pulmicort and Hepatitis--Autoimmune

The gold-standard treatment for autoimmune hepatitis (AIH) is a prednisone/azathioprine combination. However, subgroups of patients may be unresponsive to this treatment. The aim of this study is to evaluate the efficacy of second-line immunosuppressive therapies for AIH through a systematic review and meta-analysis in adult patients.. The systematic review was registered at the PROSPERO platform under number 42015019831. Databases MEDLINE (PubMed), Lilacs, Cochrane, and Scielo were searched. The keywords used were 'Hepatitis, Autoimmune' and descriptors terms (MeSH and DeCS). These terms were linked with each immunosuppressant of interest.. A total of 1532 studies were identified. Of these, 1492 were excluded on the basis of title and abstract reading. Among the 40 studies retrieved for detailed full-text analysis, a total of 15 fulfilled the inclusion criteria for the analysis. The most studied second-line immunosuppressive was mycophenolate mofetil (MM). The mean reduction of aminotransferases was observed in 94.3% with tacrolimus/prednisone, 91.3% for cyclosporine/prednisone, 85.5% for budesonide, and 78.7% MM/prednisone. For MM/prednisone, the mean rate of histological remission was 88.6%, liver transplantation was indicated in 11.4%, and the mortality rate was 7.2%. Limitations were also present, such as the lack of randomized-controlled trials and prospective studies, the small number of patients, and the heterogeneity between remission criteria.. This is the first systematic review and meta-analysis to compare the second-line imunossupressant therapy for AIH. The most studied second-line immunosuppressive is the MM, with a reasonable histological remission. The use of combined tacrolimus/prednisone was the most effective for the normalization of aminotransferases.

Topics: Anti-Inflammatory Agents; Budesonide; Cyclophosphamide; Drug Therapy, Combination; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Mycophenolic Acid; Prednisone; Retreatment; Tacrolimus

In this study, a meta-analysis of randomized controlled trials comparing ursodeoxycholic acid (UDCA) monotherapy with combination therapies utilizing UDCA and budesonide was performed. We found that combination therapy with UDCA and budesonide was more effective than UDCA monotherapy for primary biliary cirrhosis-autoimmune hepatitis overlap syndrome. Moreover, compared to prednisone, budesonide has fewer side effects.

Topics: Budesonide; Chi-Square Distribution; Cholagogues and Choleretics; Drug Therapy, Combination; Glucocorticoids; Hepatitis, Autoimmune; Humans; Liver Cirrhosis, Biliary; Odds Ratio; Randomized Controlled Trials as Topic; Syndrome; Treatment Outcome; Ursodeoxycholic Acid

Topics: Budesonide; Hepatitis, Autoimmune; Humans; Liver; Liver Transplantation; Standard of Care; Treatment Failure

Corticosteroids alone or in combination with azathioprine are the mainstay therapies of autoimmune hepatitis. Suboptimal responses (treatment failure, partial response, drug toxicity), frequent relapse after drug withdrawal, and the emergence of alternative immunosuppressive medications have fueled the pursuit of new treatments. The goals of this review are to present current management strategies and evolving interventions.. PubMed searches from 1970 - 2014 provide the bases for this review. Corticosteroid regimens should be administered until resolution of symptoms, laboratory tests, and liver tissue abnormalities. Treatment failure warrants high doses of the original regimen, and relapse warrants re-treatment followed by long-term maintenance with azathioprine. The calcineurin inhibitors, budesonide, and mycophenolate mofetil are evolving as frontline therapies, and they may be considered as salvage therapies with the exception of budesonide. Rapamycin, rituximab, and infliximab have also rescued refractory patients but experiences are limited. Anti-oxidants, recombinant molecules, mAbs, and modulators of critical cell populations are key prospects.. Autoimmune hepatitis must be managed by multiple medications that supplement or supplant current regimens depending on the clinical situation. Rescue therapies will emerge as adjunctive interventions to minimize tissue damage (prevent fibrosis and hepatocyte apoptosis) and improve immune tolerance (regulatory T cell manipulations).

Topics: Adrenal Cortex Hormones; Animals; Antibodies, Monoclonal, Murine-Derived; Azathioprine; Budesonide; Hepatitis, Autoimmune; Humans; Immunologic Factors; Immunosuppressive Agents; Liver; Mycophenolic Acid; Rituximab; Salvage Therapy; Sirolimus

Autoimmune hepatitis is chronic liver disease with two subtypes, type 1 with anti nuclear or smooth muscle antibodies and type 2 with LKM1 or LC1 antibodies, and both with hypergammaglobulinemia and typical histology. Prevalence of AIH is between 10 to 17 per 100000 in Europe. Up to 20-40 % of cases present with acute hepatitis. Budesonide can be used as a first line induction therapy in non-cirrhotic patients, and tiopurines, mercaptopurine or mycophenolic acid as maintenance therapies. Patients not responding to conventional therapy can be treated with ciclosporin, tacrolimus or rituximab or finally with liver transplantation.

Topics: Budesonide; Europe; Glucocorticoids; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Liver Transplantation; Prevalence

The aim of the present study was to assess the efficacy and tolerability of budesonide as an alternative first line treatment option for autoimmune hepatitis (AIH) and the overlap syndrome.. A total of 18 AIH or overlap syndrome patients were evaluated. Outcomes of treatment by the end of the study were defined as treatment failure, partial response, complete response and remission.. Complete response and remission were achieved in 61.1% (11/18) of patients, while 38.9% (7/18) of patients were considered treatment failures. Liver fibrosis was observed in 55.5% of patients' biopsies. More patients with liver fibrosis failed to respond to treatment compared to patients without fibrosis, a difference bordering on statistical significance (60% vs. 12.5%; p=0.066). Although statistically insignificant, the presence of at least one side effect was observed more frequently in patients with fibrosis compared to those without fibrosis (80% vs. 37.5%; p=0.145). Overall, side effects occurred significantly more commonly in non-responders than responders (100% vs. 36%; p=0.013).. Budesonide is an effective treatment option for the management of AIH, with a low incidence of side effects in patients without findings of advanced liver disease. The presence of liver fibrosis may increase the likelihood of treatment failure as well as the risk of developing side effects. Our study findings suggest that budesonide may be effective in a select group of AIH patients. Further studies are needed to determine its exact place for the treatment of AIH and overlap syndrome.

