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)

Ninety-two British, caucasian, alcoholic patients with liver disese were grouped on the basis of hepatic histology into fatty change, hepatitis with or without cirrhosis, and cirrhosis alone. Men with alcoholic hepatitis with or without cirrhosis showed an increased incidence of the histocompatibility antigen HLA-B8 (P less than 0.02). Increased measles antibody titres were found in patients without cirrhosis with or without hepatitis and were associated with the B8 phenotype in both sexes. Rubella antibody titres and percentage DNA-binding were raised in patients with cirrhosis and showed no association with the B8 phenotype. Concentrations of IgM and IgA were were raised in patients with stetosis and with hepatitis, while in patients with cirrhosis IgG concentrations were also increased. Low titres of autoantibodies were found in all histological groups. It is possible that the development of hepatitis in response to alcohol abuse may be influenced, at least in men, by a gene linked to the B locus. Otherwise, immune processes associated with alcohol-related liver disease are probably secondary phenomena.
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PMID:HLA-B8, immunoglobulins, and antibody responses in alcohol-related liver disease. 740 Mar 47

The pharmacokinetics and therapeutic efficacy of praziquantel (Distocide; Epico, El-Asher-Men-Ramadan City, Egypt) were studied in 40 patients with schistosomiasis mansoni and various degrees of hepatic dysfunction. The patients were allocated into four groups: the first included 10 patients with simple active schistosomiasis while the other three were made up of patients with schistosomiasis associated with liver cirrhosis and splenomegaly according to Child's classification of hepatocellular function. Every patient was treated with 40 mg/kg of praziquantel as a single oral dose. The efficacy of the drug was evaluated after two months by rectal snip examination. The pharmacokinetic parameters did not differ significantly between patients with simple active schistosomiasis (group 1) and those with hepatosplenomegaly with liver involvement but without ascites and jaundice (group 2). However, as liver cell dysfunction became more evident (groups 3 and 4), pharmacokinetic parameters of praziquantel such as the half-life of elimination, the half-life of absorption, the maximum concentration, the time to maximum concentration, and the area under the concentration-time curve increased proportional to the degree of hepatic insufficiency. Linear correlations were found between each of the these parameters on the one hand and hepatic function test results (total bilirubin, direct bilirubin, and serum albumin) on the other. In spite of these pharmacokinetic differences, the cure rates were 70%, 80%, 90%, and 90% in the four groups, respectively. Although the incidence of side effects was high (53%), such effects were transient and mild.
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PMID:Clinical and pharmacokinetic study of praziquantel in Egyptian schistosomiasis patients with and without liver cell failure. 781 Aug 16

There has been controversy over the relationship between alcohol consumption and related problems amongst the Irish in England. Irish migrants have high Standardised Mortality Ratios for chronic liver disease and cirrhosis and high hospital admission rates for alcohol-related diagnoses in England. Yet it has been considered that people from the Republic of Ireland, whether living in Ireland (Conniffe et al., 1990) or in England (Pearson et al., 1991), actually drink less than the English. This paper reviews the evidence. In recent years Irish per capita volume alcohol consumption has been comparable to that of the U.K., although the distribution of consumption differs. Women in Ireland are less likely to drink than women in England and Wales, while men in Ireland are more likely to drink at high-risk levels than men in England and Wales: their average weekly consumption levels are closer to those of high-consuming men in Yorkshire and Humberside, who also drink more than the U.K. national average. Men in Ireland also appear to be more likely to experience drinking problems than their counterparts in England and Wales, although this may be related to factors other than the total amount of alcohol consumed. Although a previous study of General Household Survey data indicated low-risk alcohol consumption levels for people from the Irish Republic living in Britain, a reanalysis of these data adjusting for age and gender shows drinking rates that are very high.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Consumption and harm: drinking patterns of the Irish, the English and the Irish in England. 814 80

Factors influencing the progression of liver disease and the development of hepatocellular carcinoma (HCC) in chronic hepatitis C virus (HCV) infection are poorly understood. Inherited variations of drug-metabolizing enzyme (DME) activities may affect liver damage and cancer risk by modifying individual susceptibility to endogenous or exogenous toxic compounds. We investigated the association of liver disease severity with common alleles of microsomal epoxide hydrolase (mEH), an enzyme involved in the metabolism of highly reactive epoxide intermediates. Three polymorphisms (Tyr113His, His139Arg, and -613C/T) were analyzed by polymerase chain reaction (PCR) restriction fragment length polymorphisms (RFLPs) in 394 patients at different stages of disease, including 92 asymptomatic carriers, 109 patients with chronic hepatitis, 100 patients with cirrhosis, and 93 patients with HCC. Reference allele frequencies were obtained from 99 healthy blood donors. Allele distributions between categories were compared using the chi(2) test; odds ratios (ORs) and 95% CI were calculated to express relative risks. Allele frequencies among 99 healthy controls were as follows: 15.1% for 113His/His, 4.0% for 139Arg/Arg, and 46.5% for -613C/T. mEH 113His/His homozygotes were overrepresented in advanced stages of disease, in particular among HCC patients (27.9%; P =.03; OR, 2.2; 95% CI, 1.0-4.6). Differences were more pronounced among men and between extreme patient categories. When mEH genotypes were combined to express a metabolic phenotype, very slow metabolizers were highly prevalent among cirrhotic and HCC patients (18% vs. 3.3% in carriers; P <.001). In conclusion, mEH gene polymorphisms were significantly associated with HCV-related liver disease severity and HCC risk. Men were at higher risk than women; this might be explained by hormonal regulation of gene expression or by differential exposure to environmental toxins.
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PMID:Polymorphisms of microsomal epoxide hydrolase gene and severity of HCV-related liver disease. 1208 65

