Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0239946 (liver fibrosis)
 8,268 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aetiology of chronic liver disease covers a wide range of congenital or acquired abnormalities of the hepatocellular biochemical network. Although our knowledge has considerably increased in recent years, the aetiology of chronic liver disease often remains obscure. Acquired irreversible disturbances of normal liver function can be mediated by hepatotrophic viruses, chemicals, chronic oxygen depletion, or interference with the immune system. Considerable progress has been made in the detection and characterisation of hepatitis B, C, and D viruses as causative agents of chronic active hepatitis. Alcohol abuse remains the predominant cause of chronic liver disease in the Western world. The targets of autoantibodies used to diagnose autoimmune diseases of the liver and primary biliary cirrhosis continue to be biochemically defined. Their significance for the aetiology of the disease, however, remains to be established. Nonparenchymal cells play an important role in the sequence of events following hepatocellular injury and ultimately leading to liver cirrhosis. They release vasoactive compounds, cytokines, and other important mediators, and participate in the modulation of the extracellular matrix that is characteristic of liver fibrosis and cirrhosis. The biochemical basis of liver cell necrosis remains poorly defined. In spite of recent progress, and the detection of some new pathogenic principles that help in the understanding of the complications of chronic liver disease such as portal hypertension, oesophagogastric variceal bleeding, portosystemic encephalopathy, ascites, and other metabolic disturbances, many questions concerning the aetiology and pathophysiology of chronic liver disease and its complications remain to be answered.
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PMID:Aetiology and pathophysiology of chronic liver disorders. 208 79

Procollagen type III N-peptide (PIII NP) and laminin P1 fragment (LP1) have both been proposed as markers of liver fibrosis. In this study we evaluated the diagnostic application of both peptides in alcoholic liver disease and primary biliary cirrhosis. Serum concentrations of the peptides were measured by radioimmunoassay. PIII NP and LP1 levels appeared to be significantly raised in patients with alcoholic and primary biliary cirrhosis. Patients with alcohol abuse without cirrhosis had normal or slightly elevated PIII NP levels, but significantly raised LP1 levels. There was a strong correlation between PIII NP and LP1 concentrations.
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PMID:Serum procollagen III N-terminal peptide and laminin P1 fragment concentrations in alcoholic liver disease and primary biliary cirrhosis. 323 63

Carbohydrate-deficient transferrin (CDT) in serum was analyzed by isocratic microanion exchange chromatography at pH 5.65 followed by a transferrin radioimmunoassay in 102 patients with biopsy-verified liver diseases. CDT values were normal in all of the 87 nonalcohol-abusing patients irrespective of type or degree of liver disease. Thirteen of the 15 alcoholic patients (87%) with current abuse showed elevated CDT values while in abstaining alcoholics with remaining liver disease the values were normal. No correlations were found between CDT level and volume density of liver fibrosis or steatosis or values of a number of clinicochemical liver tests. The only significant correlation demonstrated was between CDT concentration and the level of present daily alcohol consumption in the alcoholic patients. These results indicate that CDT can be used as a marker of present but not previous alcohol abuse, even in patients with various liver diseases.
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PMID:Carbohydrate-deficient transferrin in serum in patients with liver diseases. 331 62

Antiphospholipid antibodies (APAs) have been reported in various clinical conditions. However, the pathogenesis and clinical significance of these antibodies are still unclear. The objective of this study was to assess the prevalence of APAs in patients with chronic alcohol- or hepatitis C virus (HCV)-related liver disease and to evaluate their relation to the underlying liver disease. We prospectively studied 201 patients referred to an hepato-gastroenterology department, including 77 patients with a history of alcohol abuse (group I) and 124 with chronic HCV infection (group II), and 107 healthy subjects (control population). Liver biopsy was performed in all patients. In cirrhotic patients, the severity of the liver disease was assessed with the use of Child's classification, as modified by Pugh. Several biologic parameters, including lupus anticoagulant and anticardiolipin antibodies, were determined. Forty-eight percent of patients in group I and 33% of those in group II had APAs. Among cirrhotic patients, APAs were more frequent in patients with Child grade B or C than in those with grade A severity. In patients with chronic HCV-related liver disease, a correlation was found between APA levels and liver fibrosis (P = 0.009); no relation was found between APA levels and histologic liver disease activity (P = 0.25). In the control group, one subject was APA-positive. None had lupus anticoagulant. APAs seem to be frequently associated with chronic liver disease of various causes. These results suggest further investigations on the potential role of these antibodies in fibrosis or liver injury.
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PMID:Prevalence of antiphospholipid antibodies in patients with chronic liver disease related to alcohol or hepatitis C virus: correlation with liver injury. 952 48

