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)

To make liver biopsy unnecessary in certain cases, PGA (P, prothrombin time; G, gamma-glutamyl transpeptidase; A, apoliprotein AI), a simple biological index combining a specific test for severe liver disease (prothrombin time), a sensitive test of alcoholic liver disease (serum gamma-glutamyl transpeptidase), and a test for liver fibrosis (serum apolipoprotein AI), was evaluated in a training sample of 333 drinkers and validated in 291 other drinkers. All patients underwent an intercostal liver biopsy, and the specimen was independently read by two pathologists. The PGA index varied from 0 to 12. When PGA was less than or equal to 2, the probability of cirrhosis was 0% and the probability of normal liver or minimal changes 83%. Conversely, when PGA was greater than or equal to 9, the probability of normal liver or minimal changes was 0% and the probability of cirrhosis 86%. These values did not vary between training and validation periods, between asymptomatic vs. symptomatic subjects or between PGA at admission vs. PGA 1 week later. This index could be useful for general practitioners in identifying subjects at high risk for severe alcoholic liver disease.
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PMID:A simple biological index for detection of alcoholic liver disease in drinkers. 179 91

The aim of this study was to assess the specific correlation of apolipoprotein-AI to hepatic fibrosis in alcoholic patients. Four hundred eighty two patients were prospectively included with serum measurement of apolipoprotein-AI within 10 days before liver biopsy. Pathologic features were semiquantitatively assessed by two observers. In 28 patients liver biopsy was used for histomorphometric assessment of fibrosis and immunohistochemical labeling of apolipoprotein-AI. Serum apolipoprotein-AI was negatively correlated to semiquantitative score of fibrosis (r = -0.50; p less than 0.001), independently of the scores of steatosis and alcoholic hepatitis (r = -0.44; p less than 0.001) and of the value of serum albumin, bilirubin, and prothrombin time (r = -0.22; p less than 0.001) and independently of the nutritional parameters (r = -0.29; p less than 0.009). The mean value of apolipoprotein-AI decreased according to the grade of fibrosis from 220 +/- 6 mg/dl (mean +/- SEM) to 110 +/- 8 mg/dl. Serum apolipoprotein-AI was negatively correlated to the percentage of fibrosis (r = -0.70; p less than 0.001) in the biopsies morphometrically assessed. The labeling was superimposed to the extracellular matrix. In conclusion, this study shows that decrease of apolipoprotein-AI is a serum and tissue marker of liver fibrosis independently of steatosis, alcoholic hepatitis, liver function tests, and nutritional parameters.
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PMID:Apolipoprotein AI is a serum and tissue marker of liver fibrosis in alcoholic patients. 251 36

It has been suggested that glycosaminoglycans are involved in the pathogenesis of liver fibrosis. Furthermore, recent studies have reported that one of them, hyaluronate, was mainly taken up and degraded by the liver. Using an enzymoimmunological assay, based on hyaluronate-hyaluronectin interaction, serum levels of hyaluronate were measured in 113 patients with various liver diseases. Patients were divided into six groups according to clinical, biological and histological data: Group 1-alcoholic cirrhosis (n = 47) including alcoholic cirrhosis with alcoholic hepatitis (n = 24); Group 2-primary biliary cirrhosis (n = 21); Group 3-cirrhosis related to viral hepatitis (n = 10); Group 4-idiopathic hemochromatosis (n = 17); Group 5-alcoholic fatty liver (n = 8); and Group 6-viral or drug acute hepatitis (n = 10). Ninety-four blood donors were studied as controls. Levels of hyaluronate were found to be strikingly elevated in Group 1 (1,225 +/- 1,137 micrograms per liter), Group 2 (792 +/- 739 micrograms per liter), Group 3 (649 +/- 373 micrograms per liter), and Group 4 (246 +/- 242 micrograms per liter), whereas patients in Group 5 (94 +/- 63 micrograms per liter) and Group 6 (73 +/- 57 micrograms per liter) had values close to controls (23 +/- 17 micrograms per liter). There was a significant correlation between serum hyaluronate and serum albumin, prothrombin time, factor V concentration and serum gamma-globulins. It is suggested that hyaluronate levels reflect both active fibrosis and hepatic failure and may be a quantitative marker of severity of hepatic injury.
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PMID:Serum hyaluronate in liver diseases: study by enzymoimmunological assay. 371 Apr 27

