Complex non‐invasive fibrosis models are more accurate than simple models in non‐alcoholic fatty liver disease

Adams, Leon A.; George, Jacob; Bugianesi, Elisabetta; Rossi, Enrico; Boer, W. Bastiaan de; Poorten, David van der; Ching, Helena; Bulsara, Max; Jeffrey, Gary P.

doi:10.1111/j.1440-1746.2011.06774.x

Cited by 147 publications

(126 citation statements)

References 23 publications

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“…Standard laboratory parameters were measured, including liver function tests, serum triglycerides, high‐density lipoprotein cholesterol, free (nonesterified) fatty acids, glucose, insulin, glycosylated hemoglobin (HbA1C), 75‐g oral glucose tolerance test, transferrin saturation, serum ferritin, and full blood count. Hepascore, a validated serum measure of hepatic fibrosis in NAFLD,18 was performed at the Western Australia state referral laboratory (Pathwest, Queen Elizabeth II Medical Center, Nedlands, Australia). Serum cytokeratin‐18 fragments were measured using an m30 Aptosense enzyme‐linked immunosorbent assay (ELISA) kit (Peviva, Nacka, Sweden).…”

Section: Methodsmentioning

confidence: 99%

Hepatic iron concentration correlates with insulin sensitivity in nonalcoholic fatty liver disease

Britton

Bridle

Reiling

et al. 2018

Hepatology Communications

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Rodent and cell‐culture models support a role for iron‐related adipokine dysregulation and insulin resistance in the pathogenesis of nonalcoholic fatty liver disease (NAFLD); however, substantial human data are lacking. We examined the relationship between measures of iron status, adipokines, and insulin resistance in patients with NAFLD in the presence and absence of venesection. This study forms part of the Impact of Iron on Insulin Resistance and Liver Histology in Nonalcoholic Steatohepatitis (IIRON2) study, a prospective randomized controlled trial of venesection for adults with NAFLD. Paired serum samples at baseline and 6 months (end of treatment) in controls (n = 28) and patients who had venesection (n = 23) were assayed for adiponectin, leptin, resistin, retinol binding protein‐4, tumor necrosis factor α, and interleukin‐6, using a Quantibody, customized, multiplexed enzyme‐linked immunosorbent assay array. Hepatic iron concentration (HIC) was determined using MR FerriScan. Unexpectedly, analysis revealed a significant positive correlation between baseline serum adiponectin concentration and HIC, which strengthened after correction for age, sex, and body mass index (rho = 0.36; P = 0.007). In addition, there were significant inverse correlations between HIC and measures of insulin resistance (adipose tissue insulin resistance (Adipo‐IR), serum insulin, serum glucose, homeostasis model assessment of insulin resistance, hemoglobin A1c, and hepatic steatosis), whereas a positive correlation was noted with the insulin sensitivity index. Changes in serum adipokines over 6 months did not differ between the control and venesection groups. Conclusion: HIC positively correlates with serum adiponectin and insulin sensitivity in patients with NAFLD. Further study is required to establish causality and mechanistic explanations for these associations and their relevance in the pathogenesis of insulin resistance and NAFLD. (Hepatology Communications 2018;2:644‐653)

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Section: Methodsmentioning

confidence: 99%

Hepatic iron concentration correlates with insulin sensitivity in nonalcoholic fatty liver disease

Britton

Bridle

Reiling

et al. 2018

Hepatology Communications

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“…Indeed, mean Hepascore values in both study arms were less than the previously reported cutoff of 0.44 for significant fibrosis (Kleiner fibrosis grade 2), whereas, similarly, mean cytokeratin 18 fragment levels were lower than that (275 U/L) suggested to indicate NASH. 4,5 Baseline hepatic iron concentration (HIC) values for both patient groups were within normal limits, indicating a lack of iron excess in the study population.…”

Section: Does the Death Knell Toll For Phlebotomy In Nafld?mentioning

confidence: 99%

“…A hepatic iron concentration above the upper limit of normal (1.5 mg/g) is even more uncommon, being present in less than 10% of individuals overall. 3,4 Thus, the proportion of NAFLD subjects with NASH and true iron overload represent only a small subset of the wider population of patients with NAFLD.…”

Section: Replymentioning

confidence: 99%

Does the death knell toll for phlebotomy in NAFLD?

2015

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“…While existing predictive models have proven useful in excluding advanced fibrosis, many require further validation in cases of intermediate severity. Their positive predictive value is also modest at best, and likely inferior to that of more complex scoring panels [129] , which are again limited as the direct biomarkers they employ lack standardization as well as liver-specificity. A number of suggestions have been proposed in an attempt to address these shortcomings, including the concurrent use of multiple prognostic models towards the same goal [130] .…”

Section: Lack Of Consensus Regarding Clinically Meaningful Thresholdsmentioning

confidence: 99%

Composite prognostic models across the non-alcoholic fatty liver disease spectrum: Clinical application in developing countries

Luckhoff

Kruger

Kotze

2015

WJH

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Heterogeneity in clinical presentation, histological severity, prognosis and therapeutic outcomes charac teristic of nonalcoholic fatty liver disease (NAFLD) necessitates the development of scientifically sound classification schemes to assist clinicians in stratifying patients into meaningful prognostic subgroups. The need for replacement of invasive liver biopsies as the standard method whereby NAFLD is diagnosed, graded and staged with biomarkers of histological severity injury led to the development of composite prognostic models as potentially viable surrogate alternatives. In the present article, we review existing scoring systems used to (1) confirm the presence of undiagnosed hepatosteatosis; (2) distinguish between simple steatosis and NASH; and (3) predict advanced hepatic fibrosis, with particular emphasis on the role of NAFLD as an independent cardiometabolic risk factor. In addition, the incorporation of functional genomic markers and application of emerging imaging technologies are discussed as a means to improve the diagnostic accuracy and predictive performance of promising composite models found to be most appropriate for widespread clinical adoption. Composite prognostic models across the non-alcoholic fatty liver disease spectrum: Clinical application in developing countries have entered the clinical domain as potentially viable alternatives. Lifestylebased intervention remains the cornerstone of treatment in patients with NAFLD. The widespread clinical adoption of composite diagnostic and predictive models could however prove useful in informing clinical and therapeutic decision making with the goal of adding value to patient care across the NAFLD spectrum.Lückhoff HK, Kruger FC, Kotze MJ. Composite prognostic models across the non-alcoholic fatty liver disease spectrum:

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Complex non‐invasive fibrosis models are more accurate than simple models in non‐alcoholic fatty liver disease

Abstract: In NAFLD subjects, non-invasive models have modest accuracy for determining significant fibrosis and have predictive values less than 90% in the majority of subjects. Complex models are more accurate than simple bedside models across a range of fibrosis.

Cited by 147 publications

References 23 publications

Hepatic iron concentration correlates with insulin sensitivity in nonalcoholic fatty liver disease

Hepatic iron concentration correlates with insulin sensitivity in nonalcoholic fatty liver disease

Does the death knell toll for phlebotomy in NAFLD?

Composite prognostic models across the non-alcoholic fatty liver disease spectrum: Clinical application in developing countries

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