About

Mary Rinella, MD is a Professor of Medicine in the Gastroenterology, Hepatology and Nutrition section at the University of Chicago since January 2021. She is the director of the Metabolic and Fatty Liver Program and also serves as the Director of Clinical Trials for the section. Her research and clinical focus are centered on metabolic liver disease, including fatty liver disease, cholestatic liver diseases such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), autoimmune liver diseases, and complications of cirrhosis and portal hypertension. Dr. Rinella has held several national leadership roles, including on the Governing Board of the American Association for the Study of Liver Disease (AASLD), and has contributed significantly to the field through her work as lead author of the 2023 AASLD Clinical Practice Guidance on the diagnosis and management of NAFLD, now MASLD. She has led efforts to revise the nomenclature of NAFLD, served as Chair of the AASLD Steatotic Liver Disease (SLD) task force, and has been involved in increasing disease awareness, developing best practices, and fostering global collaborations to improve patient care and outcomes. Her multidisciplinary clinic provides personalized care for patients with fatty liver disease, offering access to the latest therapies and clinical trials.

Research topics

• Medicine
• Gastroenterology
• Pathology
• Internal medicine
• Political Science
• Art history
• Endocrinology
• Gerontology
• History
• Classics
• Law

Selected publications

• Semaglutide 2.4 mg in Participants With Metabolic Dysfunction‐Associated Steatohepatitis: Baseline Characteristics and Design of the Phase 3 <scp>ESSENCE</scp> Trial

  Alimentary Pharmacology & Therapeutics · 2024 · 116 citations

  • Medicine
  • Internal medicine
  • Gastroenterology

  BACKGROUND: Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated potential beneficial effects in metabolic dysfunction-associated steatohepatitis (MASH). AIMS: To describe the trial design and baseline characteristics of the 'Effect of Semaglutide in Subjects with Non-cirrhotic Non-alcoholic Steatohepatitis' (ESSENCE) trial (NCT04822181). METHODS: ESSENCE is a two-part, phase 3, randomised, multicentre trial evaluating the effect of subcutaneous semaglutide 2.4 mg in participants with biopsy-proven MASH and fibrosis stage 2 or 3. The primary objective of Part 1 is to demonstrate that semaglutide improves liver histology compared with placebo. The two primary endpoints are: resolution of steatohepatitis and no worsening of liver fibrosis, and improvement in liver fibrosis and no worsening of steatohepatitis. The Part 2 objective is based on clinical outcomes. The current work reports baseline characteristics of the first 800 randomised participants which includes demographics, laboratory parameters, liver histology, non-invasive tests and presence of metabolic dysfunction-associated steatotic liver disease (MASLD) cardiometabolic criteria. RESULTS: , 55.5% had type 2 diabetes and > 99% had at least one MASLD cardiometabolic criterion according to the published definition. CONCLUSION: The ESSENCE baseline population includes participants with clinically significant fibrosis stages 2 and 3. Although MASLD cardiometabolic criteria were not a requirement for study enrolment, almost all participants (> 99%) had at least one MASLD cardiometabolic criterion. TRIAL REGISTRATION: NCT04822181.

  DOI

• A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis

  New England Journal of Medicine · 2024 · 1585 citations

  • Internal medicine
  • Medicine
  • Gastroenterology

  BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a progressive liver disease with no approved treatment. Resmetirom is an oral, liver-directed, thyroid hormone receptor beta-selective agonist in development for the treatment of NASH with liver fibrosis. METHODS: We are conducting an ongoing phase 3 trial involving adults with biopsy-confirmed NASH and a fibrosis stage of F1B, F2, or F3 (stages range from F0 [no fibrosis] to F4 [cirrhosis]). Patients were randomly assigned in a 1:1:1 ratio to receive once-daily resmetirom at a dose of 80 mg or 100 mg or placebo. The two primary end points at week 52 were NASH resolution (including a reduction in the nonalcoholic fatty liver disease [NAFLD] activity score by ≥2 points; scores range from 0 to 8, with higher scores indicating more severe disease) with no worsening of fibrosis, and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score. RESULTS: Overall, 966 patients formed the primary analysis population (322 in the 80-mg resmetirom group, 323 in the 100-mg resmetirom group, and 321 in the placebo group). NASH resolution with no worsening of fibrosis was achieved in 25.9% of the patients in the 80-mg resmetirom group and 29.9% of those in the 100-mg resmetirom group, as compared with 9.7% of those in the placebo group (P<0.001 for both comparisons with placebo). Fibrosis improvement by at least one stage with no worsening of the NAFLD activity score was achieved in 24.2% of the patients in the 80-mg resmetirom group and 25.9% of those in the 100-mg resmetirom group, as compared with 14.2% of those in the placebo group (P<0.001 for both comparisons with placebo). The change in low-density lipoprotein cholesterol levels from baseline to week 24 was -13.6% in the 80-mg resmetirom group and -16.3% in the 100-mg resmetirom group, as compared with 0.1% in the placebo group (P<0.001 for both comparisons with placebo). Diarrhea and nausea were more frequent with resmetirom than with placebo. The incidence of serious adverse events was similar across trial groups: 10.9% in the 80-mg resmetirom group, 12.7% in the 100-mg resmetirom group, and 11.5% in the placebo group. CONCLUSIONS: Both the 80-mg dose and the 100-mg dose of resmetirom were superior to placebo with respect to NASH resolution and improvement in liver fibrosis by at least one stage. (Funded by Madrigal Pharmaceuticals; MAESTRO-NASH ClinicalTrials.gov number, NCT03900429.).

