Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Circular RNAs reminiscent of viroids and the human hepatitis delta virus have been proposed as possible nonconventional pathogens responsible for Crohn's disease and ulcerative colitis, two inflammatory bowel diseases. Consequently, RNA was extracted from various areas of intestinal tissues from individuals with either Crohn's disease or ulcerative colitis as well as several appropriate control diseases, and analyzed by two-dimensional gel electrophoresis. No circular viroid-like RNAs (< 1500 nucleotides) were detected, confirming a previous report that was limited to the investigation of small RNAs (< 300 nucleotides). However, three small, unusually stable, linear RNAs were shown to be associated to both Crohn's disease and ulcerative colitis tissues: a specific 28S ribosomal RNA cleavage product characterized previously; a 5.8S ribosomal RNA conformer; and a fragment homologous to transcripts from DNA CpG islands. The two last RNAs were detected prior to visible morphological tissue alterations, suggesting that they are produced early during the inflammation and that they have value as molecular diagnostic tools for the inflammatory bowel diseases. The potential cellular mechanisms producing these RNAs and their involvement in inflammatory bowel disease are discussed.
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PMID:Characterization of stable RNAs from the resected intestinal tissues of individuals with either Crohn's disease or ulcerative colitis. 959 69

Hypobetalipoproteinemia (HBLP) is characterized by plasma concentrations of apolipoprotein B (apoB) and low density lipoprotein cholesterol (LDL-C) below the fifth percentile. Some forms of HBLP have been shown to be due to truncated forms of apoB-100. A total of 3873 subjects participating in the Framingham Offspring Study had LDL-C levels measured every 4 to 5 years throughout a 25-year period. Seventy-five subjects were identified with persistent HBLP, defined as an LDL-C <70 mg/dL on at least 2 observations, for a prevalence of 1.9% in this population. Compared with subjects with LDL- C >/=70 mg/dL, subjects with HBLP had significantly lower mean levels of total cholesterol, LDL-C, triglyceride, and apoB; higher levels of high density lipoprotein cholesterol; and a higher prevalence of the E2/E3 genotype: 38.7% versus 10.9% (P<0.001). Men with HBLP had a larger mean LDL particle size than did men with an LDL- C >/=70 mg/dL. One individual had a truncated apoB as a cause of HBLP, for a prevalence of 0.03%. Medical causes of HBLP included 2 cases of Crohn's disease, 1 of hemochromatosis, and 1 of hepatitis. Three subjects with HBLP developed coronary heart disease, for an incidence of 4% compared with 5% in those with an LDL- C >/=70 mg/dL (P=NS). The incidence of cancer was 8% in those with HBLP compared with 4% in those with an LDL-C >/=70 mg/dL (P=0.21). In conclusion, a truncated apoB was a rare cause of HBLP, whereas the E2/E3 genotype was a much more common cause. A large prospective study is needed to evaluate the incidence of cancer and atherosclerosis in subjects with HBLP.
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PMID:Frequency of ApoB and ApoE gene mutations as causes of hypobetalipoproteinemia in the framingham offspring population. 981 13

The present study aimed to describe the clinical manifestations of celiac sprue related to malnutrition and to analyze the associations between celiac sprue and other diagnoses. A case-control study compared the occurrence of comorbid diagnoses in case and control subjects with and without celiac sprue, respectively. All patients with a primary or secondary diagnosis of celiac sprue (ICD-579.0) who were discharged from hospitals of the Department of Veterans Affairs between 1986 and 1995 were selected as case subjects. In a multivariate logistic regression analysis, the occurrence of celiac disease served as outcome variable, while age, gender, ethnicity, and the comorbid occurrences of other diagnoses served as predictor variables. A total of 458 individual patients with celiac sprue were identified. The data confirmed the known associations of celiac sprue with dermatitis herpetiformis, lactase deficiency, enlargement of lymph nodes, and lymphoma. Celiac sprue was also found to be statistically significantly associated with pancreatic insufficiency, Crohn's disease, functional bowel symptoms, chronic nonalcoholic hepatitis, and pulmonary eosinophilia. The nutritional manifestations associated with celiac disease included nutritional marasmus, cachexia, weight loss, hypocalcemia, osteoporosis, vitamin B-complex deficiency, and various types of iron- and vitamin-deficiency anemias. The large variety of complex associations clearly indicates that celiac sprue is a systemic disease that involves multiple organs and exceeds an isolated nutritional intolerance to gluten.
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PMID:Celiac sprue among US military veterans: associated disorders and clinical manifestations. 1023 5

