Gastro

Tempo de espera aceitável para a colonoscopia

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MGFamiliar ® – Wednesday, June 21, 2017

 

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Pergunta clínica: O tempo decorrido entre uma pesquisa de sangue oculto nas fezes com resultado positivo e a realização de colonoscopia tem influência no risco e estadiamento do cancro do cólon e recto?

Enquadramento: O cancro do cólon e recto é a segunda causa de morte por cancro nos Estados Unidos da América e uma das mais frequentes no mundo. A realização de rastreio do cancro do cólon e recto mostrou reduzir a mortalidade por esta patologia. A pesquisa de sangue oculto nas fezes é um teste frequentemente usado como rastreio do cancro do cólon e recto. Embora esteja estabelecido que um resultado positivo na pesquisa de sangue oculto nas fezes implica a realização subsequente de colonoscopia, o espaço temporal entre estes não está definido, pelo que o tempo decorrido entre a realização dos dois exames é muito variável, podendo resultar na progressão da doença.

Desenho do estudo: Estudo coorte retrospetivo. Do total de 7,5 milhões clientes de uma empresa seguradora dos Estados Unidos da América selecionaram-se todos os adultos com idade entre 50-75 anos e com pesquisa de sangue oculto nas fezes positiva realizada entre 1 de Janeiro de 2010 e 31 de julho de 2013. Critérios de exclusão: história prévia de cancro do cólon e recto; contrato com a seguradora com duração inferior a um ano após a realização da pesquisa de sangue oculto nas fezes e sem colonoscopia realizada no período segurado; duração de contrato de seguro inferior a um ano antes da realização da pesquisa de sangue oculto nas fezes; suspensão de contrato de seguro superior a 3 meses após a realização da pesquisa de sangue oculto nas fezes ; colonoscopia realizada há menos de 10 anos ou sigmoidoscopia realizada há menos de 5 anos; diagnóstico de cancro do cólon e recto (com ou sem colonoscopia) nos 1-7 dias após pesquisa de sangue oculto nas fezes positiva (nestes casos a pesquisa de sangue oculto nas fezes  poderia ser considerada como teste diagnóstico e não teste de rastreio).  Os outcomes primários foram o diagnóstico imediato ou aos 6 meses após colonoscopia de cancro do cólon e recto de qualquer tipo, de doença avançada (cancro em estadios III e IV) ou de adenomas com histologia de alto grau. Odds-ratio (OR) e intervalos de confiança a 95% (IC) foram ajustados para os dados sociodemográficos e outros fatores de risco.

Resultados: Identificaram-se 81518 doentes elegíveis. Destes, 70124 indivíduos realizaram colonoscopia subsequente (média de idades de 61 anos; 52,7% do género masculino) Foram  identificados 2191 casos de cancro do cólon e recto, dos quais 601 correspondiam a casos de doença em estadio avançado. Em relação ao tempo decorrido até à realização da colonoscopia verificou-se que não existiram diferenças significativas no risco de cancro do cólon e recto ou doença avançada entre a sua realização nos primeiros 8-30 dias, 2 meses, 3 meses, 4-6 meses ou 7-9 meses. Os riscos foram significativamente maiores quando a colonoscopia foi realizada após 10-12 meses quer para o diagnóstico de cancro do cólon e recto (casos de cancro do cólon e recto em 1000=49; OR 1.48 [IC95% 1.05-2.08]) quer para o diagnóstico de doença avançada (casos de cancro do cólon e recto em 1000=19; OR 1.97 [IC95% 1.14-3.42]) e após os 12 meses (n=747) de igual forma quer para o diagnóstico de cancro do cólon e recto (casos de cancro do cólon e recto em 1000=76; OR 2.25 [IC95% 1.89-2.68]) quer para o diagnóstico de doença avançada (casos de cancro do cólon e recto em 1000=31; OR 3.22 [IC95% 2.44-4.25])

Conclusão: Nos doentes que realizaram pesquisa de sangue oculto nas fezes e obtêm um resultado positivo, a realização de colonoscopia subsequente passados mais de 10 meses está associada a um maior risco de cancro do cólon e recto e de doença em estadio avançado no momento de diagnóstico, quando comparada com a sua realização após 8-30 dias. Mais estudos são necessários para estabelecer uma relação de causalidade.

Comentário: Embora nos últimos anos se verifique um aumento da taxa de incidência de diagnósticos oncológicos em Portugal, a mortalidade associada a estes tem vindo a diminuir. No SNS, a acessibilidade à colonoscopia após pesquisa de sangue oculto nas fezes positiva tem vindo a melhorar. Este estudo alerta para a necessidade dos profissionais de saúde e doentes estarem atentos perante a positividade de um teste de pesquisa de sangue oculto nas fezes, de forma a proceder à realização da colonoscopia num período temporal adequado, idealmente nos primeiros 10 meses, e que permita uma deteção precoce e tratamento atempado de qualquer patologia oncológica diagnosticada.