  DOI

• Colonel Stephen A. Harrison, M.D. – The passing of a Titan

  Journal of Hepatology · 2024

  Senior authorCorresponding
  • Political Science
  • Classics
  • History
  DOI

• A global research priority agenda to advance public health responses to fatty liver disease

  Journal of Hepatology · 2023 · 128 citations

  • Political Science
  • Computer Science
  • Medicine

  BACKGROUND & AIMS: An estimated 38% of adults worldwide have non-alcoholic fatty liver disease (NAFLD). From individual impacts to widespread public health and economic consequences, the implications of this disease are profound. This study aimed to develop an aligned, prioritised fatty liver disease research agenda for the global health community. METHODS: Nine co-chairs drafted initial research priorities, subsequently reviewed by 40 core authors and debated during a three-day in-person meeting. Following a Delphi methodology, over two rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the priorities, via Qualtrics XM, indicating agreement using a four-point Likert-scale and providing written feedback. The core group revised the draft priorities between rounds. In R2, panellists also ranked the priorities within six domains: epidemiology, models of care, treatment and care, education and awareness, patient and community perspectives, and leadership and public health policy. RESULTS: The consensus-built fatty liver disease research agenda encompasses 28 priorities. The mean percentage of 'agree' responses increased from 78.3 in R1 to 81.1 in R2. Five priorities received unanimous combined agreement ('agree' + 'somewhat agree'); the remaining 23 priorities had >90% combined agreement. While all but one of the priorities exhibited at least a super-majority of agreement (>66.7% 'agree'), 13 priorities had <80% 'agree', with greater reliance on 'somewhat agree' to achieve >90% combined agreement. CONCLUSIONS: Adopting this multidisciplinary consensus-built research priorities agenda can deliver a step-change in addressing fatty liver disease, mitigating against its individual and societal harms and proactively altering its natural history through prevention, identification, treatment, and care. This agenda should catalyse the global health community's efforts to advance and accelerate responses to this widespread and fast-growing public health threat. IMPACT AND IMPLICATIONS: An estimated 38% of adults and 13% of children and adolescents worldwide have fatty liver disease, making it the most prevalent liver disease in history. Despite substantial scientific progress in the past three decades, the burden continues to grow, with an urgent need to advance understanding of how to prevent, manage, and treat the disease. Through a global consensus process, a multidisciplinary group agreed on 28 research priorities covering a broad range of themes, from disease burden, treatment, and health system responses to awareness and policy. The findings have relevance for clinical and non-clinical researchers as well as funders working on fatty liver disease and non-communicable diseases more broadly, setting out a prioritised, ranked research agenda for turning the tide on this fast-growing public health threat.

  DOI

• Bifidobacteria metabolize lactulose to optimize gut metabolites and prevent systemic infection in patients with liver disease

