Elevated systemic monocyte chemoattractrant protein-1 in hepatic steatosis without significant hepatic inflammation

Kirovski, Georgi; Dorn, Christoph; Huber, Hanna; Moleda, Lukas; Niessen, Catrin; Wobser, Hella; Schacherer, Doris; Buechler, Christa; Wiest, Reiner; Hellerbrand, Claus

doi:10.1016/j.yexmp.2011.08.001

Cited by 35 publications

(32 citation statements)

References 23 publications

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“…() However, there have been few human studies investigating the role of MCP1 in NAFLD. Of the available studies, MCP1 was shown to be elevated in patients with both NAFLD and NASH() compared to healthy controls and patients with NAFLD with simple steatosis. () Our results indicate that elevated MCP1 is associated with fibrosis in NAFLD.…”

Section: Discussionmentioning

confidence: 99%

Serum Interleukin‐8, Osteopontin, and Monocyte Chemoattractant Protein 1 Are Associated With Hepatic Fibrosis in Patients With Nonalcoholic Fatty Liver Disease

Glass

Henao

Patel

et al. 2018

Hepatology Communications

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The severity of hepatic fibrosis is the primary predictor of liver‐related morbidity and mortality in patients with nonalcoholic fatty liver disease (NAFLD). Unfortunately, noninvasive serum biomarkers for NAFLD‐associated fibrosis are limited. We analyzed baseline serum samples for 24 cytokines of 97 patients with biopsy‐proven NAFLD. These patients were prospectively enrolled in a clinical study (ClinicalTrials.gov NCT00794716) to identify cytokines associated with liver fibrosis in patients with nonalcoholic steatohepatitis. Patients were stratified according to severity of hepatic fibrosis (mild, stage 0‐1, n = 37; moderate, stage 2, n = 40; and advanced, stage 3‐4, n = 20) while controlling for age, race, sex, body mass index, and diabetes mellitus. Interleukin‐8 (IL‐8), osteopontin (OPN), and monocyte chemoattractant protein 1 (MCP1) were associated with liver fibrosis (P < 0.001, P = 0.005, P = 0.016, respectively). After controlling for steatosis, lobular inflammation, hepatocyte ballooning, age, sex, body mass index, diabetes mellitus, hypertension, and metabolic syndrome status, IL‐8 remained strongly associated with fibrosis (P = 0.001). Furthermore, IL‐8 was also a strong predictor of increased fibrotic liver injury compared to established markers of hepatic fibrosis. Hepatic gene expression from 72 patients with NAFLD (n = 40 mild fibrosis; n = 32 advanced fibrosis) from the Duke University Health System NAFLD Clinical Database and Biorepository revealed IL‐8, MCP1, and OPN gene expression to be increased and differentially expressed in patients with advanced hepatic fibrosis. Thus, serum IL‐8, MCP1, and OPN may reflect up‐regulated gene expression during liver fibrosis in NAFLD. Conclusion: Serum IL‐8, MCP1, and OPN may serve as a test for advanced hepatic fibrosis in NAFLD and thus reveal novel targets for antifibrotic therapies. The increased serum IL‐8, MCP1, and OPN that correspond with associated hepatic gene expression lend strength to such analytes as ideal surrogate serum biomarkers for severity of hepatic fibrosis.

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Section: Discussionmentioning

confidence: 99%

Serum Interleukin‐8, Osteopontin, and Monocyte Chemoattractant Protein 1 Are Associated With Hepatic Fibrosis in Patients With Nonalcoholic Fatty Liver Disease

Glass

Henao

Patel

et al. 2018

Hepatology Communications

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“…CC‐chemokine ligand‐2, also known as monocyte chemoattractant protein‐1 (MCP‐1), is a potent chemokine, which is responsible for hepatic recruitment of macrophages during liver inflammation . In another study of 104 subjects, high CCL2 level was associated with elevated alanine aminotransferase (ALT) . In addition, CCL2 level was significantly higher in patients diagnosed with NAFLD by ultrasound.…”

Section: Non‐invasive Diagnosis Of Nashmentioning

confidence: 99%

Systematic review with meta‐analysis: non‐invasive assessment of non‐alcoholic fatty liver disease – the role of transient elastography and plasma cytokeratin‐18 fragments