Topics: Adult; Aged; Budesonide; Female; Glucocorticoids; Hepatitis, Autoimmune; Humans; Liver Cirrhosis; Male; Middle Aged; Treatment Outcome; Young Adult

Nonstandard drugs that target critical pathogenic pathways or immune regulatory mechanisms constitute the next generation of treatments for autoimmune hepatitis. Mycophenolate mofetil impairs the proliferation of lymphocytes, decreases autoantibody production, and induces apoptosis of activated immunocytes. Patients treated for azathioprine intolerance improve more frequently than patients treated for refractory liver disease (54% versus 10%), and mycophenolate mofetil is emerging as a rescue therapy for this population. Complete corticosteroid withdrawal is possible in 40% of patients treated with mycophenolate mofetil, and the frequency of side effects ranges from 3-34%. Budesonide in combination with azathioprine has normalized liver tests more frequently (47% versus 18%) and with fewer side effects (28% versus 53%) than standard therapy after 6 months. Budesonide is emerging as a frontline treatment in non-cirrhotic patients with uncomplicated disease or contraindications to conventional corticosteroids. Cyclosporine and tacrolimus are effective salvage agents for steroid-refractory disease, but side effects have been common and occasionally serious. The 6- thioguanine nucleotides and rapamycin are feasible treatments for autoimmune hepatitis, but 6-thioguanine has major obstacles to overcome, especially the risk of liver toxicity or nodular regenerative hyperplasia. The nonstandard drug therapies emerging for autoimmune hepatitis reflect the need to supplement or supplant current treatment regimens. None has been licensed for use in autoimmune hepatitis, and their applications have been based on results from small singlecenter experiences.

Topics: Animals; Budesonide; Cyclosporine; Drug Discovery; Hepatitis, Autoimmune; Humans; Immunosuppression Therapy; Mycophenolic Acid; Tacrolimus; Thioguanine

Autoimmune hepatitis is an immune-mediated disease targeting hepatocytes. It is more common in middleaged Caucasian females, although may affect other patient populations and age groups. The diagnosis is made according to criteria based on the alkaline phosphatase: ALT ratio, IgG, the presence of autoantibodies, liver histology, response to therapy, and the absence of a viral, alcohol or drug etiology. More recently a simplified scoring system has been proposed. In the absence of treatment, the prognosis is very poor with a 60% three year mortality. There are guidelines on the indications for treatment and some groups of patients may not require treatment. The main element of treatment is prednisolone which decreases the 3 year mortality to 10%. Prednisolone is tapered down to 5-10 mg per day, as monotherapy or in combination with azathioprine. Approximately 80% of patients will respond to therapy with prednisolone with or without azathioprine and this should be given for at least 2 years. Remission is defined as an asymptomatic patient with serum aminotransferases that are normal or less than two-fold elevated, a normal level of IgG and inactive liver histology. Relapse occurs in up to 90% of patients following drug withdrawal. The sensitivity and specificity of liver histology to predict relapse off treatment is not high. Other treatments that have been proposed include mycophenolate mofetil, budesonide, cyclosporine A, tacrolimus, 6-MP, methotrexate, ursodeoxycholic acid, rapamycin and rituximab although experience with all these agents is limited.

Topics: Azathioprine; Budesonide; Cyclosporine; Hepatitis, Autoimmune; Humans; Mycophenolic Acid

Prednisone and prednisolone are the mainstays of treatment for autoimmune hepatitis. Prednisone is converted in the liver to the active metabolite, prednisolone. The principal therapeutic action of prednisolone is to suppress cytokine gene expression and to inhibit the differentiation and proliferation of activated lymphocytes. It also has anti-inflammatory effects that include decreased production of adhesion molecules, increased apoptosis of lymphocytes and decreased hepatic collagen deposition. Advanced liver disease does not sufficiently suppress hepatic conversion of prednisone to warrant the preferential use of prednisolone. Budesonide combined with azathioprine has been more effective and safer than the conventional prednisone-based regimen when given for 6 months to treatment-naive patients. It is emerging as a frontline treatment, especially for noncirrhotic patients with uncomplicated disease.

Topics: Budesonide; Glucocorticoids; Hepatitis, Autoimmune; Humans; Prednisolone; Prednisone

Autoimmune hepatitis (AIH) is a chronic, progressive hepatitis of uncertain cause which has fluctuating activity characterized by periods of flares and remissions. Initial placebo-controlled trials carried out in the 1970s demonstrated that immunosuppression with steroids was extremely effective in reducing flares and progression of disease. The late 1980s-1990s could be described as the 'Dark Ages' of AIH treatment research. Very few clinical studies were performed during this time, although it became increasingly apparent that not all patients tolerated or responded to traditional immunosuppression, and that not all patients were easy to diagnose because of overlapping features with other autoimmune conditions. Fortunately, clinical research in the treatment of AIH has experienced a renaissance in the 21st century.. This review highlights some of the more important recent discoveries, including the creation of the clinically useful short form of the autoimmune hepatitis diagnostic scoring system; accumulation of data supporting the use of mycophenolate and tacrolimus as second-line treatment; and the recent completion of the largest, double-blind, placebo-controlled trial of AIH treatment to date, comparing budesonide to prednisone.. These new findings are pertinent to the everyday clinical management of patients with AIH.

Topics: Azathioprine; Budesonide; Drug Hypersensitivity; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Mycophenolic Acid; Purine-Pyrimidine Metabolism, Inborn Errors; Tacrolimus

To evaluate the use of budesonide for the treatment of autoimmune hepatitis (AIH).. Literature was accessed through PubMed/MEDLINE (1966-June 2011) and Web of Science (1965-June 2011) using the terms autoimmune hepatitis and budesonide. Literature was limited to English-language publications. In addition, references from publications identified were reviewed.. All articles in English identified from the data sources were evaluated.. The initial treatment of choice for AIH is prednisone alone or with azathioprine. However, a significant number of patients do not respond adequately or have adverse reactions to this regimen; therefore, alternative treatments are required. Budesonide is an orally administered synthetic corticosteroid with high affinity for the glucocorticoid receptor that undergoes extensive first-pass metabolism. It has Food and Drug Administration-approved labeling for the treatment and maintenance of remission of mild-to-moderate Crohn disease involving the ileum and/or ascending colon. One prospective, active-controlled study of budesonide in the treatment of AIH was identified, as well as 5 small open-label studies and 1 retrospective chart review. Budesonide appears to have efficacy in the treatment of AIH, including in patients intolerant to standard therapy with prednisone alone or with azathioprine, with a reduced incidence of corticosteroid-related adverse reactions. However, in patients with AIH and cirrhosis, the efficacy of budesonide may be reduced and the incidence of corticosteroid-related adverse reactions may be increased.. Budesonide may be an additional treatment option for patients with AIH but without cirrhosis who are intolerant to standard therapy with prednisone or prednisone with azathioprine.

