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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary biliary cirrhosis (PBC) is characterized by an immune mediated, irreversible destruction of the small intrahepatic bile ducts leading to progressive liver cirrhosis and frequently to liver failure. The course of the disease is variable and an early diagnosis is desirable to identify individuals with rapidly progressing disease, to initiate adequate therapeutic measures and to evaluate the necessity of liver transplantation. Serological tests represent the single most important diagnostic feature of PBC because liver histology, biochemistry, or clinical syndrome alone are not reliable in this respect. The molecular definition of the autoantigen targets of antimitochondrial antibodies (AMA) has resulted in the development of reproducible and effective serological testing strategies. AMA directed against the ketoacid dehydrogenase complex are highly disease-specific but not directed against liver-specific target structures. Despite a high disease specificity, their usefulness for predicting the course of disease, the timing of liver transplantation, or disease recurrence after transplantation is limited. The realization that about 5% of patients with PBC do not display AMA has led to the identification of PBC-specific antinuclear autoantibodies directed against the nuclear pore complex and other targets. The overlap of PBC with autoimmune hepatitis and primary sclerosing cholangitis represents a diagnostic challenge in which autoantibody determinations play a central role and contribute to the administration of suitable treatment options.
Baillieres Best Pract Res Clin Gastroenterol 2000 Aug
PMID:Autoimmune tests in primary biliary cirrhosis. 1097 16

Although primary biliary cirrhosis (PBC) is generally a progressive disease, the rate of progression varies greatly from one patient to another. The terminal phase is characterized by hyperbilirubinaemia (>100 micromol/l), a major decrease in the number of intrahepatic bile ducts, and extensive fibrosis or cirrhosis. It is now well established that orthotopic liver transplantation is the treatment of choice for patients entering the terminal phase of the disease.A variety of therapeutic agents have been proposed for treatment of patients with PBC. However, most have been found ineffective or too toxic to be widely used. In contrast, there is accumulating evidence from large therapeutic trials that long-term administration of ursodeoxycholic acid (UDCA) is safe and prolongs survival free of liver transplantation. Treatment with UDCA slows the histological progression and delays the onset of cirrhosis. In patients who have a sub-optimal response to UDCA therapy alone, the combination of colchicine or methotrexate with UDCA has minimal or no additional benefit, whereas that with corticosteroids is more promising but not yet demonstrated. Among causes of non-response to UDCA therapy, the most common is the PBC-autoimmune hepatitis overlap syndrome. The benefit from the combination of corticosteroids and UDCA in this setting is obvious.Further studies are needed to define the patients who are most likely to respond to UDCA therapy and to assess the benefit of combined medical treatments.
Baillieres Best Pract Res Clin Gastroenterol 2000 Aug
PMID:Treatment of primary biliary cirrhosis. 1097 18

Primary biliary cirrhosis, the most common chronic cholestatic liver disease in adults, usually progresses to cirrhosis and its complications. Ursodeoxycholic acid therapy delays disease progression, but most patients will ultimately succumb. Liver transplantation is now accepted as the standard treatment for end-stage PBC. Development of major complications of portal hypertension and liver failure, poor quality of life and short survival without transplantation are the major indications for this surgical intervention in patients with primary biliary cirrhosis. Resource use is another key variable to be considered in the timing of liver transplantation. Prognostic models have been developed to predict survival and resource utilization with and without liver transplantation. Prognostic models aid the clinician in the selection and timing of liver transplantation in the patient with primary biliary cirrhosis.
Baillieres Best Pract Res Clin Gastroenterol 2000 Aug
PMID:The timing of liver transplantation in primary biliary cirrhosis. 1097 21

