Insulin Resistance In Chronic Hepatitis Research Articles

Insulin Resistance and Chronic Hepatitis C: Relationship With Serum Iron and Hepcidin.

Backgrounds and aimBesides the clinical evidence supporting insulin resistance in chronic hepatitis C (CHC) patients, the exact mechanism elucidating insulin resistance is still under discussion. The present study aimed to observe any relationship between serum hepcidin, serum iron, and insulin resistance in CHC patients.MethodologyA total of 54 individuals were recruited in this study, assorted into group A (CHC population with diabetes) and control group B (CHC population without diabetes). Both groups were tested for serum hepcidin, iron, ferritin, and serum glycemic indices (fasting blood glucose, serum insulin, and insulin resistance). Serum parameters were compared between diabetic and non-diabetic CHC patients by using the Mann-Whitney U test. Correlation analysis was done between serum hepcidin and serum iron, serum hepcidin, and insulin resistance, and serum iron and insulin resistance by applying the Spearman correlation test.ResultsDiabetic and non-diabetic CHC populations exhibited an iron profile of chronic illness, i.e., low serum iron and hepcidin along with normal ferritin levels. Also, the diabetic and non-diabetic CHC population exhibited normal serum insulin and insulin resistance. However, the fasting serum glucose of the diabetic CHC population was higher than normal. Correlation analysis indicated a negative significant correlation (rho=-0.404, p=0.036) between serum iron and insulin resistance among the diabetic CHC population.ConclusionOur study could not provide any mounting evidence in favor of insulin resistance in the chronic hepatitis C population via serum iron or hepcidin. Hepatitis C virus causing diabetes mellitus may have some etiology other than iron metabolism.

Chronic hepatitis C virus infection impairs insulin secretion by regulation of p38δ MAPK-dependent exocytosis in pancreatic β-cells.

Chronic hepatitis C virus (HCV) infection has a close association with type 2 diabetes mellitus. Although the mechanisms of insulin resistance in chronic hepatitis C (CHC) patients have been extensively studied, little attention has been given to the role of β-cell function in HCV-associated diabetes. Here, we analysed β-cell function in CHC patients and HCV-infected mouse model and found in addition to insulin resistance, impaired pancreatic β-cell function occurred in CHC patients and HCV-infected C/OTg mice, not only in diabetic individuals but also in individuals with impaired fasting glucose levels. Both first-phase and second-phase insulin secretion were impaired, at least partially due to the reduction of exocytosis of secretory insulin-containing granules following HCV infection. Up-regulated p38δ in HCV-infected β-cells resulted in inactivation of protein kinase D (PKD), which was responsible for impaired insulin secretory capacity of β-cells. Thus, impaired insulin secretion due to HCV infection in β-cells contributes to HCV-associated type 2 diabetes. These findings provided a new inspiration for the important prognostic and therapeutic implications in the management of CHC patients with impaired fasting glucose.

Circulating microRNA-155 is associated with insulin resistance in chronic hepatitis C patients

Background and study aimHepatitis C represents a potential public health problem worldwide. Insulin resistance (IR) and type 2 diabetes (T2D) are among the serious metabolic complications for chronic hepatitis C virus (HCV) infection. MicroRNAs (miRNAs) are a group of small non-coding RNAs which are implicated in the modulation of almost all biological processes. The objective of this study was to investigate the levels of both miR-155 and miR-34a in sera of chronic HCV patients with or without T2D. Patients and methodsIn this study, we investigated the expression of both miR-155 and miR-34a in 80 subjects (20 HCV, 19 HCV/T2D, 21 T2D and 19 healthy controls), using quantitative real-time PCR. ResultsOur results revealed significantly higher levels of both miR-155 and miR-34a in chronic HCV patients compared to healthy control subjects. However, only circulating miR-155 levels showed significant decline in diabetic HCV patients compared to non-diabetic HCV group. Intriguingly, the circulating levels of miR-155 were inversely correlated with HOMA-IR, fasting blood glucose and HbA1c levels. ConclusionOur findings indicate that the insulin resistance and T2D in HCV are strongly related to miR-155. This may suggest a role for miR-155 in the pathogenesis of IR caused by HCV. However, further large-scale studies are required to confirm our findings.

