Evidence map›Paper›PMID 22036053›Full record

ArticleHuman pathology2012

Costaining for keratins 8/18 plus ubiquitin improves detection of hepatocyte injury in nonalcoholic fatty liver disease.

Cynthia D Guy, Ayako Suzuki, James L Burchette, Elizabeth M Brunt, Manal F Abdelmalek, Diana Cardona, Shannon J McCall, Aynur Ünalp, Patricia Belt, Linda D Ferrell and 2 more

Abstract read
In one paragraph

Article in Human pathology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
1.9field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 74 citations in OpenAlex.

  1. [Current research progress status in identifying hepatocellular ballooning degeneration in nonalcoholic steatohepatitis].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025
    Review
  2. Digital pathology for nonalcoholic steatohepatitis assessment.Nature reviews. Gastroenterology & hepatology · 2024
    Review
  3. Review
  4. A new preclinical model of western diet-induced progression of non-alcoholic steatohepatitis to hepatocellular carcinoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022
    Article
  5. Review
  6. Article
  7. DNA Methylation in Nonalcoholic Fatty Liver Disease.International journal of molecular sciences · 2020
    Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Histological Assessment of NAFLD.Digestive diseases and sciences · 2016
    Review
  20. Characterization of lipid metabolism in a novel immortalized human hepatocyte cell line.American journal of physiology. Endocrinology and metabolism · 2015
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 5 institutions in 1 country.

Cynthia D GuyDepartment of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
Ayako Suzuki
James L Burchette
Elizabeth M Brunt
Manal F Abdelmalek
Diana Cardona
Shannon J McCall
Aynur Ünalp
Patricia Belt
Linda D Ferrell
Anna Mae Diehl
Nonalcoholic Steatohepatitis Clinical Research Network
Duke University Hospital · USJohns Hopkins University · USDuke Medical Center · USUniversity of California, San Francisco · USWashington University in St. Louis · US

Funding

ZOVIRAX CREAM TO TREAT HERPES LABIALIS IN ADOLESCENTSM01RR000827 · NCRR · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHANG, R JEFFREY · 1985 to 2010
$74.3M
CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR024989 · NCRR · CASE WESTERN RESERVE UNIVERSITY · PI DAVIS, PAMELA B · 2007 to 2011
$53.7M
ZOLENDRONIC ACID IN CHILDREN W/ SEVERE OSTEOGENESIS IMPERFECTAM01RR000188 · NCRR · BAYLOR COLLEGE OF MEDICINE · PI SHEARER, WILLIAM THOMAS · 1985 to 2011
$30.6M
ZOSUQUIDAR TRIHYDROCHLORIDE DURING CONVENTIONAL INDUCTION AND POST-REMISSIONM01RR000750 · NCRR · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI RODRIGUEZ, HENRY · 1985 to 2008
$25.5M
X-LINKED HYPOPHOSPHATEMIAM01RR000065 · NCRR · VIRGINIA COMMONWEALTH UNIVERSITY · PI SANYAL, ARUN J · 1985 to 2010
$24.8M
Pediatric Trials in Non-Alcoholic Steatohepatitis (NASH)U01DK061734 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ROHIT LOOMBA · 2002 to 2026
$24.4M
Continuation of the Non-Alcoholic Steatohepatitis Clinical Research Network (NASHU01DK061730 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI TONASCIA, JAMES A · 2002 to 2018
$23.2M
ZAP-70 EXPRESSION, CD38 EXPRESSION AND PROGNOSIS IN CHRONIC LYMPHOCYTIC LEUKEMIAM01RR020359 · NCRR · CHILDREN'S RESEARCH INSTITUTE · PI HINDS, PAMELA S · 2005 to 2010
$13.8M
Non Alcoholic Steatohepatitis Clinical Research NetworkU01DK061732 · NIDDK · CLEVELAND CLINIC LERNER COM-CWRU · PI Srinivasan Dasarathy · 2002 to 2026
$12.2M
The Saint Louis University Component of the NASH CRNU01DK061718 · NIDDK · SAINT LOUIS UNIVERSITY · PI BRENT A NEUSCHWANDER-TETRI · 2002 to 2026
$12.0M
Nonalcoholic Steatohepatittis Clinical Research Network (NASH CRN)U01DK061731 · NIDDK · VIRGINIA COMMONWEALTH UNIVERSITY · PI ARUN J SANYAL · 2002 to 2026
$11.2M
Pathogenesis, prognosis, and treatment of NAFLD patientsU01DK061713 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI ANNA MAE ELIZABETH DIEHL · 2002 to 2026
$10.3M
NCRR NIH HHS M01 RR000065NCRR NIH HHS M01RR000065NCRR NIH HHS M01 RR000188NCRR NIH HHS M01 RR000750NCRR NIH HHS M01RR000750NCRR NIH HHS M01 RR000827NCRR NIH HHS M01RR000827NCRR NIH HHS M01RR00188NCRR NIH HHS M01 RR020359NCRR NIH HHS M01RR020359NCRR NIH HHS UL1RR02413101NCRR NIH HHS UL1 RR024989NCRR NIH HHS UL1RR024989NCRR NIH HHS UL1RR02501401NIDDK NIH HHS K23 DK062116NIDDK NIH HHS K23-DK062116NIDDK NIH HHS R01 DK077794NIDDK NIH HHS U01 DK061713NIDDK NIH HHS U01DK061713NIDDK NIH HHS U01 DK061718NIDDK NIH HHS U01DK061718NIDDK NIH HHS U01 DK061728NIDDK NIH HHS U01DK061728NIDDK NIH HHS U01 DK061730NIDDK NIH HHS U01DK061730NIDDK NIH HHS U01 DK061731NIDDK NIH HHS U01DK061731NIDDK NIH HHS U01 DK061732NIDDK NIH HHS U01DK061732NIDDK NIH HHS U01 DK061734NIDDK NIH HHS U01DK061734NIDDK NIH HHS U01 DK061737NIDDK NIH HHS U01DK061737NIDDK NIH HHS U01 DK061738NIDDK NIH HHS U01DK061738
6 · The paper itself