Topics: Azathioprine; Budesonide; Drug Labeling; Glucocorticoids; Hepatitis, Autoimmune; Humans; Prednisone

Autoimmune hepatitis is a chronic liver disease of unknown aetiology characterized by interface hepatitis, hypergammaglobulinaemia and circulating autoantibodies. In the last decade a number of advancements have been made in the field of clinical and basic research: the simplified diagnostic criteria, the complete response defined as normalization of transaminase levels, the molecular identification of the antigenic targets of anti-liver cytosol antibody type 1 and anti-soluble liver antigen, the detection of anti-actin antibodies, the description of de novo autoimmune hepatitis after liver transplantation for non-autoimmune liver diseases, the characterization of autoimmune hepatitis with overlapping features of primary biliary cirrhosis or primary sclerosing cholangitis, the preliminary experience with novel treatment strategies based on cyclosporine, mycophenolate mofetil and budesonide, the role played by "impaired" regulatory T cells and the development of novel animal models of autoimmune hepatitis.

Topics: Animals; Autoantibodies; Autoantigens; Biomarkers; Budesonide; Cholangitis, Sclerosing; Cyclosporine; Glucocorticoids; Hepatitis, Autoimmune; Humans; Hypergammaglobulinemia; Immunity, Cellular; Immunoglobulin G; Immunosuppressive Agents; Liver Cirrhosis, Biliary; Liver Transplantation; Mice; Mycophenolic Acid; Rats; Transaminases

Autoimmune hepatitis is a chronic inflammatory disease of the liver with a dismal prognosis when left untreated. Key for the improvement of prognosis is a timely diagnosis before cirrhosis has developed. This is reached by the exclusion of other causes of hepatitis, elevated immunoglobulin G, autoantibody profile and histological assessment. Treatment achieves remission rates in 80% of individuals and consists of immunosuppression with corticosteroids and azathioprine. A recent randomised controlled multicenter trial has added budesonide to the effective treatment options in non-cirrhotic patients and leads to a reduction of unwanted steroid side effects. Autoimmune hepatitis is an autoimmune disease of unknown aetiology. Association studies of major histocompatibility complex and other genes demonstrate an influence of immunogenetics. However, apart from the autoimmune polyglandular syndrome type 1, in which 10% of patients suffer from an autoantibody-positive autoimmune hepatitis linked to mutations of the autoimmune regulator gene, there is no clear evidence for a hereditary aetiology of this disease.

Topics: Animals; Azathioprine; Budesonide; Diagnosis, Differential; Drug Therapy, Combination; Genetic Predisposition to Disease; Glucocorticoids; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Liver Cirrhosis; Liver Transplantation; Major Histocompatibility Complex; Polyendocrinopathies, Autoimmune; Prednisone; Prognosis; Recurrence

Prednisone alone or a lower dose in combination with azathioprine is effective in improving symptoms, resolving laboratory and histologic features, and prolonging survival in patients with autoimmune hepatitis. The combination regimen of prednisone and azathioprine is preferred because of its lower frequency of corticosteroid-related side effects. Only patients with severe inflammatory activity have absolute indications for therapy. Treatment must be individualized in patients with mild-to-moderate disease. Medication should be continued at fixed daily maintenance levels until a remission, treatment failure, drug intolerance, or incomplete response has been established. Histologic examination before drug withdrawal ensures remission when symptoms and laboratory tests are normal or near normal. Treatment failure warrants high-dose therapy, whereas drug toxicity and incomplete response compel regimens that are modified individually according to response. Low-dose prednisone or indefinite azathioprine therapy are indicated in patients who have relapsed multiply. Empiric nonsteroidal treatments include ursodeoxycholic acid, cyclosporine, mycophenolate mofetil, and tacrolimus, and they have been used in limited studies to treat recalcitrant disease or corticosteroid intolerance. Investigational therapies promise to target critical pathogenic mechanisms affecting immunocyte activation, autoantigen recognition, cytokine interactions, and regenerative activity.

Topics: Azathioprine; Budesonide; Clinical Trials as Topic; Cyclosporine; Disease Progression; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Mycophenolic Acid; Prednisolone; Tacrolimus; Treatment Outcome; Ursodeoxycholic Acid

Refinements in the understanding of the mechanisms of immunocyte activation and the emergence of new immunosuppressive agents with highly selective actions has created opportunities for improving the treatment of autoimmune hepatitis. Drugs, such as budesonide and deflazacort, may inhibit immunocyte activation and limit corticosteroid-related side effects. Agents, such as cyclosporine and tacrolimus, can impair calcineurin activity and restrict the generation of transcription factors necessary for T cell responses. Intravenous immunoglobulin can bind anti-idiotype antibodies and reduce interleukin-2 secretion, and monoclonal antibodies directed against critical components of the T cell activation cascade can dampen the immune reaction. Drugs, such as mycophenolate mofetil, cyclophosphamide, methotrexate, and KF20444, can inhibit T cell proliferation, and other interventions promise to deplete activated T cells, impair effector mechanisms, and induce self-tolerance.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Autoantibodies; Budesonide; Cyclophosphamide; Cyclosporine; Hepatitis, Autoimmune; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Methotrexate; Mycophenolic Acid; Signal Transduction; Tacrolimus