Hepatitis C virus clearance by direct-acting antiviral treatments and impact on insulin resistance in chronic hepatitis C patients.

Chronic hepatitis C virus (HCV), particularly genotype 1, is associated with insulin resistance (IR) and diabetes. This study evaluated the impact of HCV clearance by all-oral direct-acting antiviral treatments on IR and glycemic control. Included in this prospective case-control study were 133 consecutive HCV-genotype 1 patients with advance liver fibrosis (F3-F4) without type 2 diabetes. Sixty eight were treated with direct-acting antiviral and 65 were untreated. Liver fibrosis was assessed by transient elastography. Pre-treatment, end-treatment, and 3months post-treatment withdrawal IR homeostasis was assessed by homeostatic model assessment (HOMA)-IR, HOMA-S, and HOMA-B. At baseline, treated, and untreated patients showed similar liver fibrosis levels, HOMA-IR was 4.90±4.62 and 4.64±5.62, respectively. HOMA-IR correlated with HCV RNA levels. At the end of treatment, all patients cleared HCV RNA, regardless of liver fibrosis and body mass index, and a reduction in HOMA-IR at 2.42±1.85 was showed (P<0.001); in addition, increased insulin sensitivity, decreased insulin secretion, reduction of serum glucose, and insulin levels were observed. Data were confirmed 3months after treatment withdrawal in the 65 patients who cleared HCV. No variation occurred in untreated patients. Overall, 76.5% of sustained virologic response patients showed IR improvements, of which 41.2% normalized IR. Improvement of IR was strictly associated with HCV clearance; however, patients with the highest levels of fibrosis remain associated with some degree of IR. The data underline a role of HCV in development of IR and that viral eradication reverses IR and improves glycemic control and this could prevent IR-related clinical manifestations and complications.

FRI-158 - Genetic and Metabolic Factors Related with Insulin Resistance in Chronic Hepatitis C

FRI-158 - Genetic and Metabolic Factors Related with Insulin Resistance in Chronic Hepatitis C

P166: A study of the prevalence and effects of insulin resistance in chronic hepatitis C patients with genotype 4

Journal of Viral HepatitisVolume 22, Issue S2 p. 101-102 Poster PresentationFree Access P166: A study of the prevalence and effects of insulin resistance in chronic hepatitis C patients with genotype 4 First published: 25 June 2015 https://doi.org/10.1111/jvh.150_12425AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume22, IssueS2Special Issue: 15th International Symposium on Viral Hepatitis and Liver Diseases (ISVHLD) held from June 26th to 28th, 2015, in Berlin, GermanyJune 2015Pages 101-102 RelatedInformation

PTU-094 A study of the prevalence and effects of insulin resistance in chronic hepatitis c patients with genotype 4

Introduction During the past years, studies have provided evidence that hepatitis C virus (HCV) can independently contribute to insulin resistance (IR) and may interfere with insulin signalling pathway using genotype-specific mechanisms. HCV-associated insulin resistance may cause accelerated fibrogenesis, reduced response to IFN-based therapy and hepatocellutar carcinoma. Our aim was to evaluate the prevalence of insulin resistance in Egyptian patients infected with chronic hepatitis C virus genotype 4; being the most prevalent genotype, to assess factors associated with insulin resistance in those patients and to test the impact of insulin resistance on treatment outcome. Method One hundred non diabetic adult patients with histologically proven chronic hepatitis C (CHC), genotype4 were randomly enrolled to test the prevalence of insulin resistanceusing the homeostasis model assessment-IR (HOMA-IR). Based on the results of the prevalence study, 71 consecutive treatment-naive patients were chosen for testing treatment outcomes associated with various degrees of insulin resistance. All patients were given a combination of pegylated interferon and ribavirin for an intended duration of 48 weeks. Quantitative HCV RNA estimation and HOMA-IR testing were done at baseline, during therapy and at the end of treatment. Results Insulin resistance (HOMA-IR >3) was detected in 31 patients (31%). HOMA-IR was positively correlated with age, basal viral load, BMI, triglycerides, fibrosis and steatosis with results regarding basal viral load and incidence of fibrosis mounting to a statistical significance (p = 0.029 and p = 0.026 respectively). When data were analysed by multivariate linear regression, viral load remained the only independent factor associated with elevated HOMA-IR levels (p = 0.001). Overall, 59 patients of those followed for assessing treatment outcomes achieved an end of treatment response (ETR) (59/71,83%). A univariate analysis showed that those were significantly younger, had lower HOMA-IR scores, less viral load and less steatosis compared with non-responders. However, after logistic regression, baseline viral load remained the only independent factor associated with ETR (odds ratio = 0.098, p = 0.006). A progressive significant decline in HOMA-IR scores was noted in this group of patients when comparing values before commencement of therapy, during therapy and at end of follow-up period. Conclusion Insulin resistance is frequently encountered in genotype 4 CHC patients and is independently correlated with HCV viral load. Low baseline HOMA-IR is associated with favourable response to interferon-based therapy and may be a useful predictor for treatment responsiveness. Viral eradication leads to improvement in insulin sensitivity. Disclosure of interest None Declared.