  Nature Microbiology · 2023 · 62 citations

  • Biology
  • Gastroenterology
  • Microbiology
  PublisherOA PDFDOI

• Advancing the global public health agenda for NAFLD: a consensus statement

  Nature Reviews Gastroenterology & Hepatology · 2021 · 721 citations

  • Political Science
  • Medicine
  • Environmental health

  Non-alcoholic fatty liver disease (NAFLD) is a potentially serious liver disease that affects approximately one-quarter of the global adult population, causing a substantial burden of ill health with wide-ranging social and economic implications. It is a multisystem disease and is considered the hepatic component of metabolic syndrome. Unlike other highly prevalent conditions, NAFLD has received little attention from the global public health community. Health system and public health responses to NAFLD have been weak and fragmented, and, despite its pervasiveness, NAFLD is largely unknown outside hepatology and gastroenterology. There is only a nascent global public health movement addressing NAFLD, and the disease is absent from nearly all national and international strategies and policies for non-communicable diseases, including obesity. In this global Delphi study, a multidisciplinary group of experts developed consensus statements and recommendations, which a larger group of collaborators reviewed over three rounds until consensus was achieved. The resulting consensus statements and recommendations address a broad range of topics - from epidemiology, awareness, care and treatment to public health policies and leadership - that have general relevance for policy-makers, health-care practitioners, civil society groups, research institutions and affected populations. These recommendations should provide a strong foundation for a comprehensive public health response to NAFLD.

  DOI

• TVB-2640 (FASN Inhibitor) for the Treatment of Nonalcoholic Steatohepatitis: FASCINATE-1, a Randomized, Placebo-Controlled Phase 2a Trial

  Gastroenterology · 2021 · 214 citations

  • Gastroenterology
  • Internal medicine
  • Medicine

  BACKGROUND & AIMS: Increased de novo lipogenesis creates excess intrahepatic fat and lipotoxins, propagating liver damage in nonalcoholic steatohepatitis. TVB-2640, a fatty acid synthase inhibitor, was designed to reduce excess liver fat and directly inhibit inflammatory and fibrogenic pathways. We assessed the safety and efficacy of TVB-2640 in patients with nonalcoholic steatohepatitis in the United States. METHODS: 3V2640-CLIN-005 (FASCINATE-1) was a randomized, placebo-controlled, single-blind study at 10 US sites. Adults with ≥8% liver fat, assessed by magnetic resonance imaging proton density fat fraction, and evidence of liver fibrosis by magnetic resonance elastography ≥2.5 kPa or liver biopsy were eligible. Ninety-nine patients were randomized to receive placebo or 25 mg or 50 mg of TVB-2640 (orally, once-daily for 12 weeks). The primary end points of this study were safety and relative change in liver fat after treatment. RESULTS: Liver fat increased in the placebo cohort by 4.5% relative to baseline; in contrast TVB-2640 reduced liver fat by 9.6% in the 25-mg cohort (n = 30; least squares mean: -15.5%; 95% confidence interval, -31.3 to -0.23; P = .053), and 28.1% in the 50-mg cohort (n = 28; least squares mean: -28.0%; 95% confidence interval, -44.5 to -11.6; P = .001). Eleven percent of patients in the placebo group achieved a ≥30% relative reduction of liver fat compared to 23% in the 25-mg group, and 61% in the 50-mg group (P < .001). Secondary analyses showed improvements of metabolic, pro-inflammatory and fibrotic markers. TVB-2640 was well tolerated; adverse events were mostly mild and balanced among the groups. CONCLUSIONS: TVB-2640 significantly reduced liver fat and improved biochemical, inflammatory, and fibrotic biomarkers after 12 weeks, in a dose-dependent manner in patients with nonalcoholic steatohepatitis. ClinicalTrials.gov, Number NCT03938246.

  DOI

• MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease

  Gastroenterology · 2020 · 3222 citations

  • Medicine
  • Computational biology
  • Biology
  DOI

• Selonsertib for patients with bridging fibrosis or compensated cirrhosis due to NASH: Results from randomized phase III STELLAR trials

  Journal of Hepatology · 2020 · 458 citations

  • Computer Science
  • Medicine
  • Internal medicine
  DOI

• Emricasan to prevent new decompensation in patients with NASH-related decompensated cirrhosis

  Journal of Hepatology · 2020 · 60 citations

  • Medicine
  • Intensive care medicine
  • Internal medicine
  PublisherDOI

Frequent coauthors

• Philip N. Newsome

  King's College London

  14 shared

• Vlad Ratziu

  Sorbonne Université

  11 shared

• Quentin M. Anstee

  9 shared

• Arun J. Sanyal

  Virginia Commonwealth University

  5 shared

• Jörn M. Schattenberg

  University Medical Center of the Johannes Gutenberg University Mainz

  5 shared

• Rohit Loomba

  4 shared

• David Sheridan

  University of Plymouth

  4 shared

• Juan M. Pericàs

  4 shared

Awards & honors

• Lead author of the 2023 AASLD Clinical Practice Guidance on…
• Chair of the AASLD Steatotic Liver Disease (SLD) task force

Similar researchers at University of Chicago

• Everett E. Vokesh-185
• Ian Fosterh-150
• Jack W. Szostakh-142
• Jean Decetyh-142
• Graeme Bellh-141