To compare the effect of budesonide vs prednisone therapy both in combination with azathioprine in pediatric patients with autoimmune hepatitis (AIH).. Forty-six patients with AIH (11 males and 35 females) aged 9-17 years were enrolled in a 6-month, prospective, double-blind, randomized, active-controlled, multicenter phase IIb study evaluating budesonide (n = 19; 3 mg twice or 3 times daily) vs prednisone (n = 27; 40 mg/day tapered to 10 mg/day), both with azathioprine (1-2 mg/kg/day), followed by a further 6 months of open-label budesonide therapy. The primary efficacy endpoint was complete biochemical remission (normal serum alanine aminotransferase and aspartate aminotransferase levels) without predefined steroid-specific side effects.. We observed no statistically significant difference in the percentage of patients who met the primary endpoint between the budesonide (3 of 19; 16%) and prednisone groups (4 of 27; 15%) after 6 months, nor in the percentage of patients who experienced biochemical remission (budesonide, 6 of 19 [32%]; prednisone, 9 of 27 [33%]), lack of steroid-specific side effects (budesonide, 10 of 19 [53%]; prednisone, 10 of 27 [37%]). The mean weight gain was 1.2 ± 3.5 kg in the budesonide group and 5.1 ± 4.9 kg in the prednisone group (P = .006). A total of 42 patients received open-label budesonide treatment for another 6 months. After 12 months, 46% of these patients achieved complete remission.. Oral budesonide with azathioprine can induce and maintain remission in pediatric patients with AIH and may be considered an alternative therapy to prednisone. The treatment causes fewer side effects and does not lead to weight gain; however, it may be less effective than prednisone in inducing remission.

Topics: Adolescent; Alanine Transaminase; Aspartate Aminotransferases; Azathioprine; Budesonide; Child; Child, Preschool; Double-Blind Method; Female; Glucocorticoids; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Male; Prednisone; Prospective Studies; Remission Induction; Treatment Outcome

Autoimmune hepatitis (AIH) is a chronic liver disease associated with cirrhosis and liver failure. Corticosteroid therapy induces long-term remission but has many side effects. We compared the effects of budesonide (a steroid that is rapidly metabolized, with low systemic exposure) and prednisone, both in combination with azathioprine.. We performed a 6-month, prospective, double-blind, randomized, active-controlled, multicenter, phase IIb trial of patients with AIH without evidence of cirrhosis who were given budesonide (3 mg, three times daily or twice daily) or prednisone (40 mg/d, tapered to 10 mg/d); patients also received azathioprine (1-2 mg/kg/d). Treatment was followed by a 6-month, open-label phase during which all patients received budesonide in addition to azathioprine. The primary end point was complete biochemical remission, defined as normal serum levels of aspartate aminotransferase and alanine aminotransferase, without predefined steroid-specific side effects, at 6 months.. The primary end point was achieved in 47/100 patients given budesonide (47.0%) and in 19/103 patients given prednisone (18.4%) (P < .001; 97.5% 1-side confidence interval [CI] = 16.2). At 6 months, complete biochemical remission occurred in 60% of the patients given budesonide versus 38.8% of those given prednisone (P = .001; CI: 7.7); 72.0% of those in the budesonide group did not develop steroid-specific side effects versus 46.6% in the prednisone group (P < .001; CI = 12.3). Among 87 patients who were initially given prednisone and then received budesonide after 6 months, steroid-specific side effects decreased from 44.8% to 26.4% at month 12 (P < .002).. Oral budesonide, in combination with azathioprine, induces and maintains remission in patients with noncirrhotic AIH, with a low rate of steroid-specific side effects.

Topics: Adolescent; Adult; Aged; Budesonide; Child; Double-Blind Method; Female; Hepatitis, Autoimmune; HLA-DR3 Antigen; Humans; Male; Middle Aged; Prednisone; Prospective Studies

Prednisone and azathioprine represent the standard treatment for autoimmune hepatitis (AIH). However, only 65% of the patients enter complete histological remission. Recently, budesonide (BUD) was reported to be a promising alternative. In this study we assessed the efficacy and safety of BUD in AIH.. Eighteen patients (12 women, 6 men; mean age 45.4+/-21 years)with AIH were treated with BUD (Budenofalk) 3 mg thrice daily and followed up for at least 24 wk. Seven patients also had features of primary biliary cirrhosis (n=5) or primary sclerosing cholangitis (n=2). Advanced liver fibrosis or cirrhosis was present in 6 patients.. Fifteen (83%) patients had a complete clinical and biochemical remission. Ten patients, including five with acute hepatitis,were given BUD as first-line therapy, of which seven enter remission. Three patients, two with liver cirrhosis, did not improve.All patients with second-line therapy experienced long-term remission. A histological remission was also seen in three patients. Clinically relevant BUD-induced side effects were recorded only in patients with liver cirrhosis (n=4).. BUD is effective in remission induction in the majority of our patients with AIH. Side effects and treatment failure was mainly observed in patients with liver cirrhosis.

Topics: Adult; Aged; Anti-Inflammatory Agents; Budesonide; Female; Hepatitis, Autoimmune; Humans; Liver; Liver Cirrhosis; Male; Middle Aged; Remission Induction; Salvage Therapy

Autoimmune hepatitis (AIH) is a chronic liver disease that is effectively treated with immunosuppressive therapy. Predniso(lo)ne, often in combination with azathioprine, is the basic therapeutic option to induce remission. However, this regimen can cause numerous side effects. The aim of the present study was to evaluate budesonide as a treatment option in the induction of remission in patients with previously untreated AIH.. Between October 1998 and August 1999, 12 patients were treated with 3 mg budesonide thrice daily for 3 months in this open one-arm multicenter phase IIa study. Primary end point was induction of remission indicated by a drop of aspartate aminotransferase and alanine aminotransferase levels below two times the upper limit of normal.. Seven of the 12 patients (58%) reached complete remission, three patients (25%) had a partial response. Thus, 10/12 individuals (83.3%) responded to therapy. Therapy was tolerated well in 10/12 cases (83.3%).. Budesonide monotherapy was effective in the induction of remission and well tolerated in treatment naïve patients with AIH. It should be further evaluated in prospective controlled trials and should be compared to predniso(lo)ne both in monotherapy and in combination with azathioprine.

Topics: Adult; Aged; Alanine Transaminase; Budesonide; Female; Hepatitis, Autoimmune; Humans; Male; Middle Aged

Budesonide has a high hepatic first-pass clearance and metabolites virtually devoid of glucocorticoid activity. Our goals were to assess budesonide in patients with treatment-dependent autoimmune hepatitis and to determine if efficacy and safety justified a controlled trial.. Ten patients who were dependent on continuous treatment to prevent exacerbation of their disease were treated with budesonide, 3 mg thrice daily.. Laboratory indices did not improve significantly during 5 +/- 1 months of therapy (range, 2-12 months). Three patients entered clinical and biochemical remission; 2 of them achieved histologic remission. Seven patients either deteriorated during therapy or became drug intolerant. Withdrawal symptoms complicated conversion from prednisone to budesonide treatment, and every patient developed at least 1 side effect. Lumbar spine density decreased in 2 patients, and femur density decreased in 2 patients, including 1 with lumbar spine changes. However, mean bone densities actually increased slightly in the entire group.. Budesonide therapy was associated with a low frequency of remission and high occurrence of treatment failure and side effects in treatment-dependent autoimmune hepatitis. Findings did not support the need for a controlled treatment trial in this select population.