1. When acute liver damage is induced in rats treated with CCl4, both prothrombin biosynthesis and gamma carboxylase activity decreases, originating a prolongation of prothrombin time in plasma. 2. Then, during the regenerative process, prothrombin biosynthesis increases higher than normal, but gamma carboxylase activity remain decreased. In this case, prolongation of prothrombin time occurs in spite of high levels of descarboxylated prothrombin in plasma. 3. An increase of descarboxylated prothrombin in plasma is also detected in the CCl4-liver fibrosis model.
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PMID:Induction of prothrombin biosynthesis and inhibition of gamma carboxylase activity in experimental models of liver regeneration and fibrosis. 846 53

The ratio of serum aspartate aminotransferase to alanine aminotransferase (AST/ALT ratio) has been proposed as a noninvasive method of assessing liver fibrosis and cirrhosis. Our aims were to confirm the usefulness of the AST/ALT ratio in diagnosing cirrhosis noninvasively as well as to verify the existence of a relationship between the ratio and liver functional impairment. In all, 348 patients (177 with chronic hepatitis, 171 with cirrhosis) were retrospectively evaluated and the AST/ALT ratio was related to monoethyl glycine xylidide (MEGX) formation. Moreover, in a subgroup of 54 patients we analyzed the relationships among the AST/ALT ratio and indocyanine green clearance and half-life. The AST/ALT ratio was able to separate patients with mild fibrosis from those with severe fibrosis and cirrhosis. The AST/ALT ratio, MEGX, prothrombin activity, and platelet count were selected by multivariate analysis as variables associated with cirrhosis. The AST/ALT ratio showed significant correlations both with MEGX formation and with indocyanine green clearance and half-life. The alterations of indocyanine green kinetics, which depend upon liver blood flow and uptake, were likely due to progressive fibrosis. These findings might partially explain the increase in the AST/ALT ratio as disease progresses.
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PMID:Progressive liver functional impairment is associated with an increase in AST/ALT ratio. 1038 5

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

It has not been fully determined whether isolated small bowel transplantation (ISBTx) can reverse liver dysfunction caused by intestinal failure requiring long-term total parenteral nutrition (TPN). A boy with congenital microvillus inclusion disease presented with vomiting and severe diarrhea since the first day of life and had been managed by TPN since then. He suffered from catheter-related sepsis several times. At 14 yr of age he developed progressive hepatosplenomegaly with thrombocytopenia and coagulopathy. He underwent ISBTx with an ileal graft from his blood-identical grandmother at the age of 16 yr. Oral feeding was started on the 14th day after ISBTx and gradually increased. TPN was completely withdrawn after 5 months. Liver was palpated 5 cm below the costal margin before ISBTx, while it became non-palpable 5 months after ISBTx. Serum liver enzyme levels and prothrombin time normalized in the 5 months following ISBTx. Liver biopsy showed marked steatosis, slight cholestasis, and mild bridging fibrosis before ISBTx. Although histological examination of liver biopsy revealed complete disappearance of steatosis 7 and 11 months after ISBTx, liver fibrosis remained unchanged. This clinical experience has shown that although steatosis and cholestasis are reversible after successful ISBTx and withdrawal of TPN, liver fibrosis may remain unchanged.
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PMID:Effects of isolated small bowel transplantation on liver dysfunction caused by intestinal failure and long-term total parenteral nutrition. 1210 May 9

