygotes (patients 1 and 2) and one H63D heterozygote]. Patient 1 had four children (all C282Y heterozygotes with no iron overload) and seven brothers and sisters: two sisters (66 and 76 years old) were C282Y homozygotes and both had an iron overload (a liver biopsy in one showed severe iron deposits), one sister (79 years old) was a compound heterozygote with no iron overload, one brother (78 years old) was a C282Y heterozygote with no iron overload, two individuals were H63D heterozygotes (one brother, 49 years old, obese, with a body iron overload and abnormal liver enzymes - a biopsy showed non-alcoholic steatohepatitis, and one 70-year-old sister with no iron overload). Patient 2 had two children (22 and 24 years old who were C282Y heterozygotes with no iron overload) but no brothers or sisters. These results showed that HH was uncommon among individuals attended at our hospital, although HFE mutations were found in all patients. Familial screening is valuable for the early diagnosis of individuals at risk since it allows treatment to be initiated before the onset of the clinical manifestations of organ damage associated with HH.

Frequency, clinical characteristics, and respiratory parameters of hepatopulmonary syndrome.

OBJECTIVES: To determine the frequency and the clinical characteristics of hepatopulmonary syndrome (HPS) in cirrhotic candidates for orthotopic liver transplantation and to identify the major respiratory parameters predictive of the presence of changes in arterial oxygenation. PATIENTS AND METHODS: Patients underwent transthoracic contrast-enhanced echocardiography, pulmonary scintigraphy, pulmonary function test with diffusing capacity of lung for carbon monoxide (DLCO), and measurement of arterial blood gases. RESULTS: Fifty-six patients were studied. Twenty-five patients (45%) presented with intrapulmonary vascular dilatations, but only 9 (16%) fulfilled the criteria for HPS. The clinical or demographic characteristics considered did not differ in the patients with and without HPS. The DLCO value was significantly lower in patients with HPS (P=.01). However, 32 (80%) of 40 patients with low DLCO values did not fulfill the criteria for HPS. An alveolar arterial oxygen gradient (AaPO2) of more than 20 mm Hg showed a higher diagnostic accuracy (91%) in the assessment of HPS than did the DLCO of less than 80% predicted (41%) and the AaPO2 of more than 15 mm Hg (71%). CONCLUSIONS: The AaPO2 proved to be a more reliable index than PaO2 and DLCO for the determination of changes in arterial oxygenation in HPS. The DLCO does not seem to be a good marker for HPS screening. Intrapulmonary vascular dilatations were frequent, even in patients who did not fulfill the criteria for HPS.

Interleukin 6 concentration in ascitic fluid of cirrhotic patients: relationship with previous episodes of spontaneous bacterial peritonitis.

BACKGROUND: We aimed to determine whether inter-leukin (IL)-6 concentrations in plasma and ascitic fluid from cirrhotic patients with previous episodes of spontaneous bacterial peritonitis (SBP) differred from those with no previous episodes of SBP. METHODS: Cirrhotic patients with ascites were divided into two groups: G1, without previous episodes of SBP (n = 6), and G2, with previous episodes of SBP (n = 6). Patients with chronic heart failure (n = 5) with ascites, without hepatic diseases, were included as controls (G3). IL-6 concentration was determined in ascitic fluid and plasma by enzyme-linked immunosorbent assay (ELISA). A group of healthy subjects (n = 8) was used as a control for the blood IL-6 assay. RESULTS: IL-6 concentration in ascitic fluid was significantly higher in G1 (P < 0.05) than in G2 or G3. No significant difference in plasma IL-6 concentrations was observed between the groups or between each group and the healthy subjects. A significant positive linear correlation (P < 0.002) was observed between IL-6 concentration and total protein in ascitic fluid. CONCLUSIONS: A low concentration of IL-6 in ascitic fluid could predispose cirrhotic patients to SBP.

[Trends in the occurrence (1980-1999) and clinical features of Crohn's disease and ulcerative colitis in a university hospital in southeastern Brazil]. / Evolução da ocorrência (1980-1999) da doença de Crohn e da retocolite ulcerativa idiopática e análise das suas caracter sticas clínicas em um hospital universitário do sudeste do Brasil.