Topics: Adult; Aged; Anti-Inflammatory Agents; Azathioprine; Bone Density; Budesonide; Female; Femur; Hepatitis, Autoimmune; Humans; Male; Middle Aged; Pilot Projects; Prednisone; Retreatment; Spine; Treatment Failure; Ursodeoxycholic Acid

In patients with non-severe acute or chronic autoimmune hepatitis (AIH) without cirrhosis, clinical practice guidelines recommend indistinct use of prednisone or budesonide. However, budesonide is infrequently used in clinical practice. We aimed to describe its use and compare its efficacy and safety with prednisone as first-line options.. This was a retrospective, multicenter study of 105 naive AIH patients treated with budesonide as the first-line drug. The control group included 276 patients treated with prednisone. Efficacy was assessed using logistic regression and validated using inverse probability of treatment weighting propensity score. The median time to biochemical response (BR) was 3.1 months in patients treated with budesonide and 4.9 months in those with prednisone. The BR rate was significantly higher in patients treated with prednisone (87% vs. 49% of patients with budesonide, p < 0.001). The probability of achieving BR, assessed using the inverse probability of treatment weighting propensity score, was significantly lower in the budesonide group (OR = 0.20; 95% CI: 0.11-0.38) at any time during follow-up, and at 6 (OR = 0.51; 95% CI: 0.29-0.89) and 12 months after starting treatment (0.41; 95% CI: 0.23-0.73). In patients with transaminases <2 × upper limit of normal, BR was similar in both treatment groups. Prednisone treatment was significantly associated with a higher risk of adverse events (24.2% vs. 15.9%, p = 0.047).. In the real-life setting, the use of budesonide as first-line treatment is low, and it is generally prescribed to patients with perceived less disease activity. Budesonide was inferior to prednisone as a first-line drug but was associated with fewer side effects.

Topics: Budesonide; Glucocorticoids; Hepatitis, Autoimmune; Humans; Prednisone; Retrospective Studies

Topics: Azathioprine; Budesonide; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Prednisone

The Swiss Autoimmune Hepatitis Cohort Study is a nationwide registry, initiated in 2017, that collects retrospective and prospective clinical data and biological samples from patients of all ages with autoimmune hepatitis treated at Swiss hepatology centres. Here, we report the analysis of the first 5 years of registry data.. A total of 291 patients with autoimmune hepatitis have been enrolled, 30 of whom were diagnosed before 18 years of age and composed the paediatric cohort. Paediatric cohort: median age at diagnosis 12.5 years (range 1-17, interquartile range (IQR) 8-15), 16 (53%) girls, 6 (32%) with type 2 autoimmune hepatitis, 8 (27%) with autoimmune sclerosing cholangitis, 1 with primary biliary cholangitis variant syndrome, 4 (15%) with inflammatory bowel disease and 10 (41%) with advanced liver fibrosis at diagnosis. Adult cohort: median age at diagnosis 54 years (range 42-64, IQR 18-81), 185 (71%) women, 51 (20%) with primary biliary cholangitis variant syndrome, 22 (8%) with primary sclerosing cholangitis variant syndrome, 9 (4%) with inflammatory bowel disease and 66 (32%) with advanced liver fibrosis at diagnosis. The median follow-up time for the entire cohort was 5.2 years (IQR 3-9.3 years). Treatment in children: 29 (97%) children were initially treated with corticosteroids, 28 of whom received combination treatment with azathioprine. Budesonide was used in four children, all in combination with azathioprine. Mycophenolate mofetil was used in five children, all of whom had previously received corticosteroids and thiopurine. Treatment in adults (data available for 228 patients): 219 (96%) were treated with corticosteroids, mostly in combination with azathioprine. Predniso(lo)ne was the corticosteroid used in three-quarters of patients; the other patients received budesonide. A total of 78 (33%) patients received mycophenolate mofetil, 62 of whom had previously been treated with azathioprine. Complete biochemical response was achieved in 13 of 19 (68%) children and 137 of 182 (75%) adults with available follow-up data. All children were alive at the last follow-up, and none had undergone liver transplantation. Five (2%) adults underwent liver transplantation, two of whom had a fulminant presentation. Four (2%) adults with autoimmune hepatitis died (two from liver-associated causes).. Patients with autoimmune hepatitis in Switzerland had clinical features similar to those in other cohorts. The proportion of patients diagnosed with primary biliary cholangitis variant syndrome was higher than expected. Autoimmune hepatitis was managed according to guidelines, except for the use of budesonide in a small proportion of paediatric patients. The outcomes were excellent, but the findings must be confirmed over a longer follow-up period.

Topics: Adolescent; Adult; Azathioprine; Budesonide; Child; Child, Preschool; Cohort Studies; Female; Hepatitis, Autoimmune; Humans; Infant; Inflammatory Bowel Diseases; Liver Cirrhosis; Liver Cirrhosis, Biliary; Male; Middle Aged; Mycophenolic Acid; Prospective Studies; Retrospective Studies; Switzerland

Topics: Budesonide; Female; Glucocorticoids; Hepatitis, Autoimmune; Humans; Prednisone; Pregnancy

Topics: Adult; Age of Onset; Biopsy; Budesonide; Dose-Response Relationship, Drug; Drug Monitoring; Female; Glucocorticoids; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Liver; Liver Function Tests; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Symptom Flare Up; Treatment Outcome; United Kingdom

To compare the early biochemical response and rate of adverse effects in patients who received prednisolone (PRED)/azathioprine (AZA) and those who received budesonide (BUD)/AZA as the first-line treatment for autoimmune hepatitis.. The study involved 25 patients receiving PRED 30 mg/day + AZA 50 mg/day and 25 patients receiving BUD 9 mg/day + AZA 50 mg/day from February 2015 to February 2018. Biochemical and hemogram data at baseline and after 6 months of treatment, and adverse effects observed in the follow-up, were compared.. There was no difference between the groups in biochemical response (17 patients receiving PRED/AZA and 18 receiving BUD/AZA) and the rate of adverse effects (9 patients receiving PRED/AZA and 5 receiving BUD/AZA). The total number of adverse effects in the BUD/AZA group was lower (15 vs 7) and the treatment was discontinued in 2 (8%) patients in PRED/AZA group, while no treatment discontinuation was observed in BUD/AZA group.. This study showed no differences in biochemical response between the groups. Lower, although not significantly, rate of adverse effects and lower total number of adverse effects indicate that BUD/AZA may potentially be used as the first-line treatment of choice, especially in patients with obesity, diabetes, resistant hypertension, glaucoma, or osteoporosis.