Liver biopsy is required for staging hepatic fibrosis in patients with chronic hepatitis C, but it is an expensive procedure with occasional complications and poor patient acceptance. This cohort study was designed to assess the accuracy of a noninvasive method aimed to discriminate between patients with and without significant liver fibrosis (stages 2-4 versus 0-1). Clinically relevant variables were analyzed in a cohort of 476 consecutive untreated patients (estimation group, 351 patients; validation group, 125 patients) with chronic hepatitis C who underwent a liver biopsy. Multivariate analysis identified age, gamma glutamyl transpeptidase (GGT), cholesterol, platelet count, and prothrombin time as independent predictors of fibrosis. We constructed a model and a score system combining age, GGT, cholesterol, and platelet count that proved useful to identify patients without significant hepatic fibrosis. The area under the ROC curve was 0.86 for the estimation group and 0.81 for the validation group. Using the best cutoff score (less than 4.2), presence of significant fibrosis (F2 to F4) could be excluded with high accuracy (negative predictive value of 96%) in 125 (36%) of 351 patients. Similarly, it could be excluded with the same certainty in 49 (39%) of the 125 patients of the validation group. Only 2 patients with liver fibrosis stage 2 were incorrectly classified. In conclusion, a combination of easily accessible variables accurately predicts the absence of significant fibrosis and might render liver biopsy unnecessary in more than one third of patients with chronic hepatitis C.
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PMID:Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model. 1271 4

Non-invasive serum markers of extensive liver fibrosis are required in clinical practice for several reasons: (1) although histological analysis is considered to be the gold standard for the diagnosis of extensive fibrosis and cirrhosis, the rate of false-negative results is approximately 15-20%; (2) liver biopsy is an invasive method with a 1/10 000 mortality rate, even though occurrence of death is exceptional in patients with diffuse liver disease; (3) patients with chronic viral hepatitis have to undergo multiple liver biopsies during follow-up to assess the progression of tissue injury. In this leading article, we briefly overview the recent progress in non-invasive serum markers for the prediction of the extent of liver fibrosis. Among those serum markers, we focused on prothrombin index, which seems to be a reliable and non-expansive marker for the diagnosis of extensive fibrosis.
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PMID:Prothrombin index decrease: a useful and reliable marker of extensive fibrosis? 1236 5

Hepatic fibrosis is the main determinant of clinical outcomes of chronic hepatitis C. Liver histology is frequently considered the gold standard for assessing hepatic fibrosis. However, liver biopsy is associated with sampling error, interobserver variability, and potential complications. Thus, there is a need for simple, inexpensive, and reliable noninvasive means to assess disease severity in patients with chronic hepatitis C. Clinical examination is unreliable in differentiating different stages of compensated liver disease. Among the routine laboratory tests, decreased platelet count, increase in the ratio of aspartate to alanine aminotransferase (AST/ALT), and prolonged prothrombin time are the earliest indicators of cirrhosis and portal hypertension. Individual serum fibrosis markers have limited accuracy in predicting hepatic fibrosis. Indices composed of a panel of markers correlate better with histological fibrosis, but their reliability requires further validation. Currently, noninvasive monitoring of patients with chronic hepatitis C relies on clinical evaluation, routine laboratory tests, and ultrasound and endoscopic surveillance in patients with cirrhosis. Initial evaluation should focus on assessment of activity and stage of liver disease for prognostication and decisions regarding treatment, and to rule out coinfections and other causes of liver disease. Subsequent follow-up should focus on detection of liver disease progression and the need for treatment. The frequency of monitoring and the tests used will depend on the patient's age, stage of liver disease, and comorbid conditions. There is an urgent need to develop and validate noninvasive tests that can accurately reflect the full spectrum of hepatic inflammation and fibrosis in chronic hepatitis C.
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PMID:Noninvasive monitoring of patients with chronic hepatitis C. 1644 Mar 44


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