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Journal ArticleDOI

Histopathological algorithm and scoring system for evaluation of liver lesions in morbidly obese patients

TL;DR: The aim was to build an algorithm along with a scoring system for histopathologic classification of liver lesions that covers the entire spectrum of lesions in morbidly obese patients, and suggest describing liver lesions using the SAF score.
About: This article is published in Hepatology.The article was published on 2012-11-01. It has received 645 citations till now. The article focuses on the topics: Nonalcoholic fatty liver disease & Liver biopsy.
Citations
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Journal ArticleDOI
TL;DR: This guidance provides a data-supported approach to the diagnostic, therapeutic, and preventive aspects of NAFLD care.

4,431 citations


Cites methods from "Histopathological algorithm and sco..."

  • ...Utility and appropriateness of the fatty liver inhibition of progression (FLIP) algorithm and steatosis, activity, and fibrosis (SAF) score in the evaluation of biopsies of nonalcoholic fatty liver disease....

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  • ...Guidelines are developed by a multidisciplinary panel of experts and rate the quality (level) of the evidence and the strength of each recommendation using the Grading Abbreviations: AASLD, American Association for the Study of Liver Diseases; ACG, American College of Gastroenterology; AIH, autoimmune hepatitis; ALT, alanine aminotransferase; APRI, AST to platelet ratio index; AST, aspartate aminotransferase; AUROC, area under the receiver operating curve; BMI, body mass index; CI, confidence interval; CLD, chronic liver disease; CT, computed tomography; CVD, cardiovascular disease; ELF, Enhanced Liver Fibrosis; FDA, U.S. Food and Drug Administration; FIB-4, fibrosis-4 index; FLD, fatty liver disease; GFR, glomerular filtration rate; GLP-1, glucagon-like peptide-1; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HDL, high-density lipoprotein; HF, hepatic fibrosis; HS, hepatic steatosis; ICD-10, International Classification of Diseases, Tenth Revision; IR, insulin resistance; LDL, low-density lipoprotein; LT, liver transplantation; METs, metabolic equivalents; MetS, MetS, metabolic syndrome; MR, magnetic resonance; MRE, MR elastography; MRI, magnetic resonance imaging; NAFL, nonalcoholic fatty liver; NAFLD, nonalcoholic fatty liver disease; NAS, NAFLD activity score; NASH, nonalcoholic fatty liver disease; NASH CRN, NASH Clinical Research Network; NFS, NAFLD fibrosis score; NIAAA, National Institute on Alcohol Abuse and Alcoholism; OCA, obeticholic acid; PNPLA-3, patatin-like phospholipase domain-containing protein 3; PPAR, peroxisome proliferator-activated receptor gamma; RCT, randomized controlled trial; SAF, Steatosis Activity Fibrosis; SH, steatohepatitis; T2DM, type 2 diabetes mellitus; TE, transient elastography; TG, triglyceride; TONIC, treatment of nonalcoholic fatty liver disease in children; UDCA, ursodeoxycholic acid; ULN, upper limit of normal; VCTE, vibration controlled transient elastography; WD, Wilson’s disease....

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  • ...There are two systems for semiquantitative assessment of necroinflammatory lesions in NAFLD: NAFLD Activity Score (NAS) from the NASH CRN((128)) and Steatosis Activity Fibrosis (SAF) from the European Fatty Liver Inhibition of Progression Consortium.((129,130)) Both utilize the lesions stated above, but exact criteria and stated goals for utilization differ....

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  • ...Specific scoring systems such as NAS((128)) and/or SAF((128,129)) may be used as deemed appropriate....

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  • ...(126,127) There are two systems for semiquantitative assessment of necroinflammatory lesions in NAFLD: NAFLD Activity Score (NAS) from the NASH CRN(128) and Steatosis Activity Fibrosis (SAF) from the European Fatty Liver Inhibition of Progression Consortium....

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Journal ArticleDOI
TL;DR: In this, the largest ever study of biopsy-proven NAFLD, the presence of NASH did not increase the risk of liver-specific morbidity or overall mortality.

666 citations


Cites methods from "Histopathological algorithm and sco..."

  • ...[15] The FLIP algorithm was used to define presence of NASH....

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  • ...In table 4b, comparisons are against F0 or absence of NASH....