Two patients with abnormal liver biochemistry are presented with hepatobiliary disorders rarely described in trisomy 21. The first was considered to have primary sclerosing cholangitis (PSC) and Crohn's disease. Liver biochemistry was normal after six months' treatment with ursodeoxycholic acid and diarrhea resolved after sulfasalazine. The second patient had autoimmune hepatitis that responded to immunosuppression. Autoimmune hepatobiliary disorders, highlighted by this report, occur in trisomy 21 but are rare. A high index of suspicion for these potentially treatable disorders is required.
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PMID:Autoimmune hepatobiliary disease in trisomy 21. 1077 2

The overlap syndrome between autoimmune hepatitis and primary sclerosing cholangitis is a rare condition and only few cases have been published, partly associated with ulcerative colitis, but not with Crohn's disease. We report an autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome in a female patient with Crohn's disease. In addition, a second case of overlap syndrome is reported in a man without inflammatory bowel disease. A 24-year-old woman was referred with a 10-month history of diarrhoea and biochemical changes including elevated serum levels of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and immunoglobulin G. Enzyme linked immunosorbent assay showed that antinuclear autoantibodies were elevated. Immunofluorescence for perinuclear-staining antineutrophil cytoplasmatic antibodies was positive. Diagnostic criteria of definite autoimmune hepatitis according to the International Autoimmune Hepatitis Group were fulfilled. Liver biopsy simultaneously showed criteria of autoimmune hepatitis and primary sclerosing cholangitis. Endoscopic retrograde cholangiography demonstrated features of primary sclerosing cholangitis. Colonoscopy and colonoscopic biopsies indicated an active Crohn's disease affecting the terminal ileum and the ascending and transverse colon. Furthermore, we report the case of a 28-year-old man with known primary sclerosing cholangitis for the previous 6 years, and who developed jaundice and a marked increase of aspartate aminotransferase, alanine aminotransferase and immunoglobulin G, leading to the diagnosis of definite autoimmune hepatitis. A review of the literature revealed only 16 cases of an autoimmune hepatitis/primary sclerosing cholangitis syndrome in patients without inflammatory bowel disease or in association with ulcerative colitis. We report two additional cases, one case showing an association with Crohn's disease.
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PMID:Overlap syndrome between autoimmune hepatitis and primary sclerosing cholangitis in two cases. 1083 1

Despite limited understanding of therapeutic aetiopathogenesis of ulcerative colitis and Crohn's disease, there is a strong evidence base for the efficacy of pharmacological and biological therapies. It is equally important to recognise toxicity of the medical armamentarium for inflammatory bowel disease (IBD). Sulfasalazine consists of sulfapyridine linked to 5-aminosalicylic acid (5-ASA) via an azo bond. Common adverse effects related to sulfapyridine 'intolerance' include headache, nausea, anorexia, and malaise. Other allergic or toxic adverse effects include fever, rash, haemolytic anaemia, hepatitis, pancreatitis, paradoxical worsening of colitis, and reversible sperm abnormalities. The newer 5-ASA agents were developed to deliver the active ingredient of sulfasalazine while minimising adverse effects. Adverse effects are infrequent but may include nausea, dyspepsia and headache. Olsalazine may cause a secretory diarrhoea. Uncommon hypersensitivity reactions, including worsening of colitis, pancreatitis, pericarditis and nephritis, have also been reported. Corticosteroids are commonly prescribed for treatment of moderate to severe IBD. Despite short term efficacy, corticosteroids have numerous adverse effects that preclude their long term use. Adverse effects include acne, fluid retention, fat redistribution, hypertension, hyperglycaemia, psycho-neurological disturbances, cataracts, adrenal suppression, growth failure in children, and osteonecrosis. Newer corticosteroid preparations offer potential for targeted therapy and less corticosteroid-related adverse effects. Azathioprine and mercaptopurine are associated with pancreatitis in 3 to 15% of patients that resolves upon drug cessation. Bone marrow suppression is dose related and may be delayed. The adverse effects of methotrexate include nausea, leucopenia and, rarely, hypersensitivity pneumonia or hepatic fibrosis. Common adverse effects of cyclosporin include nephrotoxicity, hypertension, headache, gingival hyperplasia, hyperkalaemia, paresthesias, and tremors. These adverse effects usually abate with dose reduction or cessation of therapy. Seizures and opportunistic infections have also been reported. Antibacterials are commonly employed as primary therapy for Crohn's disease. Common adverse effects of metronidazole include nausea and a metallic taste. Peripheral neuropathy can occur with prolonged administration. Ciprofloxacin and other antibacterials may be beneficial in those intolerant to metronidazole. Newer immunosuppressive agents previously reserved for transplant recipients are under investigation for IBD. Tacrolimus has an adverse effect profile similar to cyclosporin, and may cause renal insufficiency. Mycophenolate mofetil, a purine synthesis inhibitor, has primarily gastrointestinal adverse effects. Biological agents targeting specific sites in the immunoinflammatory cascade are now available to treat IBD. Infliximab, a chimeric antibody targeting tumour necrosis factor-or has been well tolerated in clinical trials and early postmarketing experience. Additional trials are needed to assess long term adverse effects.
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PMID:Comparative tolerability of treatments for inflammatory bowel disease. 1108 48

