Bailliere's clinical gastroenterology最新文献

This chapter primarily concerns three main categories of diarrhoeagenic Escherichia coli, enteropathogenic (EPEC), enterohaemorrhagic (EHEC) and enteroaggregative (EAEC) E. coli. They have distinctive virulence factors and vary in the enteropathies they produce. The molecular biological approach has opened up the complex way in which they interact with the intestine. EPEC and EHEC show a subversive approach to colonization in that they adapt the host cell to their requirements in the formation of the attaching effacing lesion. EAEC appear to co-opt the host defence system to produce a biofilm-like colony and currently go unrecognized in routine laboratories.

Gene expression is central to the pathogenesis of many disorders. An ability to alter the expression of genes would, if their relationship to disease processes were fully understood, constitute a new modality of treatment. This review examines the evidence that nutritional factors can regulate genes in the gastrointestinal epithelium and it discusses the physiological relevance of such alterations in gene expression. Dietary regulation of the genes expressed by the epithelium confers three fundamental advantages for mammals. It enables the epithelium to adapt to the luminal environment to digest and absorb food better; it provides the means whereby mother's milk can influence the development of the gastrointestinal tract; when the proteins expressed by the epithelium act on the immune system, it constitutes a signalling mechanism from the intestinal lumen to the body's defences. Each of these mechanisms is amenable to manipulation for therapeutic purposes.

The term portal hypertensive gastropathy (PHG) defines a wide spectrum of diffuse macroscopic lesions that appear in the gastric mucosa of patients with portal hypertension. Histologically, these lesions correspond to dilated vessels in the mucosa and submucosa in the absence of erosions or inflammation. Endoscopically, the lesions are classified as mild when mosaic pattern or superficial reddening are present, and severe when gastric mucosa appear with diffuse cherry red spots. Mild lesions are highly prevalent (65–90%), whereas severe lesions are present in only 10–25% of cirrhotic patients.

The pathogenesis of PHG is not well known, but both venous congestion related with raised portal pressure and increased gastric blood flow seem to be crucial factors for its development. Variceal sclerosis may contribute to the development or aggravation of the lesions.

Bleeding is the unique clinical manifestation of PHG, and occurs only in those patients with severe lesions. During a 5-year follow-up, the risk of overt bleeding or chronic bleeding, which induces anaemia, is 60% and 90%, respectively, for patients with severe PHG.

Propranolol is the only pharmacological treatment that has been proven useful in preventing bleeding from PHG. Porto-systemic shunts and liver transplantation are also effective.

Recent advances in the pharmacology of portal hypertension are reviewed, against the background of existing knowledge and current clinical research. The most recent trials are analysed, and conclusions made about the use of drugs in acute variceal haemorrhage, as well as directions for further clinical trials and research.

Patients with suspected portal hypertension must first be evaluated by physical examination, upper digestive endoscopy and ultrasonography with Doppler. Moreover, the evaluation of patients with portal hypertension depends on the cause of portal hypertension, the presence of complications and the specific treatment considered. Haemodynamic assessment with measurement of the hepatic venous pressure gradient is useful in confirming the origin of portal hypertension. This technique is the ‘gold-standard’ for evaluating haemodynamic treatments. Splanchnic and systemic circulation must also be measured. Quantitative evaluation of the splanchnic territory by Doppler sonography and other non-invasive investigations, may be performed. Further clinical studies are, however, needed to determine their interest in portal hypertension.

The role of surgery in portal hypertension remains a topic of debate. For the past 100 years, various surgical procedures have been used to treat variceal bleeding, refractory ascites, and end-stage liver disease. The past decade has seen significant advances in pharmacotherapy, endoscopy, interventional radiology, and surgery for the management of patients with portal hypertension. Liver transplantation has come of age in the 1990s and is now an accepted therapy for patients with end-stage liver disease. The wide array of management options can complicate the decision making process and defines the need to evaluate these patients fully. Factors such as the aetiology and extent of liver disease, response to prior medical, endoscopic, and other interventional treatments, and possibility of future liver transplantation must be considered. This manuscript will review the history of surgical treatments of portal hypertension, describe the surgical procedures with their advantages and disadvantages, and evaluate their role in the elective and emergent settings.

Transjugular intrahepatic portosystemic shunt (TIPS) is a procedure recently introduced for the management of complications of portal hypertension. TIPS can be placed in the liver with relative ease by a skilled radiologist with a low risk of mortality. The major complications following the procedure are infection, especially in patients undergoing emergency TIPS, intra-abdominal haemorrhage from capsular punctures, and long-term problems related to encephalopathy and stenosis of the shunt. Encephalopathy is more of a problem in older patients with wide diameter shunts. Stenosis of the shunt is related to pseudo-intimal hyperplasia, probably related to transection of bile ductules during placement of the shunt. In view of the high rate of encephalopathy and stenosis following the shunt, a careful follow-up of all patients, including ultrasonographic and angiographic examination of the shunt, is mandatory. TIPS is used predominantly for the control of acute variceal haemorrhage, prevention of recurrent variceal bleeding, and refractory ascites when conventional treatment has failed. However, the role of TIPS in the management of complications of portal hypertension still awaits the outcome of clinical trials.

In the past few years, there have been important advances in the field of pathogenesis and management of ascites and hepatorenal syndrome in cirrhosis. A new pathogenic theory of ascites and renal dysfunction in cirrhosis has been presented and previously ill-defined conditions, such as refractory ascites and hepatorenal syndrome, have been defined precisely. The link between the diseased liver and the disturbances in renal function and vasoactive systems is not completely known, but a large body of evidence indicates that it consists of a circulatory dysfunction that affects mainly the arterial circulation and is characterized by an inability to maintain an effective arterial blood volume within normal limits. The research on the mechanisms of this circulatory dysfunction will give valuable information in the design of more pathophysiologically oriented therapeutic approaches to the management of ascites.

Promoting the development of oesophageal varices and ascites, portal hypertension dominates the clinical course of cirrhosis. Varices appear in patients with portal pressure gradient above 10 mmHg and enlarge in 10–20% within 1–2 years of their detection. Bleeding occurs in patients with portal pressure gradient above 12 mmHg when the wall tension causes the rupture of varices, with an incidence of about 10% per year. Indicators of bleeding risk are portal pressure gradient, variceal pressure, large varices and liver dysfunction. Mortality per bleeding episode is 30–50%. Among survivors 60% will rebleed and 30% will die in the following year. The risk of rebleeding decreases in patients with spontaneous or treatment induced reduction of portal pressure gradinent or variceal pressure. Ascites develops in almost all patients along the course of the disease. Median survival after its appearance is less than 2 years. Less than 5% of cirrhotic patients die without ascites or without a previous bleeding. Thus portal hypertension is a major determinant of survival in cirrhosis.