BACKGROUND: Crohn's disease and ulcerative colitis are regarded as uncommon in developing countries, but studies on their occurrence in Brazil are scarce. Aims - To determine the occurrence of Crohn's disease and ulcerative colitis in a Brazilian university hospital throughout a 20-year period, and analyze the demographical, clinical and evolutive features of these cases. METHODS: The frequencies of new cases of Crohn's disease and ulcerative colitis admitted from January 1980 up to December 1999 were calculated and a descriptive analysis of the features of all cases seen from January 1990 up to December 1999 was performed. RESULTS: A total of 257 new cases (126 with Crohn's disease and 131 with ulcerative colitis) was recorded. The frequencies of admissions for both Crohn's disease and ulcerative colitis have increased progressively from 40 up to 61 cases/10.000 new admissions and Crohn's disease gradually became more common than ulcerative colitis. For both diseases, there was predominance of women, age at admission in the range of 30-40 years, Caucasian origin, married state and non-smokers. Digestive symptoms presented were similar to those already described for both diseases and there were no differences between Crohn's disease and ulcerative colitis regarding the frequencies of general complaints and extra-intestinal manifestations (29.5% vs 23.3%), including thromboembolism (5.9% vs 5.4%). Obstruction and/or perforation were seen in up to 59.2% of Crohn's disease cases, whereas 53.7% of all ulcerative colitis cases presented as severe forms. In Crohn's disease cases with obstruction, smoking was significantly more common than in non-complicated cases. In ulcerative colitis cases of increased severity, general complaints, extra-intestinal manifestations and pancolitis were significantly more frequent than in less severe forms. CONCLUSIONS: For the last 20 years, there have been an increased frequency of admission of inflammatory bowel diseases, and Crohn's disease have become more prevalent than ulcerative colitis. Demographical, clinical and evolutive features of these diseases seems to be similar to those already described, but there seems to be a predominance of more severe forms of both diseases.

Relationship between plasma cells and hepatic stellate cells in autoimmune hepatitis.

Autoimmune hepatitis is an inflammatory chronic disease of the liver, which frequently results in cirrhosis. The present study aimed to verify the relationship between plasma cells and stellate cells in autoimmune hepatitis. Thirty-three pre-treatment, 11 post-treatment, and 10 normal liver biopsies were reviewed. Sirius Red staining (for semi-quantitative analysis of hepatic fibrosis) and immunohistochemistry were carried out: double staining for smooth muscle α-actin and plasma cell marker (for detection and localization of activated hepatic stellate cells and plasma cells, respectively); and single staining for glial fibrillary acid protein (for detection of hepatic stellate cells). We found an increase in the stellate cell population, mainly with an activated phenotype in autoimmune hepatitis, compared to the control group (liver specimens with no histological evidence of liver disease, obtained from patients undergoing hepatic resection for benign liver mass). A positive significant correlation was observed between stellate cells and scores of fibrosis (measured by Sirius Red) and the number of plasma cells. Additionally, there was a co-localization of plasma cells and activated stellate cells. We also observed a reduction in the number of plasma cells, hepatic stellate cells, and fibrosis in patients who had successfully been treated and had a second liver biopsy post-treatment. Our findings support that the number of plasma cells can be a surrogate marker for the severity of liver disease, reflecting the number of hepatic stellate cells and the amount of fibrosis. It remains to be seen if this is a result of a direct interaction between the plasma cells and hepatic stellate cells or the response to the same stimulus that affects both cellular types.

Evolution of hepatitis C virus infection under host factor influence in an ethnically complex population.

