Bailliere's clinical gastroenterology最新文献

The introduction of pharmacological therapy has been one of the major advances in the treatment of the complications of portal hypertension. Many drugs have been shown to reduce portal hypertension in patients with cirrhosis. However, the most widely used drugs and the only ones for which there is sufficient evidence, are the beta-blockers. These drugs have been, up to now, the only accepted prophylactic therapy for oesophageal variceal bleeding and are also an alternative treatment to sclerotherapy or surgery to prevent variceal rebleeding. A reduction in portal pressure gradient by beta-blockers below 12 mmHg or by more than 20% of baseline values is associated with almost a total protection from oesophageal bleeding. Such a marked response in portal pressure is only achieved in some patients receiving propranolol. New pharmacological approaches with a greater portal pressure reducing effect may improve the beneficial effect of drugs in preventing variceal bleeding. The more promising approach is the combined administration of beta-blockers and isosorbide-5-mononitrate, which has been shown to potentiate the reduction in portal pressure and to be highly effective in initial randomized clinical trials.

The current chapter deals with the concept, clinical manifestations and diagnostic tools of the hepatopulmonary syndrome (HPS) and highlights its most salient pathophysiological, mechanistic and therapeutic aspects. Defined as a clinical triad, including a chronic liver disorder, pulmonary gas exchange abnormalities and generalized pulmonary vascular dilatations, in the absence of intrinsic cardiopulmonary disease, this entity is currently growing in interest with both clinicians and surgeons. The combination of arterial hypoxaemia, high cardiac output with normal or low pulmonary artery pressure, and finger clubbing in a patient with advanced liver disease should strongly suggest the diagnosis of HPS. Its potential high prevalence together with failure of numerous therapeutic approaches depicts a life-threatening unique clinical condition that may dramatically benefit with an elective indication of liver transplantation (LT). A better orchestration of the concepts of the pathophysiology of this lung-liver interplay may foster our knowledge and improve the clinical management and indications of LT.

Portal hypertension is a common clinical syndrome associated with chronic liver diseases and is characterized by a pathological increase in portal pressure. Increase in portal pressure is because of an increase in vascular resistance and an elevated portal blood flow. The site of increased intrahepatic resistance is variable and is dependent on the disease process. The site of obstruction may be: pre-hepatic, hepatic, and/or post-hepatic. In addition, part of the increased intrahepatic resistance is because of increased vascular tone. Another important factor contributing to increased portal pressure is elevated blood flow. Peripheral vasodilatation initiates the classical profile of decreased systemic resistance, expanded plasma volume, elevated splanchnic blood flow and elevated cardiac index. The elevated portal pressure leads to formation of portosystemic collaterals and oesophageal varices. Pharmacotherapy for portal hypertension is aimed at reducing both intrahepatic vascular tone and elevated splanchnic blood flow.

Endoscopic treatments for bleeding gastro-oesophageal varices include injection sclerotherapy, variceal obturation with tissue adhesives and variceal rubber band ligation. Today, endoscopic treatments are not recommended for the primary prophylaxis of variceal bleeding. Acute injection sclerotherapy remains a quick and simple technique for the control of active bleeding from oesophageal varices. Its efficacy may be improved by the early administration of vasoactive drugs. Banding ligation is the optimal endoscopic treatment for the prevention of rebleeding from oesophageal varices. The use of tissue adhesives and thrombin as injectates to treat bleeding fundal gastric varices and oesophageal varices not responding to vasoactive drugs or sclerotherapy is promising but needs further assessment by means of randomized controlled trials.

Prompt diagnosis and exclusion of infection requires a minimum of rigid sigmoidoscopy, rectal mucosal biopsy and stool culture. Admission to hospital is mandatory for patients with features of severe disease, or who are in their first attack of ulcerative colitis and have bloody diarrhoea, even if the criteria for severe disease are not met. Once admitted, the patient should be monitored by plain abdominal X-ray, full blood count, serum albumin and C reactive protein on alternate days; temperature and pulse rate should be recorded four times per day. Treatment should be instituted as soon as the diagnosis is made with an intravenous corticosteroid (hydrocortisone 100 mg intravenously, four times daily, or equivalent). Antibiotics may be included if infection cannot be confidently excluded. Free diet can be allowed but attention should be given to nutritional, fluid and electrolyte status with intravenous replacement if necessary. Any evidence of colonic dilatation occurring despite maximal therapy should be regarded as an absolute indication for colectomy. The patient should be kept fully informed from an early stage about the likely natural history of the condition and about the possible therapeutic options including surgery. Cyclosporin therapy should be reserved for patients who have a poor response to the first 3–4 days of corticosteroid therapy, particularly those with serum C reactive protein >45 mg/1 and who do not yet have absolute indications for colectomy. Most patients who have not convincingly responded within 10 days of starting full medical therapy should undergo colectomy, although partial responders who are afebrile may reasonably continue for up to 14 days before a final decision.

Approximately 30–40% of patients with severe colitis will need colectomy within the first 6 months. With optimal management, mortality should be zero, but better medical therapies are urgently needed to reduce the colectomy rate.

For many years, corticosteroids have been the mainstay for treating acute ulcerative colitis. In patients with refractory disease, immunosuppressive therapy may be indicated, including azathioprine or its metabolite 6-mercaptopurine, cyclosporin and possibly methotrexate. Their benefits in ulcerative colitis must be weighed up against their possible adverse effects, the availability of surgical cure for this condition, and the long-term risk of carcinoma complicating colitis that applies in patients with chronic extensive disease. Information about the safety of corticosteroids and immunosuppressive agents has accumulated as a result of their extensive use in inflammatory bowel disease, organ transplantation and various other disorders.

A number of lines of evidence support the hypothesis that ulcerative colitis is an inherited disorder in a proportion of cases. First, there is a pattern of familial aggregation. Second, there are differences in the prevalence of the disease in different ethnic groups. Finally, the concordance rate in monozygotic twin pairs is higher than that of dizygotic twin pairs, although not as high as the concordance rates observed in Crohn's disease. Genetic models of the inheritance patterns suggest that ulcerative colitis is probably caused by one major gene, although that gene (or genes) remains to be identified. While at least one localization for susceptibility to Crohn's disease now seems certain, efforts to localize and characterize the susceptibility genes involved in the inheritance of ulcerative colitis are still underway. While the genes of the major histocompatibility complex have been imputed as causal in susceptibility to ulcerative colitis, a consensus of proof continues to elude us.

About one-half of patients with ulcerative colitis develop abnormal liver function tests at some time during the course of the illness. This should prompt an investigation for primary sclerosing cholangitis and other common hepatobiliary diseases. Primary sclerosing cholangitis occurs in 2–10% of patients with ulcerative colitis. The diagnosis of primary sclerosing cholangitis is most often made by endoscopic retrograde cholangiography. Liver histopathology is often inconclusive but magnetic resonance cholangiography shows promise as a useful non-invasive diagnostic tool. Cholangiocarcinoma complicates 20–40% of patients with end-stage primary sclerosing cholangitis and is now one of the most common causes of death in patients with ulcerative colitis. Distinction between benign and malignant strictures can be difficult and is best done with a combination of clinical suspicion, repeated imaging for mass lesions, cholangiography, and endoscopic brushings and/or biopsies. Dominant lesions of the common bile duct or common hepatic duct produce progressive jaundice and liver damage. Early treatment may improve prognosis. Single strictures can be dilated endoscopically. If the stricture is more complicated and extends into the intrahepatic ducts or there is suspicion of cholangiocarcinoma, surgical resection may be more appropriate. Liver transplantation should be considered in end-stage disease.