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)

New drugs and advances in molecular biology afford opportunities to upgrade the treatment of autoimmune hepatitis. The aims of this study were to define treatment problems, identify possible solutions, and stimulate investigations to improve patient care. A clinical subcommittee of the International Autoimmune Hepatitis Group reviewed current management difficulties and proposed corrective actions. The assessment of new front-line and salvage therapies for adults and children were given top priority. Cyclosporine and mycophenolate mofetil were endorsed as drugs worthy of rigorous study in severe disease, and budesonide was endorsed for study as front-line therapy in mild disease. Diagnostic criteria and treatment regimens for children required codification, and pharmacokinetic studies were encouraged to develop optimal dosing schedules based on therapeutic ranges. Collaborative efforts were proposed to help understand racial, geographical, and genetic factors affecting outcome and to establish definitions and therapies for variant syndromes and graft dysfunction after transplantation. The development of experimental animal models was deemed essential for the study of site-specific molecular interventions, and gene therapy was endorsed as a means of bolstering reparative processes. In conclusion, evolving pharmacological and technical advances promise to improve the treatment of autoimmune hepatitis, and investigations of these advances are timely, feasible, and necessary.
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PMID:Treatment challenges and investigational opportunities in autoimmune hepatitis. 1569 Apr 85

Drug rash with eosinophilia and systemic symptoms or DRESS syndrome is a distinct severe drug-induced hypersensitivity reaction characterized by skin rash, fever, eosinophilia and visceral involvement. The latter leads to a 10% mortality rate, with interstitial nephritis occurring in about 10% of the cases. The outcome is usually favorable after withdrawal of drug therapy; systemic corticosteroid therapy may hasten the recovery, although there are no data from prospective, randomized trials evaluating the efficacy of this approach. Administration of other immunosuppressive agents (cyclophosphamide, cyclosporine) has also been suggested. We report on a patient with vancomycin-induced DRESS syndrome with acute interstitial nephritis and hepatitis. There was no improvement after withdrawal of the offending agent and empiric corticosteroid use. After tapering the steroids, a five-day course of cyclosporine was followed by quick resolution of the skin rash and recovery of renal function. Cyclosporine could represent a treatment option in cases of severe visceral involvement such as persistent renal insufficiency that do not improve after discontinuation of the offending agent and administration of high doses of steroids.
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PMID:Vancomycin-induced hypersensitivity reaction with acute renal failure: resolution following cyclosporine treatment. 1611 93

Autoimmune hepatitis (AIH) is a progressive inflammatory hepatitis of unknown etiology that is responsive to immunosuppressive therapy. The diagnosis of AIH should be guided by the descriptive criteria and scoring system set forth by the International Autoimmune Hepatitis Group. Standard therapy is prednisone with or without azathioprine (AZA). Combination therapy with prednisone and AZA is preferred, as it allows treatment with lower individual doses of each drug and is thus associated with fewer side effects. Treatment goals include complete biochemical, clinical, and histologic remission. Treatment outcomes include complete remission with or without relapse, incomplete response, or treatment failure. Treatment withdrawal, once remission has been attained, may be associated with relapse of disease. Recurrent relapse may be addressed with long-term, lower dose maintenance treatment with prednisone or AZA. Incomplete response is addressed by attempting high-dose immunosuppressive regimens or by considering investigational medical regimens. Treatment failure is also addressed by considering investigational medical regimens. Medication toxicity is addressed with dose reduction or drug discontinuation. Should the patient progress to decompensated cirrhosis, liver transplantation is an effective treatment for AIH. Calcium and vitamin D supplementation, a well-balanced diet, and exercise are advocated in patients with AIH. Cyclosporine, mycophenolate mofetil, and tacrolimus are promising agents among the new therapies for autoimmune hepatitis. Unfortunately, newer therapeutic agents have been studied in small numbers. Larger, controlled treatment trials are needed to expand the repertoire of therapeutics to treat patients with fewer side effects and to provide alternatives for patients who are refractory to conventional therapy.
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PMID:Autoimmune hepatitis. 1631 66

