BackgroundAutoimmune hepatitis (AIH) is a rare, chronic inflammatory disease of the liver. The treatment goal is reaching complete biochemical response (CR), defined as the normalisation of... Show moreBackgroundAutoimmune hepatitis (AIH) is a rare, chronic inflammatory disease of the liver. The treatment goal is reaching complete biochemical response (CR), defined as the normalisation of aspartate and alanine aminotransferases and immunoglobulin gamma. Ongoing AIH activity can lead to fibrosis and (decompensated) cirrhosis. Incomplete biochemical response is the most important risk factor for liver transplantation or liver-related mortality. First-line treatment consists of a combination of azathioprine and prednisolone. If CR is not reached, tacrolimus (TAC) or mycophenolate mofetil (MMF) can be used as second-line therapy. Both products are registered for the prevention of graft rejection in solid organ transplant recipients. The aim of this study is to compare the effectiveness and safety of TAC and MMF as second-line treatment for AIH.MethodsThe TAILOR study is a phase IIIB, multicentre, open-label, parallel-group, randomised (1:1) controlled trial performed in large teaching and university hospitals in the Netherlands. We will enrol 86 patients with AIH who have not reached CR after at least 6 months of treatment with first-line therapy. Patients are randomised to TAC (0.07 mg/kg/day initially and adjusted by trough levels) or MMF (max 2000 mg/day), stratified by the presence of cirrhosis at inclusion. The primary endpoint is the difference in the proportion of patients reaching CR after 12 months. Secondary endpoints include the difference in the proportion of patients reaching CR after 6 months, adverse effects, difference in fibrogenesis, quality of life and cost-effectiveness.DiscussionThis is the first randomised controlled trial comparing two second-line therapies for AIH. Currently, second-line treatment is based on retrospective cohort studies. The rarity of AIH is the main issue in clinical research for alternative treatment options. The results of this trial can be implemented in existing international clinical guidelines.Trial registrationClinicalTrials.gov NCT05221411. Retrospectively registered on 3 February 2022; EudraCT number 2021-003420-33. Prospectively registered on 16 June 2021. Show less
While global patterns of human genetic diversity are increasingly well characterized, the diversity of human languages remains less systematically described. Here, we outline the Grambank database.... Show moreWhile global patterns of human genetic diversity are increasingly well characterized, the diversity of human languages remains less systematically described. Here, we outline the Grambank database. With over 400,000 data points and 2400 languages, Grambank is the largest comparative grammatical database available. The comprehensiveness of Grambank allows us to quantify the relative effects of genealogical inheritance and geographic proximity on the structural diversity of the world’s languages, evaluate constraints on linguistic diversity, and identify the world’s most unusual languages. An analysis of the consequences of language loss reveals that the reduction in diversity will be strikingly uneven across the major linguistic regions of the world. Without sustained efforts to document and revitalize endangered languages, our linguistic window into human history, cognition, and culture will be seriously fragmented. Show less