Azathioprine-related side-effects occur in about 15% of treated patients. Liver toxicity is a rare complication of this drug, but is considered, in most cases, a contraindication to the continuation of treatment. However, abnormal liver tests may occur in patients under azathioprine treatment also due to infections. The distinction between toxic and infective causes of abnormal liver tests is important in order to identify patients that can be rechallenged with the drug. Cytomegalovirus infection is common in immunosuppressed transplant recipients, while the incidence is lower in patients with inflammatory bowel disease treated with immunosuppressive drugs. To our knowledge, only 2 cases of cytomegalovirus hepatitis occurring during azathioprine treatment for Crohn's disease had been reported so far. Here, we describe two patients who experienced mild hepatitis associated with the onset of cytomegalovirus infection during azathioprine treatment. The infection was documented by the appearance of IgM anti cytomegalovirus. Both cases were self-limiting. In one of the 2 patients, azathioprine was given again after resolution of the hepatitis with good control of Crohn's disease and without other complications. We also retrospectively evaluated the incidence of liver abnormalities assessed by blood tests in 58 consecutive patients with Crohn's disease treated with azathioprine at our institution. Abnormal results were obtained in 8 out of these 58 patients, requiring discontinuation of the drug in 3 patients, two of whom were the cytomegalovirus cases described above.
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PMID:Hepatitis related to cytomegalovirus infection in two patients with Crohn's disease treated with azathioprine. 1114 64

Galectin-3, a member of beta-galactoside-binding lectins, is expressed and secreted by a variety of cell types including human intestinal epithelial cells. The presence of anti-galectin-3 antibody in the sera of patients was analyzed by immunoblotting using recombinant human galectin-3. A substantially higher percentage of sera from Crohn's disease patients contained anti-galectin-3 IgG autoantibodies than from patients with ulcerative colitis, primary biliary cirrhosis, or autoimmune hepatitis and of apparently healthy control volunteers. In Crohn's disease patients the titer of autoantibodies was high and interestingly correlated negatively with disease activity. To characterize and generate artificial epitopes (mimotopes), the anti-galectin-3 monoclonal antibodies A3A12 and B2C10 were used for biopannings of phage display nonapeptide libraries. These mimotopes interfered with the binding of autoantibodies to recombinant and native intestinal epithelial galectin-3. Our data may suggest that galectin-3 mimotopes could be used for the induction of IgG with desired specificity to regulate immune responses in Crohn's disease patients.
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PMID:Anti-Galectin-3 IgG autoantibodies in patients with Crohn's disease characterized by means of phage display peptide libraries. 1172 7

