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)

A Hungarian family with four heterozygotes for Hb Lepore Washington is described. One, a 43-year-old male, had high levels of serum iron, saturated iron-binding capacity, and ferritin, and normal levels of folic acid and vitamin B12. Liver biopsy showed slight cirrhosis and marked iron deposition in parenchymal cells and in cells of the reticuloendothelial system. Heavy iron deposition was also found in the bone marrow. The patient is not an alcoholic and has no disease that requires blood transfusion. The hemochromatosis thus seems to be of idiopathic nature.
Hemoglobin 1979
PMID:Hemoglobin Lepore Washington and hemochromatosis in a Hungarian patient. 47 79

Clinical studies show that patients with liver cirrhosis associated with portal hypertension have a high incidence of duodenal ulcer and duodenitis. However, little information is available concerning pathophysiological process of such duodenal diseases in liver cirrhosis. Hemodynamics of the duodenal mucosa was studied in cirrhotics with esophageal varices (68 cases) and in noncirrhotics with non-ulcer dyspepsia (37 cases) as well. In each group, hemoglobin concentration in the peripheral venous blood was measured, and mucosal hemodynamics was examined in 4 regions of the duodenum by endoscopic reflectance spectrophotometer. No significant intergroup difference was noted in the mean age or sex ratio. Hemoglobin concentration in the peripheral venous blood was significantly lower (p less than 0.01) in the cirrhotics. There were no significant intergroup differences in duodenal mucosal blood volume. However, the cirrhotics showed significantly lower oxygen saturation of hemoglobin in all regions of the duodenum (p less than 0.01). These results show that the cirrhotics with esophageal varices had relative increase in blood volume and decrease in oxygen saturation of hemoglobin in the duodenal mucosa. Such microcirculatory disturbances seem to predispose liver cirrhosis patients to duodenal injury.
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PMID:Duodenal mucosal hemodynamics in patients with liver cirrhosis. 226 Apr 99

Clinical and laboratory observations were made on 220 chronic alcoholics, regularly taking at least 150 g of alcohol daily. Haematological data concerning white blood cells, platelets and red cells counts, mean corpuscolar volume, hemoglobin and serum iron in these patients were compared with control values obtained from 150 healthy teetotal subjects. Hematological changes in chronic alcoholics were correlated with histological liver damages in transcutaneous needle-biopsies. No statistical differences were evident for white cells and platelets counts and for serum iron content; however, in chronic alcoholics, serum iron content showed a great dispersion around the mean. Mean corpuscolar volume (MCV) was significantly increased (P less than 0,001) in chronic alcoholics (even in those with a normal liver biopsy) but there was no significant difference in the degree and the incidence of macrocytosis between patients showing normal liver appearances or fatty changes only, and those showing more severe damage, i.e, acute alcoholic hepatitis (with or without steatosis), central hyaline-sclerosing necrosis and or hepatofibrosis, cirrhosis and hepatocarcinoma. No significant difference was seen between male and female alcoholics. Macrocytosis may be considered as an early marker for alcoholism but it does not correlate with the type of histological liver damage. Hemoglobin levels were significantly reduced in chronic alcoholics (P less than 0,01): the degree and incidence of anemia were more severe in those patients with advanced liver diseases and in female alcoholics. There is no statistically significant correlation between macrocytosis and anemia.
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PMID:[Macrocytosis and anemia in chronic alcoholism. Correlation with the results of hepatic needle biopsy]. 724 21

We evaluated the performance of a homogeneous assay for the automated measurement of high-density lipoprotein cholesterol (HDL-C) and compared it with a conventional precipitation technique in the following groups of people: control subjects (group A), clinically-healthy elderly (group B), myocardial infarction patients (group C), nephrotic syndrome patients (group D), and liver cirrhosis patients (group E). The performance of the technique was acceptable with respect to precision, accuracy, linearity, and detection limit. Triglycerides up to 40 mmol/L and bilirubin up to 150 micromol/L did not cause interferences. Hemoglobin decreased HDL-C measurements. Samples were stable at -20 degrees C for up to four months. Bland-Altman plots showed a good agreement between both techniques in the control group but with a progressive divergence in the patient groups B to E. Results indicate limitations of the technique in certain clinical conditions and, coincidentally, the need for reliable calibration materials.
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PMID:Evaluation of a homogeneous assay for high-density lipoprotein cholesterol: limitations in patients with cardiovascular, renal, and hepatic disorders. 962 47

