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

Both hepatocyte necrosis and organ fibrosis and intracellular reparative regeneration of the injured cells took place in the posttoxic cirrhosis development. The outcome of cirrhosis is supposed to be determined by the prevalence of one of the processes--either the irreversible destruction, restoration or the hypertrophy of the parenchymal cells. The progress of cirrhosis evidently depended on the overstraining and progressive exhaustion of the intracellular compensatory adaptive mechanisms.
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PMID:[Ultrastructural changes in hepatocytes in the dynamics of the development of esperimental liver cirrhosis in rats]. 122 63

Between July 1986 and April 1989, 334 hospitalized adult Ethiopian patients with chronic liver disease were studied according to a protocol to define their clinical features and to identify risk factors with the aim of preventive intervention. Of these, 14 had chronic hepatitis, 208 cirrhosis and 112 hepatocellular carcinoma (HCC). Both clinical and histological diagnostic criteria were employed. A detailed questionnaire was used to document demographic and clinical data. A common clinical presentation among patients with chronic hepatitis was darkening of the face and hands with or without hypertrichosis of the face and blisters over the dorsi of the hands. This overt or latent form of porphyrea cutanea tarda (PCT) responds to chloroquine. Patients with cirrhosis of the liver commonly present for the first time with ascites, splenomegaly, haematemesis and/or melena from oesophageal varices, and mental changes due to hepatic encephalopathy. Overt or latent forms of PCT are also common features. Peculiar to these cirrhotics is the rarity of spider naevi, gynaecomastia, testicular atrophy, Dupuytren's contracture, parotid gland enlargement and clubbing of the fingers. Exhaustion, loss of appetite, rapid loss of weight, right upper quadrant and/or epigastric pain (all often of less than 6 months' duration, a big, hard, tender and grossly nodular liver with bruit, signs of portal hypertension, and/or hepatic encephalopathy, in a young male with a rapid down hill course characterize the Ethiopian patient with HCC. Serum anti-nuclear factor, anti-mitochondrial anti-bodies and anti-smooth muscle anti-bodies were absent in those with chronic hepatitis and were uncommon in the cirrhotics and HCC cases. One or more hepatitis B virus markers were found in 86% of chronic hepatitis, 88% cirrhosis and 78% HCC and the HBsAg carrier state was found in 36%, 29% and 23%, respectively. Among the HBsAg carriers, HBeAg positivity was less common than anti-HBe but anti-HDV was significantly higher than in the healthy general population. Alphafetoprotein (AFP) levels greater than 500 mg/ml were present in 16 (8%) cirrhotics and 58 (52%) patients with HCC. Histologically, 3 of the chronic hepatitis patients had progressed to cirrhosis, 8 of the cirrhotic patients had chronic active hepatitis and 85% of HCC cases occurred in a background of macronodular cirrhosis. Three cirrhotics developed HCC during follow-up.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Chronic liver disease in Ethiopia: a clinical study with emphasis on identifying common causes. 131

We studied maximal aerobic work capacity in 24 cirrhotic patients whose clinical condition was well compensated. Nineteen of our patients had no heart or lung disease, and five had mild mechanical ventilatory impairment. The patients performed incremental exercise on a treadmill until subjective exhaustion. The maximal exercise levels reached by all were relatively low and led to a lower observed maximal oxygen uptake (VO2 max), than predicted uptake (19.6 +/- 0.5 vs. 37.9 +/- 0.6 ml/kg; p less than 0.001). Observed VO2 max values correlated strongly with the Pugh score, which reflects the degree of liver failure (r = -0.571; p less than 0.01). Since there were no clear cardiac or pulmonary causes to explain the decrease in work capacity, these observations suggest that liver cirrhosis might induce or be accompanied by muscular impairment. VO2 max, which seems to decline with the functional severity of the disease, may be a useful index for evaluating the capacity of patients for physical rehabilitation.
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PMID:Submaximal oxygen consumption in liver cirrhosis. Evidence of severe functional aerobic impairment. 233 86

Serum ferritin, an index of iron stores, was studied in 60 patients with porphyria cutanea tarda (PCT), in 21 patients who had other liver diseases without siderosis (cirrhosis [LC] and chronic active hepatitis [CAH]), and in 32 patients with associated liver siderosis (alcoholic LC, LC and CAH in minor thalassemia). Ferritin levels were higher in patients with porphyria than in healthy controls and patients without liver siderosis (P less than 0.001), whereas no statistical difference was observed between patients with porphyria and those with liver siderosis. Because iron removal is considered the treatment of choice for PCT, some patients with PCT underwent phlebotomy and others received chelating therapy with subcutaneous infusion of deferoxamine. Follow-up of the patients showed a correlation between serum ferritin level and urinary porphyrin excretion; when the clinical and biochemical syndrome became normal, serum iron and ferritin had fallen to normal values (t test pair data analysis before and after: P less than 0.001 in each group). No appreciable difference was found between controls and patients with PCT whose conditions had been normalized, irrespective of the chronic liver damage always present in PCT. Our results suggest that serum ferritin increase in PCT is related more to liver iron overload than to liver damage, and ferritin follow-up is recommended to indicate the exhaustion of hepatic iron stores during iron depletion therapy, as well as to detect an early replenishment after remission.
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PMID:Serum ferritin in the assessment of liver iron overload and iron removal therapy in porphyria cutanea tarda. 394 Dec 93

