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)

Approximately 1.5 million persons in the United States are affected by iron overload diseases, which are primarily caused by hereditary hemochromatosis--the most common genetic disorder in the United States. Hereditary hemochromatosis is characterized by increased iron absorption in the gastrointestinal tract, which may cause lifelong excessive iron absorption and accumulation and serious health effects, including arthritis, cirrhosis, diabetes, impotence, heart failure, and death. Hereditary hemochromatosis is an autosomal recessive disease; the estimated prevalence of the homozygous genotype is 1:200 - 1:250 persons, and 10% of persons are carriers. Although the disease was previously believed to affect primarily white males of northern European descent, recent data indicate hereditary hemochromatosis also occurs among blacks. Moreover, iron overload diseases are underdiagnosed among whites and may not be considered in other racial/ethnic groups (e.g., Hispanics) even when compatible symptoms and clinical findings are present. As part of a joint demonstration project during August-October 1995 to determine the overall prevalence of iron overload, CDC reviewed data from a health-maintenance organization (HMO) in San Diego, California; the prevalence among Hispanics appeared similar to that for non-Hispanic whites. This report presents the preliminary findings of an analysis of the prevalence of iron overload among Hispanics and compares these findings with nationally representative data from the Third National Health and Nutrition Examination Survey (NHANES III). These findings indicate that the prevalence of possible iron overload among Hispanic clients of the HMO based on initial screening was consistent with the nationwide prevalence of possible iron overload based on a single screening test for Hispanics of Mexican descent and non-Hispanic whites.
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PMID:Iron overload disorders among Hispanics--San Diego, California, 1995. 900 7

Various endocrine disturbances are often observed in the patients with liver cirrhosis. We focused this paper on the sex hormones. Clinical features of male cirrhotic subjects are feminization(gynecomastia etc) and hypogonadism(testicular atrophy, reduced fertility, loss of libido, impotence etc). Chief abnormalities of sex hormones are a decrease in serum testosterone levels and an increase in serum estrogen levels accompanied by an increase in ratio of estrogen to testosterone in the patients with severe liver cirrhosis associated with the severity of hepatic dysfunction. Hyperestrogenization may be related with feminization of male cirrhotic subjects, whereas hypogonadism is the result of alcohol abuse per se, rather than the indirect consequence of liver cirrhosis.
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PMID:[Endocrine disturbances in liver cirrhosis--focused on sex hormones]. 939 3

To evaluate the efficacy and safety of human lymphoblastoid interferon treatment (interferon alfa) for patients with compensated cirrhosis caused by hepatitis C virus (HCV) infection, we randomly assigned 82 cirrhotic patients with chronic HCV infection (44 men, 38 women; mean age, 58.6 years) to two groups: 41 patients were treated with interferon alfa (480 million U over 6 months), and the other patients received no drug treatment. HCV RNA genotypes were determined by polymerase chain reaction (PCR) testing using type-specific primers. HCV RNA levels were measured by competitive PCR testing. No untreated patients eliminated HCV RNA from the serum or had a decrease in the level of alanine aminotransferase to normal during the observation period. Of the 34 patients who completed interferon alfa treatment, 6 (17.6%) who were considered complete responders eliminated HCV RNA from the serum by the end of treatment and sustained this elimination throughout a 6-month follow-up period. Complete responders constituted 6 (46.2%) of 13 patients with HCV RNA levels < or = 10(5) copies/50 microL, but none of the 21 patients with levels > 10(5) copies/50 microL were complete responders. Two (7.1%) of 28 patients with genotype 1b infection and 4 (66.7%) of 6 with genotype 2a were complete responders. Five patients withdrew because of interferon alfa-induced side effects (1 for thrombocytopenia, 3 for severe general malaise, and 1 for impotence), and 2 withdrew after being diagnosed with hepatocellular carcinoma. Hepatic failure did not occur in any treated patient in the present study. These findings indicate that interferon alfa treatment is useful for compensated cirrhosis caused by HCV infection if the HCV RNA levels are low and the infection is of genotype 2a.
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PMID:Human lymphoblastoid interferon treatment for patients with hepatitis C virus-related cirrhosis. 944 45