Schistosomiasis mansoni is a widespread parasitic disease in the Brazilian territory that affects over 8 million individuals. Hepatosplenic schistosomiasis is a serious clinical presentation of this disease, associated with splenomegaly, liver fibrosis, and portal hypertension, and is responsible for approximately 7% of schistosomotic patients. The surgical treatment of portal hypertension in schistosomotic patients has distinct features when compared with cirrhotic patients, mostly because hepatic function is preserved in schistosomotic liver disease. Therefore, when attempting to reduce the portal pressure, the surgeon must be aware that the surgery might interfere with hepatic perfusion, and consequently with hepatic function. The aim of this study was to report the results achieved with splenectomy, division of the left gastric vein, devascularization of great gastric curvature, and postoperative endoscopic variceal sclerosis, as a surgical option to esophageal varices in hepatosplenic schistosomiasis. A total of 111 patients were studied, and the following is a list of inclusion criteria: age >16 years, history of gastrointestinal (GI) bleeding, presence of esophageal varices on preoperative endoscopy, hematocrit >22% and prothrombin enzymatic activity >50%, negative viral hepatitis on serologic tests (anti-HBV and anti-HCV), and definition, after liver biopsy, of exclusive schistosomotic liver disease. The following list includes exclusion criteria used: presence of liver disease other than schistosomotic, history of alcohol abuse, and preoperative thrombosis of the portal vein. The rebleeding rate was 14.4% during a mean 30-month follow-up period; portal vein thrombosis was 13.2%, and there was a global mortality of 5.4%. Gastric varices were present in 46.9% of the patients; for those patients, a gastrotomy and running suture of the varices achieved an eradication rate of the varices of 75.6%. The degree of periportal fibrosis was also analyzed. Periportal fibrosis staging revealed that patients with class II or III liver fibrosis had a significant increased risk of recurrent GI bleeding when compared with patients with class I liver fibrosis. Despite the elevation on alanine aminotransferase (ALT) and aspartate aminotransferase (AST), most other liver function tests showed no alteration or were corrected after surgery. We conclude that splenectomy, division of the left gastric vein, devascularization of great gastric curvature, and postoperative endoscopic variceal sclerosis showed good results globally and should be considered as therapeutic options in the treatment of hepatosplenic schistosomiasis.
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PMID:Surgical treatment of schistosomal portal hypertension. 1189 Mar 33

Colchicine decreases liver fibrosis in experimental and human disease, but a meta-analysis recently concluded that colchicine should not be used for liver fibrosis or cirrhosis irrespective of the aetiology. In this issue, Cortez-Pinto et al. confirm such negative conclusions in their series of 55 outpatients with biopsy-proven alcoholic cirrhosis followed for a median of 3.5 years. Although well tolerated, colchicine did not affect either the annual incidence rate of complications or liver function tests. Current treatment of alcoholic cirrhosis includes correction of nutritional deficiencies, exogenous administration of antioxidants (notably S-adenosylmethionine and polyenylphosphatidylcholine), and liver transplantation. In the future, preventive/therapeutic strategies will include campaigns to decrease alcohol abuse aimed at subjects genetically prone to develop alcoholic liver injury, prevention of liver fibrosis via inhibition of the Na+/H+ exchange, stimulation of apoptosis of stellate cells, antagonism of cytokines involved in liver injury, degradation of extracellular matrix, and reversal of ethanol-induced inflammatory and fibrotic changes via increased nitric oxide levels. On the grounds that it renders the hepatocyte more vulnerable to necrosis, steatosis has a key role in the pathogenesis of alcoholic and non-alcoholic liver disease. Conditions associated with insulin resistance have been recognized as risk factors for chronic liver disease and hepatocellular carcinoma in the alcoholic. This suggests that, through steatosis, insulin resistance could be a co-factor of alcoholic liver disease. Were such a hypothesis confirmed, it would unify our view of the pathogenesis of alcoholic and non-alcoholic liver disease, with all its inherent therapeutic implications.
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PMID:Of liver, whisky and plants: a requiem for colchicine in alcoholic cirrhosis? 1194 49