Artigo original: JAMA

Por Carla Martins, USF Vale do Vez

Pediatric Celiac Disease

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Resultado de imagem para celiac disease

Background
Celiac disease (CD) is the most common genetically related food intolerance, worldwide. Celiac disease is a multifactorial, autoimmune disorder that occurs in genetically susceptible individuals. [1] It is triggered by a well-identified environmental factor (gluten and related prolamins present in wheat, rye, and barley), and the autoantigen is also well known (ie, the ubiquitous enzyme tissue transglutaminase). The disease primarily affects the small intestine, where it progressively leads to flattening of the small intestinal mucosa.
Within this definition, patients can further be defined as having silent, potential, or latent celiac disease. [2] The term silent celiac disease refers to patients fulfilling the definition above, but presenting no symptoms. Typically, such diagnoses are made by screening asymptomatic individuals who are at increased risk for celiac disease. The term potential celiac disease describes patients who have specific serum autoantibodies and may or may not have symptoms consistent with celiac disease, but lack evidence of the autoimmune insult to the intestinal mucosa. A final category of celiac patients is represented by the so-called latent celiac disease: individuals with normal mucosal morphology (like the potential) but known to have had a gluten-dependent enteropathy at some point in their life.
The genetic susceptibility to celiac disease is conferred by well-identified haplotypes in the human leukocyte antigen (HLA) class II region (ie, DR3 or DR5/DR7 or HLA DR4). Such haplotypes are expressed on the antigen-presenting cells of the mucosa (mostly dendritic cells); approximately 90% of patients express the DQ2 heterodimer, and approximately 7% of patients express the DQ8 heterodimer. The remaining 3% of patients possess only half of the DQ2 heterodimer.
Celiac disease can occur at any stage in life; a diagnosis is not unusual in people older than 60 years.
Data from Rubio-Tapia et al [3] showed that undiagnosed celiac disease in the United States has dramatically increased in the past half century, going from 0.2% in the late 1940s to 0.9% 50 years later.

Pathogenesis

Celiac disease is an autoimmune disease, and the enzyme tissue transglutaminase (tTG) has been discovered to be the autoantigen against which the abnormal immune response is directed. Gluten is the single major environmental factor that triggers celiac disease, which has a narrow and highly specific association with class II haplotypes of HLA DQ2 (haplotypes DR-17 or DR5/7) and, to a lesser extent, DQ8 (haplotype DR-4).
Scientific knowledge on the pathogenesis of celiac disease has markedly increased in the past few years; the combined roles of innate and adaptive immunity are now better understood.
Innate immunity

Intraepithelial lymphocytes (IELs) play an important role in the destruction of epithelial cells. Through specific natural killer receptors (NKR) expressed on their surface, IELs recognize nonclassical major histocompatibility complex (MHC)-I molecules induced on the surface of enterocytes by stress and inflammation. This interaction leads to activation of these armed effector IELs to become lymphokine-activated killing cells; they cause epithelial cell death in a T-cell receptor (TCR)–independent manner. This killing is particularly enhanced through the cytokine interleukin (IL)-15, which is highly expressed in celiac mucosa. NKG2D has been found to play a crucial role in intestinal inflammation in celiac disease. [4]
Adaptive immunity

The adaptive immune response to gluten has been well described, with the identification of specific peptide sequences demonstrated in specific binding to HLA-DQ2 or DQ8 molecules and in stimulating gluten-specific CD4 T cells. These T cells express α/β TCR, and can be isolated from the lamina propria and cultivated. In vitro, they have been shown to recognize specific gluten peptides presented through interaction with DQ2 or DQ8 molecules.
Gluten is a complex macromolecule that contains abundant proline and glutamine residues, rendering it largely indigestible. Under usual circumstances, gluten is left (in part) unabsorbed by the GI tract. Gluten is composed of glutenins and gliadins, the alcohol-water soluble fraction. These gliadins are further divided into alpha, gamma, and omega fractions based on electrodensity. [5]
Among these fractions, one particular peptide fragment is the alpha gliadin 33-mer, which contains an immunodominant peptide fragment. This fragment is deamidated by tTG. tTG is a ubiquitous enzyme and is known to deamidate glutamine to glutamic acid, creating a strong negative charge within the peptide. This modification is crucial in increasing selection to the positive charges within the binding pocket of HLA-DQ2 or DQ8 molecules on antigen-presenting cells in the lamina propria. When conveyed to gluten specific CD4+ T cell, it induces proliferation and induction of a Th1 cytokine response, primarily with the release of interferon-γ.
B cells receive signals through this HLA interaction, leading to tTG autoantibody production. The role of these autoantibodies is still unclear; they have been shown to be deposited along the subepithelial region even in normal-appearing intestinal biopsy findings prior to positive serology and without the onset of overt epithelial cell damage.
Relevant anatomy

Celiac disease primarily affects the small intestine. This organ is schematically divided into 3 areas: the duodenum (which begins beyond the pylorus, located at the end of the stomach), the jejunum, and the ileum (ending at the ileocecal junction, the beginning of the large intestine). These 3 parts share similar tissue architecture and are responsible for most of the body’s nutrient absorption. The intestinal wall has 4 layers, which (from the lumen inward) are termed the mucosa, submucosa, muscularis, and serosa. The 2 main functions of the mucosa are to accomplish all digestive-absorptive processes for nutrients and electrolytes and to provide a barrier function by excluding foreign antigens and toxins.