Patients with Crohn's disease (CD) are at higher risk of hepatitis C (HCV) and B virus (HBV) infection, because of surgical and/or endoscopic procedures. However, the prevalence of HCV and HBV infection in CD is unknown. This issue may be relevant because of the growing use of immunomodulatory drugs in CD. The purpose of this study was to assess, in a multicenter study, the prevalence and risk factors of HCV and HBV infection in CD. The effect of immunomodulatory drugs for CD on the clinical course of hepatitis virus infections and of interferon-alpha (IFN-alpha) on the course of CD was examined in a small number of patients. Sera from 332 patients with CD and 374 control subjects (C) were tested for the following: hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), HBcAb, HBeAg, HBeAb, anti-HCV, and HCV-RNA. An additional 162 patients with ulcerative colitis (UC) were tested as a disease control group. Risk factors were assessed by multivariate statistical analysis. Infection by either HCV or HBV was detected in 24.7% of patients with CD. In the age groups younger than 50 years, HCV prevalence was higher in CD than in C (p = 0.01). HCV infection in CD was associated with surgery (OR 1.71; 95% CI 1.00-2.93; p = 0.04), blood transfusions (OR 3.39; 95% CI 1.04-11.04; p = 0.04), and age (OR 2.3; 95% CI 1.61-3.56; p < 0.001). The event CD-related surgery appeared to be the main risk factor for HCV infection in CD. HCV prevalence was higher in CD (7.4%) than in UC (0.6%) (p = 0.001). HBcAb positivity was higher in CD (10.9%) and UC (11.5%) than in C (5.1%) (CD vs. C: p = 0.016; UC vs. C: p = 0.02), associated with age (OR 2.08; 95% CI 1.37-3.17; p = 0.001) and female gender (OR 2.68; 95% CI 1.37-3.17; p = 0.001) in CD and to UC duration (OR 1.20; 95% CI 1.06-1.36; p = 0.002). Immunomodulatory drugs did not influence the course of HBV or HCV infection in seven patients with CD, and IFN-alpha for chronic hepatitis C did not affect CD activity in six patients with CD. It is concluded that HBV prevalence is higher in CD than in C at all ages, whereas HCV prevalence is increased in young patients with CD, because of a greater need for surgery. The higher HCV (but not HBV) prevalence in CD than in UC suggests that the host immune response may influence the risk of HCV infection. Although a relatively high proportion of patients with CD showed HBV and/or HCV infections, this should not influence treatment strategies for CD.
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PMID:Hepatitis B and C virus infection in Crohn's disease. 1172 Mar 17

Our experience regarding serum soluble interleukin-2 receptor (sIL-2R) measurement as a marker of lymphocyte activation consists of patients with autoimmune disease: 37 with systemic lupus erythematosus (SLE), 23 with autoimmune hepatitis (AIH), 74 with inflammatory bowel disease and six with Wegener's granulomatosis (WG). The influence of immunosuppressive therapy has also been assessed. Serum sIL-2R in SLE is significantly higher than in healthy controls and good correlation is found between sIL-2R and disease activity. Severity of kidney inflammation in lupus nephritis can be reflected by the increased excretion of sIL-2R. It was found that sIL-2R level significantly falls when the disease becomes clinically inactive after immunosuppressive therapy, but in many cases (up to 50%) it does not reach normal levels. The last finding suggests that lymphocyte activation may still be present even though the disease is considered inactive under clinical criteria and support the need of prolonged immunosuppression after the first signs of remission. In AIH the serum levels of sIL-2R are elevated in all patients with active disease; all cases with "highly active" disease have significantly higher concentrations than patients with "mild activity". A good correlation has been demonstrated between elevated serum sIL-2R values and anti-asialoglycoprotein receptor (ASGPR) titer (the specific marker of AIH). The follow-up study showed a significant decrease of both sIL-2R levels and anti-ASGPR titer after 3-9 month immunosuppressive therapy. The findings support that sIL-2R and anti-ASGPR titer could serve as reliable humoral markers for disease-specific activity. Compared with inactive ulcerative colitis (UC) and Crohn's disease (CD), significantly higher levels of sIL-2R were present in the serum of patients with active disease, and in inactive disease than in healthy age-matched controls. Methotrexate (MTX) therapy of patients with refractory UC resulted in sIL-2R decrease at the end of therapeutic period (20 i.m. injections of once a week 25 mg), good responders showing > 50% decrease even at 5-7 weeks of treatment. Serum sIL-2R is elevated in all six patients with WG. Contrary to anti-neutrophil cytoplasmic antibodies (ANCA), sIL-2R remains elevated above cut-off for normal range, despite clinical improvement following immunosuppressive treatment. The last observation suggests that serum sIL-2R is not a good measure of the disease activity and argue for the need of longer immunosuppressive therapy just after the first days of clinical remission.
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PMID:Serum soluble IL-2 receptor as a marker of lymphocyte activation in some autoimmune diseases. Effect of immunosuppressive therapy. 1216 73


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