Chronic fatigue, arthralgia, infertility, impotence, cardiac disease, diabetes and abnormality of liver enzymes could point to the presence of haemochromatosis. A patient with one of these symptoms, a normal haemoglobin content, but an increased transferrin saturation and serum ferritin level most probably has a primary haemochromatosis. Most primary haemochromatoses have a genetic background. The diagnosis 'HFE-related haemochromatosis' is made when a homozygous Cys282Tyr mutation is found in the HFE-gene. However, in approximately 10% of the patients with the clinical features of primary haemochromatosis this mutation is absent. The treatment of primary haemochromatosis consists of regular phlebotomy. Liver biopsy is indicated if fibrosis, cirrhosis or another hepatic disease is suspected. Family screening of first-grade relatives is indicated for all patients with primary haemochromatosis.
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PMID:[Diagnosis and treatment of primary hemochromatosis]. 1042 53

Universal screening for hereditary hemochromatosis (HH) has been proposed by many experts, with understandable enthusiasm: HH can cause fatal complications, which are preventable with early treatment. The disorder involves excess iron accumulation that can result in tissue iron overload, with secondary cirrhosis, diabetes, heart failure, impotence and arthritis. These complications are preceded by years of iron accumulation, and most are believed to be preventable by removal of excess iron by phlebotomy. Thus, early identification and treatment - the quintessential functions of health screening - seem to make sense for HH. However, the available screening tests are imperfect. While they can identify many persons at increased risk from HH, the proportion that will develop serious clinical manifestations related to iron overload is not known with certainty. DNA-based tests do not provide a simple resolution to these questions.
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PMID:Screening for hereditary hemochromatosis: are DNA-based tests the answer? 1049 10

Spironolactone, a competitive aldosterone receptor antagonist (ARA), has traditionally been the treatment of first choice in idiopathic hyperaldosteronism (IHA) and for preoperative management of aldosterone producing adenoma (APA). Spironolactone is partially absorbed, is extensively metabolized mainly by the liver and its therapeutic properties are attributable to active metabolite canrenone. At therapeutic doses of 25 to 400 mg per day, spironolactone effectively controls blood pressure and hypokalemia in the majority of cases. Endocrine side effect are often associated and mainly consist of gynecomastia, decreased libido and impotence in man and menstrual irregularities in women. Canrenone and the K+ salt of canrenoate are also in clinical use: they avoid the formation of intermediate products with anti-androgenic and progestational actions, resulting in a decreased incidence of side effects. Furthermore, a relatively new selective ARA compound (eplerenone) with reduced affinity for androgen and progesterone receptors, is currently undergoing clinical trials. In essential hypertension aldosterone can contribute to hypertension and increases the incidence of myocardial hypertrophy and cardiovascular events. On the other hand, inhibition of Renin-Angiotensin-Aldosterone System (RAAS) is associated with a decrease in blood pressure, with a regression of left ventricular hypertrophy and a reduction of target organ damage. Thus, ARA have been proposed as complementary treatment associated to ACE inhibitors and angiotensin receptor antagonists. Aldosterone is also known to play an important role in pathophysiolgy of congestive heart failure (CHF). In vitro and in vivo evidences suggest that aldosterone promotes myocardial fibrosis. This effect reflects direct, extra-epithelial actions of aldosterone via cardiac MR which are counteracted by ARAs in animal models. The RAAS is chronically activated in CHF. Non potassium-sparing diuretics further stimulate the RAAS and cause hypokalemia. Thus, use of ARAs in CHF was first proposed to correct potassium and magnesium depletion. At present ARAs are indicated in the management of primary hyperaldosteronism, in oedematous conditions in patients with CHF, in cirrhosis of the liver accompanied by oedema and ascites, in essential hypertension and in hypokalemic states. Its indication as adjunctive therapy of heart failure is currently under investigation. In fact, it is well known that even high doses of ACE inhibitors may not completely suppress the RAAS; aldosterone 'escape' may occur through non angiotensin II dependent mechanisms. Addition of spironolactone to an ACE inhibitor causes marked diuresis and symptomatic improvement. During the last few years, the RALES study (Randomized Aldactone Evaluation Study) was organized to explore the efficacy of combination therapy with spironolactone and ACE inhibitor in patients with CHF, class III or IV NYHA. The study was stopped 18 months early because the results were so statistically and clinically significant that it would be unethical to continue the trial. It is reported a 30 percent decrease in mortality and hospitalisation for cardiac causes in spironolactone-treated group vs placebo group.
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PMID:Aldosterone antagonists in hypertension and heart failure. 1079 May 93