One third of patients with cystic fibrosis are adults. The respiratory disease, which conditions the vital prognosis, consists of bronchiectasis with chronic bronchial infection and bursts of acute infection, leading to respiratory insufficiency. Pseudomonas aeruginosa is the most frequent bacteria in adulthood. Exocrine pancreatic insufficiency is associated in 80% of patients. Some complications, such as diabetes, hepatic cirrhosis or osteoporosis, are more frequent in adults. Treatment is based on chest physiotherapy and antibiotics with intravenous courses when there is a colonisation with P. aeruginosa. Pregnancy can be considered in women when respiratory and nutritional status is acceptable. Men are sterile because of congenital bilateral atresia of vas deferens, but can be proposed medical assistance for procreation.
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PMID:[Cystic fibrosis in adults]. 1266 47

Early esophageal squamous cell carcinoma detected by esophageal iodine staining can be easily treated by endoscopic mucosectomy, and identifying its predictors is important in better selecting candidates to screen for this high-mortality cancer. The common etiologies of elevated mean corpuscular volume (MCV) and esophageal cancer, including folate deficiency, smoking, drinking and high acetaldehyde exposure, suggest testing MCV as such a predictor. Japanese alcoholic men with (n = 65) and without (n = 206) esophageal squamous cell carcinomas, excluding those with liver cirrhosis, were assessed for MCV within 7 days of their last drink, alone or in combination with findings from either the alcohol flushing questionnaire or genotyping to identify inactive aldehyde dehydrogenase-2 (ALDH2*1/2*2) and the less-active form of alcohol dehydrogenase-2 (ADH2*1/2*1), which pose risks for esophageal squamous cell carcinoma. MCV was higher in cancer patients than in the control group. MCV was higher in both groups in those who were heavier smokers, had lower body mass index (BMI), experienced alcohol flushing, and had ALDH2*1/2*2. After adjusting for age, drinking and smoking habits, BMI and ALDH2/ADH2 genotypes, macrocytosis of MCV > or =106 fl was associated with increased risk for esophageal cancer (OR = 2.75). Men with both MCV > or =106 fl and alcohol flushing had an even higher cancer risk (OR = 5.51). The combinations of MCV > or =106 fl with ALDH2*1/2*2 or ADH2*1/2*1 alone, and both ALDH2*1/2*2 and ADH2*1/2*1 (ORs = 11.44, 21.22 and 319.7, respectively) showed consistently higher risk than the corresponding group with MCV <106 fl (ORs = 7.24, 4.71 and 27.01, respectively). In conclusion, MCV measurement, alone or in combination with the markers of alcohol sensitivity, provides a new means of predicting risk for esophageal squamous cell carcinoma in Japanese alcoholic men.
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PMID:Macrocytosis, a new predictor for esophageal squamous cell carcinoma in Japanese alcoholic men. 1294 54

Hepatitis C virus (HCV) infections pose a growing challenge to health care systems. Although chronic HCV infection begins as an asymptomatic condition with few short-term effects, it can progress to cirrhosis, hepatic decompensation, hepatocellular carcinoma (HCC), and death. The rate of new HCV infections is decreasing, yet the number of infected people with complications of the disease is increasing. In the United States, people born between 1945 and 1964 (baby boomers) are developing more complications of infection. Men and African Americans have a higher prevalence of HCV infection. Progression of fibrosis can be accelerated by factors such as older age, duration of HCV infection, sex, and alcohol intake. Furthermore, insulin resistance can cause hepatic steatosis and is associated with fibrosis progression and inflammation. If more effective therapies are not adopted for HCV, more than 1 million patients could develop HCV-related cirrhosis, hepatic decompensation, or HCC by 2020, which will impact the US health care system. It is important to recognize the impact of HCV on liver disease progression and apply new therapeutic strategies.
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PMID:Prevalence and challenges of liver diseases in patients with chronic hepatitis C virus infection. 2071 78