Abstract

Nonalcoholic fatty liver disease is a global health dilemma. The gold standard for diagnosis is liver biopsy. Ballooned hepatocytes are histologic manifestations of hepatocellular injury and are characteristic of steatohepatitis, the more severe form of nonalcoholic fatty liver disease. Definitive histologic identification of ballooned hepatocytes on routine stains, however, can be difficult. Immunohistochemical evidence for loss of the normal hepatocytic keratin 8/18 can serve as an objective marker of ballooned hepatocytes. We sought to explore the utility of a keratin 8/18 plus ubiquitin double immunohistochemical stain for the histologic evaluation of adult nonalcoholic fatty liver disease. Double immunohistochemical staining for keratin 8/18 and ubiquitin was analyzed using 40 adult human nonalcoholic fatty liver disease core liver biopsies. Ballooned hepatocytes lack keratin 8/18 staining as previously shown by others, but normal-size hepatocytes with keratin loss are approximately 5 times greater in number than keratin-negative ballooned hepatocytes. Keratin-negative ballooned hepatocytes, normal-size hepatocytes with keratin loss, and ubiquitin deposits show a zonal distribution, are positively associated with each other, and are frequently found adjacent to or intermixed with fibrous matrix. All 3 lesions correlate with fibrosis stage and the hematoxylin and eosin diagnosis of steatohepatitis (all P < .05). Compared with hematoxylin and eosin staining, immunohistochemical staining improves the receiver operating characteristics curve for advanced fibrosis (0.77 versus 0.83, 0.89, and 0.89 for keratin-negative ballooned hepatocytes, normal-size hepatocytes with keratin loss, and ubiquitin, respectively) because immunohistochemistry is more sensitive and specific for fibrogenic hepatocellular injury than hematoxylin and eosin staining. Keratin 8/18 plus ubiquitin double immunohistochemical stain improves detection of hepatocyte injury in nonalcoholic fatty liver disease. Thus, it may help differentiate nonalcoholic steatohepatitis from nonalcoholic fatty liver.

Indexed as

BiomarkersFatty LiverFemaleHepatocytesHumansImmunohistochemistryKeratin-18Keratin-8MaleMiddle AgedNon-alcoholic Fatty Liver DiseaseUbiquitinBiomarkersKeratin-18Keratin-8KRT18 protein, humanUbiquitin

Identifiers

PMID22036053
PMCPMC3288773
OpenAlexW1985903411

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.