Topics: Adult; Aged; Azathioprine; Budesonide; Drug Therapy, Combination; Female; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Male; Middle Aged; Prednisolone; Remission Induction; Retrospective Studies; Socioeconomic Factors

Autoimmune hepatitis is widely assumed by health-care professionals to be a disease that is easily controlled through the use of corticosteroids and immunosuppressants but recent studies in the UK indicate highly variable treatment regimens and often unsatisfactory treatment outcomes, such as dependence on long-term high-dose steroids and ongoing need for liver transplantation in some cases. The therapeutic use of the systemically acting corticosteroid prednisolone results in unacceptable side effects in many patients. Recent evidence suggests that it is not always necessary to use high-dose steroids (>0.5 mg/kg/d) to attain remission; and side effects may also be minimised through more targeted therapy with the less systemically-absorbed corticosteroid, budesonide. The authors offer advice on the stratification of treatment for these patients and suggest changes to improve the services available for people with autoimmune hepatitis in the UK.

Topics: Adrenal Cortex Hormones; Budesonide; Dose-Response Relationship, Drug; Hepatitis, Autoimmune; Humans; Liver Transplantation; Medication Adherence; Patient Satisfaction; Prednisolone; Quality Improvement; Quality of Life

Topics: Alanine Transaminase; Azathioprine; Budesonide; Hepatitis, Autoimmune; Humans

In common variable immunodeficiency (CVID) there is a deregulation of the immune system, which frequently leads to an increased risk of infections, but also to autoimmunity phenomena. Autoimmune hepatitis may develop at any time of CVID's evolution, but it is difficult to diagnose due to the frequent absence of autoantibodies and low levels of IgG. Early diagnosis is important because targeted treatment may allow disease improvement. We present a case of autoimmune hepatitis in a patient with CVID.

Topics: Adult; Alanine Transaminase; Anti-Inflammatory Agents; Budesonide; Common Variable Immunodeficiency; Female; Hepatitis, Autoimmune; Humans; Treatment Outcome

Many patients with autoimmune hepatitis (AIH) develop steroid-specific side effects or require doses of steroids that are unacceptable for long-term treatment. We investigated the efficacy of budesonide as an alternative steroid for patients previously treated with prednisolone who developed side effects or were unable to reduce their dose of prednisolone below acceptable levels. We also report the effects of more than 12 months of budesonide treatment in a large cohort of patients with AIH.. We performed a retrospective analysis of data from 60 patients (51 female) with AIH who were treated initially with prednisolone (mean time, 47 mo) but then switched to budesonide, managed at a single center in Germany from 2001 through June 2016. Patients were evaluated after 6 months, 12 months, 24 months, 36 months, and at the last follow-up evaluation; response to treatment with budesonide was assessed based on normal serum levels of aminotransferases and IgG (biochemical response).. Thirty patients were switched to budesonide therapy because of prednisolone-induced side effects and 30 patients switched because of prednisolone dependency. Overall, a biochemical response was detected in 55% of patients after 6 months of budesonide treatment, in 70% after 12 months, and in 67% after 24 months. At the last follow-up evaluation (mean time, 63 mo) 23 patients (38%) still were receiving budesonide treatment. Fifteen patients (25%) had switched back to prednisolone therapy because of insufficient response to budesonide or its side effects. Fifteen patients with osteopenia at the beginning of budesonide treatment were followed up and evaluated by dual-energy X-ray absorptiometry. After a median of 24 months of budesonide treatment, bone mineral density had improved in 6 patients, remained stable in 8 patients, and worsened in 1 patient.. We performed a retrospective analysis of patients with AIH that confirmed the therapeutic value of budesonide beyond 12 months of treatment in patients who are intolerant to or dependent on prednisolone. Although budesonide-induced side effects appear to be mild in real life, effectiveness was limited in a considerable proportion of patients; close monitoring is advised.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Autoantibodies; Bone Density; Budesonide; Child; Child, Preschool; Female; Germany; Hepatitis, Autoimmune; Humans; Immunoglobulin G; Male; Middle Aged; Retrospective Studies; Transaminases; Treatment Outcome; Young Adult

High-quality data on the management of autoimmune hepatitis (AIH) are scarce. Despite published guidelines, management of AIH is still expert based rather than evidence based.. To survey expert hepatologists, asking each to describe their practices in the management of patients with AIH.. A survey questionnaire was distributed to members of the International AIH Group. The questionnaire consisted of four clinical scenarios on different presentations of AIH.. Sixty surveys were sent, out of which 37 were returned. None reported budesonide as a first line induction agent for the acute presentation of AIH. Five (14%) participants reported using thiopurine S-methyltransferase measurements before commencement of thiopurine maintenance therapy. Thirteen (35%) routinely perform liver biopsy at 2 years of biochemical remission. If histological inflammatory activity is absent, four (11%) participants reduced azathioprine, whereas 10 (27%) attempted withdrawal altogether. Regarding the management of difficult-to-treat patients, mycophenolate mofetil is the most widely used second-line agent (n = ~450 in 28 centres), whereas tacrolimus (n = ~115 in 21 centres) and ciclosporin (n = ~112 in 18 centres) are less often reported. One centre reported considerable experience with infliximab, while rescue therapy with rituximab has been tried in seven centres.. There is a wide variation in the management of patients with autoimmune hepatitis even among the most expert in the field. Although good quality evidence is lacking, there is considerable experience with second-line therapies. Future prospective studies should address these issues, so that we move from an expert- to an evidence- and personalised-based care in autoimmune hepatitis.