The treatment of autoimmune hepatitis is evolving as the pathogenic pathways that underlie the disease are defined, new immunosuppressive agents are tested, and site-specific molecular interventions become feasible. Prednisone alone or at a reduced dose combined with azathioprine is the conventional treatment. Patients with HLA genotype DRB1*0301 have a poorer treatment response and a more frequent need for liver transplantation than those with HLA genotype DRB1*0401. Therapy to the point when liver test results and histological findings are normal reduces, but does not eliminate, the occurrence of relapse. Treatment failure warrants reassessment with regard to the accuracy of the original diagnosis and the exclusion of variant forms of hepatitis or concomitant alternative diseases. Ciclosporin might be effective as short-term, front-line therapy in infants and adults, and calcineurin inhibitors might salvage patients who are refractory to corticosteroid regimens. Mycophenolate mofetil can induce an improvement in laboratory test results and reduce the requirement for corticosteroids. Sirolimus is effective for treatment of de novo autoimmune hepatitis that develops after liver transplantation. Synthetic peptides that block autoantigen presentation, cytokine manipulations, oral tolerance regimens, T-cell vaccination, and gene therapy are all interventions that will be able to emerge after a reliable animal model of the human disease has been developed.
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PMID:Current therapy for autoimmune hepatitis. 1740 88

The diagnostic criteria for autoimmune hepatitis have been codified, and a scoring system can quantify the strength of the diagnosis. Centrilobular (zone 3) necrosis signifies acute disease, and severe acute and fulminant presentations of autoimmune hepatitis are recognized. The absence of symptoms at presentation may identify some patients who do not require treatment, but therapeutic decisions must be based on disease activity not symptoms, especially since 26-70% of asymptomatic patients become symptomatic. Elderly patients have more advanced disease at presentation, but they respond well to treatment. Antibodies to soluble liver antigen/liver pancreas, asialoglycoprotein receptor, actin, and liver cytosol type 1 have prognostic value. Molecular mimicry between viral and self-antigens is the likely basis for the autoimmune response. Susceptibility alleles optimize antigen presentation. Polymorphisms influence immunocyte activation, counter-regulatory actions within the cytokine milieu, and apoptotic pathways for hepatocyte and immunocyte death. Perturbations in the populations of T regulatory cells and natural killer T cells disrupt immune homeostasis. Cyclosporine, mycophenolate mofetil, and budesonide afford new treatment opportunities, and molecular interventions at critical pathogenic pathways are feasible, especially within the cytokine network. Confident animal models of the human disease and a collaborative network of clinical investigators are the requisites for progress.
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PMID:Evolving concepts in the diagnosis, pathogenesis and treatment of autoimmune hepatitis. 1741 44

Cyclosporine (CsA) microemulsion has been the mainstay immunosuppressive agent for renal transplant recipients for years. A single daily dosing of cyclosporine (SD) is rarely used. The objective of this study was to evaluate the efficacy of SD versus twice daily dosing of CsA. Retrospective evaluation of SD use was conducted for 44 renal transplant recipients for 12 months (study group). Equal numbers of matched recipients were selected for age, sex, HLA mismatch, donor type, and immunosuppressive regimen (control group). We measured CsA trough (C0) and peak (C2) blood levels, 12-hour CsA profile, and the area under the concentration-time curve (AUC). There were significant differences in C0, C2, and calculated AUC after shifting to SD. In the study group, the mean AUC was 4619 ng/mL/h before versus 6567 ng/mL/h after shifting to SD (P=.004). This became more therapeutic and identical to the mean AUC in the control group, which was 6551 ng/mL/h. Total daily CsA dose was significantly lower in the study group compared with the control group (P<.0001). A significantly higher incidence of hepatitis was observed among the study group (P=.011). There were significantly fewer adverse effects in patients in the study group than the control group. There were no significant differences in graft and patient outcomes between the groups. We concluded that CsA dose should be individualized in renal transplant recipients especially if they have viral hepatitis. SD has the advantage of decreasing dosage and CsA-related adverse effects while maintaining optimal graft function.
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PMID:Single daily dose administration of cyclosporine in renal transplant recipients. 1752 39