[Study of the mechanism underlying the effect of SOCS3 rs4969170 A/G polymorphism on the occurrence of insulin resistance in chronic hepatitis C patients].

To study the mechanism underlying the effect of the SOCS3 rs4969170 A/G alleles on the occurrence of insulin resistance (IR) in patients with chronic hepatitis C. The promoter region of the SOCS3 gene was amplified by PCR,and luciferase expression vectors were constructed and transfected into HepG2,Huh7 cell lines.The relative luciferase activity of each expression vector was assessed by the dual luciferase reporter gene assay system.Western blotting was used to detect SOCS3 protein expression in PBMCs from groups of patients with the rs4969170 AA and AG genotypes.The state of IR in eight patients was evaluated by determining their HOMA-IR. The pGL3-A, PGL3-G and pGL3-control vectors showed significantly different luciferase expression in the HepG2 cells (0.121 00 ± 0.022 07,0.027 00+/-0.012 49 and 0.043 33 ± 0.005 51; F =48.068, P=0.001) and in the Huh7 cell lines (0.164 70 ± 0.007 10,0.027 33 ± 0.017 04 and 0.033 67 ± 0.014 98; F =115.137, P=0.001). The expression of SOCS3 protein was significantly higher in the rs4969170 AA genotype group than in the AG genotype group (1.22 ± 0.40 vs. 0.30 ± 0.19; t =4.149, P=0.006).The IR index of patients with the rs4969170 AA genotype and the AG genotype was 4.11 ± 2.62 and 1.47 ± 1.01 respectively.There were three patients with IR in the rs4969170 AA genotype group and one in the rs4969170 AG group. There was no statistically significant difference between the two genotype groups (t=1.881, P=0.109). The SOCS3 rs4969170 A haplotype may enhance transcriptional activity of the gene promoter to regulate gene expression, thereby increasing intracellular SOCS3 protein level and ultimately interfering with insulin signaling and causing IR in patients with chronic hepatitis C.

The impact of pegylated interferon and ribavirin combination treatment on lipid metabolism and insulin resistance in chronic hepatitis C patients.

Background/AimsLipid profile and insulin resistance (IR) are associated with hepatitis C virus (HCV) and may predict the chronic hepatitis C (CHC) treatment response. The aim of this study was to determine the association between CHC treatment response and lipid profile and IR change during treatment.MethodsIn total, 203 CHC patients were reviewed retrospectively between January 2005 and December 2011 at Soon Chun Hyang University Hospital. The lipid profile, homeostasis model for assessment (HOMA) of IR (HOMA-IR), and HOMA of β cells (HOMA-β) were evaluated before interferon plus ribavirin therapy (BTx), at the end of treatment (DTx), and 24 weeks after the end of treatment (ATx).ResultsA sustained virologic response (SVR) was achieved by 81% of all patients (49/60), 60% (n=36) of whom possessed genotype 1, with the remainder being non-genotype-1 (40%, n=24). Apart from age, which was significantly higher in the non-SVR group (SVR, 48.0±11.2 years, mean±SD; non-SVR, 56.6±9.9 years; P<0.01), there were no significant differences in the baseline characteristics between the SVR and non-SVR groups. In the SVR group, low density lipoprotein-cholesterol (LDL-C) had significantly changed at DTx and ATx compared to BTx. In addition, HOMA-IR and HOMA-β were significantly changed at DTx in the SVR group. Among those with a high baseline insulin resistance (HOMA-IR >2.5), HOMA-IR was significantly changed at DTx in the SVR group.ConclusionsLDL-C appears to be associated with HCV treatment in SVR patients. Furthermore, eradication of HCV may improve whole-body IR and insulin hypersecretion, as well as high baseline insulin resistance (HOMA-IR >2.5).