Pulmonary hypertension is one of the major causes of morbidity and mortality of patients with sickle cell hemoglobinopathy (SCH). Although a clinically recognized complication of sickle cell disease (SCD), there are few published pathologic studies of pulmonary findings in these patients. The aim of this study was to define the pulmonary pathologic changes and to investigate correlation between the pathologic changes, the antemortem diagnosis of pulmonary hypertension, and the severity of SCH. Cases of SCH were identified from the autopsy database using Snomed codes. Clinical and echocardiograph data were collected for correlation with the pathologic data. A total of 20 adult patients (12 males and 8 females) were identified. Hemoglobin electrophoresis results were available for 16 patients, with hemoglobin S fraction percentages ranging from 23% to 97.8%. Eleven patients had SCD, 5 patients had sickle cell trait (SCT), and the remaining 4 patients without hemoglobin electrophoresis were included in the SCT group. The mean age of the SCT group was higher than that of the SCD group (P = 0.03). Histologically, all 20 patients demonstrated changes in pulmonary vasculature considered diagnostic of pulmonary hypertension grade I to grade IV, associated with plexiform lesions in 60% of patients. Medial hypertrophy and intimal hyperplasia/fibrosis, considered potentially reversible lesions, were seen in all patients. A weak association was found between SCD and plexiform lesions. Fibroelastic degeneration of small arteries, arterioles, and venules was identified in almost all (95%) cases. Clinically, tricuspid regurgitation was detected by echocardiogram in 10 of 20 (50%) patients; 6 of these 10 had significant regurgitation to allow estimation of systolic pressure. Sudden death occurred in 8 patients, with males having a significantly higher incidence. Cardiomegaly was present in 95% of patients, however, autosplenectomy and hepatic cirrhosis/hemochromatosis were observed almost exclusively in patients with SCD. Cirrhosis was found to have a strong positive association with SCD. This study demonstrates pulmonary hypertensive changes in all 20 autopsied patients who had SCH but died from various causes. We conclude that a high prevalence of pulmonary hypertension is associated with SCH with consequent high mortality. Therefore, patients with SCH would benefit from a regular periodic assessment for pulmonary hypertension regardless of age, sex, and severity of hemoglobinopathy.
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PMID:Pulmonary hypertension in sickle cell hemoglobinopathy: a clinicopathologic study of 20 cases. 1239 78

