Epidemiology of Autoimmune Hepatitis (AIH) in the United States Between 2014 and 2019: A Population-based National Study.

BACKGROUND AND AIMS: Autoimmune hepatitis (AIH) is a chronic, inflammatory disease of the liver with increasing prevalence. However, limited epidemiological data exist for the prevalence of AIH in the United States. We used a large database to describe the prevalence of AIH in the United States and the autoimmune diseases associated with it. APPROACH AND RESULTS: Data was collected from a commercial database (Explorys Inc., Cleveland, OH), an aggregate of Electronic Health Record data from 26 major integrated health care systems in the United States. We identified a cohort of patients with a diagnosis of AIH from April 2014 to April 2019 based on a Systemized Nomenclature of Medicine-Clinical Terms and calculated the prevalence of AIH. Of the 37,161,280 individuals active in the database from April 2014 to 2019, we identified 11,600 individuals with a diagnosis of AIH with an overall prevalence rate of 31.2/100,000. The prevalence of AIH was increased in females compared with males [odds ratio (OR)=3.21, P<0.0001], elderly (aged above 65 y) compared with adults (aged 18 to 65 y) and children (aged below 18 y) (OR=2.51, P<0.0001) and whites compared with African Americans, Asians, and Hispanics (OR=1.12, P<0.0001). Moreover, patients with AIH were more likely to have Sjögren syndrome, systemic lupus erythematosus, ulcerative colitis, celiac disease, rheumatoid arthritis, Crohn's disease, and autoimmune thyroiditis as compared with patients without AIH. CONCLUSIONS: We found that the estimated prevalence of AIH in the United States is 31.2/100,000, which is comparable to the reported prevalence of AIH in Europe. We confirmed that AIH has a strong association with other autoimmune diseases studied in the literature.

Scientific rationale underpinning the development of biosimilar rituximab in hematological cancers and inflammatory diseases.

Sandoz rituximab (SDZ-RTX; Rixathon®; GP2013), a rituximab biosimilar, was approved in June 2017 in Europe in all indications of reference rituximab. The stepwise SDZ-RTX development program generated extensive physicochemical, structural, functional, and biological data demonstrating a match with reference rituximab on all clinically relevant attributes. A focused clinical development program followed, in two indications selected for sensitivity to detect potential differences versus reference rituximab: rheumatoid arthritis (pivotal pharmacokinetics and efficacy evaluation) and follicular lymphoma (pivotal efficacy/safety evaluation). These trials demonstrated highly similar pharmacokinetics, pharmacodynamics, efficacy, safety, and immunogenicity profiles. The totality of evidence for biosimilarity for SDZ-RTX, combined with knowledge that B-cell depletion is common to each approved indication, allowed SDZ-RTX approval for use in all indications of reference rituximab.

Once-weekly oral alendronate 70 mg in patients with glucocorticoid-induced bone loss: a 12-month randomized, placebo-controlled clinical trial.

OBJECTIVE: Glucocorticoid-induced osteoporosis is the most common iatrogenic form of osteoporosis. We evaluated the efficacy and safety of once-weekly bisphosphonate therapy for prevention and treatment of bone loss in patients on glucocorticoid therapy. METHODS: We conducted a 12-month, multicenter, randomized, double-blind, placebo-controlled trial with 114 and 59 patients in the treatment and placebo arms, respectively. Participants were stratified according to the duration of prior oral glucocorticoid therapy at randomization. Participants received alendronate 70 mg once weekly (ALN OW) or placebo; all received supplemental daily calcium (1000 mg) and 400 IU vitamin D. Clinical evaluations were performed at baseline, 3, 6, 9, and 12 months. RESULTS: At 12 months, there was a significant mean percentage increase from baseline in the ALN OW group for lumbar spine (2.45%), trochanter (1.27%), total hip (0.75%), and total body (1.70%) bone mineral density (BMD). Comparing ALN OW versus placebo at 12 months, a significant treatment difference for the mean percentage change from baseline was observed for lumbar spine (treatment difference of 2.92%; p

Use of complementary medicine in pediatric patients with inflammatory bowel disease: results from a multicenter survey.

