Fibrosis is associated with adiponectin resistance in chronic hepatitis C virus infection

Corbetta, Sabrina; Redaelli, A.; Pozzi, Massimo; Bovo, Giorgio; Ratti, Laura; Redaelli, Elena; Pellegrini, Caterina; Beck‐Peccoz, Paolo; Spada, Anna

doi:10.1111/j.1365-2362.2011.02498.x

Cited by 31 publications

(29 citation statements)

References 34 publications

(46 reference statements)

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“…The major driving force for decreasing adiponectin after SVR was thus directed to, at least partly, attenuated hepatic fibrosis in many aspects. However, the current study did not support the connection between adiponectin alterations and adiponectin resistance, 19 as IHC studies failed to demonstrated a significant difference in hepatic adiponectin receptor expression between CHC patients and the controls. In addition, after SVR, the HCV-associated hypolipidemia was reversed (Table S2).…”

Section: Discussioncontrasting

confidence: 94%

“…[14][15][16] Because both HCV infection and adiponectin are critically involved in metabolism, their precise relationship might aid to probe the therapeutic targets for HCV-associated cardiometabolic complications but remains inconclusive. For example, compared with controls, serum adiponectin levels have been reported to be higher, [17][18][19] lower 20 or not different 21 in chronic hepatitis C (CHC) patients. All studies 17,[22][23] but one 24 failed to correlate HCV viral load with adiponectin levels.…”

Section: Introductionmentioning

confidence: 99%

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The evolving relationship between adiponectin and insulin sensitivity in hepatitis C patients during viral clearance

et al. 2017

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(2017) The evolving relationship between adiponectin and insulin sensitivity in hepatitis C patients during viral clearance, Virulence, 8:7, 1255-1264, DOI: 10.1080/21505594.2017 ABSTRACT Background: The evolution of the relationship between adiponectin and insulin sensitivity in hepatitis C virus (HCV) patients during viral clearance is unclear and warrants investigation. Methods: A prospective study including 747 consecutive chronic hepatitis C (CHC) patients, of whom 546 had completed a course of anti-HCV therapy and underwent pre-, peri-and post-therapy surveys for anthropomorphic, viral, metabolic and hepatic profiles and adiponectin levels, was conducted in a tertiary care center. Results: Multivariate analyses indicated associations of sex, triglyceride levels and hepatic steatosis with adiponectin levels and of triglyceride levels and interferon λ3 (IFNL3) genotype with homeostasis model assessment-estimated insulin resistance (HOMA-IR) levels before anti-HCV therapy. In patients with a sustained virological response (SVR; n D 455), at 24 weeks post-therapy, sex, BMI, aspartate aminotransferase to platelet ratio index (APRI), HOMA-IR and steatosis were associated with adiponectin levels, and IFNL3 genotype was associated with HOMA-IR levels. GEE analysis demonstrated that SVR affected longitudinal trends in adiponectin levels. Compared with pre-therapy levels, adiponectin and APRI levels decreased 24 weeks post-therapy in SVR patients, regardless of baseline insulin resistance (IR). However, HOMA-IR levels decreased in SVR patients with baseline IR but increased in those without baseline IR. Compared with controls, immunohistochemical studies showed that pre-therapy CHC patients had higher hepatic adiponectin expression associated with hepatic fibrosis. Conclusions: During HCV infection, adiponectin may affect insulin sensitivity through triglycerides. After viral clearance, adiponectin levels were directly associated with insulin sensitivity and decreased upon improved hepatic fibrosis; with a link to the IFNL3 genotype, insulin sensitivity improved only in patients with baseline IR.

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Section: Discussioncontrasting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

The evolving relationship between adiponectin and insulin sensitivity in hepatitis C patients during viral clearance

et al. 2017

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“…[43, 44] Cirrhosis is thought to lead to a state of adiponectin resistance, with downregulation of adiponectin receptors in liver tissue and decreased clearance of adiponectin. [45–48]. However, we did not find a statistically significant association between liver fibrosis and peripheral adiponectin levels.…”