Topics: Azathioprine; Biopsy; Budesonide; Cyclosporine; Health Care Surveys; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Methyltransferases; Mycophenolic Acid; Rituximab; Tacrolimus

Therapy for autoimmune hepatitis has been prednisone based for decades; however, budesonide may be equally effective with fewer side effects. Our aim was to evaluate quality-adjusted life years and health care costs of three different treatment regimens.. Treatment using prednisone, budesonide or a combination of both over a three-year period in newly diagnosed children with type I autoimmune hepatitis were simulated with a Markov model. Transition probabilities were calculated over consecutive three-month period. Costs were determined from a hospital database and health utilities were estimated from the literature. A Monte Carlo probabilistic sensitivity analysis was used to simulate the outcomes of 5000 patients in each treatment arm.. Compared to standard therapy, budesonide leads to a gain of 0.09 quality-adjusted life years, costing $17,722 per QALY over a three-year period. Standard therapy led to significantly lower QALY's compared to other strategies (p < 0.001). Health utilities of patients in remission in each treatment group had the greatest impact on the model. Budesonide remained the treatment of choice if the probability of inducing remission was 55% or greater.. Budesonide therapy in non-cirrhotic, treatment naïve patients with type I autoimmune hepatitis yielded greater QALY's compared to the current standard therapy with an acceptable increase in costs.

Topics: Adolescent; Anti-Inflammatory Agents; Budesonide; Child; Child, Preschool; Decision Support Techniques; Drug Administration Schedule; Drug Therapy, Combination; Follow-Up Studies; Health Care Costs; Hepatitis, Autoimmune; Humans; Illinois; Markov Chains; Mercaptopurine; Monte Carlo Method; Prednisone; Quality-Adjusted Life Years; Treatment Outcome

Autoimmune hepatitis (AIH) is defined as a chronic liver disease with loss of tolerance against liver tissue eventually leading to cirrhosis if left untreated. 80%-90% of patients can be treated with a life-long immunosuppression. Unfortunately, there are strong drug-related side effects and steroid-refractory patients. Therefore, there is a need for a model system to investigate the complex immunopathogenesis of this chronic disease and subsequently to develop new therapeutic interventions. We developed a new model of experimental murine AIH (emAIH) by a self-limited adenoviral infection with the hepatic autoantigen formiminotransferase cyclodeaminase (FTCD). After an initial transient hepatitis there was a chronic evolving AIH, finally leading to portal and lobular fibrosis. We could show that the genetic predisposition provided by the NOD background was essential for creating a fertile field for the development of liver-specific autoimmunity. However, a strong environmental trigger was additionally necessary to initiate the disease. Besides the break of humoral tolerance, T-cell tolerance against hepatic self-antigens was also broken and CD4(+) T cells were identified as essential drivers of the disease. As the disease was successfully treated with prednisolone and budesonide, the model will be helpful to develop and test new therapeutic interventions.. We developed a new murine AIH model closely resembling AIH in patients that explains the mechanisms of AIH pathophysiology. In addition, emAIH provides options to test therapeutic alternatives for patients not achieving remission, with reduced side effects of chronic nonspecific immunosuppression.

Topics: Adenoviridae; Ammonia-Lyases; Animals; Budesonide; CD4-Positive T-Lymphocytes; Disease Models, Animal; Gene-Environment Interaction; Genetic Predisposition to Disease; Glucocorticoids; Glutamate Formimidoyltransferase; Green Fluorescent Proteins; Hepatitis, Autoimmune; Humans; Mice; Mice, Inbred NOD; Multifunctional Enzymes; Prednisolone; Treatment Outcome

In this study we aimed to assess the incidence, prevalence and clinical outcomes of patients with autoimmune hepatitis (AIH) in southern Israel.. Case-finding methods and population-based administrative data were used to evaluate the epidemiology and prognostic factors of AIH from 1995 to 2010.. During the study period, the average annual prevalence and incidence of AIH in southern Israel were 11.0/100000 and 0.67/100000, respectively. We identified 100 AIH cases with a mean age of 47.9 years, including 95 women and five men. Type 1 AIH was found in 77 cases, and liver fibrosis and cirrhosis were found in 73.4% and 22.3% of all patients who underwent liver biopsy. In all, 98 patients were treated with a combination of steroids and azathioprine or steroids alone (prednisone and azathioprine in 71, budesonide and azathioprine in 11, prednisone or budesonide alone in six and ten, respectively). Complete remission was recorded in 56 patients, whereas partial response or failure of treatment was noted in 42 patients. In multivariate analysis the independent predictors of remission were the degree of liver fibrosis (mild vs bridging fibrosis (F3) and cirrhosis [F4]) (P=0.003) and level of albumin (P=0.031). The estimated 1-year and 10-year survival for AIH were 96.5% and 89.7%, respectively.. The prevalence of AIH in Israel is quite similar to that of other European Caucasian populations, with a relatively long-term good prognosis, despite a low rate of response to immunosuppressive therapy.

Topics: Adult; Azathioprine; Biopsy; Budesonide; Drug Therapy, Combination; Female; Glucocorticoids; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Incidence; Israel; Liver; Male; Middle Aged; Prednisone; Prevalence; Prognosis; Retrospective Studies; Treatment Outcome

Topics: Azathioprine; Budesonide; Female; Hepatitis, Autoimmune; Humans; Male; Prednisone

Topics: Alanine Transaminase; Aspartate Aminotransferases; Azathioprine; Budesonide; Female; Glucocorticoids; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Prednisolone; Recurrence; Young Adult

This paper analyzes the results of different treatments overlap (OS) of primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH): ursodeoxycholic acid monotherapy (UDCA) monotherapy with prednisolone (PD), the combination of PD with UDCA. Results of treatment of 16 OS patients with glucocorticoid last generation--budesonide (BS) in combination with UDCA. The treatment results were estimated in reducing severity of intrahepatic cholestasis (IHC), proposed by the author, as well as the degree of reduction of the biochemical activity of enzymes. Evaluated the quality of life by SF-36 questionnaire. In addition, the efficacy of budesonide in combination with UDCA was assessed by morphological examination of liver tissue in the dynamics after 6 months of treatment. The paper convincingly demonstrate that combination therapy OS is more effective in monotherapy reducing clinical and biochemical disease activity, as well as positive effects on quality of life. The advantages of the use of budesonide in combination with UDCA prior systemic glucocorticoids: a high efficiency and low risk of side effects.