Changes of serum omentin-1 levels and relationship between omentin-1 and insulin resistance in chronic hepatitis C patients.

Omentin-1 is a novel adipokine that has a pivotal role in modulating the insulin sensitivity, immunity and inflammation. The current study was conducted to evaluate the serum omentin-1 level in hepatitis C virus (HCV) infected patients, with or without type 2 diabetes, and to investigate its correlation with liver function parameters and insulin resistance. Eighty subjects were enrolled in this study divided into four groups: chronic HCV infected patients (n=20), chronic hepatitis C patients with concomitant type 2 diabetes (n=18), type 2 diabetic patients (n=22) and 20 healthy controls. Serum omentin-1 levels were assessed using enzyme-linked immunosorbent assay (ELISA). Fasting blood glucose, insulin levels, and liver parameters including aminotransferases (ALT and AST) were determined. Serum omentin-1 levels were significantly elevated in HCV infected patients compared to all other groups. Omentin-1 levels were positively correlated with AST and ALT levels (r =0.43, p< 0.001; r =0.423, p<0.001, respectively). Additionally, a significant negative correlation was found between omentin-1 and both fasting insulin levels and homeostasis model assessment of insulin resistance (HOMA-IR) (r = -0.238, p<0.05; r = -0.277, p<0.05, respectively). Furthermore, fasting blood glucose, HbA1c and HOMA-β were negatively correlated to serum omentin-1 levels however these correlations were not statistically significant. Serum omentin-1 level is elevated in HCV infected patients and is positively associated with liver enzymes AST and ALT. This suggested that omentin-1 may be implicated in the pathogenesis of hepatitis C and its metabolic complications. However its role needs to be elucidated by further studies.

Prevalence of insulin resistance in chronic hepatitis C genotype 1 and 3 patients

Background and rationale. Chronic infection with the hepatitis C virus (HCV) is associated with a higher prevalence of insulin resistance compared to the general population. This finding is associated with hepatic steatosis, increased liver fibrosis and lower rates of sustained virological response to interferon based therapy. The relationship of insulin resistance and HCV genotype is controversial. Our aim was to compare the prevalence of insulin resistance between patients with HCV genotype 1 and 3. The association of insulin resistance, hepatic steatosis and liver fibrosis was also investigated.Results. Forty four consecutive treatment naïve patients with HCV genotypes 1 or 3, without cirrhosis and without risk factors for metabolic syndrome were prospectively included. Insulin resistance was defined as a homeostasis model assessment for insulin resistance (HOMA-IR) above 2.0. Steatosis and fibrosis were assessed histologically. Insulin resistance was found in 27 (61%) patients and significant steatosis in 37 (84%) patients. Comparison between patients with HCV genotype 1 and 3 showed insulin resistance in 15 (65%) vs. 12 (57%), respectively (P = 0.81) and steatosis in 19 (83%) vs. 18 (86%), respectively (P = 0.93). Comparison between patients with and without insulin resistance showed, respectively, a higher prevalence of significant fibrosis (56% vs. 6%; P = 0.0001), and a higher mean degree of steatosis (1.3 ± 0.72 vs. 0.76 ± 0.56; P = 0.01). Conclusions. Prevalence of insulin resistance was not different between HCV infected patients with genotype 1 vs. 3. Nevertheless, independent of HCV genotype, there was a statistically significant relationship between insulin resistance and a higher amount of liver fibrosis and steatosis.