New developments in the epidemiology, treatment and prognosis of thalassemia have dramatically altered the approach to the care of affected patients, and these developments are likely to have an even greater impact in the next few years. Demographic changes have required an awareness and understanding of the unique features of thalassemia disorders that were previously uncommon in North America but are now seen more frequently in children and recognized more consistently in adults. New methods for measuring tissue iron accumulation and new drugs to remove excessive iron are advancing two of the most challenging areas in the management of thalassemia as well as other transfusion-dependent disorders. Improved survival of patients with thalassemia has given new importance to adult complications such as endocrinopathies and hepatitis that have a major impact on the quality of life. This chapter describes how these changes are redefining the clinical management of thalassemia. In Section I, Dr. Renzo Galanello describes recent advances in iron chelation therapy. Several new chelators are either licensed in some countries, are in clinical trials or are in the late stages of preclinical development. Some of these iron chelators, such as deferiprone (DFP) and ICL670, are orally active. Others, such as hydroxybenzyl-ethylenediamine-diacetic acid (HBED) and starch deferoxamine, require parenteral administration but may be effective with less frequent administration than is currently required for deferoxamine. Chelation therapy employing two chelators offers the possibility of more effective removal of iron without compromising safety or compliance. Other strategies for chelation therapy may take advantage of the ability of particular chelators to remove iron from specific target organs such as the heart and the liver. In Section II, Dr. Dudley Pennell addresses cardiac iron overload, the most frequent cause of death from chronic transfusion therapy. The cardiac complications related to excessive iron may result from long-term iron deposition in vulnerable areas or may be due to the more immediate effects of nontransferrin-bound iron. Cardiac disease is reversible in some patients with intensive iron chelation therapy, but identification of cardiac problems prior to the onset of serious arrhythmias or congestive heart failure has proven difficult. New methods using magnetic resonance imaging (MRI) have recently been developed to assess cardiac iron loading, and studies suggest a clinically useful relationship between the results using these techniques and critical measures of cardiac function. Measurements such as T2* may help guide chelation therapy in individual patients and may also enhance the assessment of new chelators in clinical trials. The use of MRI-based technology also holds promise for wider application of non-invasive assessment of cardiac iron in the management of patients with thalassemia. In Section III, Dr. Melody Cunningham describes some of the important complications of thalassemia that are emerging as patients survive into adulthood. Hepatitis C infection is present in the majority of patients older than 25 years. However, antiviral therapy in patients with thalassemia has been held back by the absence of large clinical trials and concern about ribavirin-induced hemolysis. More aggressive approaches to the treatment of hepatitis C may be particularly valuable because of the additive risks for cirrhosis and hepatocellular carcinoma that are posed by infection and iron overload. Thrombosis is recognized with increasing frequency as a significant complication of thalassemia major and thalassemia intermedia, and pulmonary hypertension is now the focus of intense study. Risk factors for thrombosis such as splenectomy are being identified and new approaches to anticoagulation are being initiated. Pregnancies in women with thalassemia are increasingly common with and without hormonal therapy, and require a better understanding of the risks of iron overload and cardiac disease in the mother and exposure of the fetus to iron chelators. In Section IV, Dr. Elliott Vichinsky describes the dramatic changes in the epidemiology of thalassemia in North America. Hemoglobin E-beta thalassemia is seen with increasing frequency and poses a particular challenge because of the wide variability in clinical severity. Some affected patients may require little or no intervention, while others need chronic transfusion therapy and may be appropriate candidates for hematopoietic stem cell transplantation. Enhancers of fetal hemoglobin production may have a unique role in Hb E-beta thalassemia since a modest increase in hemoglobin level may confer substantial clinical benefits. Alpha thalassemia is also being recognized with increasing frequency in North America, and newborn screening for Hemoglobin Barts in some states is leading to early detection of Hb H disease and Hb H Constant Spring. New data clarify the importance of distinguishing these two disorders because of the increased severity associated with Hb H Constant Spring. The use of intrauterine transfusions to sustain the viability of fetuses with homozygous alpha thalassemia has created a new population of patients with severe thalassemia and has raised new and complex issues in genetic counseling for parents with alpha thalassemia trait.
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PMID:Thalassemia. 1556 74

Hepatocellular carcinoma (HCC) is a complication of cirrhosis. Due to blood transfusions, patients with beta-thalassemia (thal) are often infected with either hepatitis C virus (HCV) or hepatitis B virus (HBV). In the past, many patients did not survive long enough to develop HCC. The recent improvements in prognosis have helped in the diagnosis of HCC that has developed. The aim of this study was to evaluate HCC incidence in beta-thal. We performed liver ultrasound (US) on all adults without a previous diagnosis of HCC. Risk factors (iron overload, HCV infection, HBV infection, cirrhosis) were evaluated. One hundred and eight thalassemia patients have been evaluated; of whom three were excluded (two patients as they were under the age of 18 years and one patient because he had a previous history of HCC). Seventy-two patients [31 had thalassemia major (TM), 41 had thalassemia intermedia (TI)] with risk factors (iron overload in 72, HCV infection in 46, HBV infection in two, cirrhosis in 10) and 33 (four with TM and 29 with TI) without risk factors underwent liver US. Overall, two patients were found to have a newly developed HCC. Of these two patients, one was treated with surgery and the other with percutaneous radiofrequency. Further follow-up did not show any evidence of recurrence after 23 and 15 months, respectively. Ultrasound screening can allow early detection and treatment of HCC in thalassemia patients.
Hemoglobin 2006
PMID:A prospective study of hepatocellular carcinoma incidence in thalassemia. 1654 Apr 24