BACKGROUND: The ethnic influence makes it difficult to reach a consensual definition of host-dependent genetic factors controlling the hepatitis C virus (HCV) disease course. AIMS: To investigate, in an ethnically complex Brazilian population, whether human leucocyte antigen (HLA) molecules are associated with susceptibility to HCV infection, self-limiting viral clearance and predisposition to chronic disease. METHODS: One hundred and four HCV-antibody-positive patients (stratified into groups with spontaneous viral clearance and chronic HCV infection) and 166 healthy controls were submitted to HLA genotyping. RESULTS: Two strong associations were observed between the susceptibility to HCV infection and DRB3 [odds ratio (OR), 4.03; 95% confidence interval (CI), 2.40-6.77; P(c)=0.0000041] and DQB1*02 (OR, 1.72; 95% CI, 1.05-2.84; P=0.041), and between the spontaneous viral clearance and DRB1*01 (OR, 4.59; 95% CI, 1.70-12.41; P=0.003) and DQB1*03 (OR, 2.83; 95% CI, 1.14-7.02; P=0.029). No evidence was observed regarding the epidemiology or viral genotype influence on the disease course. CONCLUSION: We could confirm with a highly admixed population the association of viral clearance with two allele groups (DRB1*01 and DQB1*03) previously reported in homogeneous populations. The identification of DRB1*01 and DQB1*03 involved with self-limiting hepatitis in different ethnic groups is a very important finding that will contribute to the current knowledge about HCV-host interaction and the development of therapeutic vaccines.

Liver iron concentration evaluated by two magnetic methods: magnetic resonance imaging and magnetic susceptometry.

Quantification of liver iron concentration (LIC) is crucial in the management of patients suffering from certain pathologies that can produce iron overload, such as Cooley's anemia and hemochromatosis. All of these patients must control the level of iron deposits in their organs to avoid the toxicity of high LIC, which is potentially lethal. This paper describes experimental protocols for LIC measurement using two magnetic techniques: magnetic resonance imaging (MRI) and biomagnetic liver susceptometry (BLS). MRI proton transverse relaxation rate (R2) and image intensity, evaluated pixel by pixel, were used as indicators of iron load in the tissue. LIC measurement by BLS was performed using an AC superconducting susceptometer system. A group of 23 patients with a large range of iron overload (0.9 to 34.5 mgFe/g(dry tissue)) was evaluated with both techniques (MRI x BLS). A significant linear correlation (r = 0.89-0.95) was found between the LIC by MRI and by BLS. These results show the feasibility of using two noninvasive methodologies to evaluate liver iron store in a large concentration range. Both methodologies represent an equivalent precision.

Hepatic stellate cells in hepatitis C patients: relationship with liver iron deposits and severity of liver disease.

BACKGROUND AND AIM: To determine the relationship between hepatic stellate cell (HSC) populations and severity of liver disease and liver iron deposits in patients with chronic hepatitis C virus (HCV). We also studied the relationship between iron cellular distribution and HSC population and the role of HFE mutations in the determination of iron deposits. METHODS: Forty-nine chronic HCV patients with varying degrees of liver damage and liver iron deposits were studied. A liver biopsy was scored for histology activity index (HAI), fibrosis and iron deposits. The number of HSC in the liver was evaluated by an immunohistochemical double-staining method to identify glial fibrillary acid protein (GFAP) and smooth muscle alpha-actin (alpha-SMA). RESULTS: The HSC population was significantly higher in HCV patients than in normal controls and was predominant in zones 1 and 3. Liver iron deposits were observed in 49% of patients and were mild/moderate in most cases. We found a significantly higher number of GFAP and alpha-SMA positive cells in patients with liver iron deposits compared with those without iron deposits, and a positive correlation between liver iron scores and number (%) of GFAP and alpha-SMA positive cells. We observed a significantly higher number of GFAP and alpha-SMA positive cells in moderate/severe hepatitis than in minimal/mild hepatitis, and a positive correlation between GFAP and alpha-SMA positive cells and HAI and fibrosis scores. CONCLUSIONS: Liver iron deposits in chronic HCV are common and are associated with activation of HSC. Thus, even mild iron deposits might stimulate HSC and contribute to liver damage.

Gastric motility in patients with presinusoidal portal hypertension.

