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)

Several lung disorders can occur as a consequence of chronic liver disease. In addition to the common findings of splanchnic and systemic vasodilatation in patients with chronic liver disease, pulmonary vasodilatation may also occur. This "hepatopulmonary syndrome' results in hypoxemia through pulmonary vasodilation and VA/Q mismatch, and in its advanced form leads to significant intrapulmonary arteriovenous shunting. Portal hypertension commonly results in the development of ascites, which may cause a restrictive lung pattern or pleural effusions. Rarely, thrombi formed in congested portal vein branches pass through portosystemic shunts and cause pulmonary hypertension, and plexogenic pulmonary hypertension may also occur in patients with portal hypertension. The autoimmune liver diseases, primary biliary cirrhosis and autoimmune hepatitis, may be accompanied by immune-mediated lung disease. These pulmonary abnormalities represent important extrahepatic manifestations of chronic liver disease.
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PMID:Pulmonary manifestations of chronic liver disease. 865 39

In a retrospective analysis, 18 instances of invasive fungal infections were observed in 512 (3.5%) renal transplant recipients. These included candidiasis (8), aspergillosis (5), cryptococcosis (3) and zygomycosis (2). All patients with candidiasis had Candida isolated from blood and one or more additional sites. One of them had superadded fungaemia with Torulopsis glabrata. Pulmonary disease in four and subcutaneous infection in one were encountered in the five patients with aspergillosis. Central nervous system involvement in two and cutaneous lesion in one were the findings in patients with cryptococcosis. Zygomycosis involved the lung in one and the allograft itself in the other. Prolonged fever not responding to antibacterial drugs was the most common clinical presentation. Fungal infections occurred during the first 4 months in 10 (55.5%) and 12 to 108 months in eight (44.5%) patients. Infections with cytomegalovirus and hepatitis viruses were concommitantly present in 12 (66.7%) and eight (44.5%) patients respectively. Fourteen episodes of fungal infections (77.8%) occurred in live unrelated kidney recipients who formed only 48% of our total transplant population. Nine patients were treated with systemic and/or local amphotericin B and six with amBisome. Fluconazole was administered alone in three and in combination with amphotericin B in two. Fourteen patients died but mortality was only directly attributable to fungal infection in 11. We conclude that invasive fungal infections continue to be an important cause of morbidity and mortality in renal transplant recipients. A high index of suspicion. prompt diagnosis and early institution of specific antifungal therapy are needed.
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PMID:Invasive fungal infections in renal transplant recipients. 888 96

We report four cases of the side effects of minocycline seen during the last two years in our department. There was one case of drug-related lupus and three cases of hypersensitivity reactions, including one eosinophilic pneumopathy with pericarditis, one nephropathy and one severe, pseudo-infectious episode of high fever, rash, lympadenopathy, hepatitis and eosinophilia. Minocycline is a tetracycline agent widely used for acne therapy in France and all over the world. During the last few years, there has been an increasing number of reports concerning systemic adverse reactions to minocycline, with on the one hand auto-immune disorders (lupus, autoimmune hepatitis, vascularitis with ANCA), occurring after a prolonged course of therapy and reported recently in the last few years, and on the other hand, hypersensitivity reactions (eosinophilic pneumopathies, hepatitis, nephropathies, myocarditis, serum sickness or pseudo-infectious reactions), occurring precociously in the course of therapy, and potentially severe. Although these side effects are uncommon in the context of the high number of patients who have been prescribed the drug, the first-line antibiotic therapy in acne must probably be reconsidered.
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PMID:[Systemic reaction induced my minocycline treatment: a report of four patients and a review of the literature]. 1057 23

MRL/lpr mouse is an established animal model which develops autoimmune diseases including glomerulonephritis, sialoadenitis, hepatitis and inflammatory lung disease. Additionally, it has been reported that lpr strains uniquely accumulate CD3+ CD4- CD8- B220+ (double negative, DN) T cells in lymphoid organs leading to lymphadenopathy and splenomegaly. To investigate the role of CD28/CTLA4-B7 pathway in the development of lymphadenopathy and splenomegaly, MRL/lpr mice were treated with soluble form of CTLA4 molecules, CTLA4IgG, which efficiently blocks this pathway. It was demonstrated that (i) the development of DN T cells was independent of the CD28/CTLA4-B7 pathway, (ii) the CD28/CTLA4-B7 pathway was required for the development of lymphadenopathy and splenomegaly, (iii) the CD28/CTLA4-B7 pathway was important for the accumulation of various cell populations in the lymph node and spleen, (iv) composition of the accumulating cell populations was not altered by CTLA4IgG treatment, and (v) activation of conventional T cells and IL-4 production from conventional T cells were the CD28/CTLA4-B7 pathway dependent. Thus, we concluded that the CD28/CTLA4-B7 pathway was required for the development of full-blown lymphadenopathy and splenomegaly in MRL/lpr mice.
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PMID:Involvement of CD28/CTLA4-B7 costimulatory pathway in the development of lymphadenopathy and splenomegaly in MRL/lpr mice. 1067 86