OBJECTIVES: We examined the use of complementary and alternative medicine (CAM) at 3 US pediatric medical centers, comparing a group of children with inflammatory bowel disease (IBD) with children presenting with chronic constipation. MATERIALS AND METHODS: Surveys were administered by postal mail and at pediatric IBD centers in San Francisco, Houston, and Atlanta from 2001 to 2003. A comparison group consisting of pediatric patients with chronic constipation also was surveyed. Data were analyzed by t tests and by exact tests of contingency tables. RESULTS: In all, 236 surveys were collected from the IBD group; 126 surveys were collected from the chronic constipation comparison group. CAM therapies were used by 50% in the IBD group and 23% in the chronic constipation group. The overall regional breakdown of CAM use in IBD revealed no differences, although the types of CAM therapy used varied by site. The most commonly used CAM therapies in the IBD group were spiritual interventions (25%) and nutritional supplements (25%). Positive predictors for CAM use in IBD include the patient's self-reported overall health, an increase in the number of side effects associated with allopathic medications, white ethnicity, and parental education beyond high school. CONCLUSIONS: This is the first US study to characterize CAM use in pediatric patients with IBD with another chronic gastrointestinal disorder. CAM use was twice as common with the IBD group compared with the chronic constipation group. Regional variations exist with the types of CAM therapy used. Practitioners should know that half of their pediatric patients with IBD may be using CAM in conjunction with or as an alternative to other treatments and that certain predictors can help identify those using CAM therapies.

Folate concentrations in pediatric patients with newly diagnosed inflammatory bowel disease.

BACKGROUND: Folate is postulated to protect against cell injury and long-term risk of cancer. Folate deficiency has been shown to be associated with inflammatory bowel disease (IBD). However, folate concentrations are poorly delineated in children with IBD. OBJECTIVE: The objective was to compare folate concentrations between children with newly diagnosed IBD and healthy controls. DESIGN: Red blood cell folate (RBCF) and whole-blood folate (WBF) concentrations were measured in 78 children (mean age: 12.8 +/- 2.7 y): 22 patients with newly diagnosed untreated Crohn disease, 11 patients with ulcerative colitis, 4 patients with indeterminate colitis, and 41 controls. Vitamin supplementation and dietary intakes determined by food-frequency questionnaire were recorded for 20 IBD patients and 28 controls. RESULTS: RBCF concentrations were 19.4% lower in controls (587.0 +/- 148.6 ng/mL) than in patients (728.7 +/- 185.8 ng/mL; P = 0.0004), and WBF concentrations were 11.1% lower in controls (218.2 +/- 49.7 ng/mL) than in patients (245.3 +/- 59.1 ng/mL; P = 0.031). Total folate intake was 18.8% higher in controls (444.7 +/- 266.7 microg/d) than in IBD patients (361.1 +/- 230.6 microg/d), but this difference was not statistically significant (P = 0.264). Folate intakes were below the Recommended Dietary Allowance (200-400 microg/d), adjusted for age and sex, in 35.4% of study subjects. CONCLUSIONS: In contrast with previous evidence of folate deficiency in adult IBD patients, our data indicate higher folate concentrations in children with newly diagnosed untreated IBD than in controls. This finding was unexpected, especially in light of the higher dietary folate intakes and hematocrit values in children without IBD. The influence of IBD therapy on folate metabolism and the long-term clinical implications of high RBCF and WBF concentrations at the time of IBD diagnosis should be explored further.

Effects of prasterone on bone mineral density in women with systemic lupus erythematosus receiving chronic glucocorticoid therapy.

