Browsing by Author "Lammert, Craig S."

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    A polygenic risk score for alcohol-associated cirrhosis among heavy drinkers with European ancestry
    (Wolters Kluwer, 2024-05-10) Schwantes-An, Tae-Hwi; Whitfield, John B.; Aithal, Guruprasad P.; Atkinson, Stephen R.; Bataller, Ramon; Botwin, Greg; Chalasani, Naga P.; Cordell, Heather J.; Daly, Ann K.; Darlay, Rebecca; Day, Christopher P.; Eyer, Florian; Foroud, Tatiana; Gawrieh, Samer; Gleeson, Dermot; Goldman, David; Haber, Paul S.; Jacquet, Jean-Marc; Lammert, Craig S.; Liang, Tiebing; Liangpunsakul, Suthat; Masson, Steven; Mathurin, Philippe; Moirand, Romain; McQuillin, Andrew; Moreno, Christophe; Morgan, Marsha Y.; Mueller, Sebastian; Müllhaupt, Beat; Nagy, Laura E.; Nahon, Pierre; Nalpas, Bertrand; Naveau, Sylvie; Perney, Pascal; Pirmohamed, Munir; Seitz, Helmut K.; Soyka, Michael; Stickel, Felix; Thompson, Andrew; Thursz, Mark R.; Trépo, Eric; Morgan, Timothy R.; Seth, Devanshi; GenomALC Consortium; Medical and Molecular Genetics, School of Medicine
    Background: Polygenic Risk Scores (PRS) based on results from genome-wide association studies offer the prospect of risk stratification for many common and complex diseases. We developed a PRS for alcohol-associated cirrhosis by comparing single-nucleotide polymorphisms among patients with alcohol-associated cirrhosis (ALC) versus drinkers who did not have evidence of liver fibrosis/cirrhosis. Methods: Using a data-driven approach, a PRS for ALC was generated using a meta-genome-wide association study of ALC (N=4305) and an independent cohort of heavy drinkers with ALC and without significant liver disease (N=3037). It was validated in 2 additional independent cohorts from the UK Biobank with diagnosed ALC (N=467) and high-risk drinking controls (N=8981) and participants in the Indiana Biobank Liver cohort with alcohol-associated liver disease (N=121) and controls without liver disease (N=3239). Results: A 20-single-nucleotide polymorphisms PRS for ALC (PRSALC) was generated that stratified risk for ALC comparing the top and bottom deciles of PRS in the 2 validation cohorts (ORs: 2.83 [95% CI: 1.82 -4.39] in UK Biobank; 4.40 [1.56 -12.44] in Indiana Biobank Liver cohort). Furthermore, PRSALC improved the prediction of ALC risk when added to the models of clinically known predictors of ALC risk. It also stratified the risk for metabolic dysfunction -associated steatotic liver disease -cirrhosis (3.94 [2.23 -6.95]) in the Indiana Biobank Liver cohort -based exploratory analysis. Conclusions: PRSALC incorporates 20 single-nucleotide polymorphisms, predicts increased risk for ALC, and improves risk stratification for ALC compared with the models that only include clinical risk factors. This new score has the potential for early detection of heavy drinking patients who are at high risk for ALC.
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    Autoimmune hepatitis: Current and future therapies
    (Wolters Kluwer, 2024-06-05) Reau, Nancy S.; Lammert, Craig S.; Weinberg, Ethan M.; Medicine, School of Medicine
    Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that can lead to cirrhosis and liver failure. AIH can present in all ages, races, and ethnicities, but it predominantly affects women. As a heterogeneous disease, AIH presents variably in different patients, making diagnosis and treatment a challenge. Currently, the standard treatment for AIH comprises immunosuppressants; however, their long-term use is associated with adverse effects. The pathogenesis of AIH is complex, involving T cells, macrophages, and plasma cells that invade the periportal parenchyma and lead to an inflammatory cascade that can result in liver damage. Due to the complexity of AIH pathogenesis, treatment targets several inflammatory pathways. However, unlike other autoimmune diseases in which targeted treatments have been approved, there has been little progress made in advancing the treatment paradigm for AIH. Major obstacles to progress include challenges in conducting clinical trials, particularly patient recruitment and ensuring a diverse range of backgrounds; poorly defined outcomes to assess treatment response and improved quality of life; and a lack of study designs that account for the stage of disease and variations in treatment. A focus on individualized and steroid-free treatment approaches is needed to improve AIH prognosis and minimize steroid-associated adverse effects.
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    A Novel Approach Using Social Media to Investigate Patient-Centric Data in Autoimmune Hepatitis
    (2018) Kulanthaivel, Anand; Lammert, Craig S.; Jones, Josette F.
    Autoimmune hepatitis (AIH) is a rare liver disease characterized by immune-mediated destruction of hepatocytes. Despite adequate treatment, most patients experience severe extrahepatic symptoms that may reduce quality of life to date. The extent and impact of these symptoms remain poorly characterized as focused investigation in this realm has been deficient. In rare diseases, such as AIH, online support groups may provide the only environment where a sufficiently sized sample of patients can be examined for such issues. We aimed to electronically survey the text content of an AIH-affiliated online support group with over 1,000 users making over 18,000 communications. HYPOTHESIS: We hypothesized that we could use AIH-online support group text to identify key topics of clinically-related discussion and classify demographics and correlate these features to clinical topics, medications, and symptoms.
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    Studying Rare Patients with Commonly-Available Information: Social Mediomics for Researching Patient Histories in Autoimmune Hepatitis (AIH)
    (2019-12) Kulanthaivel, Anand; Jones, Josette F.; Milojevic, Stasa; Lammert, Craig S.; Wild, David J.
    Autoimmune Hepatitis (AIH), an incurable chronic condition of unknown cause where the body attacks its own liver, is a rare disease, with a current diagnosed worldwide prevalence of < 150,000. Inadequately treated, AIH can cause progressive liver damage and ultimately liver failure. A wide variety of symptoms are associated with AIH including severe fatigue, joint pain, depression, anxiety, and insomnia. While precision medicine’s genomics has attempted to shed light on the disease, other non-molecular “-omics” approaches can be taken in studying AIH patients, who often utilize social media to gather information from other patients or care providers to apply to their own AIH disease course. It is proposed that these patient-generated social mediomes can create self-report health records for patients – and facets of their lives - otherwise unreachable by conventional research. In this feasibility study, I examined in an exploratory fashion the social mediome of a large (N > 1000) gathering of AIH patients and caregivers as present on a Facebook Group to determine the potential of mining various types health-related user information. The following types of information were mined, with feasible indicating a reliability of F >= 0.670: 1) Types of health information shared and structures of information sharing (Feasible) 2) Types and directionality of support provided by and to users (Portions feasible) 3) Clinical factors (AIH-related and otherwise) disclosed by users a. Medication intake (Feasible) b. Signs and symptoms (including pain and injury) and diagnosed comorbidities (Portions feasible) c. Results of disease monitoring blood tests (Portions feasible) 4) Contextual (non-clinical; environmental; social) factors disclosed by users (Detection of which type of factor discussed occasionally feasible). The resulting knowledge is required to adequately describe the disease not only clinically, but also environmentally and socially, and will form part of the basis for future disease studies.