Topics: Anti-Inflammatory Agents; Budesonide; Cholagogues and Choleretics; Drug Therapy, Combination; Female; Hepatitis, Autoimmune; Humans; Liver Cirrhosis, Biliary; Male; Prednisolone; Quality of Life; Surveys and Questionnaires; Ursodeoxycholic Acid

Topics: Anti-Inflammatory Agents; Budesonide; Cholagogues and Choleretics; Drug Therapy, Combination; Hepatitis, Autoimmune; Humans; Liver Cirrhosis, Biliary; Treatment Outcome; Ursodeoxycholic Acid

Topics: Anemia, Hemolytic, Autoimmune; Anti-Inflammatory Agents; Budesonide; Female; Hashimoto Disease; Hepatitis, Autoimmune; Humans; Liver Cirrhosis, Biliary; Middle Aged; Polyendocrinopathies, Autoimmune; Syndrome; Ursodeoxycholic Acid

Topics: Budesonide; Drug Therapy, Combination; Hepatitis, Autoimmune; Immunosuppressive Agents; Liver Cirrhosis, Biliary; Long-Term Care; Prognosis; Ursodeoxycholic Acid

Autoimmune hepatitis (AIH) is a chronic inflammatory disease that is successfully treated with prednisone and/or azathioprine immunosuppressive therapy in 70% to 80% of patients. The remaining patients are intolerant or refractory to these standard medications. Budesonide, a synthetic glucocorticoid, undergoes a high degree of first-pass metabolism, reducing its systemic bioavailability, and has a 15-fold greater affinity for the glucocorticoid receptor than prednisolone. Budesonide may be a potentially useful systemic steroid-sparing immunosuppressive agent in the treatment of AIH.. To review the Canadian experience using budesonide to treat AIH.. Patients with AIH currently or previously treated with budesonide were identified through the Canadian Association for the Study of the Liver membership. Data were collected regarding their clinical and treatment history.. A total of nine patients were identified. All patients were female, with an average age of 39 years (range 12 to 66 years). The indications for budesonide were adverse side effects of prednisone in two patients, noncompliance with prednisone and azathioprine in one patient and intolerance to azathioprine resulting in prednisone dependence in the remaining six patients. Patients were treated in doses ranging from 9 mg daily to 3 mg every other day for 24 weeks to eight years. Seven of nine patients had a complete response, defined as sustained normalization of the aminotransferase levels. The remaining two patients were classified as nonresponders (less than a 50% reduction in pretreatment aminotransferase levels).. In Canada, budesonide has been successfully used in seven of nine patients with autoimmune hepatitis who were either intolerant to prednisone and azathioprine or prednisone-dependent. No adverse effects were reported with budesonide. Budesonide is potentially a valuable treatment option for AIH patients refractory or intolerant to standard therapy, and is deserving of further study.

Topics: Adolescent; Adult; Aged; Alanine Transaminase; Budesonide; Canada; Child; Female; Glucocorticoids; Hepatitis, Autoimmune; Humans; Middle Aged; Retrospective Studies; Treatment Outcome

Topics: Acute Disease; Adjuvants, Immunologic; Aged; Anti-Inflammatory Agents; Antibodies, Antinuclear; Budesonide; Drug Synergism; Glatiramer Acetate; Hepatitis, Autoimmune; Humans; Iatrogenic Disease; Interferon beta-1b; Interferon-beta; Liver; Male; Mannitol; Multiple Sclerosis; Mycophenolic Acid; Peptides; Treatment Outcome

Topics: Anti-Inflammatory Agents; Budesonide; Cyclophosphamide; Cyclosporine; Hepatitis, Autoimmune; Humans; Immunologic Factors; Immunosuppressive Agents; Interleukins; Methotrexate; Mycophenolic Acid; Prednisolone; Tacrolimus; Treatment Outcome

Autoimmune hepatitis is a rare chronic disease that mainly affects young women and may influence fertility and pregnancy in these patients.. To describe pregnancy and labor in a patient suffering from autoimmune hepatitis and to review the relevant literature.. Computerized literature research.. The disease of 9 years' duration did not relapse during pregnancy under continuous treatment with steroids, cytotoxic drugs, ursodeoxycholic acid and vitamins. Pregnancy was uneventful and ended with preterm vaginal delivery at 35 weeks, of a 2299 gram healthy neonate. The patient did well during the postpartum period and 6 months thereafter. Since there is no single diagnostic test for the disease, the diagnosis is based on the combination of clinical, laboratory, and histopathological findings and by exclusion of other causes of hepatitis.. There is paucity of data in the literature on pregnancy in these patients but the treatment protocols seem to be effective for the mother and safe for the fetus. Maternal and fetal complications rates appear to be currently lower than in the past. Given that relapse cannot be predicted, close surveillance during pregnancy is warranted.

Topics: Adult; Autoantibodies; Azathioprine; Budesonide; Female; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Infant, Newborn; Male; Obstetric Labor Complications; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Ursodeoxycholic Acid

To investigate the systemic availability of budesonide in a patient with Child A cirrhosis due to autoimmune hepatitis (AIH) and primary hepatocellular carcinoma, who developed serious side effects.. Serum levels of budesonide, 6beta-OH-budesonide and 16alpha-OH-prednisolone were measured by HPLC/MS/MS; portosystemic shunt-index (SI) was determined by 99mTc nuclear imaging. All values were compared with a matched control patient without side effects.. Serum levels of budesonide were 13-fold increased in the index patient. The ratio between serum levels of the metabolites 6beta-OH-budesonide and 16alpha-OH-prednisolone, respectively, and serum levels of budesonide was diminished (1.0 vs. 4.0 for 6beta-OH-budesonide, 4.2 vs. 10.7 for 16alpha-OH-prednisolone). Both patients had portosystemic SI (5.7% and 3.1%) within the range of healthy subjects.. Serum levels of budesonide vary up to 13-fold in AIH patients with Child A cirrhosis in the absence of relevant portosystemic shunting. Reduced hepatic metabolism, as indicated by reduced metabolite-to-drug ratio, rather than portosystemic shunting may explain systemic side effects of this drug in cirrhosis.

Topics: Aged; Anti-Inflammatory Agents; Budesonide; Carcinoma, Hepatocellular; Female; Hepatitis, Autoimmune; Humans; Liver; Liver Neoplasms; Portasystemic Shunt, Surgical

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents; Azathioprine; Budesonide; Drug Therapy, Combination; Female; Hepatitis, Autoimmune; Humans; Liver Function Tests; Prednisolone