Browsing by Author "Long, Michelle T."

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    A multiancestry genome-wide association study of unexplained chronic ALT elevation as a proxy for nonalcoholic fatty liver disease with histological and radiological validation
    (Springer Nature, 2022) Vujkovic, Marijana; Ramdas, Shweta; Lorenz, Kim M.; Guo, Xiuqing; Darlay, Rebecca; Cordell, Heather J.; He, Jing; Gindin, Yevgeniy; Chung, Chuhan; Myers, Robert P.; Schneider, Carolin V.; Park, Joseph; Lee, Kyung Min; Serper, Marina; Carr, Rotonya M.; Kaplan, David E.; Haas, Mary E.; MacLean, Matthew T.; Witschey, Walter R.; Zhu, Xiang; Tcheandjieu, Catherine; Kember, Rachel L.; Kranzler, Henry R.; Verma, Anurag; Giri, Ayush; Klarin, Derek M.; Sun, Yan V.; Huang, Jie; Huffman, Jennifer E.; Townsend Creasy, Kate; Hand, Nicholas J.; Liu, Ching-Ti; Long, Michelle T.; Yao, Jie; Budoff, Matthew; Tan, Jingyi; Li, Xiaohui; Lin, Henry J.; Chen, Yii-Der Ida; Taylor, Kent D.; Chang, Ruey-Kang; Krauss, Ronald M.; Vilarinho, Silvia; Brancale, Joseph; Nielsen, Jonas B.; Locke, Adam E.; Jones, Marcus B.; Verweij, Niek; Baras, Aris; Reddy, K. Rajender; Neuschwander-Tetri, Brent A.; Schwimmer, Jeffrey B.; Sanyal, Arun J.; Chalasani, Naga; Ryan, Kathleen A.; Mitchell, Braxton D.; Gill, Dipender; Wells, Andrew D.; Manduchi, Elisabetta; Saiman, Yedidya; Mahmud, Nadim; Miller, Donald R.; Reaven, Peter D.; Phillips, Lawrence S.; Muralidhar, Sumitra; DuVall, Scott L.; Lee, Jennifer S.; Assimes, Themistocles L.; Pyarajan, Saiju; Cho, Kelly; Edwards, Todd L.; Damrauer, Scott M.; Wilson, Peter W.; Gaziano, J. Michael; O'Donnell, Christopher J.; Khera, Amit V.; Grant, Struan F. A.; Brown, Christopher D.; Tsao, Philip S.; Saleheen, Danish; Lotta, Luca A.; Bastarache, Lisa; Anstee, Quentin M.; Daly, Ann K.; Meigs, James B.; Rotter, Jerome I.; Lynch, Julie A.; Regeneron Genetics Center; Geisinger-Regeneron DiscovEHR Collaboration; EPoS Consortium; VA Million Veteran Program; Rader, Daniel J.; Voight, Benjamin F.; Chang, Kyong-Mi; Medicine, School of Medicine
    Nonalcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver disease. Using a proxy NAFLD definition of chronic elevation of alanine aminotransferase (cALT) levels without other liver diseases, we performed a multiancestry genome-wide association study (GWAS) in the Million Veteran Program (MVP) including 90,408 cALT cases and 128,187 controls. Seventy-seven loci exceeded genome-wide significance, including 25 without prior NAFLD or alanine aminotransferase associations, with one additional locus identified in European American-only and two in African American-only analyses (P < 5 × 10-8). External replication in histology-defined NAFLD cohorts (7,397 cases and 56,785 controls) or radiologic imaging cohorts (n = 44,289) replicated 17 single-nucleotide polymorphisms (SNPs) (P < 6.5 × 10-4), of which 9 were new (TRIB1, PPARG, MTTP, SERPINA1, FTO, IL1RN, COBLL1, APOH and IFI30). Pleiotropy analysis showed that 61 of 77 multiancestry and all 17 replicated SNPs were jointly associated with metabolic and/or inflammatory traits, revealing a complex model of genetic architecture. Our approach integrating cALT, histology and imaging reveals new insights into genetic liability to NAFLD.