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  • ...[15] The FLIP algorithm was used to define presence of NASH.[16, 17] Fibrosis stage was scored...

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  • ...Model 3: further adjusted for fibrosis stage or NASH....

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  • ...There was a clear collinearity between NASH and higher stages of fibrosis, with 94% of patients with F4 having NASH compared to 35% of patients with F0, and 17% of patients with NASH having stage 3-4 fibrosis compared to 2% of patients without NASH....

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Journal ArticleDOI
TL;DR: In a prospective analysis of patients with NAFLD, FibroScan vibration-controlled transient elastography controlled attenuation parameter (CAP) and liver stiffness measurement (LSMs) found to be effective in assessing liver steatosis and fibrosis, respectively, with AUROC values ranging from 0.70 to 0.89.

640 citations


Cites background from "Histopathological algorithm and sco..."

  • ...…title: Diagnostic accuracy of CAP and LSM in NAFLD patients Peter J Eddowes1,2,3,4, Magali Sasso5, Michael Allison6, Emmanuel Tsochatzis7, Quentin M Anstee8, David Sheridan9, Indra N Guha4, Jeremy F Cobbold10, Jonathan J Deeks11, Valérie Paradis12, Pierre Bedossa12, Philip N Newsome*1,2,3....

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  • ...M AN US CR IP T AC CE PT ED Steatosis Fibrosis > 450 patients with suspicion of NAFLD prospectively recruited >Underwent liver biopsy within 2 weeks of FibroScan (M or XL probe according to the automatic probe recommendation tool) >Results and conclusions CAP (dB/m) LSM (kPa) CAP for steatosis (S≥1): > AUC = 0.87 (0.82-0.92) LSM for advanced fibrosis (F≥3): > AUC = 0.80 (0.75-0.84) LSM for cirrhosis (F=4): > AUC = 0.89 (0.84-0.93) S e n si ti v it y Specificity > Steatosis or probe type had no impact on LSM (multivariable analysis) >>> CAP and LSM by FibroScan are reliable biomarkers to non-invasively assess liver steatosis and fibrosis respectively in NAFLD M AN US CR IP T AC CE PT ED 1 Title: Accuracy of FibroScan Controlled Attenuation Parameter and Liver Stiffness Measurement in Assessing Steatosis and Fibrosis in Patients With Non-alcoholic Fatty Liver Disease Short title: Diagnostic accuracy of CAP and LSM in NAFLD patients Peter J Eddowes1,2,3,4, Magali Sasso5, Michael Allison6, Emmanuel Tsochatzis7, Quentin M Anstee8, David Sheridan9, Indra N Guha4, Jeremy F Cobbold10, Jonathan J Deeks11, Valérie Paradis12, Pierre Bedossa12, Philip N Newsome*1,2,3....

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Journal ArticleDOI
TL;DR: It is demonstrated that cellular senescence drives hepatic Steatosis and elimination of senescent cells may be a novel therapeutic strategy to reduce steatosis.
Abstract: The incidence of non-alcoholic fatty liver disease (NAFLD) increases with age. Cellular senescence refers to a state of irreversible cell-cycle arrest combined with the secretion of proinflammatory cytokines and mitochondrial dysfunction. Senescent cells contribute to age-related tissue degeneration. Here we show that the accumulation of senescent cells promotes hepatic fat accumulation and steatosis. We report a close correlation between hepatic fat accumulation and markers of hepatocyte senescence. The elimination of senescent cells by suicide gene-meditated ablation of p16Ink4a-expressing senescent cells in INK-ATTAC mice or by treatment with a combination of the senolytic drugs dasatinib and quercetin (D+Q) reduces overall hepatic steatosis. Conversely, inducing hepatocyte senescence promotes fat accumulation in vitro and in vivo. Mechanistically, we show that mitochondria in senescent cells lose the ability to metabolize fatty acids efficiently. Our study demonstrates that cellular senescence drives hepatic steatosis and elimination of senescent cells may be a novel therapeutic strategy to reduce steatosis.

603 citations

Journal ArticleDOI
TL;DR: Bariatric surgery induced the disappearance of NASH from nearly 85% of patients and reduced the pathologic features of the disease after 1 year of follow-up, suggesting it could be a therapeutic option for appropriate morbidly obese patients with NASH who do not respond to lifestyle modifications.