Preliminary study of the level of visfatin and the relationship with insulin resistance in Chinese patients with chronic hepatitis C.

Many studies have suggested that visfatin expression is closely related to the occurrence of insulin resistance (IR), while the precise role of visfatin in the regulation of IR in chronic hepatitis C (CHC) is not clear. We investigated fasting glucose, fasting insulin (FINS), C peptide, visfatin, visfatin mRNA, interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein (CRP) and other parameters of 315 patients with CHC and 150 control cases in China. Meanwhile we collected clinical and other laboratory data for further analysis. Compared with the control group, the CHC group had a significant increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), the AST to platelet ratio index (APRI), ratio of AST to ALT (AAR), gammaglutamyl trans-peptidase, IL-6, TNF-α, visfatin, visfatin mRNA, FINS, fasting C peptide, and IR index. The visfatin, visfatin mRNA, insulin, IR index, Homaβ cell function index (HBCI), and fasting β-cell function index (FBCI) of the subjects with high body mass index (BMI) from the CHC sub-group were significantly higher than the normal BMI sub-group of CHC patients. We found a positive correlation between visfatin, visfatin mRNA and BMI, IL-6, TNF-α, and IR index. Our data suggest that visfatin may be related to IR in Chinese CHC patients.

F-08 IL28B genotype is not associated with insulin resistance in chronic hepatitis C patients

F-08 IL28B genotype is not associated with insulin resistance in chronic hepatitis C patients

Amino Acid Substitutions in the Core Region Associate with Insulin Resistance in Chronic Hepatitis C

Background/Aims: Hepatitis C virus (HCV) core protein can induce liver steatosis and glucose intolerance in transgenic mice. We aimed to clarify the association of HCV core region heterogeneity with the development of insulin resistance (IR) among patients with chronic hepatitis C (CHC). Methods: A total of 56 non-diabetic CHC genotype-1b patients were enrolled. IR was evaluated by the homeostasis model assessment (HOMA). The amino acid (aa) sequences in the core region were determined by polymerase chain reaction and direct sequencing. Results: Patients with a higher HOMA-IR (≥3.5) had a higher ratio of aa substitutions in core 70 (p = 0.025), a higher body mass index (p = 0.021) and serum total cholesterol level (p = 0.044) and presence of hepatic steatosis (≥5%) as compared with those with a lower HOMA-IR (<3.5). Multivariate analysis showed that independent factors of higher HOMA-IR were mutated aa70 (odds ratio 3.80, p = 0.033) and body mass index (odds ratio 1.20, p = 0.042). Patients with mutated aa70 had a higher serum tumor necrosis factor-α level than those with wild-type (p = 0.014). Conclusions: Substitution of the HCV-1b core region at position 70 was an independent factor associated with developing IR among patients with CHC.

Insulin resistance in chronic hepatitis C: the search for effective drug treatment continues

An estimated 200 million people are infected worldwide with chronic hepatitis C (CHC) and insulin resistance (IR) is one of the pathological features of hepatitis C virus (HCV) infection. Retrospective analyses have estimated that approximately 21–24% of CHC patients are diabetic, with as many as 54% demonstrating IR

Patomechanizm insulinooporności w przewlekłym wirusowym zapaleniu wątroby typu C

Patomechanizm insulinooporności w przewlekłym wirusowym zapaleniu wątroby typu C

Chronic hepatitis c genotype-4 infection: role of insulin resistance in hepatocellular carcinoma

