Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prevalence of hepatitis C is 7-10-fold higher in alcoholics than it is in the general population. Among alcoholics, the prevalence of hepatitis C is higher in alcoholics with advanced liver disease. Serum ALT and hepatitis C viral load may improve if alcoholic patients with hepatitis C stop drinking for more than 4 months.Up to 60% of patients with hepatitis C have a past history of alcohol use. In patients with hepatitis C, chronic alcohol consumption of more than 5 drinks per day increases the rate of liver fibrosis. Hepatitis C patients who ingest more than 5 alcoholic drinks per day are at increased risk for cirrhosis, hepatocellular carcinoma and, possibly, death from liver disease. Recent alcohol use decreases the response rate to interferon treatment. The detrimental effects of small amounts (3 or fewer drinks per day) of alcohol consumption in patients with hepatitis C are not known.
Best Pract Res Clin Gastroenterol 2003 Aug
PMID:Liver disease in alcohol and hepatitis C. 1282 60

The consumption of excess alcohol in patients with liver iron storage diseases, in particular the iron-overload disease hereditary haemochromatosis (HH), has important clinical consequences. HH, a common genetic disorder amongst people of European descent, results in a slow, progressive accumulation of excess hepatic iron. If left untreated, the condition may lead to fibrosis, cirrhosis and primary hepatocellular carcinoma. The consumption of excess alcohol remains an important cause of hepatic cirrhosis and alcohol consumption itself may lead to altered iron homeostasis. Both alcohol and iron independently have been shown to result in increased oxidative stress causing lipid peroxidation and tissue damage. Therefore, the added effects of both toxins may exacerbate the pathogenesis of disease and impose an increased risk of cirrhosis. This review discusses the concomitant effects of alcohol and iron on the pathogenesis of liver disease. We also discuss the implications of co-existent alcohol and iron in end-stage liver disease.
Best Pract Res Clin Gastroenterol 2003 Aug
PMID:Effect of alcohol on iron storage diseases of the liver. 1282 61

Patients with advanced cirrhosis and portal hypertension often show an abnormal regulation of extracellular fluid volume, resulting in the accumulation of fluid as ascites, pleural effusion or oedema. The mechanisms responsible for ascites formation include alterations in the splanchnic circulation as well as renal functional abnormalities that favour sodium and water retention. Renal abnormalities occur in the setting of a hyperdynamic state characterized by an increase cardiac output, a reduction in total vascular resistance and an activation of neurohormonal vasoactive systems. This circulatory dysfunction, due mainly to intense arterial vasodilation in the splanchnic circulation, is considered to be a primary feature in the pathogenesis of ascites. A major factor involved in the development of splanchnic arterial vasodilation is nitric oxide (NO), a potent vasodilator that is elevated in the splanchnic circulation of patients with cirrhosis. This event decreases effective arterial blood volume and leads to fluid accumulation and renal function abnormalities which are a consequence of the homeostatic activation of vasoconstrictor and antinatriuretic factors triggered to compensate for a relative arterial underfilling. The net effect is avid retention of sodium and water as well as renal vasoconstriction. The mechanisms of sodium and water retention and ascites formation in patients with cirrhosis are discussed in this review.
Best Pract Res Clin Endocrinol Metab 2003 Dec
PMID:Mechanisms of water and sodium retention in cirrhosis and the pathogenesis of ascites. 1468 92

The gut flora plays an important role in the pathogenesis of the complications of cirrhosis. Cirrhotic patients are prone to develop bacterial infections, mainly the 'spontaneous' infection of ascites or spontaneous bacterial peritonitis. Other complications of cirrhosis, such as variceal haemorrhage and ascites, occur mostly or solely as a consequence of portal hypertension. Portal pressure increases initially as a consequence of an increased intrahepatic resistance but, once collaterals have formed, high portal pressure is maintained by an increased splanchnic blood inflow secondary to vasodilatation. Splanchnic vasodilatation is the initiating event in the hyperdynamic circulatory state that aggravates the complications of cirrhosis. The gut flora plays a role in both the development of infections and in the hyperdynamic circulatory state of cirrhosis and, although less prominently, it also plays a role in the pathogenesis of hepatic encephalopathy. This chapter presents evidence regarding gut flora and its modification in the pathogenesis and management of these complications of cirrhosis.
Best Pract Res Clin Gastroenterol 2004 Apr
PMID:Gut microflora in the pathogenesis of the complications of cirrhosis. 1512 75

