Clinical, laboratory and histological associations in adults with nonalcoholic fatty liver disease
Brent A Neuschwander-Tetri, Jeanne M Clark, Nathan M Bass, Mark L Van Natta, Aynur Unalp-Arida, James Tonascia, Claudia O Zein, Elizabeth M Brunt, David E Kleiner, Arthur J McCullough, Arun J Sanyal, Anna Mae Diehl, Joel E Lavine, Naga Chalasani, Kris V Kowdley, NASH Clinical Research Network, Arthur McCullough, Diane Bringman, Srinivasan Dasarathy, Kevin Edwards, Carol Hawkins, Yao-Chang Liu, Nicholette Rogers, Ruth Sargent, Margaret Stager, Anna Mae Diehl, Manal Abdelmalek, Marcia Gottfried, Cynthia Guy, Paul Killenberg, Samantha Kwan, Yi-Ping Pan, Dawn Piercy, Melissa Smith, Naga Chalasani, Prajakta Bhimalli, Oscar W Cummings, Ann Klipsch, Lydia Lee, Jean Molleston, Linda Ragozzino, Raj Vuppalanchi, Brent A Neuschwander-Tetri, Sarah Barlow, Jose Derdoy, Joyce Hoffmann, Debra King, Joan Siegner, Susan Stewart, Judy Thompson, Elizabeth Brunt, Joel E Lavine, Cynthia Behling, Lisa Clark, Janis Durelle, Tarek Hassanein, Lita Petcharaporn, Jeffrey B Schwimmer, Claude Sirlin, Tanya Stein, Nathan M Bass, Kiran Bambha, Linda D Ferrell, Danuta Filipowski, Raphael Merriman, Mark Pabst, Monique Rosenthal, Philip Rosenthal, Tessa Steel, Arun J Sanyal, Sherry Boyett, Daphne Bryan, Melissa J Contos, Michael Fuchs, Martin Graham, Amy Jones, Velimir A C Luketic, Bimalijit Sandhu, Carol Sargeant, Kimberly Selph, Melanie White, Kris V Kowdley, Grace Gyurkey, Jody Mooney, James Nelson, Sarah Roberts, Cheryl Saunders, Alice Stead, Chia Wang, Matthew Yeh, David Kleiner, Edward Doo, Jay Everhart, Jay H Hoofnagle, Patricia R Robuck, Leonard Seeff, James Tonascia, Patricia Belt, Fred Brancati, Jeanne Clark, Ryan Colvin, Michele Donithan, Mika Green, Milana Isaacson, Wana Kim, Laura Miriel, Alice Sternberg, Aynur Unalp, Mark Van Natta, Laura Wilson, Katherine Yates, Brent A Neuschwander-Tetri, Jeanne M Clark, Nathan M Bass, Mark L Van Natta, Aynur Unalp-Arida, James Tonascia, Claudia O Zein, Elizabeth M Brunt, David E Kleiner, Arthur J McCullough, Arun J Sanyal, Anna Mae Diehl, Joel E Lavine, Naga Chalasani, Kris V Kowdley, NASH Clinical Research Network, Arthur McCullough, Diane Bringman, Srinivasan Dasarathy, Kevin Edwards, Carol Hawkins, Yao-Chang Liu, Nicholette Rogers, Ruth Sargent, Margaret Stager, Anna Mae Diehl, Manal Abdelmalek, Marcia Gottfried, Cynthia Guy, Paul Killenberg, Samantha Kwan, Yi-Ping Pan, Dawn Piercy, Melissa Smith, Naga Chalasani, Prajakta Bhimalli, Oscar W Cummings, Ann Klipsch, Lydia Lee, Jean Molleston, Linda Ragozzino, Raj Vuppalanchi, Brent A Neuschwander-Tetri, Sarah Barlow, Jose Derdoy, Joyce Hoffmann, Debra King, Joan Siegner, Susan Stewart, Judy Thompson, Elizabeth Brunt, Joel E Lavine, Cynthia Behling, Lisa Clark, Janis Durelle, Tarek Hassanein, Lita Petcharaporn, Jeffrey B Schwimmer, Claude Sirlin, Tanya Stein, Nathan M Bass, Kiran Bambha, Linda D Ferrell, Danuta Filipowski, Raphael Merriman, Mark Pabst, Monique Rosenthal, Philip Rosenthal, Tessa Steel, Arun J Sanyal, Sherry Boyett, Daphne Bryan, Melissa J Contos, Michael Fuchs, Martin Graham, Amy Jones, Velimir A C Luketic, Bimalijit Sandhu, Carol Sargeant, Kimberly Selph, Melanie White, Kris V Kowdley, Grace Gyurkey, Jody Mooney, James Nelson, Sarah Roberts, Cheryl Saunders, Alice Stead, Chia Wang, Matthew Yeh, David Kleiner, Edward Doo, Jay Everhart, Jay H Hoofnagle, Patricia R Robuck, Leonard Seeff, James Tonascia, Patricia Belt, Fred Brancati, Jeanne Clark, Ryan Colvin, Michele Donithan, Mika Green, Milana Isaacson, Wana Kim, Laura Miriel, Alice Sternberg, Aynur Unalp, Mark Van Natta, Laura Wilson, Katherine Yates
Abstract
The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) was formed to conduct multicenter studies on the etiology, contributing factors, natural history, and treatment of nonalcoholic steatohepatitis (NASH). The aim of this study was to determine the associations of readily available demographic, clinical, and laboratory variables with the diagnosis of NASH and its key histological features, and determine the ability of these variables to predict the severity of nonalcoholic fatty liver disease (NAFLD). A total of 1266 adults were enrolled in NASH CRN studies between October 2004 and February 2008, of whom 1101 had available liver histology. The median age was 50 years; 82% were white and 12% Hispanic. The median body mass index was 33 kg/m(2); 49% had hypertension and 31% had type 2 diabetes. On liver biopsy, 57% were judged to have definite NASH and 31% bridging fibrosis or cirrhosis. Using data from the 698 patients with liver biopsies within 6 months of clinical data, patients with definite NASH were more likely to be female and have diabetes, higher levels of aspartate and alanine aminotransferases, alkaline phosphatase, gamma glutamyl transpeptidase, and homeostasis model assessment of insulin resistance (HOMA-IR). Progressive models for predicting histological diagnoses performed modestly for predicting steatohepatitis or ballooning (area under receiver operating characteristic curves [AUROC] ranged from 0.70-0.79), and better for advanced fibrosis (AUROC 0.73-0.85).
Conclusion: Readily available clinical and laboratory variables can predict advanced fibrosis in adults with NAFLD, but additional information is needed to reliably predict the presence and severity of NASH. Prospective studies of this well-characterized population and associated tissue bank samples offer a unique opportunity to better understand the cause and natural history of NAFLD and develop more precise means for noninvasive diagnosis.
Source: PubMed