590 citations


Additional excerpts

  • ...07), NAS score (median [IQR] 5 [4-5] vs....

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References
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Journal ArticleDOI
TL;DR: A strong scoring system and NAS for NAFLD and NASH with reasonable inter‐rater reproducibility that should be useful for studies of both adults and children with any degree ofNAFLD are presented.

8,253 citations


"Histopathological algorithm and sco..." refers background or methods in this paper

  • ...NAFLD is characterized by macrovesicular steatosis; indeed, the presence of steatosis in at least 5% of hepatocytes is generally accepted as a definition.(9,10) Nonalcoholic steatohepatitis (NASH), a subgroup of NAFLD, deserves particular attention because of the risk for of evolution to cirrhosis....

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  • ...The diagnosis relies on an association of histological features and a consensus exists on the main elementary features that are commonly observed in NASH (ballooning/clarification, inflammation, perisinusoidal fibrosis, predominance of lesions in zone 3).(10,12)....

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  • ...The histological check-list was from the NASH-CRN with few additional comments.(10) Among major features, ballooning was graded from 0 to 2 (0: normal hepatocytes with cuboidal shape and pink eosinophilic cytoplasm; 1: presence of clusters of hepatocytes with a rounded shape and pale cytoplasm usually reticulated....

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  • ...Although the likelihood of NASH increases with NAS, there exists a wide gray zone (NAS 3-4) where NASH may or may not be present.(10) Therefore, the aims of our study were to devise an algorithm for categorization of obesity-associated liver diseases, to apply this algorithm to a large population of morbidly obese patients so as to assess the prevalence of liver lesions in a well-defined group of obese undergoing bariatric surgery, to validate the algorithm in a series of biopsies in patients with metabolic syndrome without morbid obesity, and to make new proposals regarding the scoring of obesity-associated liver diseases....

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  • ...Indeed, liver cell ballooning/clarification is among the most difficult lesions to consistently identify and grade among pathologists.(10) In the present study, we added references to the shape and size of adjacent normal hepatocytes in order to complement the current definition; this should help to better recognize and semiquantify this feature....

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Journal ArticleDOI
TL;DR: A simple algorithm that generates a single activity score based on basic pathological features in chronic hepatitis C is proposed and tested, showing its accuracy is as high as that obtained using a statistical approach.

3,567 citations

Journal ArticleDOI
TL;DR: There are no systems for grading necroinflammatory activity or for staging fibrosis as exist for various other forms of chronic liver disease and this study proposes a grading and staging system that reflects the unique histological features of nonalcoholic steatohepatitis.

3,553 citations


"Histopathological algorithm and sco..." refers background in this paper

  • ...Based on a seminal article, the definition included steatosis, ballooning, mixed acute and chronic lobular inflammation, and zone 3 perisinusoidal fibrosis.(12) More recently, the NASH-CRN stated that NASH was ‘‘established by the presence of a characteristic pattern of steatosis, inflammation and hepatocellular ballooning on liver biopsies in the absence of significant alcohol consumption,’’ thereby eliminating sinusoidal fibrosis from the definition....

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  • ...The diagnosis relies on an association of histological features and a consensus exists on the main elementary features that are commonly observed in NASH (ballooning/clarification, inflammation, perisinusoidal fibrosis, predominance of lesions in zone 3).(10,12)....

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Journal ArticleDOI
TL;DR: The prevalence of hepatic steatosis was greater in men than women among whites, but not in blacks or Hispanics, and significant ethnic and sex differences in the prevalence may have a profound impact on susceptibility to Steatosis‐related liver disease.

3,429 citations

Journal ArticleDOI
TL;DR: The outcome of cirrhosis and liver-related death is not uniform across the spectrum of nonalcoholic fatty liver, and poor outcomes are more frequent in patients in whom biopsies show ballooning degeneration and Mallory hyaline or fibrosis.

3,167 citations


"Histopathological algorithm and sco..." refers background in this paper

  • ...Nonalcoholic steatohepatitis (NASH), a subgroup of NAFLD, deserves particular attention because of the risk for of evolution to cirrhosis.(11) There is general...

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