Cyclosporin has been used for many years in transplantation, and in this field its role is widely documented. However, other fields of application merit to be investigated, including the role of cyclosporin in treating autoimmune hepatitis and its possible role as an antiviral agent in hepatitis C virus (HCV) infections in both immunocompetent patients and in recipients of orthotopic liver transplants. Cyclosporin A has given promising results in small studies, and experience in transplantation and other immunological disorders indicates that its side-effects can be adequately managed. Cyclosporin certainly deserves further clinical investigation for first-line therapy in autoimmune hepatitis. Cyclosporin A suppresses the HCV genome dose-dependently in vitro at clinically relevant concentrations (150-250 ng/mL). The maximum effect is similar to that obtained with IFN alpha, and the effects of these two agents are certainly additive, and possibly synergistic. The inhibitory action of cyclosporin A appears to be independent upon its immunosuppressive action. Analysis of indirect endpoints in clinical trials on cyclosporin A for immunosuppression in transplant recipients indicates that cyclosporin A treatment can delay recurrence of HCV. Small, open label studies suggest that the observed anti-HCV activity of cyclosporin A can be translated into a real clinical benefit; nevertheless, these findings need to be confirmed in randomized, controlled clinical trials.
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PMID:Cyclosporin in steroid-resistant autoimmune hepatitis and HCV-related liver diseases. 1806 59

This retrospective review presented the prevalence and manifestations of tuberculosis among renal transplant recipients in our center between 1987 and mid 2007. The prevalence of tuberculosis was 5/151 (3.3%) recipients with a median age of 49 years (range = 38-55). The median time of diagnosis after transplantation was 23 months (range = 1-47). All five patients had pulmonary tuberculosis. None developed extrapulmonary infection. Presenting symptoms were fever (60%), productive cough (80%), weight loss (40%), and hemoptysis (20%). One patient had non-parathyroid-related hypercalcemia. Cyclosporine dosage needed to be increased in all patients. Two subjects who experienced side effects of hepatitis and/or jaundice from rifampicin were switched to second-line drugs. Infection with Mycobacterial tuberculosis is a not uncommon problem in renal transplant recipients especially in endemic areas. Tuberculosis must be excluded for immunosuppressed patients with clinical or radiological suspicion.
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PMID:Prevalence and manifestations of tuberculosis in renal transplant recipients: a single-center experience in Thailand. 1879 Feb 40

Autoimmune hepatitis has diverse clinical presentations which complicate its diagnosis and adverse outcomes which demand new treatments. The aims of this review are to indicate the progress that has been made in solving these problems and to illuminate the pathway for additional solutions. Prime source and review articles in English were selected through Medline from 1970-2008 and assimilated into a personal library spanning 31 years. Two diagnostic scoring systems with complementary virtues have been developed that are useful in evaluating patients with confusing features. Acute severe and fulminant presentations require prompt corticosteroid therapy, and coincidental bile duct changes and centrilobular zone 3 necrosis on histological examination do not discount the diagnosis. Cholangio-graphic changes may be present in children and adults with the disease, and antibodies to soluble liver antigen have prognostic value. Autoimmune hepatitis must be considered in patients without autoantibodies and with graft dysfunction after liver transplantation. Asymptomatic patients may not require immediate treatment, and the Model of End Stage Liver Disease identifies problematic patients early. Normal liver tests and tissue constitute the optimal end point of treatment, and the first relapse is an indication for long-term azathioprine therapy. Cyclosporine, tacrolimus and mycophenolate mofetil are promising salvage therapies, and budesonide with azathioprine can be used as frontline treatment in select patients. Progress has been made in the diagnosis and treatment of autoimmune hepatitis, but more work must be done. Multicenter clinical trials are essential before the incorporation of new drugs into the treatment algorithm.
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PMID:Progress in the diagnosis and treatment of autoimmune hepatitis. 1903 54