Infection with hepatitis C and the alcohol abuse that frequently accompanies it, impose major worldwide healthcare burdens. The scientific knowledge base that would inform and direct the development of more effective treatment and intervention strategies for these linked pandemics is inadequate. Therefore, the National Institute on Alcohol Abuse and Alcoholism (NIAAA) organized a workshop in which a multidisciplinary group of experts was asked to review the state-of-the-science specific to alcohol in the context of hepatitis C infection. The panel was charged with identifying newly emerging areas likely to lead to advances in fundamental research and to identify those with the greatest potential for accelerating the development of more effective treatment options. The workshop panel made recommendations for research in four major categories: clinical studies of alcohol and HCV; virology and immunology; liver fibrosis and mechanisms of liver injury; and the development of model systems. This article summarizes the panel's deliberations and their recommendations for future research on alcohol and hepatitis C.
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PMID:Hepatitis C and alcohol: fundamental and translational research directions. 1271 37

Alcohol abuse and hepatitis C virus (HCV) infection coexist with chronic liver disease in many patients. The mechanism of injury in these patients is probably multifactorial and involves, but is not limited to, a combination of diminished immune clearance of HCV, oxidative stress, emergence of HCV quasi-species, hepatic steatosis, increased iron stores, and increased rate of hepatocyte apoptosis. In patients with HCV infection, alcohol consumption is known to cause accelerated progression of liver fibrosis, higher frequency of cirrhosis, and increased incidence of hepatocellular carcinoma (HCC). These patients also have decreased survival as compared with patients with either alcohol abuse or HCV liver injury alone. Alcohol abuse causes decreased response to interferon treatment in HCV patients. It is therefore necessary for patients with HCV infection to abstain from alcohol consumption.
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PMID:Alcohol and hepatitis C. 1534 7

An increase in liver-related causes of death in HIV-positive patients who are coinfected with the hepatitis C virus (HCV) has been acknowledged over the last few years, particularly since the mid 1990s, when the natural history of HIV infection started to improve with the use of highly active antiretroviral therapy (HAART). Chronic hepatitis C is very common among HIV-infected patients who were infected through intravenous drugs use or contaminated blood products (e.g., hemophiliacs). The bidirectional interferences between HIV and HCV modify the natural history of both infections. Moreover, interactions between anti-HIV and anti-HCV drugs are of concern, and a lower response to anti-HCV therapy limits its benefit in HIV-coinfected patients. Although a slower HCV RNA decay is seen in coinfected patients after standard therapy is initiated with pegylated interferon plus ribavirin, the stopping rule at week 12 that is recommended for HCV-monoinfected individuals seems to be equally valid in HIV-positive patients. This finding is of great value, because it allows treatment to be offered in the absence of contraindication (e.g., low CD4 count, alcohol abuse, etc.) but discontinued as early as 12 weeks when no chances of cure are predicted, which saves costs and deleterious side effects. HAART therapy seems to temper somehow the negative impact exerted by HIV infection over HCV-related liver fibrosis. Liver transplantation is currently the best option for HIV-infected patients with end-stage liver disease. However, the management of patients on the waiting list and after transplantation carries significant new challenges. New anti-HCV drugs are urgently needed and new strategies with the currently available drugs need to be assessed to reduce the negative impact of hepatitis C in HIV-coinfected individuals.
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PMID:New hopes for HIV and HCV coinfection in 2004. 1547 98

Liver fibrosis and cirrhosis involve multiple cellular and molecular events that lead to deposition of an excess of extracellular matrix proteins and increase the distortion of normal liver architecture. Etiologies include chronic viral hepatitis, alcohol abuse and drug toxicity. Degradation of these matrix proteins occurs predominantly as a result of a family of enzymes called metalloproteases (MMPs) that specifically degrade collagenous and non-collagenous substrates. Matrix degradation in the liver is due to the action of at least four of these enzymes: MMP-1, MMP-2, MMP-3 and MMP-9. In the fibrinolytic system, MMPs can be activated through proteolytic cleavage by the action of urokinase plasminogen activator; a second mechanism includes the same metalloproteases. This activity is regulated at many levels in the fibrinolytic system. The main regulator is the PAI-1. This molecule blocks the conversion of plasminogen into plasmin, and the MMP cannot be activated. At a second level, the inhibition is possible by binding to inhibitors called TIMP that can inhibit the proteolitic activity even when the MMPs had been previously activated by plasmin. During abnormal conditions, overexpression of these inhibitors is directed by the transforming growth factor-beta that in a fibrotic disease acts as an extremely important adverse factor.
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PMID:[Hepatic fibrosis: role of matrix metalloproteases and TGFbeta]. 1616 29


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