c-peptide and Hepatitis-C--Chronic

The aim of investigation was to study the impact of insulin resistance in patients with HCV infection. 130 patients were investigated: 20 with acute hepatitis C; 38 with chronic hepatitis C; 72 with cirrhosis. The study demonstrated, that the serum level of C-peptide and Insulin in patients with liver cirrhosis is higher, than in patients with acute and chronic HCV infection. This is necessary the monitoring of patients with insulin resistance, which will contribute to the prevention of complications and can improve patients' quality of life.

Topics: Adolescent; Adult; Aged; Blood Glucose; C-Peptide; Female; Hepatitis C, Chronic; Humans; Insulin; Insulin Resistance; Liver Cirrhosis; Male; Middle Aged

Chronic hepatitis C virus infection is associated with insulin resistance (IR), and both host and viral factors are important in its development. The association and the predictors of IR in chronic hepatitis B virus (CHBV) infection remain unclear.. A total of 69 CHBV-infected subjects were examined to study the relationship between histological findings and anthropometric and biochemical data, including IR determined by the homeostasis model assessment (HOMA-IR). To assess the influence of CHBV infection on IR independent of any effect of hepatic fibrosis, overweight, or sex we also compared fasting serum insulin, C-peptide, HOMA-IR, HOMA-beta (measure of beta-cell function) and C-peptide-insulin ratio (to distinguish impaired insulin degradation (low ratio) from insulin hypersecretion (normal ratio)) levels between the subset of 14 male normal weight (body mass index, BMI<23) CHBV patients with stage 0 or 1 hepatic fibrosis and 50 male normal weight healthy controls matched by age and anthropometry (BMI and waist circumference).. A total of 31 (44.9%) CHBV-infected patients were overweight (BMI>23 kg/m(2)) and 18 (26.1%) were obese (BMI>25 kg/m(2)). IR was seen in 34 (49.3%) patients. BMI (Spearman's coefficient=-0.436; P<0.001) and serum triglyceride levels (Spearman's coefficient=-0.307; P=0.010) were univariate predictors of IR. In multiple linear regression analysis, only BMI (P<0.001) was an independent predictor of HOMA-IR. The subgroup of CHBV-infected patients and the controls had comparable levels of all markers of IR, including fasting glucose, insulin, C-peptide, and HOMA-IR.. IR in CHBV-infected patients is a reflection of the host metabolic profile and CHBV infection is not in itself correlated with IR.

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Female; Glucose Tolerance Test; Hepatitis C, Chronic; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Liver; Male

Serum gamma-glutamyltranspeptidase level is often increased in patients with chronic hepatitis C, and we aimed to identify factors associated with this phenomenon in patients completely abstinent from alcohol (teetotaller).. 71 teetotaller patients have been identified by personal history, questioning of relatives, CAGE questionnaire administration and unscheduled alcoholemia measurements.. 39 patients (55%) had elevated (>50IU/L) gamma-glutamyltranspeptidase level. Body mass index, insulin and C-peptide level, insulin resistance, piecemeal necrosis score > or =3, fibrosis score > or =2 and steatosis score > or =1 were significantly higher in these patients than in those (n=32) with normal gamma-glutamyltranspeptidase. At multiple linear regression analysis gamma-glutamyltranspeptidase level was associated with C-peptide level, insulin resistance and histopathologic grading. At multiple logistic regression analysis, C-peptide level (OR=2.13) and piecemeal necrosis score > or =3 (OR=4.59) were the only factors independently associated with elevated gamma-glutamyltranspeptidase. Sustained virological response during pegylated interferon plus ribavirine treatment was achieved by 97% and 49% patients with normal and elevated gamma-glutamyltranspeptidase, respectively (p=0.0001).. Serum gamma-glutamyltranspeptidase level is often elevated in chronic hepatitis C and is associated with metabolic and inflammatory factors; this phenomenon may contribute to explain and to predict resistance to treatment in this subgroup of patients.

Topics: Adult; C-Peptide; Enoxacin; Female; gamma-Glutamyltransferase; Hepacivirus; Hepatitis C, Chronic; Humans; Insulin; Insulin Resistance; Liver; Male; Middle Aged; Temperance

Development of diabetes mellitus (DM) during or shortly after treatment with interferon alpha (IFN-alpha) in patients with chronic hepatitis C virus (HCV) infection has been reported sporadically. We prospectively screened for DM during and after IFN-alpha therapy for chronic HCV infection.. Blood glucose levels of patients with chronic HCV infection were routinely assessed at all outpatient visits during and after treatment with pegylated-IFN-alpha (Peg-IFN-alpha) and ribavirin (Riba).. Between December 2002 and October 2005, 189 non-diabetic patients were treated with Peg-IFN-alpha/Riba, of whom five developed type 1 DM (2.6%), three type 2 DM (1.6%) and one an indeterminate type of DM. Classical symptoms of DM were present in three patients who developed DM shortly after cessation of Peg-IFN-alpha/Riba. In the other patients, symptoms of DM were either indistinguishable from side effects caused by Peg-IFN-alpha/Riba or absent.. Our study showed a high incidence of type 1 DM during Peg-IFN-alpha/Riba therapy for chronic HCV infection. Symptoms of DM may be absent or mistaken for Peg-IFN-alpha/Riba-associated side effects. To diagnose DM without delay, we propose routine assessment of blood glucose at all outpatient visits during and after Peg-IFN-alpha/Riba treatment in chronic HCV patients.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; DNA Probes, HLA; Female; Hepatitis C, Chronic; Humans; Interferon alpha-2; Interferon-alpha; Male; Polyethylene Glycols; Recombinant Proteins; Ribavirin