Celiac disease affects the mucosal layer: here, a cascade of immune events leads to the changes that can be documented by histology.
Pathology

The classic celiac lesion occurs in the proximal small intestine with typical histological changes of villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytosis. Three distinctive and progressive histological stages have been described and are termed the Marsh classification. [6] The histological changes of celiac disease are classified as follows:
Type 0 or preinfiltrative stage (normal)
Type 1 or infiltrative lesion (increased intraepithelial lymphocytes)
Type 2 or hyperplastic lesion (type 1 plus hyperplastic crypts)
Type 3 or destructive lesion (type 2 plus villous atrophy of progressively more severe degrees [termed 3a, 3b, and 3c])

Epidemiology
Frequency

United States
The availability of sensitive and specific serological tests has made it possible to assess the true prevalence of celiac disease by detecting minimally symptomatic or even asymptomatic cases with typical mucosal changes. [7] Screening studies have shown that celiac disease has a very high prevalence, occurring in almost 1% of the general population throughout North America. [8, 9]
International
Celiac disease is as common in Europe as it is in North America, but it has now been detected in populations from many other parts of the world, including African and Middle Eastern countries, and in Asia, with the highest prevalence worldwide in Saharawi children. [10]
Furthermore, the prevalence of celiac disease appears to be increasing quite dramatically during the past few decades. [8, 11, 12, 9] In Northern Sweden, an epidemiological investigation using a combined serological/endoscopic approach in an unselected population of 1000 adults found a prevalence of almost 2%. [13]
Epidemiological data do document worldwide a true increase in prevalence, with rates doubling approximately every 20 years. A concomitance of environmental factors are likely responsible for this, but most of them are still unclear. Among the hypotheses to explain such increase are: the hygiene hypothesis, [14] increased rates of births through elective cesarean delivery, [15] changes in infant feeding practices as dramatically documented by the so-called Swedish epidemic, [16] and repeated infections—by rotavirus but also generic, nongastrointestinal infections in early infancy. [17]
A recent investigation in Sweden proved that early vaccinations are not risk factors for the development of celiac disease. [18]
A study reported that children living in socioeconomically deprived areas in the UK are less likely to be diagnosed with CD. The study added that increased implementation of diagnostic guidelines could result in better case identification in more-deprived areas. [19, 20]

Mortality/Morbidity

The morbidity rate of celiac disease can be high. Its complications range from osteopenia, osteoporosis, or both to infertility in women, short stature, delayed puberty, anemia, and even malignancies (mostly related to the GI tract [eg, intestinal T-cell lymphoma]). As a result, the overall mortality in patients with untreated celiac disease is increased.
Evidence also suggests that the risk of mortality is increased in proportion to the diagnostic delay and clearly depends on the diet; subjects who do not follow a gluten-free diet have an increased risk of mortality, as high as 6 times that of the general population. The increased death rates are most commonly due to intestinal malignancies that occur within 3 years of diagnosis. [21, 22] Some indirect epidemiological evidence suggests that intestinal malignancies can be a cause of death in patients with undiagnosed celiac disease. [23]
Race

In some ethnicities, such as in the Saharawi population, celiac disease has been found in as many as 5% of the population. As mentioned, celiac disease is considered extremely rare or nonexistent in people of African, Chinese, or Japanese descent.
Sex

Most studies indicate a prevalence for the female sex, ranging from 1.5:1 to 3:1.
Age

Celiac disease can occur at any stage in life; a diagnosis is not unusual in people older than 60 years. Classic GI pediatric cases usually appear in children aged 9-18 months. Celiac disease may also occur in adults and is usually precipitated by an infectious diarrheal episode or other intestinal disease.

Patient Education
A consensus report by Ludvigsson et al stated that in adolescence, patients with CD should gradually assume exclusive responsibility for their own care, learning how to follow a gluten-free diet and the consequences of not following it. [24]

Clinical presentation

Celiac disease (CD) may occur without any symptoms; asymptomatic or minimally symptomatic celiac disease is probably the most common form of the disease, especially in older children and adults. See the figures below.