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS syndrome) or the drug hypersensitivity syndrome is a delayed and serious skin disease. It is manifest by a severe skin reaction associated with a severe visceral attack (adenopathy, hepatitis, nephritis, interstitial pneumopathy...) and haematological anomalies (raised hypereosinophilia...). The severe visceral attack is the main cause of death, which is estimated at around 10%. The principal drugs responsible are the aromatic anti-convulsants, sulphamides and minocycline. A large number of cases have been described with phenytoin, more rarely with carbamazepine and phenobarbitone.
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PMID:[The drug hypersensitivity syndrome or DRESS syndrome to phenobarbital]. 1143 97

Deficiency of circulating alpha-1-antitrypsin (AAT) is the most widely recognized abnormality of a proteinase inhibitor that causes lung disease. AAT-deficiency is caused by mutations of the AAT gene that lead to AAT protein retention in the endoplasmic reticulum (ER). Moreover, the mutant AAT accumulated in the ER predisposes the homozygote to severe liver injuries, such as neonatal hepatitis, juvenile cirrhosis, and hepatocellular carcinoma. Despite the fact that mutant AAT protein is subject to ER-associated degradation (ERAD), yeast genetic studies have determined that the ubiquitination machinery, Hrd1/Der3p-cue1p-Ubc7/6p, which plays a prominent role in ERAD, is not involved in degradation of mutant AAT. Here we report that gp78, a ubiquitin ligase (E3) pairing with mammalian Ubc7 for ERAD, ubiquitinates and facilitates degradation of ATZ, the classic deficiency variant of AAT having a Z mutation (Glu 342 Lys). Unexpectedly, gp78 over-expression also significantly increases ATZ solubility. p97/VCP, an AAA ATPase essential for retrotranslocation of misfolded proteins from the ER during ERAD, is involved in gp78-mediated degradation of ATZ. Surprisingly, unlike other ERAD substrates that cause ER stress leading to apoptosis when accumulated in the ER, ATZ, in fact, increases cell proliferation when over-expressed in cells. This effect can be partially inhibited by gp78 over-expression. These data indicate that gp78 assumes multiple unique quality control roles over ATZ, including the facilitation of degradation and inhibition of aggregation of ATZ.
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PMID:Ubiquitin ligase gp78 increases solubility and facilitates degradation of the Z variant of alpha-1-antitrypsin. 1697 36

Alpha-1-antitrypsin deficiency (AATD) is a genetic disorder that manifests as pulmonary emphysema, liver cirrhosis and, rarely, as the skin disease panniculitis, and is characterized by low serum levels of AAT, the main protease inhibitor (PI) in human serum. The prevalence in Western Europe and in the USA is estimated at approximately 1 in 2,500 and 1 : 5,000 newborns, and is highly dependent on the Scandinavian descent within the population. The most common deficiency alleles in North Europe are PI Z and PI S, and the majority of individuals with severe AATD are PI type ZZ. The clinical manifestations may widely vary between patients, ranging from asymptomatic in some to fatal liver or lung disease in others. Type ZZ and SZ AATD are risk factors for the development of respiratory symptoms (dyspnoea, coughing), early onset emphysema, and airflow obstruction early in adult life. Environmental factors such as cigarette smoking, and dust exposure are additional risk factors and have been linked to an accelerated progression of this condition. Type ZZ AATD may also lead to the development of acute or chronic liver disease in childhood or adulthood: prolonged jaundice after birth with conjugated hyperbilirubinemia and abnormal liver enzymes are characteristic clinical signs. Cirrhotic liver failure may occur around age 50. In very rare cases, necrotizing panniculitis and secondary vasculitis may occur. AATD is caused by mutations in the SERPINA1 gene encoding AAT, and is inherited as an autosomal recessive trait. The diagnosis can be established by detection of low serum levels of AAT and isoelectric focusing. Differential diagnoses should exclude bleeding disorders or jaundice, viral infection, hemochromatosis, Wilson's disease and autoimmune hepatitis. For treatment of lung disease, intravenous alpha-1-antitrypsin augmentation therapy, annual flu vaccination and a pneumococcal vaccine every 5 years are recommended. Relief of breathlessness may be obtained with long-acting bronchodilators and inhaled corticosteroids. The end-stage liver and lung disease can be treated by organ transplantation. In AATD patients with cirrhosis, prognosis is generally grave.
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PMID:Hereditary alpha-1-antitrypsin deficiency and its clinical consequences. 1856 11