Chronic infection with hepatitis C virus (HCV) can progress to cirrhosis, hepatocellular carcinoma, and end-stage liver disease. The current best treatment for HCV infection is combination therapy with pegylated interferon and ribavirin. Although this regimen produces sustained virologic responses (SVRs) in approximately 50% of patients, it can be associated with a potentially dose-limiting hemolytic anemia. Hemoglobin concentrations decrease mainly as a result of ribavirin-induced hemolysis, and this anemia can be problematic in patients with HCV infection, especially those who have comorbid renal or cardiovascular disorders. In general, anemia can increase the risk of morbidity and mortality, and may have negative effects on cerebral function and quality of life. Although ribavirin-associated anemia can be reversed by dose reduction or discontinuation, this approach compromises outcomes by significantly decreasing SVR rates. Recombinant human erythropoietin has been used to manage ribavirin-associated anemia but has other potential disadvantages. Viramidine, a liver-targeting prodrug of ribavirin, has the potential to maintain the virologic efficacy of ribavirin while decreasing the risk of hemolytic anemia in patients with chronic hepatitis C.
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PMID:Definition and management of anemia in patients infected with hepatitis C virus. 1662 41

A 38-year-old Ghanaian man presented with a 6-month history of worsening pruritus, jaundice, and ascites. He was previously fit and well and rarely drank alcohol. Screening tests for chronic liver disease including viral, autoimmune, and other metabolic causes including iron overload were unremarkable. A liver biopsy performed at the referring hospital demonstrated intralobular cholestasis and cirrhosis. He was listed for liver transplantation but subsequently developed sepsis with multiple organ failure and died. The sickle solubility test was positive. Blood smear showed cells consistent with liver failure and no sickle cells. Hemoglobin electrophoresis revealed HbA2 2.8%, HbF 0.5%, and HbS greater than HbA (49.6% vs. 41.3%) in the absence of blood transfusion. Sequence analysis of the beta-globin genes showed he was a compound heterozygote for the Hbs mutation at codon 6 (CAG --> GTG) and a novel mutation at position 844 of intron 2 (betaIVS2-844 C --> A). A diagnosis of sickle hepatopathy causing decompensated cirrhosis was made. This case is unusual insomuch as this patient was asymptomatic for over 35 years and represents a novel presentation of sickle cell disease. Sickle cell disease should be considered in appropriate patients when unusual presentations of liver disease arise.
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PMID:Sickle liver disease--an unusual presentation in a compound heterozygote for HbS and a novel beta-thalassemia mutation. 1756 24

Patients with thalassemia have disturbances in hemoglobin chain production which leads to anemia requiring long-term and multiple transfusions, increasing the risk for transfusion-related viruses, including hepatitis B and C viruses. Although this transfusion-related risk has been virtually eliminated with optimal blood screening practices, a significant number of patients transfused prior to 1990 are infected with hepatitis C virus. Treatment of hepatitis B and hepatitis C has improved rapidly leading to viral eradication - or control of viral replication - with the aim of stopping the progression to liver cirrhosis and its complications. Treatment of chronic hepatitis B in patients with thalassemia does not differ from that of other patients. However, current treatment of hepatitis C necessitates the use of ribavirin, which is associated with dose-dependent hemolysis, requiring adjustment of the transfusion protocol for thalassemia patients during the treatment period. Several measures should be taken in thalassemia patients to prevent viral infection including vaccination for hepatitis B and adequate screening of blood and blood products.
Hemoglobin 2009
PMID:Treatment and prevention of hepatitis B and C in thalassemia. 2000 18


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