OBJECTIVE: The aim of this study was to evaluate the consequences of portal hypertension (PH) for the motor functions of the human stomach. METHODS: The PH model used was the hepatosplenic form of mansonic schistosomiasis, as this is a condition characterized by PH but with considerably preserved hepatocellular function. The study included 15 patients with PH and 25 healthy volunteers who served as controls. The adaptive relaxation of the stomach was studied in 12 patients with PH and in 10 controls by a manometric method during rapid insufflation (25-30 s) of 700 ml of air into the gastric fundus. The gastric emptying of a liquid solution (15 patients with PH and 20 controls) and of a solid-liquid meal (nine patients with PH and 12 controls) was determined by gamma scintigraphy. The thickness of the gastric antrum wall was measured by ultrasonography in 12 patients with PH and in 10 controls. RESULTS: Patients with PH showed the following: 1) reduction of the adaptive relaxation of the stomach (p < 0.0001); 2) acceleration of gastric emptying of the test solution (T 1/2, p = 0.0316), which became particularly expressive 25, 30, 40, and 50 min after ingestion (p = 0.0181, 0.0215, 0.0181, and 0.0215, respectively); 3) no alteration in gastric emptying of the solid-liquid meal as judged by T 1/2 values (p = 0.9170) or lag-phase values (p = 0.7544); and 4) a conspicuous increase in gastric wall thickness as determined by antrum wall measurements (p = 0.0008). CONCLUSIONS: The reduced gastric adaptive relaxation demonstrated in patients with PH and normal hepatocellular function leads us to consider this condition as a cause of diastolic dysfunction of the stomach. In this disease, the motor alteration may be explained as a consequence of the reduction of gastric wall compliance, probably resulting from edema and vascular ectasia, which were indirectly detected by the increase thickness of the gastric antrum wall. The discrete acceleration of liquid gastric may be also related to the reduced gastric wall compliance.

Liver iron deposits in hepatitis B patients: association with severity of liver disease but not with hemochromatosis gene mutations.

BACKGROUND AND AIMS: Iron deposits in the liver and abnormalities in serum iron biochemistry are frequently observed in patients with chronic liver diseases, but data for patients with hepatitis B virus (HBV) infection are scarce. Moreover, the role of HFE mutations in iron deposits in this condition remains unknown. The aim of the present study was to determine the prevalence of serum iron biochemical abnormalities and iron deposits in the liver of chronic HBV patients, and to evaluate the consequences for the activity and severity of liver disease. Additionally, we studied the role of HFE gene mutations in iron deposits. METHODS: Eighty-one male non-cirrhotic HBV patients were studied. Serum iron biochemistry, liver enzymes and C282Y/H63D mutations were investigated. Liver biopsies were scored for necroinflammatory activity (histological activity index [HAI]), fibrosis and iron deposits. RESULTS: Elevated transferrin saturation (TS) was found in 27.1% of patients and liver iron deposits in 48.7%; these deposits were mild in 68.4% and moderate in 31.6%. Patients with liver iron deposits exhibited significantly higher scores for HAI and fibrosis than those without iron deposits. HFE mutations were identified in 23.4% of patients (14 H63D heterozygotes, four H63D homozygotes, one compound mutation). No difference in the prevalence of C282Y and H63D mutations was observed between HBV patients (1.2% and 23.4%, respectively) and the general population (4.1% and 27.8%, respectively). No association was detected between HFE mutations and elevated TS or liver iron deposits. CONCLUSIONS: Elevated TS and liver iron deposits were frequent in non-cirrhotic HBV patients. Iron deposits were mainly mild and associated with higher activity and severity of liver disease, but not with HFE mutations.

Evoluçäo da ocorrência (1980-1999) da doença de Crohn e da retocolite ulcerativa idiopática e análise das suas características clínicas em um hospital universitário do sudeste do Brasil / Trends in the occurrence (1980-1999) and clinical features of Crohn's disease and ulcerative colitis in a university hospital in southeastern Brazil