Section: Discussioncontrasting

confidence: 73%

Serum Adiponectin Is Associated with Worsened Overall Survival in a Prospective Cohort of Hepatocellular Carcinoma Patients

et al. 2014

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Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. The rise in metabolic syndrome has contributed to this trend. Adipokines, such as adiponectin, are associated with prognosis in several cancers, but have not been well studied in HCC. Methods: We prospectively enrolled 140 patients with newly diagnosed or recurrent HCC with Child-Pugh (CP) class A or B cirrhosis. We examined associations between serum adipokines, clinicopathological features of HCC, and time to death. We also examined a subset of tumors with available pathology for tissue adiponectin receptor (AR) expression by immunohistochemistry. Results: The median age of subjects was 62 years; 79% were men, 59% had underlying hepatitis C, and 36% were diabetic. Adiponectin remained a significant predictor of time to death (hazard ratio 1.90; 95% confidence interval 1.05-3.45; p = 0.03) in a multivariable adjusted model that included age, alcohol history, CP class, stage, and serum E-fetoprotein level. Cytoplasmic AR expression (AR1 and AR2) in tumors trended higher in those with higher serum adiponectin levels and in those with diabetes mellitus, but the association was not statistically significant. Conclusions: In this hypothesis-generating study, we found the serum adiponectin level to be an independent predictor of overall survival in a diverse cohort of HCC patients. Impact: Understanding how adipokines affect the HCC outcome may help develop novel treatment and prevention strategies. i 2014 S. Karger AG, Basel

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“…F>=2) are both independently associated with SVR rather than OPN simply acting as a surrogate marker of fibrosis. These findings in relation to virologic response have to be interpreted with caution given the limited size of our study cohort and absence of IL28B data for these patients that received peg-IFN and RBV prior to availability of IL28B genotyping assays (34, 35). Levels of serum adiponectin have been reported to correlate with HCV-fibrosis stage (35).…”

Section: Discussionmentioning

confidence: 92%

“…These findings in relation to virologic response have to be interpreted with caution given the limited size of our study cohort and absence of IL28B data for these patients that received peg-IFN and RBV prior to availability of IL28B genotyping assays (34, 35). Levels of serum adiponectin have been reported to correlate with HCV-fibrosis stage (35). Although we noted a positive correlation between serum OPN and adiponectin (p=0.042), serum adiponectin was not found to be independently associated with either fibrosis stage or SVR.…”

Section: Discussionmentioning

confidence: 92%

Osteopontin is up-regulated in chronic hepatitis C and is associated with cellular permissiveness for hepatitis C virus replication

et al. 2014

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Background Osteopontin (OPN) is a Hedgehog (Hh)-regulated cytokine that is up-regulated during chronic liver injury, and directly promotes fibrosis. We reported that Hh-signaling enhances viral permissiveness and replication in HCV-infected cells. Hence, we hypothesized that OPN directly promotes HCV replication, and that targeting OPN could be beneficial in HCV. Methods We compared expression of OPN mRNA and protein in HCV (JFH1)-infected Huh7 and Huh7.5 cells, and evaluated if modulating OPN levels using exogenous OPN ligands (upregulate OPN) or OPN-specific RNA-aptamers (neutralize OPN), leads to changes in HCV expression. Sera and livers from patients with chronic HCV were analyzed to determine if OPN levels were associated with disease severity or response to therapy. Results Compared with Huh7, Huh7.5 support higher levels of HCV replication (15-fold), and expressed significantly more OPN mRNA (30-fold) and protein. Treating Huh7 with OPN ligands led to dose-related increase in HCV (15-fold) and OPN (8-fold) mRNA. Conversely, treating Huh7.5 with OPN-specific RNA-aptamers inhibited HCV RNA and protein by >50% and repressed OPN mRNA to basal levels. Liver OPN expression was significantly higher (3-fold) in patients with advanced fibrosis. Serum OPN positively correlated with fibrosis-stage (p=0.009), but negatively correlated with end-of-treatment (ET) biochemical-response (BCR), ET virological-response (VR), sustained (S)BCR, and SVR (p=0.007). The OPN-Fibrosis Score (serum OPN and presence of fibrosis ≥F2) may be a predictor of SVR. Conclusions OPN is upregulated in the liver and serum of patients with chronic HCV, and supports increased viral replication. OPN neutralization may be a novel therapeutic strategy in chronic HCV.

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Fibrosis is associated with adiponectin resistance in chronic hepatitis C virus infection

Abstract: In patients with chronic HCV hepatitis, fibrosis was associated with hyperadiponectinemia. Chronic HCV-infected hepatocytes showed reduced ADIPOR1 expression, suggesting a pattern of adiponectin resistance.

Cited by 31 publications

References 34 publications

The evolving relationship between adiponectin and insulin sensitivity in hepatitis C patients during viral clearance

The evolving relationship between adiponectin and insulin sensitivity in hepatitis C patients during viral clearance

Serum Adiponectin Is Associated with Worsened Overall Survival in a Prospective Cohort of Hepatocellular Carcinoma Patients

Osteopontin is up-regulated in chronic hepatitis C and is associated with cellular permissiveness for hepatitis C virus replication

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