BackgroundHepatitis C virus (HCV) is a major cause of chronic hepatitis and hepatocellular carcinoma (HCC) and different HCV genotypes show characteristic variations in their pathological properties. Insulin resistance (IR) occurs early in HCV infection and may synergize with viral hepatitis in HCC development. Egypt has the highest reported rates of HCV infection (predominantly genotype 4) in the world; this study investigated effects of HCV genotype-4 (HCV-4) on prevalence of insulin resistance in chronic hepatitis C (CHC) and HCC in Egyptian patients.MethodsFifty CHC patients, 50 HCC patients and 20 normal subjects were studied. IR was estimated using HOMA-IR index and HCV-4 load determined using real-time polymerase chain reaction. Hepatitis B virus was excluded by enzyme-linked immunosorbent assay. Standard laboratory and histopathological investigations were undertaken to characterize liver function and for grading and staging of CHC; HCC staging was undertaken using intraoperative samples.ResultsHCC patients showed higher IR frequency but without significant difference from CHC (52% vs 40%, p = 0.23). Multivariate logistic regression analysis showed HOMA-IR index and International Normalization Ratio independently associated with fibrosis in CHC; in HCC, HbA1c, cholesterol and bilirubin were independently associated with fibrosis. Fasting insulin and cholesterol levels were independently associated with obesity in both CHC and HCC groups. Moderate and high viral load was associated with high HOMA-IR in CHC and HCC (p < 0.001).ConclusionsIR is induced by HCV-4 irrespective of severity of liver disease. IR starts early in infection and facilitates progression of hepatic fibrosis and HCC development.

T-42 A sustained virological response to interferon prevents insulin resistance in chronic hepatitis C patients

T-42 A sustained virological response to interferon prevents insulin resistance in chronic hepatitis C patients

Comparison of surrogate and direct measurement of insulin resistance in chronic hepatitis C virus infection: Impact of obesity and ethnicity

Studies using surrogate estimates show high prevalence of insulin resistance in hepatitis C infection. This study prospectively evaluated the correlation between surrogate and directly measured estimates of insulin resistance and the impact of obesity and ethnicity on this relationship. Eighty-six nondiabetic, noncirrhotic patients with hepatitis C virus (age = 48 +/- 7 years, 74% male, 44% white, 22% African American, 26% Latino, 70% genotype 1) were categorized into normal-weight (body mass index [BMI] < 25, n = 30), overweight (BMI = 25-29.9, n = 38), and obese (BMI > or = 30, n = 18). Insulin-mediated glucose uptake was measured by steady-state plasma glucose (SSPG) concentration during a 240-minute insulin suppression test. Surrogate estimates included: fasting glucose and insulin, glucose/insulin, homeostasis model assessment (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), insulin (I-AUC) and glucose (G-AUC) area under the curve during oral glucose tolerance test, and the Belfiore and Stumvoll indexes. All surrogate estimates correlated with SSPG, but the magnitude of correlation varied (r = 0.30-0.64). The correlation coefficients were highest in the obese. I-AUC had the highest correlation among all ethnic and weight groups (r = 0.57-0.77). HOMA-IR accounted for only 15% of variability in SSPG in the normal weight group. The common HOMA-IR cutoff of < or =3 to define insulin resistance had high misclassification rates especially in the overweight group independent of ethnicity. HOMA-IR > 4 had the lowest misclassification rate (75% sensitivity, 88% specificity). Repeat HOMA-IR measurements had higher within-person variation in the obese (standard deviation = 0.77 higher than normal-weight, 95% confidence interval = 0.25-1.30, P = 0.005). Because of limitations of surrogate estimates, caution should be used in interpreting data evaluating insulin resistance especially in nonobese, nondiabetic patients with HCV.

Insulin resistance in chronic hepatitis C: mechanisms and clinical relevance.

Insulin resistance is the main clinical and pathogenetic feature of the metabolic syndrome, one of the major health problems worldwide. Chronic liver diseases may induce insulin resistance. The hepatic manifestation of the metabolic syndrome is nonalcoholic fatty liver disease. Insulin promotes the storage of energy in the fed state by stimulation of glycogen synthesis, lipogenesis, suppression of gluconeogenesis and VLDL formation. Epidemiological studies have shown that chronic hepatitis C induces insulin resistance. Insulin resistance in chronic hepatitis C is associated with progression of liver fibrosis, resistance to antiviral therapy and development of hepatocellular carcinoma. Here we review the major findings from epidemiological studies from 1994 to the present which have resulted in our current knowledge of insulin resistance in chronic hepatitis C. We further summarise the preliminary pathogenetic models that explain the development of hepatitis C virus-induced insulin resistance. Finally, we draw conclusions for the clinical management of these patients.