Racional - A doença de Crohn e a retocolite ulcerativa idiopática säo consideradas pouco freqüentes nos países em desenvolvimento, sendo escassos os estudos sobre a sua ocorrência no Brasil. Objetivos - Estudar a freqüência de admissäo de casos da doença de Crohn e da retocolite ulcerativa inespecífica em um hospital universitário ao longo de 20 anos (1980-99) e descrever características demográficas e clínicas desses casos. Métodos - Calculou-se a freqüência de admissäo de casos da doença de Crohn e da retocolite ulcerativa inespecífica de janeiro de 1980 a dezembro de 1999 e analisaram-se todos os casos destas doenças admitidos nos últimos 10 anos desse período. Resultados - No período estudado, registraram-se 257 casos novos, sendo 126 da doença de Crohn e 131 da retocolite ulcerativa inespecífica. A freqüência de admissäo de casos de ambas as doenças aumentou de 40 para 61 casos/10.000 atendimentos, do primeiro para o segundo qüinqüênio, com menor crescimento subseqüente, sendo que a doença de Crohn tornou-se, gradualmente, mais freqüente que a retocolite ulcerativa inespecífica. Em ambas as doenças, houve predomínio de casos do gênero feminino, na faixa etária entre 20 e 50 anos, da cor branca, do estado civil casado e de näo-tabagistas. Ambas as doenças apresentaram-se com os sintomas digestivos próprios e näo houve diferenças entre elas quanto às freqüências de manifestaçöes sistêmicas e extra-intestinais (29,5 por cento vs 23,3 por cento), incluindo as tromboembólicas (5,9 por cento vs 5,5 por cento). Na doença de Crohn, 59,2 por cento dos casos apresentaram complicaçöes (obstruçäo e/ou perfuraçäo), enquanto que 53,7 por cento dos casos de retocolite ulcerativa inespecífica foram de formas mais graves. Nos casos de doença de Crohn com obstruçäo, o tabagismo foi significativamente mais freqüente que nas formas näo-complicadas. Na retocolite ulcerativa inespecífica, as manifestaçöes sistêmicas e as extra-intestinais, bem como o acometimento de todo o cólon, foram significativamente mais freqüentes nas formas mais graves. Conclusöes - Houve aumento da freqüência das doenças inflamatórias intestinais, com a doença de Crohn tornando-se mais comum que a retocolite ulcerativa inespecífica. Tanto uma como outra das afecçöes, apresentaram-se com as características habituais, destacando-se o predomínio das formas mais graves

Transplante de fígado: indicação e sobrevida / Liver transplantation: indication and survival

O sucesso dos transplantes de fígado certamente seria comprometido se a avaliação pré-operatória dos pacientes não fosse realizada de forma adequada. Isto se justifica devido ao reconhecimento de que o sucesso da cirurgia depende, em princípio, do diagnóstico da doença de base, da determinação de sua extensão e do grau de repercussão sistêmica. No final das décadas de setenta a noventa os progressos da hepatologia na identificação das hepatites virais e no manejo da ascite e da síndrome hepatorrenal melhoraram sobremaneira a expectativa de vida do doente portador de doença hepática crônica. Mas, sem dúvida o transplante ortotópico do fígado (TOF) foi o espetacular avanço da hepatologia moderna. Atualmente o transplante é um tratamento eficaz das hepatopatias crônicas, e o índice de sobrevivência global aos 3 anos é ao redor de 80 por cento. É, portanto, uma alternativa de tratamento indicada nos casos terminais, onde a mortalidade com tratamentos conservadores pode atingir até 70 por cento ao final de 12 meses. Neste artigo, os autores comentam aspectos do TOF, relacionados à indicação e a sobrevida.

Princípios de semiotécnica e de interpretação do exame clínico do abdômen / Principles of semiotechnic and interpretation of the abdomen clinical examination

O propósito desta publicação é o de levar aos alunos de Graduação em Medicina alguns conhecimentos básicos sobre como fazer e como interpretar o exame clínico do abdômen. Para alcançar o objetivo, procurou-se desenvolver os vinte e oito objetivos enunciados pela coordenadoria do Curso de Semiologia Médica do Departamento de Clínica Médica da Faculdade de Medicina de Ribeirão Preto (USP) e que são exigidos dos respectivos alunos, juntamente com a avaliação do desempenho prático. O conteúdo abrange, de forma sumária, os principais tópicos da inspeção, ausculta, palpação e percussão do abdômen