The celiac iceberg.
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Presentations of celiac disease.
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Currently, [2] 5 possible presentations of celiac disease are recognized, as follows:
Typical: This presentation is primarily characterized by GI signs and symptoms.
Atypical: GI signs and symptoms are minimal or absent, and various extraintestinal manifestations are present.
Silent: The small intestinal mucosa is damaged, and celiac disease autoimmunity can be detected with serology; however, no symptoms are present.
Potential: Patients have a positive specific autoimmune serology and may or may not be symptomatic, but the mucosa morphology is normal. These individuals have genetic compatibility with celiac disease and full-blown celiac disease may develop at a later stage in some or all of these individuals.
Latent: Individuals with normal mucosal morphology who “have had a gluten-dependent enteropathy at some point in their life.” This subset of patients is the rarest of the group.
Typical presentation

The so-called typical form of celiac disease presents with GI symptoms that characteristically appear at age 9-24 months. Symptoms begin at various times after the introduction of foods that contain gluten. Infants and young children typically present with chronic diarrhea, anorexia, abdominal distension, abdominal pain, poor weight gain or weight loss, and vomiting. Severe malnutrition can occur if the diagnosis is delayed. Behavioral changes are common and include irritability and an introverted attitude. Rarely, severely affected infants present with a celiac crisis, which is characterized by explosive watery diarrhea, marked abdominal distension, dehydration, hypotension, and lethargy, often with profound electrolyte abnormalities, including severe hypokalemia.

Older children with celiac disease who present with GI manifestations may have onset of symptoms at any age. The variability in the age of symptom onset possibly depends on the amount of gluten in the diet and other environmental factors, such as duration of breast feeding. In fact, in the author’s experience, if gluten is introduced during breast feeding, the symptoms tend to be less often GI related and tend to appear later in life. [25] GI symptoms in older children are typically less evident and include nausea, recurrent abdominal pain, bloating, constipation, and intermittent diarrhea.
A study by Mårild et al reported a two-way association between anorexia nervosa and celiac disease. The hazard ratio for future anorexia nervosa after celiac disease diagnosis was 1.46 and 1.31 beyond the first year. The odds ratio for a previous anorexia nervosa diagnosis associated with celiac disease was 2.18. [26, 27]
Atypical presentation

An increasing number of patients are being diagnosed without typical GI manifestations at older ages. A reasonable assumption is that approximately 70% of patients with newly diagnosed celiac disease do not present with the typical major GI symptoms. Once again, a relationship between the age of onset and the type of presentation is noted; in infants and toddlers, GI symptoms and failure to thrive predominate, whereas, during childhood, minor GI symptoms, inadequate rate of weight and height gain, and delayed puberty tend to be more common. In teenagers and young adults, anemia is the most common form of presentation. In adults and in the elderly, GI symptoms are more prevalent, although they are often minor. See the images below.