Hereditary hemochromatosis is an autosomal recessive disorder that disrupts the body's regulation of iron. It is the most common genetic disease in whites. Men have a 24-fold increased rate of iron-overload disease compared with women. Persons who are homozygous for the HFE gene mutation C282Y comprise 85 to 90 percent of phenotypically affected persons. End-organ damage or clinical manifestations of hereditary hemochromatosis occur in approximately 10 percent of persons homozygous for C282Y. Symptoms of hereditary hemochromatosis are nonspecific and typically absent in the early stages. If present, symptoms may include weakness, lethargy, arthralgias, and impotence. Later manifestations include arthralgias, osteoporosis, cirrhosis, hepatocellular cancer, cardiomyopathy, dysrhythmia, diabetes mellitus, and hypogonadism. Diagnosis requires confirmation of increased serum ferritin levels and transferrin saturation, with or without symptoms. Subtyping is based on genotypic expression. Serum ferritin measurement is the most useful prognostic indicator of disease severity. Liver biopsy is performed to stage the degree of fibrosis with severe ferritin elevation or transaminitis, or to diagnose nonclassical hereditary hemochromatosis in patients with other genetic defects. Treatment of hereditary hemochromatosis requires phlebotomy, and the frequency is guided by serial measurements of serum ferritin levels and transferrin saturation. Iron avidity can result from overtreatment. If iron avidity is not suspected, it may mimic undertreatment with persistently elevated transferrin saturation. Dietary modification is generally unnecessary. Universal screening for hereditary hemochromatosis is not recommended, but testing should be performed in first-degree relatives of patients with classical HFE-related hemochromatosis, those with evidence of active liver disease, and patients with abnormal iron study results. Screening for hepatocellular carcinoma is reserved for those with hereditary hemochromatosis and cirrhosis.
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PMID:Hereditary hemochromatosis. 2341 62

Malnutrition in the cirrhotic patient is associated to a higher morbidity and mortality rate; however, the diagnosis is complex, so the study objective was to assess the nutritional status using different methods. Adult patients with alcoholic liver cirrhosis treated in the Liver Clinic of the Mexico's General Hospital were evaluated. Anthropometric measurements and a 24 hours recall were made; screening tools (Malnutrition Universal Screening Tool, Nutritional Risk Screening-2002) and a method for assessing nutritional status specifically in cirrhotic patients (Royal Free Hospital Global Assessment) were used. We included 62 patients, 51.6% of them were men. Malnutrition by arm muscle area was 31.3% in men and 10% in women, and by arm fat area was 23.3% in women and 3.1% in men (p < 0.05). With the screening tools the percentages of malnutrition risk were 43.5% and 54.8% respectively, vs. 1.6% identified as "low weight" with the Body Mass Index. With the Royal Free Hospital Global Assessment tool the percentage of malnutrition was 45.2%. Patients with malnutrition had an energy and protein intake significantly lower than the well-nourished: 19.7 kcal/kg and 0.89 g/kg vs 30 kcal/kg and 1.25 g/kg (p < 0.005). Malnutrition is a common complication in patients with liver cirrhosis. Men have higher depletion of muscle mass and women a higher loss of body fat. The Body Mass Index is not a reliable tool for assessing malnutrition. It's advisable to use tools with indicators of body composition such as the Royal Free Hospital Global Assessment.
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PMID:[Nutritional assessment of alcoholic liver cirrhotic patients treated in the liver Clinic of the Mexico's General Hospital]. 2358 52

The majority of hepatocellular carcinomas arise in background chronic liver disease, particularly cirrhosis. The pathogenesis of noncirrhotic hepatocellular carcinomas remains unclear. While malignant transformation reportedly occurs in <15% of hepatocellular adenoma, the prevalence of noncirrhotic hepatocellular carcinomas arising from a pre-existing adenoma is a challenge to study. Cirrhotic hepatocellular carcinoma and hepatocellular adenoma may be subclassified by molecular pathways, but little is known in noncirrhotic hepatocellular carcinoma. We aim to delineate clinical, morphologic and immunohistochemical features of noncirrhotic hepatocellular carcinoma to evaluate for possible derivation from hepatocellular adenoma. We evaluated the clinicopathologic features of 74 noncirrhotic hepatocellular carcinomas from 72 patients for underlying clinical conditions and immunohistochemical markers known to be associated with hepatocellular adenoma. Men were more commonly affected (59%); however, in the <50-year-old group, women predominated (8:1). The age range was wide: 18-83 years; median-64 years. Underlying liver diseases were identified in only 7%; however, 25% had diabetes mellitus, 69% were overweight or obese and 58% had metabolic syndrome. Only 50% of the noncirrhotic hepatocellular carcinoma were encapsulated. As published in hepatocellular adenoma, multifocality and larger tumor size were more common in liver fatty acid-binding protein-negative noncirrhotic hepatocellular carcinoma. Beta-catenin nuclear positivity was uncommon (5%), and was restricted to hepatocellular carcinomas in older men. Serum amyloid A positivity was not restricted to any subtype. In summary, we present the largest series to date examining noncirrhotic hepatocellular carcinoma. We evaluated these with current hepatocellular adenoma subclassification markers for possible associations. Thirty percent of the 74 noncirrhotic hepatocellular carcinoma had some clinical, morphological or immunophenotypical associations currently described in hepatocellular adenoma. Our data also confirm the association of noncirrhotic hepatocellular carcinoma in middle-aged to elderly men, an association with metabolic syndrome, and, as with hepatocellular adenoma, that women predominated in the noncirrhotic hepatocellular carcinoma subjects <50 years of age.
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PMID:Noncirrhotic hepatocellular carcinoma: derivation from hepatocellular adenoma? Clinicopathologic analysis. 2405 94


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