Autoimmune liver diseases in childhood includes Autoimmune Hepatitis (AIH) and Primary (Autoimmune) Sclerosing Cholangitis (P(A)SC). Both diseases are characterized by a chronic, immune-mediated liver inflammation involving mainly hepatocytes in AIH and bile ducts in PSC. Both diseases, if untreated, lead to liver cirrhosis. AIH could be classified, according to the autoantibodies pattern, into two subtypes: AIH type 1 presents at any age as a chronic liver disease with recurrent flares occasionally leading to liver cirrhosis and liver failure. Characterizing autoantibodies are anti-nuclear (ANA) and anti-smooth muscle (SMA), usually at high titer (>1:100). These autoantibodies are not specific and probably do not play a pathogenic role. AIH type 2 shows a peak of incidence in younger children, however with a fluctuating course. The onset is often as an acute liver failure. Anti-liver kidney microsome autoantibodies type 1 (LKM1) and/or anti-liver cytosol autoantibody (LC1) are typically found in AIH type 2 and these autoantibodies are accounted to have a potential pathogenic role. Diagnosis of AIH is supported by the histological finding of interface hepatitis with massive portal infiltration of mononuclear cells and plasmocytes. Inflammatory bile duct lesions are not unusual and may suggest features of ''overlap'' with P(A)SC. A diagnostic scoring system has been developed mainly for scientific purposes, but his diagnostic role in pediatric age is debated. Conventional treatment with steroids and azathioprine is the milestone of therapy and it is proved effective. Treatment withdrawal however should be attempted only after several years. Cyclosporin A is the alternative drug currently used for AIH and it is effective as steroids. P(A)SC exhibit a peak of incidence in the older child, typically in pre-pubertal age with a slight predominance of male gender. Small bile ducts are always concerned and the histological picture shows either acute cholangitis (bile duct infiltration and destruction) and/or lesions suggesting chronic cholangitis as well (bile duct paucity and/or proliferation, periductal sclerosis). Small bile ducts damage may be associated, at onset or in the following years, with lesions of larger bile ducts with duct wall irregularities, strictures, dilations, and beading resulting in the characteristic ''bead-on-a-string'' appearance. The ''small duct'' (autoimmune) sclerosing cholangitis is also called autoimmune cholangitis. PSC is strictly associated to a particular form of inflammatory bowel disease (IBD) which shows features not typical of ulcerative colitis neither of Crohn's disease. Symptoms related to IBD often are present at onset (abdominal pain, weight loss, bloody stools) but the liver disease is frequently asymptomatic and it may be discovered fortuitously. Treatment of PSC is particularly challenging. In case of ''small duct'' SC or in case of evidence active inflammation on liver biopsy, immunosuppressive treatment is probably useful while in case of large bile ducts non inflammatory sclerosis, immunosuppression is probably uneffective. Ursodeoxycholic acid, however, may leads to an improvement of liver biochemistry even if there's no evidence that it may alter the course of disease. Thus, liver transplantation, is often necessary in the long term follow-up, even with a risk of disease recurrence. In adjunction to these two main disorders, many patients show an''overlap'' disease with features of both AIH and PSC. In such disorders the immune-mediated damage concerns both the hepatocyte and the cholangiocyte with a continuous clinical spectrum from AIH with minimal bile ducts lesions and PSC with portal inflammation and active inflammatory liver damage.
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PMID:Autoimmune diseases of the liver and biliary tract and overlap syndromes in childhood. 1921 8


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