GI signs and symptoms of celiac disease.
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Extraintestinal manifestations of celiac disease.
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The main extraintestinal manifestations of celiac disease are as follows:
Dermatitis herpetiformis: A blistering skin rash that involves the elbows, knees, and buttocks are associated with dermal granular immunoglobulin (Ig) A deposits. The rash and mucosal morphology improve on a gluten-free diet. Dermatitis herpetiformis is a rare occurrence in childhood and is described almost exclusively in teenagers and adults.
Dental enamel hypoplasia: These enamel defects involve mostly the permanent dentition, although they have been described also in deciduous teeth. These changes may be the only presenting manifestation of celiac disease.
Aphthous ulcers: These can be present in children and in adults with celiac disease. At this time, it is unclear if these are associated with enamel defects, and their prevalence in celiac disease patients is variable. [28] Oral ulcers are neither characteristic nor specific for celiac disease since aphthous ulcers can also be associated with other medical conditions such as inflammatory bowel disease and Behçet disease. However, it should be noted that these ulcers often regress once the patients are on a gluten-free diet. [28]
Delayed tooth eruption: This has been reported in up to 27% of patients with celiac disease. [28] This is a nonspecific sign, possibly related to malnutrition, and in conjunction with the rest of the oral examination could raise the suspicion of the dental clinician about the possibility of celiac disease.
Iron-deficiency anemia: In several studies, iron-deficiency anemia that is resistant to oral iron supplementation is reportedly the most common extraintestinal manifestation of celiac disease in adults. In children, iron deficiency with or without anemia is very common too, but seldom it is seen as the only presenting sign. Anemia can only be the result of folate, vitamin B-12 deficiency, and it may also coexist with anemia of chronic disease as a result of the chronic intestinal inflammation. In addition to anemia, a number of less common hematologic manifestations can be seen, including hyposplenism, thrombocytosis, and selective IgA deficiency. [29]
Short stature and delayed puberty: Short stature may be the only manifestation of celiac disease. As many as 10% of children with idiopathic short stature may have celiac disease that can be detected on serologic testing. Some patients with short stature also have impaired growth hormone production following provocative stimulation testing; this production returns to normal when the patient is put on a gluten-free diet. Adolescent girls with untreated celiac disease may have delayed onset of menarche.
Chronic hepatitis and hypertransaminasemia: Patients with untreated celiac disease commonly have elevated transaminase levels (alanine aminotransferase [ALT], aspartate aminotransferase [AST]). [30] As many as 9% of patients with elevated transaminase levels of unclear etiology may have silent celiac disease. Liver biopsy findings in these patients reveal nonspecific reactive hepatitis. In most cases, liver enzymes normalize on a gluten-free diet.
Arthritis and arthralgia: Arthritis can be a common extraintestinal manifestation of adults with celiac disease, including those on a gluten-free diet. As many as 3% of children with juvenile chronic arthritis may have celiac disease.
Osteopenia and osteoporosis: Approximately 50% of children and 75% of adults have a low bone mineral density at the time of diagnosis; this low density reaches severe degrees, including osteoporosis. Bone mineral density improves in most patients on gluten-free diet and returns to normal as soon as 1 year after starting the diet in children. However, the response to the diet can be much less marked in adults.
Neurological problems: Numerous neurological conditions have been attributed to celiac disease in adults and, to a lesser extent, in children. [31] Celiac disease may cause occipital calcifications and intractable epilepsy; these patients can be resistant to antiseizure medicines but can benefit from a gluten-free diet if it is started soon after onset of seizures. The association with cerebellar ataxia is well described in adults; the term gluten-induced ataxia has been proposed.
Psychiatric disorders: Although a large number of behavioral problems and disorders (eg, autism, attention deficit hyperactivity disorder) have been thought to be caused by celiac disease, no evidence has been conclusive. However, celiac disease can be associated with some psychiatric disorders, such as depression and anxiety. These conditions can be severe and usually respond to a gluten-free diet. [#fertilityandceliacdisease]
Subfertility or infertility: Although somewhat controversial, reports have indicated that as many as 6% of women who experience infertility or repeated miscarriages have celiac disease. [32] Some studies recommend increased screening for celiac disease in pregnant women; however, screening is associated with its own risks and expense. Because of the potential serious effects of undiagnosed celiac disease on the outcome of pregnancy, the need for screening pregnant women for celiac disease is currently under investigation.
Associated diseases

Celiac disease is also known to be strongly associated with numerous disorders, specifically with autoimmune conditions and genetic syndromes (eg, Down syndrome, Williams syndrome, Turner syndrome).
The association of celiac disease with autoimmune conditions is well known. A strong positive correlation between the age at diagnosis and the prevalence of autoimmune disorders (eg, type 1 diabetes mellitus, thyroiditis, alopecia) is recognized; this suggests that the continuous ingestion of gluten before diagnosis may induce the development of other autoimmune conditions.
Type 1 diabetes mellitus
Approximately 10% of patients with type 1 diabetes mellitus have typical findings of celiac disease on duodenal biopsy samples.
Many individuals with type 1 diabetes mellitus who initially had negative serological test results for celiac disease eventually had positive findings; this highlights the need for repeated testing.
Because celiac disease only occurs with specific human leukocyte antigen (HLA) haplotypes, an algorithm based on the determination of these HLA haplotypes has been proposed to avoid repeat testing in all patients with diabetes; this allows patients with diabetes in whom the HLA haplotypes are inconsistent with celiac disease to avoid repeat testing.
Typically, diagnosis of diabetes precedes diagnosis celiac disease by years; celiac disease in these patients most commonly presents with mild GI symptoms or absent symptoms. Because some of these symptoms are also seen in patients with diabetes (eg, bloating, diarrhea), diagnosis of celiac disease may be missed unless a screening is performed.
Although no convincing evidence has suggested that a gluten-free diet has any obvious effect on diabetes, these patients must follow the diet to prevent all long-term complications of celiac disease. Thus, screening patients with type 1 diabetes mellitus for celiac disease seems well founded.
Of interest, while the increased prevalence of celiac disease in patients with type 1 diabetes is well recognized, the reverse is not true: there seems to be no increased prevalence of type 1 diabetes in patients who had been diagnosed with celiac disease.
Down syndrome
The best documented and most well-known nonautoimmune disorder associated with celiac disease is Down syndrome.
As assessed by screening methods, the prevalence of Down syndrome in celiac disease is 8-12%.
Most patients with Down syndrome who have celiac disease have some GI symptoms, such as abdominal bloating, intermittent diarrhea, anorexia, or failure to thrive; however, about one third of these patients do not have GI symptoms.
As with patients who have type 1 diabetes mellitus, periodic serologic testing is indicated only in patients with Down syndrome who are genetically compatible with celiac disease (ie, those who have either HLA DQ2 or DQ8).
A similar strategy should be applied for patients with Turner syndrome or Williams syndrome, in whom an increased incidence of celiac disease has also been reported.
A study by Mårild et al found that in a review of pathology records of 7548 females with CD in Sweden, that 20 of the patients (0.26%) also had a diagnosis of Turner syndrome. In contrast, among 34,492 age- and sex-matched controls in the general Swedish population, only 21 (0.06%) had a Turner syndrome diagnosis which corresponded to an odds ratio for celiac disease of 3.29 (95% confidence interval [CI], 1.94 – 5.56). [33, 34]

