Portal chronic inflammation in nonalcoholic fatty liver disease (NAFLD): A histologic marker of advanced NAFLD - Clinicopathologic correlations from the nonalcoholic steatohepatitis clinical research network

Elizabeth M. Brunt, David E. Kleiner, Laura A. Wilson, Aynur Unalp, Cynthia E. Behling, Joel E. Lavine, Brent A. Neuschwander-Tetri, Stephanie Abrams, Diana Arceo, Denise Espinosa, Leanel Fairly, Diane Bringman, Carol Hawkins, Yao Chang Liu, Nicholette Rogers, Margaret Stager, Arthur McCullough, Srinivasan Dasarathy, Kevin Edwards, Ruth SargentMelissa Coffey, Karen Murray, Melissa Young, Parvathi Mohan, Kavita Nair, Manal Abdelmalek, Anna Mae Diehl, Marcia Gottfried, Cynthia Guy, Paul Killenberg, Samantha Kwan, Yi Ping Pan, Dawn Piercy, Melissa Smith, Prajakta Bhimalli, Naga Chalasani, Oscar W. Cummings, Lydia Lee, Linda Ragozzino, Raj Vuppalanchi, Barbara Calabrese, Debra Peglow, Ann Scheimann, Michael Torbenson, Ann Klipsch, Jean Molleston, Girish Subbarao, Sarah Barlow, Jose Derdoy, Joyce Hoffmann, Debra King, Joan Siegner, Susan Stewart, Brent A. Tetri, Judy Thompson, Cynthia Behling, Manual Celedon, Lisa Clark, Janis Durelle, Tarek Hassanein, Joel E. Lavine, Susana Mendoza, Jeffrey B. Schwimmer, Claude Sirlin, Tanya Stein, Allison Tobin, Kiran Bambha, Nathan M. Bass, Linda D. Ferrell, Danuta Filipowski, Raphael Merriman, Mark Pabst, Monique Rosenthal, Philip Rosenthal, Tessa Steel, Sherry Boyett, Daphne Bryan, Melissa J. Contos, Michael Fuchs, Martin Graham, Amy Jones, Velimir A.C. Luketic, Bimalijit Sandhu, Arun J. Sanyal, 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, Elizabeth Brunt, David Kleiner, Gilman D. Grave, Terry T.K. Huang, Edward Doo, Jay Everhart, Jay Hoofnagle, Patricia R. Robuck, Leonard Seeff, Patricia Belt, Fred Brancati, Jeanne Clark, Ryan Colvin, Michel Donithan, Mika Green, Rosemary Hollick, Milana Isaacson, Wana Kim, Alison Lyndecker, Laura Miriel, Alice Sternberg, James Tonascia, Aynur Ünalp-Arida, Mark Van Natta, Laura Wilson, Katherine Yates

Research output: Contribution to journalArticle

215 Scopus citations

Abstract

Adult nonalcoholic fatty liver disease (NAFLD) is characterized by absent or mild portal chronic inflammation (CI); in children, portal CI may be predominant. This study correlated clinical features with portal CI. Centrally-graded biopsies and temporally-related clinical parameters from 728 adults and 205 children. From the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) were evaluated. Mild, more than mild and no portal CI were found in 60%, 23% and 16% of adult biopsies and 76%, 14% and 10% of pediatric biopsies. Autoantibodies, and elevated alanine aminotransferase were not associated with portal CI. Clinical features associated with "more than mild" in adults were older age (P<0.0001), female gender (P= 0.001), higher body mass index (P < 0.0001), elevated insulin levels (P = 0.001), higher homeostasis model assessment of insulin resistance score (HOMA-IR) (P < 0.0001), and medications used for NAFLD (P=0.0004), diabetes (P<0.0001), and hypertension (P<0.0001). "More than mild" in the pediatric biopsies correlated with younger age (P=0.01), but not with body mass index, insulin or HOMA-IR. In both groups, lobular and portal inflammation scores had no association, but there was an association with definite steatohepatitis (P < 0.0001). Features associated in the adult biopsies with "more than mild" were steatosis amount (P=0.01) and location (P<0.0001), ballooning (P<0.0001), and advanced fibrosis (P<0.0001). In the pediatric biopsies, "more than mild" was associated with steatosis location (P = 0.0008) and fibrosis score (P < 0.0001), specifically, the portal/periportal fibrosis or greater fibrosis) (P < 0.01). Conclusion: Increased portal CI is associated with many clinical and pathologic features of progressive NAFLD in both adults and children, but not with ALT, autoantibodies, or lobular inflammation. More than mild portal CI in liver biopsies of untreated NAFLD may be considered a marker of advanced disease.

Original languageEnglish (US)
Pages (from-to)809-820
Number of pages12
JournalHepatology
Volume49
Issue number3
DOIs
StatePublished - Jun 24 2009

ASJC Scopus subject areas

  • Hepatology

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    Brunt, E. M., Kleiner, D. E., Wilson, L. A., Unalp, A., Behling, C. E., Lavine, J. E., Neuschwander-Tetri, B. A., Abrams, S., Arceo, D., Espinosa, D., Fairly, L., Bringman, D., Hawkins, C., Liu, Y. C., Rogers, N., Stager, M., McCullough, A., Dasarathy, S., Edwards, K., ... Yates, K. (2009). Portal chronic inflammation in nonalcoholic fatty liver disease (NAFLD): A histologic marker of advanced NAFLD - Clinicopathologic correlations from the nonalcoholic steatohepatitis clinical research network. Hepatology, 49(3), 809-820. https://doi.org/10.1002/hep.22724