New England Journal of Medicine

Sven M. Francque, M.D., Ph.D., Pierre Bedossa, M.D., Ph.D., Vlad Ratziu, M.D., Ph.D., Quentin M. Anstee, M.D., Ph.D., Elisabetta Bugianesi, M.D., Ph.D., Arun J. Sanyal, M.D., Rohit Loomba, M.D., M.H.Sc., Stephen A. Harrison, M.D., Rozalina Balabanska, M.D., Lyudmila Mateva, M.D., Ph.D., Nicolas Lanthier, M.D., Ph.D., Naim Alkhouri, M.D., Christophe Moreno, M.D., Ph.D., Jörn M. Schattenberg, M.D., Diana Stefanova-Petrova, M.D., Luisa Vonghia, M.D., Ph.D., Régine Rouzier, M.D., Maeva Guillaume, M.D., Ph.D., Alexander Hodge, M.B., B.S., Ph.D., Manuel Romero-Gómez, M.D., Ph.D., Philippe Huot-Marchand, M.Sc., Martine Baudin, M.D., Marie-Paule Richard, M.D., Jean-Louis Abitbol, M.D., Pierre Broqua, Ph.D., Jean-Louis Junien, Ph.D., and Manal F. Abdelmalek, M.D., M.P.H. for the NATIVE Study Group*

doi : 10.1056/NEJMoa2036205

N Engl J Med 2021; 385:1547-1558

Management of nonalcoholic steatohepatitis (NASH) is an unmet clinical need. Lanifibranor is a pan-PPAR (peroxisome proliferator–activated receptor) agonist that modulates key metabolic, inflammatory, and fibrogenic pathways in the pathogenesis of NASH.

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Prospective Study of Outcomes in Adults with Nonalcoholic Fatty Liver Disease

Arun J. Sanyal, M.D., Mark L. Van Natta, M.H.S., Jeanne Clark, M.D., M.P.H., Brent A. Neuschwander-Tetri, M.D., AnnaMae Diehl, M.D., Srinivasan Dasarathy, M.D., Rohit Loomba, M.D., M.H.Sc., Naga Chalasani, M.D., Kris Kowdley, M.D., Bilal Hameed, M.D., Laura A. Wilson, Sc.M., Katherine P. Yates, Sc.M., Patricia Belt, B.S., Mariana Lazo, M.D., Ph.D., David E. Kleiner, M.D., Ph.D., Cynthia Behling, M.D., Ph.D., and James Tonascia, Ph.D. for the NASH Clinical Research Network (CRN)*

doi : 10.1056/NEJMoa2029349

N Engl J Med 2021; 385:1559-1569

The prognoses with respect to mortality and hepatic and nonhepatic outcomes across the histologic spectrum of nonalcoholic fatty liver disease (NAFLD) are not well defined.

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AQP1 Promoter Variant, Water Transport, and Outcomes in Peritoneal Dialysis

Johann Morelle, M.D., Ph.D., Céline Marechal, Ph.D., Zanzhe Yu, M.D., Ph.D., Huguette Debaix, M.Sc., Tanguy Corre, Ph.D., Mark Lambie, M.D., Ph.D., Marion Verduijn, Ph.D., Friedo Dekker, Ph.D., Philippe Bovy, M.D., Pieter Evenepoel, M.D., Ph.D., Bert Bammens, M.D., Ph.D., Rafael Selgas, M.D., Ph.D., Maria A. Bajo, M.D., Ph.D., Annemieke M. Coester, M.D., Ph.D., Amadou Sow, M.D., Ph.D., Nicolas Hautem, Ph.D., Dirk G. Struijk, M.D., Ph.D., Raymond T. Krediet, M.D., Ph.D., Jean-Luc Balligand, M.D., Ph.D., Eric Goffin, M.D., Ralph Crott, Ph.D., Pierre Ripoche, Ph.D., Simon Davies, M.D., and Olivier Devuyst, M.D., Ph.D.

doi : 10.1056/NEJMoa2034279

N Engl J Med 2021; 385:1570-1580

Variability in ultrafiltration influences prescriptions and outcomes in patients with kidney failure who are treated with peritoneal dialysis. Variants in AQP1, the gene that encodes the archetypal water channel aquaporin-1, may contribute to that variability.

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Obesity-Associated GNAS Mutations and the Melanocortin Pathway

Edson Mendes de Oliveira, Ph.D., Julia M. Keogh, B.Sc., Fleur Talbot, M.B., B.S., Ph.D., Elana Henning, B.Soc.Sc., Rachel Ahmed, B.Sc., Aliki Perdikari, Ph.D., Rebecca Bounds, Ph.D., Natalia Wasiluk, M.Sc., Vikram Ayinampudi, B.Sc., Inês Barroso, Ph.D., Jacek Mokrosi?ski, Ph.D., Deepthi Jyothish, M.B., B.S., Sharon Lim, M.B., Ch.B., Sanjay Gupta, M.B., B.S., Melanie Kershaw, M.B., Ch.B., Cristina Matei, M.D., Praveen Partha, M.B., B.S., Tabitha Randell, M.B., Ch.B., Antoinette McAulay, M.B., Ch.B., M.D., Louise C. Wilson, M.B., Ch.B., Tim Cheetham, M.B., Ch.B., M.D., Elizabeth C. Crowne, M.B., B.S., M.D., Peter Clayton, M.B., Ch.B., M.D., and I. Sadaf Farooqi, M.B., Ch.B., Ph.D.

doi : 10.1056/NEJMoa2103329

N Engl J Med 2021; 385:1581-1592

GNAS encodes the G?s (stimulatory G-protein alpha subunit) protein, which mediates G protein–coupled receptor (GPCR) signaling. GNAS mutations cause developmental delay, short stature, and skeletal abnormalities in a syndrome called Albright’s hereditary osteodystrophy. Because of imprinting, mutations on the maternal allele also cause obesity and hormone resistance (pseudohypoparathyroidism).

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