 

Cirrose Hepática

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medicina

Cirrose Hepática: apresentação clínica e manifestações clássicas

Apresentação Clínica

1. Anamnese

  • Cirrose hepática compensada: Pacientes podem ser completamente assintomáticos e suas manifestações mais comuns são apenas sintomas inespecíficos, como: fadiga; emagrecimento; fraqueza e anorexia.
  • Cirrose hepática descompensada: Pode apresentar um quadro clínico rico em achados físicos e queixas, como: icterícia; prurido; distensão abdominal por ascite; edema de membros inferiores; diarreia; e queixas relacionadas a complicações da doença, como manifestações de sangramento gastrintestinal (hematêmese, hematoquezia e melena) e confusão mental (encefalopatia hepática). Podem apresentar sintomas de hipogonadismo masculino e, na mulher, manifestar-se por atraso menstrual e anovulação. Sinais e sintomas também podem estar relacionados à doença de base.
  • Doença hepática resultando em cirrose pode ser consequência de uma série de doenças e condições, que devem ser adequadamente investigadas na anamnese. Suas principais causas seguem abaixo.
  • Causas de Cirrose: Hepatite viral crônica (B e C); hepatopatia alcoólica; esteatohepatite não alcoólica; hepatite autoimune; hemocromatose; doenças biliares; colangite esclerosante; cirrose biliar primária; doença de Wilson; doença celíaca; deficiência de alfa-1 antitripsina; doença hepática policística; insuficiência cardíaca direita; doença venoclusiva; infecções e parasitoses (ex.: sífilis, esquistossomose); hepatopatia medicamentosa (ex.: isoniazida, metotrexato); doença hepáticas primárias (fibrose portal idiopática, doença hepática granulomatosa).

2. Exame Físico

Manifestações Clássicas:

  • Icterícia;
  • Ascite;
  • Esplenomegalia e hepatomegalia (embora em estágios mais avançados o fígado possa estar diminuído devido a fibrose);
  • Circulação colateral proeminente (circulação em cabeça de medusa);
  • Edema de membros inferiores;
  • Diminuição da pressão arterial (pacientes previamente hipertensos podem tornar-se normotensos ou até hipotensos);
  • Aranhas vasculares (telangiectasias);
  • Ginecomastia e atrofia testicular (no homem);
  • Eritema palmar;
  • Contratura de Dupuytren (atrofia da fáscia palmar);
  • Baqueteamento digital; osteoartropatia hipertrófica (periostite proliferativa); distrofia ungueal (unhas de Muehrcke e unhas de Terry);
  • Flapping (movimentos assincrônicos das mãos como “asas de borboleta” desencadeados por sua dorsiflexão), que geralmente acompanha o quadro de insuficiência / encefalopatia hepática.

Fatores com maior predição clínica de cirrose hepática em pacientes com hepatopatia crônica diagnosticada ou suspeita:

  • Presença de ascite (razão de verossimilhança positiva = 7,2);
  • Trombocitopenia < 160000/mm3 (razão de verossimilhança positiva = 6,3);
  • Aranhas vasculares (Telangiectasias) (razão de verossimilhança positiva = 4,3).
Este conteúdo foi desenvolvido por médicos, com objetivo de orientar médicos, estudantes de medicina e profissionais de saúde em seu dia-a-dia profissional. Ele não deve ser utilizado por pessoas que não estejam nestes grupos citados, bem como suas condutas servem como orientações para tomadas de decisão por escolha médica.

Científicos invierten el mecanismo de la enfermedad del hígado graso (Nat Commun)

Postado em

 

Eliminan a las células senescentes, disminuyen la acumulación de grasa no deseada en el hígado y restauran la función hepática normal.

Investigadores han identificado el mecanismo que causa una acumulación de grasa en el hígado en una enfermedad que afecta a una de cada cinco personas en Reino Unido y fueron capaces de invertirlo en un modelo de ratón.

El grupo de científicos internacionales informan en un artículo publicado este martes en la revista “Nature Communications” que las células senescentes o viejas en el hígado almacenan grasa excesiva porque las mitocondrias, las baterías de las células, se dañan y no pueden utilizar eficazmente la grasa como fuente de combustible, llevando a su almacenamiento.

Las personas con enfermedad hepática grasa no alcohólica (NAFLD, por sus siglas en inglés) desarrollan exceso de grasa en el hígado, aunque beban poco o nada de alcohol. La patología puede extenderse del hígado graso simple a la fibrosis ya la cirrosis, y puede conducir finalmente al cáncer del hígado.