Transplantation has become the accepted form of therapy for patients with end-stage liver disease. The diagnosis of recurrent disease in the allograft has been a matter of controversy, partly because of the difficulties in making the diagnosis in the allograft situation. The conventional criteria for diagnosing PBC may be inappropriate and there are many causes of bile duct damage in the graft. That the PBC-specific autoantibodies [such as antimitochondrial antibody (AMA) and gp-210] persist after transplantation is universally found, and some have reported the aberrant distribution of E2 in the allograft that is typical of PBC in the native liver, whether or not there is histological evidence of PBC recurrence. Most studies now accept that histological features of PBC, such as granulomatous bile duct damage, ductopenia and biliary-type fibrosis, may be found in the allograft; the histological features of PBC are variable and do not mirror the liver tests. The rate of recurrence increases with time, so that by 10 years, recurrence may be found in 30-50% of biopsies. There are no clear factors which identify those at risk of recurrence, but the pattern and degree of immunosuppression may be implicated. Cirrhosis has only rarely been reported. In the medium term, recurrence of PBC has little clinical impact. Ursodeoxycholic acid is used in some centres but there is no clear evidence for benefit.
Baillieres Best Pract Res Clin Gastroenterol 2000 Aug
PMID:Recurrent primary biliary cirrhosis. 1097 22

The surgical treatment of portal hypertension has laxed and waned over the past century. Decompressive shunts for variceal bleeding hit their peak in the 1970s, but dissatisfaction with encephalopathy and liver failure led to further developments with selective shunts and devascularization procedures in the 1970s and early 1980s. Liver transplant is the major operative intervention currently in use and of advantage to patients with portal hypertension. The role of the surgeon is as part of the team involved in the full evaluation of patients with cirrhosis and portal hypertension with its complications. The current repertoire of surgical options includes decompressive shunts, either total, partial or selective, devascularization procedures and liver transplantation. These options must be fitted into the overall management schema of pharmacologic and endoscopic therapy as the first-line approaches to managing these patients.
Baillieres Best Pract Res Clin Gastroenterol 2000 Dec
PMID:Surgical treatment of portal hypertension. 1113 46

Ascites is the most common complication of patients with cirrhosis; its development constitutes the first and most important manifestation of the disease and is an indication for liver transplantation. During the last decade significant advances have been made in regard to the pathogenesis and treatment of ascites. The description of a new hypothesis, the identification of new vasoactive factors involved in the pathogenesis of arterial vasodilation and the introduction of different therapeutic modalities (therapeutic paracentesis, transjugular intrahepatic portosystemic shunt, aquaretics drugs and liver transplantation) are all proof of this. Similarly, the description of predictive factors for the survival of patients with cirrhosis has been of major importance for the identification of candidates for liver transplantation. This chapter reviews current knowledge on the pathophysiology, diagnosis and treatment of ascites in patients with cirrhosis.
Baillieres Best Pract Res Clin Gastroenterol 2000 Dec
PMID:Pathophysiology, diagnosis and treatment of ascites in cirrhosis. 1113 47

Hepatorenal syndrome (HRS) is a common complication of advanced cirrhosis characterized not only by renal failure due to a marked vasoconstriction of the renal circulation but also by marked alterations in systemic haemodynamics and activity of endogenous vasoactive systems. The pathogenesis of HRS is not completely known but it is probably the result of an extreme underfilling of the arterial circulation secondary to an arterial vasodilation located in the splanchnic circulation. Besides the renal circulation all other extrasplanchnic vascular beds appears to be vasoconstricted. The diagnosis of HRS is currently based on the exclusion of non-functional causes of renal failure. Prognosis of patients with HRS is very poor. Liver transplantation is the best option in selected patients, but is seldom applicable due to the short survival expectancy of most patients with HRS, particularly those with the progressive type (type I HRS). Therapies introduced during the last few years, such as transjugular intrahepatic portosystemic shunts or, particularly, vasoconstrictor drugs with preferential effect on the splanchnic circulation (V1 receptor agonists) are very effective in improving renal function and reverting HRS. However, the impact of the improvement of renal function on the natural course of HRS is unknown. Finally, the development of HRS after spontaneous bacterial peritonitis can be effectively prevented by the administration of albumin together with antibiotic therapy.
Baillieres Best Pract Res Clin Gastroenterol 2000 Dec
PMID:Diagnosis and treatment of hepatorenal syndrome. 1113 48