Kwok

Tse

Wong

et al. 2013

Aliment Pharmacol Ther

358

282

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Summary Background Non‐alcoholic fatty liver disease (NAFLD) affects 15–40% of the general population. Some patients have non‐alcoholic steatohepatitis (NASH) and progressive fibrosis, and would be candidates for monitoring and treatment. Aim To review current literature on the use of non‐invasive tests to assess the severity of NAFLD. Methods Systematic literature searching identified studies evaluating non‐invasive tests of NASH and fibrosis using liver biopsy as the reference standard. Meta‐analysis was performed for areas with adequate number of publications. Results Serum tests and physical measurements like transient elastography (TE) have high negative predictive value (NPV) in excluding advanced fibrosis in NAFLD patients. The NAFLD fibrosis score comprises of six routine clinical parameters and has been endorsed by current American guidelines as a screening test to exclude low‐risk individuals. The pooled sensitivities and specificities for TE to diagnose F ≥ 2, F ≥ 3 and F4 disease were 79% and 75%, 85% and 85%, and 92% and 92% respectively. Liver stiffness measurement often fails in obese patients, but the success rate can be improved with the use of the XL probe. A number of biomarkers have been developed for the diagnosis of NASH, but few were independently validated. Serum/plasma cytokeratin‐18 fragments have been most extensively evaluated and have a pooled sensitivity of 66% and specificity of 82% in diagnosing NASH. Conclusions Current non‐invasive tests are accurate in excluding advanced fibrosis in NAFLD patients, and may be used for initial assessment. Further development and evaluation of NASH biomarkers are needed.

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“…CCL2 is responsible for monocyte and macrophage infiltration of liver and maintaining hepatic inflammation and fibrogenesis [82] . On the other hand, MCP-1 is known to be derived from visceral adipose tissue and reached liver via portal circulations [83] . Many more studies are still warranted to understand the pivotal roles of CCL2 and MCP-1 in the development of inflammatory responses in the liver.…”

Section: Immune Cells and Cytokinesmentioning

confidence: 99%

Proteomic and genomic studies of non-alcoholic fatty liver disease - clues in the pathogenesis

Lim

Dillon

Miller

2014

WJG

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Non-alcoholic fatty liver disease (NAFLD) is a widely prevalent hepatic disorder that covers wide spectrum of liver pathology. NAFLD is strongly associated with liver inflammation, metabolic hyperlipidaemia and insulin resistance. Frequently, NAFLD has been considered as the hepatic manifestation of metabolic syndrome. The pathophysiology of NAFLD has not been fully elucidated. Some patients can remain in the stage of simple steatosis, which generally is a benign condition; whereas others can develop liver inflammation and progress into non-alcoholic steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma. The mechanism behind the progression is still not fully understood. Much ongoing proteomic researches have focused on discovering the unbiased circulating biochemical markers to allow early detection and treatment of NAFLD. Comprehensive genomic studies have also begun to provide new insights into the gene polymorphism to understand patientdisease variations. Therefore, NAFLD is considered a complex and mutifactorial disease phenotype resulting from environmental exposures acting on a susceptible polygenic background. This paper reviewed the current status of proteomic and genomic studies that have contributed to the understanding of NAFLD pathogenesis. For proteomics section, this review highlighted functional proteins that involved in: (1) transportation; (2) metabolic pathway; (3) acute phase reaction; (4) antiinflammatory; (5) extracellular matrix; and (6) immune system. In the genomic studies, this review will discuss genes which involved in: (1) lipolysis; (2) adipokines; and (3) cytokines production. Key words: Non-alcoholic fatty liver disease; Proteomics; Genomics; Metabolic syndrome; Pathophysiology Core tip: Non-alcoholic fatty liver disease (NAFLD) is a widely prevalent hepatic disorder in Western populations. NAFLD can occur as a spectrum diseases, from simple steatosis, to non-alcoholic steatohepatitis characterised by hepatocellular injury and inflammation, to cirrhosis and hepatocellular carcinoma. This paper reviewed the current status of proteomic and genomic studies that have contributed to the understanding of NAFLD pathogenesis. This review highlighted several functional proteins and genetic polymoprhisms; particular those involved in insulin resistance, triglycerides metabolism and hepatic inflammation. It is hoped that this review will offer further insights into the pathophysiology of NAFLD.

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Elevated systemic monocyte chemoattractrant protein-1 in hepatic steatosis without significant hepatic inflammation

Cited by 35 publications

References 23 publications

Serum Interleukin‐8, Osteopontin, and Monocyte Chemoattractant Protein 1 Are Associated With Hepatic Fibrosis in Patients With Nonalcoholic Fatty Liver Disease

Serum Interleukin‐8, Osteopontin, and Monocyte Chemoattractant Protein 1 Are Associated With Hepatic Fibrosis in Patients With Nonalcoholic Fatty Liver Disease

Systematic review with meta‐analysis: non‐invasive assessment of non‐alcoholic fatty liver disease – the role of transient elastography and plasma cytokeratin‐18 fragments

Proteomic and genomic studies of non-alcoholic fatty liver disease - clues in the pathogenesis

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