Investigadores del Instituto de la Newcastle University para el Envejecimiento, Reino Unido, en colaboración con investigadores de la Mayo Clinic, Estados Unidos, emplearon enfoques farmacológicos y genéticos para matar a las células senescentes de ratones, disminuir la acumulación de grasa no deseada en el hígado y restaurar la función hepática normal.

La Dra. Diana Jurk, del Instituto para el Newcastle University Institute for Ageing, afirma: “Ésta es la primera vez que tenemos una terapia eficaz para la enfermedad hepática grasa. Nuestro descubrimiento muestra que mediante este nuevo método que puede matar las células senescentes, es posible que podamos tener un impacto significativo en el tratamiento de esta enfermedad muy común que amenaza la vida”.

“Aunque nuestro enfoque funcionó en ratones de laboratorio, esperamos en un futuro cercano poder probar estas intervenciones en humanos y potencialmente tener un impacto positivo en la vida de las personas”, añade esta experta, que se encargó de dirigir al equipo de investigación.

El equipo utilizó dos métodos separados para eliminar las células senescentes: en primer lugar, mediante el uso de un ratón genéticamente modificado en el que las células senescentes gastadas pueden ser “destruidas” y en segundo lugar, gracias a un tratamiento con una combinación de los fármacos –dasatinib y quercetina (D + Q)– conocidos por matar específicamente células senescentes.

Ambos enfoques fueron igualmente exitosos en la reducción de la acumulación de grasa en el hígado causada por una dieta alta en grasa o envejecimiento en ratones. El autor principal en el documento, Mikolaj Ogrodnik, estudiante de doctorado en el Instituto para el Envejecimiento, destaca: “Estamos viendo un momento muy emocionante en la investigación del envejecimiento. Los científicos se han dado cuenta de que las células senescentes son la causa de muchas enfermedades y ahora tenemos una manera de luchar contra ellas”.

“A medida que envejecemos acumulamos daño celular y hemos demostrado que estas células más antiguas están almacenando exceso de grasa debido a sus mitocondrias ineficientes. Lo que es emocionante es que hemos sido capaces de revertir este daño en los ratones mediante la eliminación de estas células mayores desgastadas, lo que abre la puerta a una posible cura”, apunta el Dr. Jurk.

El consumo habitual de café o té puede ayudar a proteger al hígado de fibrosis progresivas (J Hepatol)

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Se asocia significativamente con una menor rigidez hepática.

Se asocia significativamente con una menor rigidez hepática.

El consumo habitual de café o té, aunque sea de forma moderada, puede servir para proteger al hígado de una fibrosis progresiva que derive en una enfermedad hepática avanzada, según los resultados de un estudio del Erasmus MC University Medical Centre de Rotterdam (Países Bajos).

Los autores de este trabajo, que publica “Journal of Hepatology”, recuerdan que las enfermedades hepáticas crónicas están directamente relacionadas con hábitos de vida poco saludables que pueden favorecer la aparición de cirrosis tras una fibrosis progresiva causada por la cicatrización del hígado.

“En las últimas décadas nos hemos desviado hacia hábitos de vida menos saludables, con más sedentarismo, menos actividad física y peores dietas”, ha explicado Louise Alferink, una de las autoras de este trabajo.

Además de favorecer una epidemia de obesidad, también ha propiciado un rápido aumento de enfermedad del hígado graso no alcohólico, causando un daño hepático por la acumulación de grasa similar al que puede causar el consumo de alcohol.

Investigaciones previas sugerían que el café podía resultar beneficioso para la salud a la hora de reducir los niveles de enzimas hepáticas y el riesgo de cirrosis, hepatitis virales o cáncer de hígado. Aunque las causas son todavía desconocidas, se cree que puede deberse al potencial antioxidante de esta bebida, pero los autores querían observar si su consumo podía repercutir en la rigidez hepática.

Para ello, se recopilaron datos de 2.424 participantes de un gran estudio que incluía a población de más de 45 años de un suburbio de Rotterdam. Todos ellos se sometieron a una extensa evaluación física, incluyendo datos antropométricos, análisis de sangre e imágenes hepatológicas extraídas mediante una ecografía abdominal y una prueba que mide la rigidez hepática.

Además, completaron un cuestionario para evaluar la frecuencia de consumo de hasta 389 alimentos que, entre otros, daba información detallada sobre el consumo de café y té estableciendo tres categorías: ninguno, moderado (menos de 3 tazas al día) y frecuente (más de 3). En el caso del té se distinguió entre el verde, negro u otros tipos.

Los investigadores encontraron que el consumo frecuente de café se asoció significativamente con una menor rigidez hepática, es decir, menos cicatrización del hígado independientemente del estilo de vida y las características metabólicas y ambientales.