During the last 15 years the transjugular intrahepatic portosystemic shunt (TIPS) procedure has become a safe and effective treatment of portal hypertension. Its major obstacle, the high rate of shunt insufficiency, is going to be solved by the availability of covered stents showing a patency rate of up to 90%. The treatment of acute oesophageal and gastric variceal bleeding is an unsolved problem because variceal bleeding remains the major cause of death in patients with cirrhosis. TIPS has become the rescue treatment of choice because it combines high efficacy with low invasiveness. In this context, the timing of the rescue TIPS is of major importance for achieving definitive haemostasis before multi-organ failure develops. In the prevention of re-bleeding, TIPS is accepted as a second-line treatment, required in about 10-20% of patients. TIPS may be indicated when more than two significant re-bleedings occurred within a time frame of 12 months in spite of adequate first-line measures i.e. drugs or ligation. Refractory ascites is the third main indication for TIPS. Five randomized studies comparing TIPS with paracentesis show good response and comparable survival. Interpretations of authors and comments of reviewers are, however, controversial and do not permit a definitive recommendation.
Best Pract Res Clin Gastroenterol 2004 Feb
PMID:TIPS: an update. 1512 87

Laparoscopic cholecystectomy has become the first choice of management for symptomatic cholecystolithiasis. While it is associated with decreased postoperative morbidity and mortality, bile duct injuries are reported to be more severe and more common (0-2.7%), when compared to open cholecystectomy (0.2-0.5%) [New Engl. J. Med. 234 (1991) 1073; Am. J. Surg. 165 (1993) 9; Surg. Clin. N Am. 80 (2000) 1127]. These bile duct injuries include leaks, strictures, transection and removal of (part of) the duct, with or without vascular damage. Bile duct injury might be due to misidentification of the biliary tract anatomy due to acute cholecystitis, large impacted stones, short cystic duct, anatomical variations, but also due to technical errors leading to bleeding with subsequent clipping and coagulation trauma [Ann. Surg. 237 (2003) 460]. Early recognition and adequate multidisciplinary approach is the cornerstone for the optimal final outcome. Suboptimal management of injuries often leads to more extensive damage to the biliary tree and its vasculature with as consequences biliary peritonitis, sepsis, abscesses, multiple organ failure, a more difficult (proximal) reconstruction and in the long run, secondary biliary cirrhosis, and liver failure. Despite increasing experience in performing laparoscopic cholecystectomy, the frequency of bile duct injuries has not decreased [Ann. Surg. 234 (2001) 549]. Therapy encompasses endoscopic stenting, percutaneous transhepatic dilatation (PTCD) and surgical reconstruction.
Best Pract Res Clin Gastroenterol 2004 Oct
PMID:Endoscopic and surgical management of bile duct injury after laparoscopic cholecystectomy. 1549 81

Non-alcoholic fatty liver disease (NAFLD) is a frequent syndrome encompassing fatty liver alone and steatohepatitis (NASH). Often asymptomatic, the suspicion arises because of abnormal aminotransferases or a bright liver on abdominal ultrasound. It should be suspected during evaluation of associated conditions as obesity, diabetes or dyslipidaemia. The diagnostic evaluation must exclude other potential causes of liver disease and may include a liver biopsy, the only method able to confirm features of necroinflammation and fibrosis that define NASH and its prognostic implications. Indeed, the presence of necroinflammation has been associated with a significant risk of progression to cirrhosis and eventually hepatocellular carcinoma. Age >45 years, obesity and diabetes have also been associated with an increased risk of liver fibrosis and progression to cirrhosis. Given the high prevalence of NAFLD, general measures of life-style changes, focusing on exercise, diet, and total alcohol abstinence, should be implemented before a liver biopsy is considered.
Best Pract Res Clin Gastroenterol 2004 Dec
PMID:Non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH): diagnosis and clinical course. 1556 40