Hepatic encephalopathy arises from the combination of hepatocellular dysfunction and portal-systemic shunting. Encephalopathy is more prominent in advanced stages of liver cirrhosis and signals the presence of fulminant hepatic failure in patients with acute liver injury. As important as the extent of shunting is the presence of large spontaneous collaterals. Ammonia continues to be a leading toxin influencing brain function. Endogenous benzodiazepines and cytokines may contribute to one of ammonia's key effects in the brain: astrocyte swelling. The diagnosis of hepatic encephalopathy is a diagnosis of exclusion; the search for a precipitating factor should be started immediately in all cases of encephalopathy. The treatment of hepatic encephalopathy has three aims: decrease the nitrogenous load from the gut, improve the extra-intestinal elimination of ammonia and counteract central abnormalities of neurotransmission. The mainstay of treatment is directed at the colon. Newer approaches targeting the brain, such as flumazenil, have become available.
Baillieres Best Pract Res Clin Gastroenterol 2000 Dec
PMID:Diagnosis and treatment of hepatic encephalopathy. 1113 49

Since the aetiopathogenesis of primary sclerosing cholangitis (PSC) in humans remains undefined, investigators have studied a variety of animal models to gain insights into immunopathogenetic mechanisms associated with obliterative fibrous cholangitis of intra- and extra-hepatic bile ducts. To date, no animal model has been developed that exhibits all of the attributes of PSC. Rodent models instigated by bacterial cell components or colitis are promising because they may help to explain the strong association between PSC and inflammatory bowel disease (IBD). Other models of direct injury to biliary epithelia, peribiliary vascular endothelia or portal venous endothelia indicate that inflammation, chemokines and cytokines can produce diffuse sclerosis of bile ducts. Models of toxic, infectious or intra-luminal injury of the biliary tract also exhibit focal biliary sclerosis mediated by inflammation and cytokines. The histopathology of several models suggests a sequence of events beginning with secretion of proinflammatory cytokines by activated hepatic macrophages followed by peribiliary infiltration with CD4 and CD8 T cells with a T helper 1 phenotype. These results strongly suggest co-ordinated, pathogenetic roles for both the innate and adaptive immune responses. However, the stimuli that initiate and perpetuate peribiliary fibrosis remain unknown. Interestingly, several models are also associated with the development of anti-neutrophil cytoplasmic antibodies that react in a perinuclear and cytoplasmic pattern similar to that observed in patients with ulcerative colitis and/or PSC. Finally, models of extra-hepatic biliary obstruction continue to provide important information about the pathogenesis of portal fibrosis and secondary biliary cirrhosis that occurs in PSC and other diseases with obstruction of bile flow. Future studies in either existing or new animal models should advance our understanding of the pathogenesis of PSC, the major prerequisite for the development of effective therapies.
Best Pract Res Clin Gastroenterol 2001 Aug
PMID:Animal models for primary sclerosing cholangitis. 1149 70

Primary sclerosing cholangitis is an important cause of chronic cholestatic liver disease. The aetiology is still unknown and an immunological basis is discussed. The disease results in diffuse narrowing and irregularities of intra- and extra-hepatic bile ducts that may lead to biliary cirrhosis. Progression of the disease is highly variable and fluctuating. An important issue is the risk for developing cholangiocarcinoma. For end-stage disease liver transplantation is the only therapeutic option. If strictures of the extra-hepatic bile ducts are demonstrable, endoscopic interventions are effective palliative treatment options. The use of immunosuppressive or anti-inflammatory drugs has been shown to have no influence on the course of primary sclerosing cholangitis.
Best Pract Res Clin Gastroenterol 2001 Aug
PMID:Medical and endoscopic treatment in primary sclerosing cholangitis. 1149 74


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