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    American College of Sports Medicine (ACSM) International Multidisciplinary Roundtable report on physical activity and nonalcoholic fatty liver disease
    (Wolters Kluwer, 2023-03-30) Stine, Jonathan G.; Long, Michelle T.; Corey, Kathleen E.; Sallis, Robert E.; Allen, Alina M.; Armstrong, Matthew J.; Conroy, David E.; Cuthbertson, Daniel J.; Duarte-Rojo, Andres; Hallsworth, Kate; Hickman, Ingrid J.; Kappus, Matthew R.; Keating, Shelley E.; Pugh, Christopher J. A.; Rotman, Yaron; Simon, Tracey G.; Vilar-Gomez, Eduardo; Wong, Vincent Wai-Sun; Schmitz, Kathryn H.; Medicine, School of Medicine
    Background and aims: We present findings from the inaugural American College of Sports Medicine (ACSM) International Multidisciplinary Roundtable, which was convened to evaluate the evidence for physical activity as a means of preventing or modifying the course of NAFLD. Approach and results: A scoping review was conducted to map the scientific literature and identify key concepts, research gaps, and evidence available to inform clinical practice, policymaking, and research. The scientific evidence demonstrated regular physical activity is associated with decreased risk of NAFLD development. Low physical activity is associated with a greater risk for disease progression and extrahepatic cancer. During routine health care visits, all patients with NAFLD should be screened for and counseled about physical activity benefits, including reduction in liver fat and improvement in body composition, fitness, and quality of life. While most physical activity benefits occur without clinically significant weight loss, evidence remains limited regarding the association between physical activity and liver fibrosis. At least 150 min/wk of moderate or 75 min/wk of vigorous-intensity physical activity are recommended for all patients with NAFLD. If a formal exercise training program is prescribed, aerobic exercise with the addition of resistance training is preferred. Conclusions: The panel found consistent and compelling evidence that regular physical activity plays an important role in preventing NAFLD and improving intermediate clinical outcomes. Health care, fitness, and public health professionals are strongly encouraged to disseminate the information in this report. Future research should prioritize determining optimal strategies for promoting physical activity among individuals at risk and in those already diagnosed with NAFLD.
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    MELD-Na Is More Strongly Associated with Risk of Infection and Outcomes Than Other Characteristics of Patients with Cirrhosis
    (Springer Nature, 2021) Fricker, Zachary P.; Mukthinuthalapati, V. V. Pavan Kedar; Akinyeye, Samuel; Chalasani, Naga; Attar, Bashar M.; Balakrishnan, Maya; Ghabril, Marwan; Long, Michelle T.; Medicine, School of Medicine
    Background and aims: The nature and outcomes of infection among patients with cirrhosis in safety-net hospitals are not well described. We aimed to characterize the rate of and risk factors for infection, both present on admission and nosocomial, in this unique population. We hypothesized that infections would be associated with adverse outcomes such as short-term mortality. Methods: We used descriptive statistics to characterize infections within a retrospective cohort characterized previously. We used multivariable logistic regression models to assess potential risk factors for infection and associations with key outcomes such as short-term mortality and length of stay. Results: The study cohort of 1112 patients included 33% women with a mean age of 56 ± 10 years. Infections were common (20%), with respiratory and urinary tract infections the most frequent. We did not observe a difference in the incidence of infection on admission based on patient demographic factors such as race/ethnicity or estimated household income. Infections on admission were associated with greater short-term mortality (12% vs 4% in-hospital and 14% vs 7% 30-day), longer length of stay (6 vs 3 days), intensive care unit admission (28% vs 18%), and acute-on-chronic liver failure (10% vs 2%) (p < 0.01 for all). Nosocomial infections were relatively uncommon (4%), but more frequent among patients admitted to the intensive care unit. Antibiotic resistance was common (38%), but not associated with negative outcomes. Conclusion: We did not identify demographic risk factors for infection, but did confirm its morbid effect among patients with cirrhosis in safety-net hospitals.
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    Physical Activity and Nonalcoholic Fatty Liver Disease: A Roundtable Statement from the American College of Sports Medicine
    (Wolters Kluwer, 2023) Stine, Jonathan G.; Long, Michelle T.; Corey, Kathleen E.; Sallis, Robert E.; Allen, Alina M.; Armstrong, Matthew J.; Conroy, David E.; Cuthbertson, Daniel J.; Duarte-Rojo, Andres; Hallsworth, Kate; Hickman, Ingrid J.; Kappus, Matthew R.; Keating, Shelley E.; Pugh, Christopher J. A.; Rotman, Yaron; Simon, Tracey L.; Vilar-Gomez, Eduardo; Wai-Sun Wong, Vincent; Schmitz, Kathryn H.; Medicine, School of Medicine
    Although physical activity (PA) is crucial in the prevention and clinical management of nonalcoholic fatty liver disease, most individuals with this chronic disease are inactive and do not achieve recommended amounts of PA. There is a robust and consistent body of evidence highlighting the benefit of participating in regular PA, including a reduction in liver fat and improvement in body composition, cardiorespiratory fitness, vascular biology, and health-related quality of life. Importantly, the benefits of regular PA can be seen without clinically significant weight loss. At least 150 min of moderate or 75 min of vigorous intensity PA are recommended weekly for all patients with nonalcoholic fatty liver disease, including those with compensated cirrhosis. If a formal exercise training program is prescribed, aerobic exercise with the addition of resistance training is preferred. In this roundtable document, the benefits of PA are discussed, along with recommendations for 1) PA assessment and screening; 2) how best to advise, counsel, and prescribe regular PA; and 3) when to refer to an exercise specialist.