Current strategies for treating hepatitis B focus on clearance of active HBV infection through suppression of viral replication by interferon-alpha (IFN-alpha) and the nucleoside analogs (lamivudine and adefovir). Lamivudine therapy for 1 year leads to HBeAg seroconversion in 16-18% of patients compared to 4-6% of untreated controls, to histological improvement in 49-56% treated patients and in 23-25% controls. HBeAg seroconversion rates increase with the duration of lamivudine therapy from 17% at 1 year to 27, 40, 47 and 50% at 2, 3, 4 and 5 years, respectively. When prescribing lamivudine, drug resistance due to the emergence of tyrosine-methionine-aspartate-aspartate (YMDD) mutations that increases with duration of therapy and the potential risk of a severe flare of hepatitis with sudden cessation of therapy, probably greatest in patients with cirrhosis, are realistic concerns. After 48 weeks of treatment with 10 or 30 mg of adefovir dipivoxil per day, significantly more patients with HBeAg-positive chronic hepatitis B than those on placebo had histologic improvement (53, 59 and 25%, respectively), a reduction in serum HBV DNA levels (by a median of 3.52, 4.76 and 0.55 log copies/ml), undetectable levels of serum HBV DNA (21, 39 and 0%), normalisation of ALT levels (48, 55 and 16%) and HBeAg seroconversion (12, 14 and 6%). In HBeAg negative patients treated with adefovir dipivoxil (10mg/day) for 48 weeks, ALT levels had normalised in 72% (29% in the placebo group), serum HBV DNA levels were reduced to fewer than 400 copies/ml in 51% (none in the placebo group), liver histology improved in 64% (33% in the placebo group). No adefovir-associated resistance mutations of viral DNA were detected. Ongoing studies investigate combination therapy with lamivudine or IFN.
Best Pract Res Clin Gastroenterol 2004
PMID:Treatment of chronic viral hepatitis. 1558 3

Hereditary haemochromatosis is a primary inherited disorder of iron metabolism leading to progressive iron loading of parenchymal cells of the liver and other organs with diverse clinical manifestations, including cirrhosis, diabetes and skin pigmentation. This chapter will focus on HFE-associated hereditary haemochromatosis, which accounts for approximately 90% of cases in Caucasian populations. Penetrance is incomplete, with variable clinical expression. The majority of cases demonstrate biochemical expression, but a much lower proportion develop advanced disease. Clinical disease--especially hepatic fibrosis--is related to the level of body iron stores, which is reflected primarily in the liver. The available evidence indicates that adequate screening and diagnostic strategies ensure that early case detection and treatment occur prior to the development of irreversible end-organ damage. The most cost-effective methods of early case detection are family (cascade) screening and evaluation of potential cases by primary care physicians with a high index of clinical suspicion.
Best Pract Res Clin Haematol 2005 Jun
PMID:Role of early case detection by screening relatives of patients with HFE-associated hereditary haemochromatosis. 1573 86

Hepatocellular carcinoma (HCC) is one of the most common malignant tumours worldwide. The major etiologies and risk factors for HCC development are well defined and some of the multiple steps involved in hepatocarcinogenesis have been elucidated in recent years. Despite these scientific advances and the implementation of measures for early HCC detection in patients at risk, patient survival has not improved during the last three decades. This is due in part to the advanced stage of the disease at the time of clinical presentation, in part due to the limited therapeutic options. These fall into four main categories: (1) surgical interventions, including tumour resection and liver transplantation, (2) percutaneous interventions, including ethanol injection and radiofrequency thermal ablation, (3) transarterial interventions, including embolisation and chemoembolisation and (4) drugs as well as gene and immune therapies. These therapeutic strategies have been evaluated in part in randomised controlled clinical trials that are the basis for therapeutic recommendations. While surgery and percutaneous as well as transarterial interventions are effective in patients with limited disease (1-3 lesions, < 5 cm in diameter) and compensated underlying liver disease (cirrhosis Child A), at the time of diagnosis more than 80% patients present with multicentric HCC and advanced liver disease or comorbidities that restrict the therapeutic measures to best supportive care. In order to reduce morbidity and mortality from HCC, therefore, early diagnosis and the development of novel systemic therapies for advanced disease, including drugs, gene and immune therapies as well as primary HCC prevention are of paramount importance. Further, secondary HCC prevention after successful therapeutic interventions needs to be improved in order to make an impact on the survival of patients with HCC. New technologies, including gene expression profiling and proteomic analyses, should further elucidate the molecular events underlying HCC development and identify novel diagnostic markers as well as therapeutic and preventive targets.
Best Pract Res Clin Gastroenterol 2005 Feb
PMID:Treatment of hepatocellular carcinoma. 1575 9


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