OBJECTIVE: To assess the effects of treatment with prasterone (dehydroepiandrosterone) on bone mineral density (BMD) in female patients with mild to moderate systemic lupus erythematosus (SLE) receiving chronic treatment with glucocorticoids. METHODS: Fifty-five female patients with SLE who had received prednisone (or glucocorticoid equivalent) /= 6 months were treated for 1 year with either prasterone 200 mg/day (n = 24) or placebo (n = 31) in this randomized, double blind trial. Prasterone or placebo was added to each patient's one or more concomitant standard SLE medications, including glucocorticoids, nonsteroidal antiinflammatory drugs, antimalarials, methotrexate, azathioprine, and other immunosuppressives, which were to be maintained at fixed doses for the duration of the study. RESULTS: BMD was significantly improved in patients who received prasterone compared to placebo. At the lumbar spine, there was a mean (SEM) gain in BMD of 1.7 +/- 0.8% in the prasterone group compared to a mean loss in BMD of -1.1 +/- 0.5% in the placebo group (p = 0.003 between groups). For the total hip, mean gain was 2.0 +/- 0.9% in the prasterone group vs a mean loss of -0.3 +/- 0.4% in the placebo group (p = 0.013 between groups). In the prasterone treatment group, the mean gains from baseline at both lumbar spine and hip were statistically significant. CONCLUSION: Prasterone treatment prevented BMD loss and significantly increased BMD at both the lumbar spine and total hip in female patients with SLE receiving exogenous glucocorticoids.

Effects of prasterone on disease activity and symptoms in women with active systemic lupus erythematosus.

OBJECTIVE: To determine whether prasterone administration results in improvement or stabilization of systemic lupus erythematosus (SLE) disease activity and its symptoms. METHODS: Women with active SLE were treated with prasterone 200 mg/day plus standard SLE treatments or with placebo plus standard SLE treatments for up to 12 months in this randomized, double-blind investigation conducted at 27 centers. Standard SLE treatments included prednisone (/=6 weeks prior to enrollment and remain unchanged during protocol treatment. Responders were patients who experienced no clinical deterioration and had improvement or stabilization over the duration of the study in 2 disease activity measures (the SLE Disease Activity Index [SLEDAI] and the Systemic Lupus Activity Measure) and 2 quality of life measures (patient's global assessment and the Krupp Fatigue Severity Scale). RESULTS: A total of 381 women with SLE were enrolled. Among patients with clinically active disease at baseline (SLEDAI score >2), 86 of 147 in the prasterone group (58.5%) demonstrated improvement or stabilization without clinical deterioration, as compared with 65 of 146 in the placebo group (44.5%) (P = 0.017). Acne and hirsutism were reported in 33% and 16%, respectively, of the prasterone group and in 14% and 2%, respectively, of the placebo group (P < 0.05 for both comparisons). However, most cases of acne and hirsutism were mild and did not require withdrawal from therapy. Myalgias and oral stomatitis were reported less frequently in the prasterone group (22% and 15%, respectively) than in the placebo group (36% and 23%, respectively) (P < 0.05 for both comparisons). Serum levels of high-density lipoprotein cholesterol, triglycerides, and C3 complement significantly decreased, while levels of testosterone and, to a lesser extent, estradiol increased in the prasterone group. CONCLUSION: In adult women with active SLE, administration of prasterone at a dosage of 200 mg/day improved or stabilized signs and symptoms of disease and was generally well tolerated.

Autoimmune hepatitis associated with the use of black cohosh: a case study.

Herbal remedies generate more than 1.8 billion dollars in annual sales in the United States. Herbal products have been associated with a wide spectrum of hepatic toxicities. With the recent Women's Health Initiative Study demonstrating increased risk of breast cancer and cardiovascular events associated with hormone therapy, many women may resort to herbal remedies for persistent menopause symptoms. We report a case of autoimmune hepatitis likely triggered by the use of black cohosh (Actaea racemosa), an agent marketed to treat menopause symptoms. Given this case report, we recommend close monitoring of women using this herbal preparation.