Search

LINKED CONTENT: This article is linked to McPherson et al papers. To view these articles, visit https://doi.org/10.1111/apt.18061 and https://doi.org/10.1111/apt.18176 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to McPherson et al papers. To view these articles, visit https://doi.org/10.1111/apt.18061 and https://doi.org/10.1111/apt.18171. [ABSTRACT FROM AUTHOR]

SUMMARY: Background: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that results in substantial morbidity and mortality with many unanswered clinical and research questions. Improved understanding of disease pathogenesis, including the extra‐hepatic manifestations of AIH, may allow targeted treatments with greater efficacy and fewer associated adverse events. Aim: To identify the spectrum of unanswered clinical and research questions facing care providers in the management of patients with autoimmune hepatitis (AIH). Methods: The International Autoimmune Hepatitis Group initiated a series of research workshops to start to address these questions. Key issues were discussed in small group sessions with collation of all discussions to be summarised in this manuscript. Results: Key issues were identified as: the need for better understanding of disease pathogenesis, standardisation of the methods and assays used to evaluate autoantibodies in AIH, refinement of the histopathological criteria for "typical" or "compatible" AIH, focus on the interaction with non‐alcohol related fatty liver disease, how to treat acute severe AIH, better assessment of quality of life in adults and paediatrics, standardising use of standard, third‐line and experimental therapies in AIH and search for biomarkers early in the disease course that predict outcome. Conclusion: This workshop has outlined the key unanswered clinical and research questions to help to define the research agenda in AIH. [ABSTRACT FROM AUTHOR]

Summary: Background: Treatment paradigms in autoimmune hepatitis (AIH) have remained largely unchanged for decades. Studies report ≤20% of patients have sub‐optimal treatment response with most requiring long‐term therapy. Aim: The United Kingdom Autoimmune Hepatitis (UK‐AIH) study was established to evaluate current treatment practice and outcomes, determine the unmet needs of patients, and develop and implement improved treatment approaches. Methods: The United Kingdom Autoimmune Hepatitis study is a cross‐sectional cohort study examining secondary care management of prevalent adult patients with a clinical diagnosis of autoimmune hepatitis. Enrolment began in March 2014. Prevalent cases were defined as having been diagnosed and treated for >1 year. Demographic data, biochemistry, treatment history and response, and care location were collected. Results: In total, 1249 patients were recruited; 635 were cared for in transplant units and 614 in non‐transplant centres (81% female with median age at diagnosis 50 years). Overall, 29 treatment regimens were reported and biochemical remission rate was 59%. Remission rates were significantly higher in transplant compared to non‐transplant centres (62 vs 55%, P = 0.028). 55% have ongoing corticosteroid exposure; 9% are receiving prednisolone monotherapy. Those aged ≤20 years at diagnosis were more likely to develop cirrhosis and place of care was associated with an aggressive disease phenotype. Conclusions: There are significant discrepancies in the care received by patients with autoimmune hepatitis in the UK. A high proportion remains on corticosteroids and there is significant treatment variability. Patients receiving care in transplant centres were more likely to achieve and maintain remission. Overall poor remission rates suggest that there are significant unmet therapeutic needs for patients with autoimmune hepatitis. [ABSTRACT FROM AUTHOR]

Background and study aims: Discomfort during colonoscopymay affect acceptability of the procedure. The study aim was to determine factors, including prior hysterectomy and gender, associated with higher levels of patient discomfort during colonoscopy to help with procedural planning such as choice of instrument and sedation. Methods: A retrospective cohort study of colonoscopies (n=1098) performed between February 2007 and March 2012at the Tees Bowel Cancer Screening Centre within the English Bowel Cancer Screening Programme (BCSP). Determinants of moderate/severe discomfort assessed using the Gloucester Scale were explored, using logistic regression with a range of participant and procedural variables. Results: Rates of moderate/severe discomfort varied significantly among men, women without hysterectomy, and women with hysterectomy (5.8 %, 10.4 %, and 17.8 %, respectively; P<0.001). In an unadjusted model, women with hysterectomy were significantly more likely to experience moderate/severe discomfort than those without (odds ratio [OR]1.87, 95% confidence interval [95 %CI] 1.05-3.32, P=0.005). The very strong influence of sedation on discomfort level precluded an adjusted model. In subgroup analysis of participants receiving sedation, adjusted comparison again showed increased odds for moderate/severe discomfort for women with hysterectomy, compared with women without (OR 1.70, 95%CI 1.03-2.80, P=0.036). Conclusions: Prior hysterectomy is associated with greater levels ofmoderate/severe discomfort in women undergoing colonoscopy. Minimizing participant discomfort is desirable in any screening or surveillance program. This should be considered in preprocedural counseling and in selecting equipment, sedation, and analgesia. Further studies should examine methods to minimize discomfort in those with prior hysterectomy. [ABSTRACT FROM AUTHOR]

Background and Aims: Detection of autoantibodies is a mainstay of diagnosing autoimmune hepatitis (AIH). However, conventional autoantibodies for the workup of AIH lack either sensitivity or specificity, leading to substantial diagnostic uncertainty. We aimed to identify more accurate serological markers of AIH with a protein macroarray., Approach and Results: During the search for more-precise autoantibodies to distinguish AIH from non-AIH liver diseases (non-AIH-LD), IgG antibodies with binding capacities to many human and foreign proteins were identified with a protein macroarray and confirmed with solid-phase ELISAs in AIH patients. Subsequently, polyreactive IgG (pIgG) was exemplarily quantified by reactivity against human huntingtin-interacting protein 1-related protein in bovine serum albumin blocked ELISA (HIP1R/BSA). The diagnostic fidelity of HIP1R/BSA binding pIgG to diagnose AIH was assessed in a retrospective training, a retrospective multicenter validation, and a prospective validation cohort in cryoconserved samples from 1,568 adults from 10 centers from eight countries. Reactivity against HIP1R/BSA had a 25% and 14% higher specificity to diagnose AIH than conventional antinuclear and antismooth muscle antibodies, a significantly higher sensitivity than liver kidney microsomal antibodies and antisoluble liver antigen/liver pancreas antigen, and a 12%-20% higher accuracy than conventional autoantibodies. Importantly, HIP1R/BSA reactivity was present in up to 88% of patients with seronegative AIH and in up to 71% of AIH patients with normal IgG levels. Under therapy, pIgG returns to background levels of non-AIH-LD., Conclusions: pIgG could be used as a promising marker to improve the diagnostic workup of liver diseases with a higher specificity for AIH compared to conventional autoantibodies and a utility in autoantibody-negative AIH. Likewise, pIgG could be a major source of assay interference in untreated AIH., (© 2021 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)