Some parameters of iron metabolism in 26 patients with porphyria cutanea tarda (PCT) which is often associated with mild iron overload and hepatic siderosis, are studied. Serum iron, percent transferrin saturation and ferritin were pathologically increased. Statistical comparisons were performed between PCT patients and healthy controls, liver disease patients (cirrhosis, chronic active hepatitis) and patients with associated liver siderosis (alcoholic cirrhosis, cirrhosis and chronic active hepatitis in thalassemia). Ferritin levels are higher in patients with porphyria than in healthy controls (p less than 0,001) and in patients without liver siderosis (p less than 0,001). No statistical difference is observed between patients with porphyria and patients with siderosis. A significant decrease in ferritin levels is registered after venesection therapy. The conclusion is drawn that serum ferritin increase in PCT is related to hepatic iron store amounts rather than hepatic necrosis. It is assumed that ferritin follow-up during phlebotomy therapy and also during remission is useful to indicate the exhaustion or an early replenishment of hepatic iron stores.
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PMID:[Determination of serum ferritin in porphyria cutanea tarda. A reliable sign of hepatic siderosis]. 670 23

Plasma levels of calprotectin were determined in 84 patients with alcohol-induced cirrhosis. Calprotectin is released from disintegrating neutrophils, and plasma levels seem to reflect activation and turnover of such cells. The purpose of the study was to investigate the degree of activation of neutrophils, which has been indicated to be increased and a cause of neutrophil exhaustion in these patients. Additionally, on follow-up after a median observation period of 559 days, we investigated the prognostic value of calprotectin for survival. No difference was found in calprotectin levels when comparing healthy controls with patients with compensated cirrhosis and those with decompensated cirrhosis. However, high calprotectin concentrations (> median) were a significant prognostic marker of poor survival (P = .001, log-rank test). Using a multivariate Cox proportional hazard model, the prognostic value of calprotectin seemed independent of severity of liver disease evaluated on eight clinical and biochemical variables of liver disease. Divided into groups by the median calprotectin concentration, analysis of survival was performed in the whole series of patients (n = 84) as well as in patients who were completely without signs of recent or actual infection (n = 54). In both groups, calprotectin levels (> median) showed a much higher prognostic value than albumin, prothrombin complex, bilirubin, and ascites. During follow-up, calprotectin levels (> median) were also a predictor of recurrent infection (P = .009). Thus, in patients with alcoholic cirrhosis, plasma calprotectin seems to be a new prognostic marker of survival, which seems independent of the severity of liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma calprotectin: a new prognostic marker of survival in alcohol-induced cirrhosis. 770 9

The pathogenesis of ascites, a severe and the most frequent complication during cirrhosis, is still not completely understood, but present evidence indicates that portal hypertension principally triggers renal sodium and water retention. Ascites is associated with profound disturbances of splanchnic and systemic haemodynamics, which in turn may influence renal function. Within the kidney the balance between vasoconstricting and vasodilating factors is critical for the maintenance of renal function. As the disease progresses, vasoconstricting factors (mainly angiotensin II, catecholamines, thromboxane, leucotrienes and endothelins) prevail, probably due to the exhaustion of the vasodilating renal autacoid system (mainly prostaglandins). In this setting, vasoconstriction of the intrarenal vascular system induces marked and often irreversible sodium and water retention, leading to refractory ascites, a progressive rise in plasma creatinine levels and reduction of renal clearances (hepatorenal syndrome, HRS). This persistent renal hypoxia may also favour the occurrence of tubular damage due to several causes. A careful therapeutic approach is first based on sequential diuretic treatment (and the addition of adequate plasma expansion with human albumin for patients with diuretic resistant ascites), which may lead to control of ascites for years. However, when HRS occurs, all the proposed treatments (such as paracentesis, administration of renal vasodilators, systemic vasoconstrictors, calcium channel antagonists, TIPS, surgical portosystemic shunts) have been shown to moderately or temporarily improve renal function only, leaving liver transplantation as the only choice of treatment for patients.
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PMID:Hepatorenal syndrome and its treatment today. 1050 49