Cuando observaron el rango completo de valores de rigidez hepática, encontraron que tanto el consumo frecuente de café como cualquier consumo de té, incluso en pequeñas cantidades, se asociaba significativamente con menores valores de rigidez hepática.

Por último, aunque no se encontró una asociación directa entre el café o el té y la presencia de acumulación de grasa en el hígado, el efecto del café sobre la reducción de la rigidez hepática fue significativo tanto en el grupo con y sin grasa hepática.

Los autores aseguran que el consumo habitual de café y té parece tener efectos beneficiosos sobre la prevención de la cicatrización del hígado incluso antes de que se haya desarrollado una enfermedad hepática manifiesta. Sin embargo, añaden, es necesario analizar estos datos con cautela ya que, por ejemplo, la muestra poblacional sólo incluyó personas de raza blanca, lo que impide sacar mayores conclusiones.

Qual o melhor betabloqueador para hipertensão portal? (Conduta médica em Hepatologia)

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Qual o melhor betabloqueador para hipertensão portal? (Conduta médica em Hepatologia)

Pesquisa recém publicada no American Journal of Gastroenterology demonstrou que o carvedilol, um betabloqueador não seletivo com alfa-bloqueio adicional, é mais efetivo do que o propranolol na redução da pressão portal em pacientes com varizes esofagogástricas.

Dentre os estudos, pesquisadores compararam a resposta hemodinâmica (queda no gradiente de pressão venosa trans-hepática) em 110 pacientes randomizados para carvedilol ou propranolol. Os pacientes eram cirróticos, apresentavam hipertensão porta com pressão > 12 mmHg e varizes esofágicas grau 2 ou 3 à endoscopia com ou sem histórico de hemorragia digestiva alta. As drogas foram aumentadas gradualmente durante o estudo, até atingir um alvo de betabloqueio correspondendo a uma redução de 25% na frequência cardíaca ou quando atingido 55 bpm e mantendo pressão sistólica acima de 90. Ao final de 6 semanas de tratamento betabloqueador, nova medição do gradiente trans-hepático foi realizada.

Os resultados demonstraram que numericamente, porém não estatisticamente, pacientes que receberam carvedilol apresentaram resposta hemodinâmica mais significante. Na análise de subgrupos, no entanto, a relevância estatística aumentou, e em pacientes com cirrose avançada o carvedilol demonstrou-se superior ao propranolol. Adicionalmente, na análise multivariada, apenas o carvedilol apresentou resposta hemodinâmica quando ajustado o resultado pelo MELD.

Estes achados demonstram o maior benefício do carvedilol, quando comparado ao propranolol, na redução da pressão portal em pacientes com varizes esofagianas. Os receios quanto à adoção do carvedilol como betabloqueador padrão devem-se a seu maior potencial hipotensor e menor tolerância. Novos estudos devem focar não só na medida da resposta hemodinâmica, como também nos desfechos, e avaliar especialmente a tolerância à medicação a longo prazo.

 

Referências Bibliográficas:

  • Kim SG et al. A randomized, multi-center, open-label study to evaluate the efficacy of carvedilol vs. propranolol to reduce portal pressure in patients with liver cirrhosis. Am J Gastroenterol 2016 Aug 30; [e-pub].

Quando interromper o tratamento com inibidores da bomba de próton?

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medicamentos

Quando interromper o tratamento com inibidores da bomba de próton?

Os inibidores da bomba de próton (IBPs) reduzem o risco de hemorragia gastrointestinal, mas podem aumentar o risco de efeitos adversos como hemorragias, infecção por CDI e demência. Saber o momento correto de interromper o tratamento com os IBPs é fundamental para a saúde do paciente. No entanto, um estudo recente mostrou que a maior parte dos médicos erra na hora de determinar o fim da terapia.

Para esse estudo, foram recrutados 487 médicos, que receberam uma história fictícia envolvendo uma mulher de 70 anos de idade, tomando omeprazol 20 mg e recentemente diagnosticado com osteopenia. Os participantes receberam então uma série de outros cenários e foram questionados a respeito da troca ou suspensão de medicamentos. Os resultados foram apresentados na Digestive Disease Week 2017.

Nessa pesquisa baseada em simulação, 68% dos médicos optariam por continuar os IBPs em pacientes com baixo risco de hemorragia digestiva, 47% descontinuariam o tratamento nos pacientes de risco intermediário e 62% interromperiam a droga em doentes com maior risco de sangramento letal.

Segundo os autores do estudo, em indivíduos com risco intermediário e alto de hemorragia fatal, os benefícios dos IBPs superam o risco de eventos adversos e, por isso, não devem ser descontinuados. Já para os doentes com menor risco de hemorragia grave recomenda-se interromper os IBPs, porque os efeitos secundários superam o possível benefício.

Segundo a campanha Choosing Wisely, em pacientes com refluxo gastroesofágico não complicado, uma tentativa de parar ou reduzir a dose dos IBPs pode ser apropriada.

Referências: