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 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

203 Citations (Scopus)

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
Pages (from-to)809-820
Number of pages12
JournalHepatology
Volume49
Issue number3
DOIs
StatePublished - 2009

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Inflammation
Biopsy
Research
Fibrosis
Pediatrics
Autoantibodies
Insulin Resistance
Body Mass Index
Homeostasis
Insulin
Non-alcoholic Fatty Liver Disease
Fatty Liver
Alanine Transaminase
Hypertension
Liver

ASJC Scopus subject areas

  • Hepatology
  • Medicine(all)

Cite this

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

In: Hepatology, Vol. 49, No. 3, 2009, p. 809-820.

Research output: Contribution to journalArticle

Brunt, EM, Kleiner, DE, Wilson, LA, Unalp, A, Behling, CE, Lavine, JE, Neuschwander-Tetri, BA, Abrams, S, Arceo, D, Espinosa, D, Fairly, L, Bringman, D, Hawkins, C, Liu, YC, Rogers, N, Stager, M, McCullough, A, Dasarathy, S, Edwards, K, Sargent, R, Coffey, M, Murray, K, Young, M, Mohan, P, Nair, K, Abdelmalek, M, Diehl, AM, Gottfried, M, Guy, C, Killenberg, P, Kwan, S, Pan, YP, Piercy, D, Smith, M, Bhimalli, P, Chalasani, N, Cummings, O, Lee, L, Ragozzino, L, Vuppalanchi, R, Calabrese, B, Peglow, D, Scheimann, A, Torbenson, M, Klipsch, A, Molleston, J, Subbarao, G, Barlow, S, Derdoy, J, Hoffmann, J, King, D, Siegner, J, Stewart, S, Tetri, BA, Thompson, J, Behling, C, Celedon, M, Clark, L, Durelle, J, Hassanein, T, Lavine, JE, Mendoza, S, Schwimmer, JB, Sirlin, C, Stein, T, Tobin, A, Bambha, K, Bass, NM, Ferrell, LD, Filipowski, D, Merriman, R, Pabst, M, Rosenthal, M, Rosenthal, P, Steel, T, Boyett, S, Bryan, D, Contos, MJ, Fuchs, M, Graham, M, Jones, A, Luketic, VAC, Sandhu, B, Sanyal, AJ, Sargeant, C, Selph, K, White, M, Kowdley, KV, Gyurkey, G, Mooney, J, Nelson, J, Roberts, S, Saunders, C, Stead, A, Wang, C, Yeh, M, Brunt, E, Kleiner, D, Grave, GD, Huang, TTK, Doo, E, Everhart, J, Hoofnagle, J, Robuck, PR, Seeff, L, Belt, P, Brancati, F, Clark, J, Colvin, R, Donithan, M, Green, M, Hollick, R, Isaacson, M, Kim, W, Lyndecker, A, Miriel, L, Sternberg, A, Tonascia, J, Ünalp-Arida, A, Van Natta, M, Wilson, L & 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, vol. 49, no. 3, pp. 809-820. https://doi.org/10.1002/hep.22724
Brunt, Elizabeth M. ; Kleiner, David E. ; Wilson, Laura A. ; Unalp, Aynur ; Behling, Cynthia E. ; Lavine, Joel E. ; Neuschwander-Tetri, Brent A. ; Abrams, Stephanie ; Arceo, Diana ; Espinosa, Denise ; Fairly, Leanel ; Bringman, Diane ; Hawkins, Carol ; Liu, Yao Chang ; Rogers, Nicholette ; Stager, Margaret ; McCullough, Arthur ; Dasarathy, Srinivasan ; Edwards, Kevin ; Sargent, Ruth ; Coffey, Melissa ; Murray, Karen ; Young, Melissa ; Mohan, Parvathi ; Nair, Kavita ; Abdelmalek, Manal ; Diehl, Anna Mae ; Gottfried, Marcia ; Guy, Cynthia ; Killenberg, Paul ; Kwan, Samantha ; Pan, Yi Ping ; Piercy, Dawn ; Smith, Melissa ; Bhimalli, Prajakta ; Chalasani, Naga ; Cummings, Oscar ; Lee, Lydia ; Ragozzino, Linda ; Vuppalanchi, Raj ; Calabrese, Barbara ; Peglow, Debra ; Scheimann, Ann ; Torbenson, Michael ; Klipsch, Ann ; Molleston, Jean ; Subbarao, Girish ; Barlow, Sarah ; Derdoy, Jose ; Hoffmann, Joyce ; King, Debra ; Siegner, Joan ; Stewart, Susan ; Tetri, Brent A. ; Thompson, Judy ; Behling, Cynthia ; Celedon, Manual ; Clark, Lisa ; Durelle, Janis ; Hassanein, Tarek ; Lavine, Joel E. ; Mendoza, Susana ; Schwimmer, Jeffrey B. ; Sirlin, Claude ; Stein, Tanya ; Tobin, Allison ; Bambha, Kiran ; Bass, Nathan M. ; Ferrell, Linda D. ; Filipowski, Danuta ; Merriman, Raphael ; Pabst, Mark ; Rosenthal, Monique ; Rosenthal, Philip ; Steel, Tessa ; Boyett, Sherry ; Bryan, Daphne ; Contos, Melissa J. ; Fuchs, Michael ; Graham, Martin ; Jones, Amy ; Luketic, Velimir A C ; Sandhu, Bimalijit ; Sanyal, Arun J. ; Sargeant, Carol ; Selph, Kimberly ; White, Melanie ; Kowdley, Kris V. ; Gyurkey, Grace ; Mooney, Jody ; Nelson, James ; Roberts, Sarah ; Saunders, Cheryl ; Stead, Alice ; Wang, Chia ; Yeh, Matthew ; Brunt, Elizabeth ; Kleiner, David ; Grave, Gilman D. ; Huang, Terry T K ; Doo, Edward ; Everhart, Jay ; Hoofnagle, Jay ; Robuck, Patricia R. ; Seeff, Leonard ; Belt, Patricia ; Brancati, Fred ; Clark, Jeanne ; Colvin, Ryan ; Donithan, Michel ; Green, Mika ; Hollick, Rosemary ; Isaacson, Milana ; Kim, Wana ; Lyndecker, Alison ; Miriel, Laura ; Sternberg, Alice ; Tonascia, James ; Ünalp-Arida, Aynur ; Van Natta, Mark ; Wilson, Laura ; Yates, Katherine. / Portal chronic inflammation in nonalcoholic fatty liver disease (NAFLD) : A histologic marker of advanced NAFLD - Clinicopathologic correlations from the nonalcoholic steatohepatitis clinical research network. In: Hepatology. 2009 ; Vol. 49, No. 3. pp. 809-820.
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title = "Portal chronic inflammation in nonalcoholic fatty liver disease (NAFLD): A histologic marker of advanced NAFLD - Clinicopathologic correlations from the nonalcoholic steatohepatitis clinical research network",
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.",
author = "Brunt, {Elizabeth M.} and Kleiner, {David E.} and Wilson, {Laura A.} and Aynur Unalp and Behling, {Cynthia E.} and Lavine, {Joel E.} and Neuschwander-Tetri, {Brent A.} and Stephanie Abrams and Diana Arceo and Denise Espinosa and Leanel Fairly and Diane Bringman and Carol Hawkins and Liu, {Yao Chang} and Nicholette Rogers and Margaret Stager and Arthur McCullough and Srinivasan Dasarathy and Kevin Edwards and Ruth Sargent and Melissa Coffey and Karen Murray and Melissa Young and Parvathi Mohan and Kavita Nair and Manal Abdelmalek and Diehl, {Anna Mae} and Marcia Gottfried and Cynthia Guy and Paul Killenberg and Samantha Kwan and Pan, {Yi Ping} and Dawn Piercy and Melissa Smith and Prajakta Bhimalli and Naga Chalasani and Oscar Cummings and Lydia Lee and Linda Ragozzino and Raj Vuppalanchi and Barbara Calabrese and Debra Peglow and Ann Scheimann and Michael Torbenson and Ann Klipsch and Jean Molleston and Girish Subbarao and Sarah Barlow and Jose Derdoy and Joyce Hoffmann and Debra King and Joan Siegner and Susan Stewart and Tetri, {Brent A.} and Judy Thompson and Cynthia Behling and Manual Celedon and Lisa Clark and Janis Durelle and Tarek Hassanein and Lavine, {Joel E.} and Susana Mendoza and Schwimmer, {Jeffrey B.} and Claude Sirlin and Tanya Stein and Allison Tobin and Kiran Bambha and Bass, {Nathan M.} and Ferrell, {Linda D.} and Danuta Filipowski and Raphael Merriman and Mark Pabst and Monique Rosenthal and Philip Rosenthal and Tessa Steel and Sherry Boyett and Daphne Bryan and Contos, {Melissa J.} and Michael Fuchs and Martin Graham and Amy Jones and Luketic, {Velimir A C} and Bimalijit Sandhu and Sanyal, {Arun J.} and Carol Sargeant and Kimberly Selph and Melanie White and Kowdley, {Kris V.} and Grace Gyurkey and Jody Mooney and James Nelson and Sarah Roberts and Cheryl Saunders and Alice Stead and Chia Wang and Matthew Yeh and Elizabeth Brunt and David Kleiner and Grave, {Gilman D.} and Huang, {Terry T K} and Edward Doo and Jay Everhart and Jay Hoofnagle and Robuck, {Patricia R.} and Leonard Seeff and Patricia Belt and Fred Brancati and Jeanne Clark and Ryan Colvin and Michel Donithan and Mika Green and Rosemary Hollick and Milana Isaacson and Wana Kim and Alison Lyndecker and Laura Miriel and Alice Sternberg and James Tonascia and Aynur {\"U}nalp-Arida and {Van Natta}, Mark and Laura Wilson and Katherine Yates",
year = "2009",
doi = "10.1002/hep.22724",
language = "English",
volume = "49",
pages = "809--820",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "3",

}

TY - JOUR

T1 - Portal chronic inflammation in nonalcoholic fatty liver disease (NAFLD)

T2 - A histologic marker of advanced NAFLD - Clinicopathologic correlations from the nonalcoholic steatohepatitis clinical research network

AU - Brunt, Elizabeth M.

AU - Kleiner, David E.

AU - Wilson, Laura A.

AU - Unalp, Aynur

AU - Behling, Cynthia E.

AU - Lavine, Joel E.

AU - Neuschwander-Tetri, Brent A.

AU - Abrams, Stephanie

AU - Arceo, Diana

AU - Espinosa, Denise

AU - Fairly, Leanel

AU - Bringman, Diane

AU - Hawkins, Carol

AU - Liu, Yao Chang

AU - Rogers, Nicholette

AU - Stager, Margaret

AU - McCullough, Arthur

AU - Dasarathy, Srinivasan

AU - Edwards, Kevin

AU - Sargent, Ruth

AU - Coffey, Melissa

AU - Murray, Karen

AU - Young, Melissa

AU - Mohan, Parvathi

AU - Nair, Kavita

AU - Abdelmalek, Manal

AU - Diehl, Anna Mae

AU - Gottfried, Marcia

AU - Guy, Cynthia

AU - Killenberg, Paul

AU - Kwan, Samantha

AU - Pan, Yi Ping

AU - Piercy, Dawn

AU - Smith, Melissa

AU - Bhimalli, Prajakta

AU - Chalasani, Naga

AU - Cummings, Oscar

AU - Lee, Lydia

AU - Ragozzino, Linda

AU - Vuppalanchi, Raj

AU - Calabrese, Barbara

AU - Peglow, Debra

AU - Scheimann, Ann

AU - Torbenson, Michael

AU - Klipsch, Ann

AU - Molleston, Jean

AU - Subbarao, Girish

AU - Barlow, Sarah

AU - Derdoy, Jose

AU - Hoffmann, Joyce

AU - King, Debra

AU - Siegner, Joan

AU - Stewart, Susan

AU - Tetri, Brent A.

AU - Thompson, Judy

AU - Behling, Cynthia

AU - Celedon, Manual

AU - Clark, Lisa

AU - Durelle, Janis

AU - Hassanein, Tarek

AU - Lavine, Joel E.

AU - Mendoza, Susana

AU - Schwimmer, Jeffrey B.

AU - Sirlin, Claude

AU - Stein, Tanya

AU - Tobin, Allison

AU - Bambha, Kiran

AU - Bass, Nathan M.

AU - Ferrell, Linda D.

AU - Filipowski, Danuta

AU - Merriman, Raphael

AU - Pabst, Mark

AU - Rosenthal, Monique

AU - Rosenthal, Philip

AU - Steel, Tessa

AU - Boyett, Sherry

AU - Bryan, Daphne

AU - Contos, Melissa J.

AU - Fuchs, Michael

AU - Graham, Martin

AU - Jones, Amy

AU - Luketic, Velimir A C

AU - Sandhu, Bimalijit

AU - Sanyal, Arun J.

AU - Sargeant, Carol

AU - Selph, Kimberly

AU - White, Melanie

AU - Kowdley, Kris V.

AU - Gyurkey, Grace

AU - Mooney, Jody

AU - Nelson, James

AU - Roberts, Sarah

AU - Saunders, Cheryl

AU - Stead, Alice

AU - Wang, Chia

AU - Yeh, Matthew

AU - Brunt, Elizabeth

AU - Kleiner, David

AU - Grave, Gilman D.

AU - Huang, Terry T K

AU - Doo, Edward

AU - Everhart, Jay

AU - Hoofnagle, Jay

AU - Robuck, Patricia R.

AU - Seeff, Leonard

AU - Belt, Patricia

AU - Brancati, Fred

AU - Clark, Jeanne

AU - Colvin, Ryan

AU - Donithan, Michel

AU - Green, Mika

AU - Hollick, Rosemary

AU - Isaacson, Milana

AU - Kim, Wana

AU - Lyndecker, Alison

AU - Miriel, Laura

AU - Sternberg, Alice

AU - Tonascia, James

AU - Ünalp-Arida, Aynur

AU - Van Natta, Mark

AU - Wilson, Laura

AU - Yates, Katherine

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

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