Ascites is the most frequent major complication of liver cirrhosis. Even if a significant decrease in renal clearances may be observed in the first stages of chronic active hepatitis, true renal impairment, often with the typical signs of hepatorenal syndrome, only occurs in patients with ascites, especially when tense and refractory. Experimental and clinical data suggest the presence of primary sodium and water retention, perhaps as a consequence of an increase in intrahepatic hydrostatic pressure. The abnormal sodium retention leads to plasma volume expansion, followed by decreased peripheral vascular resistances and increased cardiac output. This second stage concords with the peripheral arterial vasodilation theory, characterized by an increase in total blood volume, but with a decrease in effective arterial blood volume. This discrepancy leads to the activation of sympathetic nervous and renin-angiotensin-aldosterone systems. This activation, while protective against splanchnic and systemic vasodilation, provoked by the increased availability of nitric oxide and other vasodilating substances, induces renal vasoconstriction. This phenomenon can be considered as the basis of the progressive renal failure that leads to hepatorenal syndrome, favored by progressive exhaustion of the renal autacoid vasodilating substances. The first therapeutic approach to ascites is sequential and based on diuretic administration. Subsequently, paracentesis with albumin infusion is carried out, as well as transjugular intrahepatic portosystemic shunting, surgical portosystemic shunting, and liver transplantation: these procedures are essential for the treatment of hepatorenal syndrome.
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PMID:Pathogenetic factors and clinical elements in ascites and hepatorenal syndrome during liver cirrhosis. 1063 19

Ascites is the most common complication occurring during liver cirrhosis. Even if a significant decrease in renal clearance may be observed in the first step of chronic active liver disease, renal impairment, at times complicated by the typical signs of hepatorenal syndrome, occurs only in patients with ascites, especially when tense and refractory. Experimental and clinical data seem to suggest a primary sodium and water retention in the pathogenesis of ascites, in the presence of an intrahepatic increase of hydrostatic pressure, which, by itself, physiologically occurs during digestion. Abnormal sodium and water handling leads to plasma volume expansion, followed by decreased peripheral vascular resistance and increased cardiac output. This second step is in agreement with the peripheral arterial vasodilation hypothesis, depicted by an increase in total blood volume, but with a decreased effective arterial blood volume. This discrepancy leads to the activation of the sympathetic nervous and renin-angiotensin-aldosterone systems associated with the progressive activation of the renal autacoid systems, especially, that of the arachidonic acid. During advanced cirrhosis, renal impairment becomes more sustained and renal autacoid vasodilating substances are less available, possibly due to a progressive exhaustion of these systems. At the same time ascites becomes refractory inasmuch as it is no longer responsive to diuretic treatment. Various pathogenetic mechanisms leading to refractory ascites are mentioned. Finally, several treatment approaches to overcome the reduced effectiveness of diuretic therapy are cited. Paracentesis, together with simultaneous administration of human albumin or other plasma expanders is the main common approach to treat refractory ascites and to avoid a further decrease in renal failure. Other effective tools are: administration of terlipressin together with albumin, implantation of the Le Veen shunt, surgical porto-systemic shunting or transjugular intrahepatic portosystemic stent-shunt, or orthotopic liver transplantation, according to the conditions of the individual patient.
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PMID:Update on ascites and hepatorenal syndrome. 1250 17

Chronic hepatitis C virus (HCV) infection is one of the major causes for development of liver cirrhosis and end-stage liver disease. This article reviews two contrasting models of HCV pathogenesis, discusses the merits of each, and presents a rationale for combining the two models into one. Any successful model of HCV pathogenesis must explain how the characteristic features of cirrhosis and end-stage liver disease arise. These features include the loss of hepatocyte function (low serum albumin and reduced clotting ability); the presence of regenerative nodules; and the deposition of excessive extracellular matrix material, especially collagen (fibrosis), which is associated with the transformation of the liver sinusoids to capillary-like structures leading to portal hypertension. A successful model should explain several observations about the rate of disease progression. HCV is characterized by slow progression of fibrogenesis and, importantly, cirrhosis seems to develop only after a long latency (and only in a subset of patients). Among the prognostic factors of disease progression, the age at infection with the HCV virus and the presence of fibrosis appear to be highly relevant in predicting the development of progressive fibrosis. Traditional models of HCV pathogenesis propose that fibrogenesis is the predominant process. Fibrogenesis is induced by activation of fibrogenic cells, such as stellate cells, which results in excessive collagen deposition. By altering the normal architecture and vasculature, the collagen bands finally lead to cirrhosis and loss of organ function. Activation of stellate cells is induced by inflammation, cytokine signaling, and possibly by hepatocyte apoptosis. The telomere model of HCV pathogenesis suggests that hepatocyte damage plays an essential role in the development of cirrhosis. According to this model, hepatocyte damage leads to increased cell turnover, and to the accelerated shortening of hepatocyte telomeres. Critical telomere shortening leads to hepatocyte senescence, loss of hepatocyte function, exhaustion of hepatocellular regeneration, and to a greatly enhanced fibrotic response to injury. This review summarizes both models and presents evidence that these models are not mutually exclusive but rather can be merged into a comprehensive pathogenesis model that outlines the pathway of HCV-induced cirrhosis.
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PMID:Merging models of hepatitis C virus pathogenesis. 1573


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