Genetic hemochromatosis is an autosomal recessive disease, characterized by an increased iron absorption, leading to progressive iron overload. The fully expressed phenotype comprises fatigue, skin pigmentation, liver disease with hepatomegaly, cirrhosis and hepatocellular carcinoma, and diabetes. Arthralgias are frequent, cardiopathy or impotence may occur. This presentation is now unfrequent with earlier diagnosis, and patients are often asymptomatic--with only biochemical expression--or pauci-symptomatic (mild fatigue, arthralgias or increased transaminases). Transferrin saturation is always increased. Serum ferritin is proportional to iron burden. Diagnosis is now easy, since most patients are homozygote for the C282Y mutation of the HFE gene. Liver biopsy can be useful to quantify iron overload and assess liver fibrosis. The disease can be lethal due to liver disease, carcinoma or heart disease, but life expectancy goes to normal if patients are treated before the occurrence of cirrhosis. Treatment relies on regular venesections. Familial screening is essential.
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PMID:[Diagnosis and treatment of genetic hemochromatosis]. 1086 97

The edematous states, specifically those in CHF and cirrhosis of the liver, are associated with excessive aldosterone secretion and represent states of secondary hyperaldosteremia. Aldosterone promotes sodium retention by the renal tubules. Spironolactone, first introduced 50 years ago (1953), blocks the action of aldosterone on renal transport of electrolytes, thus acting as an effective diuretic, and in addition, has potentiating effects on other diuretics, including the thiazides. Spironolactone has undesirable side effects that have limited its clinical use; the most significant are impotence, gynecomastia, and hirsutism. Eplerenone, a recently introduced selective ARA, decreases morbidity and mortality in patients with CHF following MI and has none of the androgenic or estrogenic side effects of spironolactone. Eplerenone is an effective alternative for spironolactone.
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PMID:The resurrection of spironolactone on its golden anniversary. 1504 44

We studied the relationship between iron removed by venesection, sex, age, and clinical characteristics in a group of 100 Spanish probands with hereditary hemochromatosis (HH), all C282Y homozygous in the HFE gene. Iron overload was higher in men than in women (P < 0.0001) and increased with age (P = 0.02). Forty-four patients presented with liver disease (28 had fibrosis-cirrhosis of the liver), 24 with diabetes, 18 with arthropathy, and 13/73 men with impotence. No clinical consequences of hemochromatosis were observed in 43 patients. The number of clinical complications was higher in men (P = 0.01) and increased with age (P = 0.006) and with the amount of iron removed (P < 0.0001). The amount of iron removed was significantly higher by univariate analysis in patients with liver disease (P < 0.0001), diabetes (P = 0.007), arthropathy (P = 0.006), and impotence (P = 0.003) than in patients without these complications. In the multivariant analysis, only liver disease maintained a significant relationship with the amount of iron removed (P < 0.0001). Diabetes and arthropathy were closely related with previous liver disease, and impotence appeared mainly in hemochromatosic men with diabetes and alcoholism.
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PMID:The relationship between iron overload and clinical characteristics in a Spanish cohort of 100 C282Y homozygous hemochromatosis patients. 1763 89

Hereditary haemochromatosis (HH) is a disease related to mutations in the HFE gene and can lead to progressive iron accumulation, especially in the liver, eventually resulting in organ damage. We have developed guidelines for the diagnosis and treatment of this disease according to CBO methodology (dutch institute for Healthcare Quality). The prevalence of clinical symptoms such as fatigue, arthropathies, impotence and diabetes mellitus among homozygotes was similar to that in a control population. Nevertheless, we recommend the assessment of serum iron indices when these symptoms remain unexplained. When transferrin saturation is >45% and ferritin exceeds local reference ranges, HFE mutations should be investigated. Homozygosity for the C282Y mutation or combined C282Y/H63d mutation confirms the diagnosis of HFE-related HH. Liver biopsy is recommended when ferritin exceeds 1000 microg/l to establish the presence or absence of cirrhosis, which will affect prognosis and management. iron accumulation confirmed by magnetic resonance imaging (MRI) in the absence of the homozygous C282Y mutation or the combined C282Y/H63d genotype may justify a search for rare hereditary forms of non-HFE HH in a specialised centre. The literature supports the benefits of adequate phlebotomy and the screening of first-degree relatives of index patients with clinically overt HH. overall, the guidelines presented here are to a great extent based on the expert opinion of the working party, as the quantity of evidence that met predefined criteria posed by the evidence-based approach was small. We therefore recommend world-wide efforts to collaboratively address these remaining issues.
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PMID:Synopsis of the Dutch multidisciplinary guideline for the diagnosis and treatment of hereditary haemochromatosis. 1807 69


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