Reactivation of Herpesviridae is well known among transplant patients, but has not been sufficiently studied in patients who receive immunosuppressive treatment for systemic inflammatory diseases. CMV infection seems relatively rare; it is easily diagnosed by real-time PCR, a fast and reliable diagnostic tool. CMV disease is most often manifested in the form of lung disease, hepatitis, or colitis. The highest risks are associated with steroid or cyclophosphamide boluses and methotrexate. Prophylactic treatment cannot be recommended in clinical practice. The utility of monitoring viremia and of preemptive therapy must be evaluated. Herpes zoster is the most frequent viral infection in systemic diseases. Most immunosuppressive treatments, except methotrexate, promote its occurrence. Visceral involvement is quite rare, and outcome almost always favorable. Prophylactic treatment cannot be recommended.
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PMID:[Cytomegalovirus and other herpes virus infections in systemic diseases]. 1944 98

Alpha(1)-antitrypsin deficiency is characterized by a pathologic reduction of the serum concentration of alpha(1)-antitrypsin, the most important antiprotease in man. It is one of the most common hereditary diseases in Caucasians. Approximately 2% of obstructive airway diseases are caused by alpha(1)-antitrypsin deficiency. Patients above 35 years may develop lung emphysema, especially in the lower lobes. Symptoms are those of chronic obstructive pulmonary disease such as cough, sputum expectoration, and progressive dyspnoea. Patients with homozygous defect often develop cholestatic hepatitis in the neonatal period. However, only few adult patients develop chronic liver disease up to liver cirrhosis with an elevated risk for malignant liver tumors. The diagnostic hallmark is the reduced serum concentration of alpha(1)-antitrypsin while genetic testing proves the defect. An early recognition of the disease is decisive for prophylactic and therapeutic measures. Smoking should be stopped immediately. Treatment of lung disease includes physiotherapy, antiobstructive and antiinflammatory medication, augmentation with human alpha(1)-antitrypsin and lung surgery including lung transplantation. Liver toxins should be avoided. Besides experimental therapeutic approaches, liver disease can only be treated by liver transplantation.
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PMID:[Alpha1-antitrypsin deficiency]. 2013 85

The demographics, immunologic parameters, medical complications, and mortality statistics from 473 subjects with common variable immune deficiency followed over 4 decades in New York were analyzed. Median immunoglobulin levels were IgG, 246 mg/dL; IgA, 8 mg/dL; and IgM, 21 mg/dL; 22.6% had an IgG less than 100 mg/dL. Males were diagnosed earlier (median age, 30 years) than females (median age, 33.5 years; P = .004). Ninety-four percent of patients had a history of infections; 68% also had noninfectious complications: hematologic or organ-specific autoimmunity, 28.6%; chronic lung disease, 28.5%; bronchiectasis, 11.2%; gastrointestinal inflammatory disease, 15.4%; malabsorption, 5.9%; granulomatous disease, 9.7%; liver diseases and hepatitis, 9.1%; lymphoma, 8.2%; or other cancers, 7.0%. Females had higher baseline serum IgM (P = .009) and were more likely to develop lymphoma (P = .04); 19.6% of patients died, a significantly shorter survival than age- and sex-matched population controls (P < .0001). Reduced survival was associated with age at diagnosis, lower baseline IgG, higher IgM, and fewer peripheral B cells. The risk of death was 11 times higher for patients with noninfectious complications (hazard ratio = 10.95; P < .0001). Mortality was associated with lymphoma, any form of hepatitis, functional or structural lung impairment, and gastrointestinal disease with or without malabsorption, but not with bronchiectasis, autoimmunity, other cancers, granulomatous disease, or previous splenectomy.
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PMID:Morbidity and mortality in common variable immune deficiency over 4 decades. 2293 39


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