The purpose of this study was to explore the initial pathogenic mechanisms of diabetes associated with hepatitis C virus (HCV) infection.. Insulin resistance, proinflammatory cytokines, and beta-cell function were evaluated in a case-control study. A total of 28 consecutive nondiabetic patients with chronic hepatitis C were included in the study (anti-HCV+). Fourteen patients with chronic hepatitis other than HCV infection served as the control group (anti-HCV-). Both groups were closely matched by the main clinical variables associated with insulin resistance and the degree of liver fibrosis. In addition, there were no differences between groups regarding hepatic insulin extraction measured by calculating the ratio between C-peptide and insulin. Serum levels of proinflammatory cytokines (tumor necrosis factor [TNF]-alpha, soluble TNF receptor [sTNFR] 1, soluble TNFR2, and interleukin-6) were measured by enzyme-linked immunosorbent assay. Insulin resistance (homeostasis model assessment [HOMA] of insulin resistance [HOMA-IR]) and insulin secretion at baseline (HOMA-beta) and after various stimulus (oral glucose tolerance test, standard food intake, and intravenous glucagon) were determined by previously validated mathematic indexes.. HOMA-IR was higher in anti-HCV+ than in anti-HCV- patients (4.35 +/- 2.27 vs. 2.58 +/- 1.74; P = 0.01). All the proinflammatory cytokines analyzed were significantly higher in anti-HCV+ patients than in anti-HCV- patients. In addition, sTNFR1 and sTNFR2 were directly correlated to HOMA-IR. HOMA-beta as well as insulin and C-peptide responses after the intravenous glucagon test were significantly higher in anti-HCV+ patients than in anti-HC- patients.. Insulin resistance mediated by proinflammatory cytokines, but not a deficit in insulin secretion, could be the primary pathogenic mechanism involved in the development of diabetes associated with HCV infection.

Topics: Adult; Area Under Curve; C-Peptide; Case-Control Studies; Cytokines; Female; Hepatitis C, Chronic; Humans; Inflammation; Insulin; Insulin Resistance; Insulin Secretion; Male; Middle Aged; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II

Genotype-3 of hepatitis C virus (HCV) has been associated with serum lipid changes (reversible with sustained viral response) and liver steatosis.. To characterize the relationships among hepatic steatosis, cholesterol and sustained viral response in these patients.. Patients (n = 215) with chronic hepatitis C (157 with genotype-1 of HCV) had age, body mass index, gender, alcohol intake, glycaemia, serum lipids, transaminases, grade and stage (METAVIR and Scheuer), degree of liver steatosis, sustained viral response, insulinaemia, leptinaemia, beta-hydroxybutyrate and glycerol measured, and were compared with 32 hepatitis B virus (HBV)-infected subjects.. Genotype-3 of HCV patients had age-adjusted hypocholesterolaemia and more frequent hepatic steatosis (P < 0.001). Steatosis was inversely correlated with serum cholesterol (P < 0.01) and directly with viral load (P < 0.03). In patients with genotype-3 of HCV and sustained viral response, serum cholesterol increased from 138 (95% CI: 120-151) to 180 mg/dL (95% CI: 171-199) 12 months after treatment conclusion (P < 0.0001). By contrast, cholesterol values were unchanged in genotype-3 of HCV non-responders and in patients with genotype-1 of HCV regardless of response. Rising cholesterol in sustained viral response did not parallel the changes in beta-hydroxybutyrate.. Besides causing hepatic steatosis, genotype-3 specifically decreases serum cholesterol. This interference with the metabolic lipid pathway is related to viral load, is reversed with sustained viral response, and seems unrelated to mitochondrial dysfunction.

Topics: C-Peptide; Cholesterol; Dyslipidemias; Fatty Liver; Female; Genotype; Hepatitis C, Chronic; Humans; Leptin; Male; Middle Aged

As acylation stimulating protein (ASP) acts on adipocytes mainly as a paracrine factor to increase triglyceride synthesis and storage; hypothetically, it may play a similar role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD).. Forty-six male patients with NAFLD (group A), age-matched 30 male patients with chronic viral hepatitis (group B) and 30 age-matched and body mass index (BMI)-matched healthy male subjects were enrolled in the study.. Among the NAFLD patients, 10 patients (24.4%) had simple steatosis and 36 patients (69.6%) had nonalcoholic steatohepatitis (NASH). The mean levels of ASP, complement 3, insulin, C-peptide, HOMA-IR, triglyceride, and very low-density lipoprotein (VLDL) were significantly higher in group A patients than both controls and group B. ASP levels correlated significantly in a positive manner with BMI, insulin, and HOMA-IR.. Dysregulation of the ASP pathway may have important metabolic consequences in NASH and is associated with insulin resistance.

Topics: Adipocytes; Adult; Biopsy, Needle; C-Peptide; Complement C3; Complement C3a; Fatty Liver; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Insulin Resistance; Lipoproteins, VLDL; Liver; Liver Cirrhosis; Liver Function Tests; Male; Middle Aged; Reference Values; Statistics as Topic; Triglycerides

Chronic hepatitis B (CHB) and C (CHC) are commonly associated with hepatic steatosis. The aims of this study were to investigate predictors of hepatic steatosis, and their impact on inflammation and fibrosis in CHB and CHC.. Consecutive patients with either CHB or CHC who underwent a liver biopsy at The Alfred Hospital between April and September 2002 were included. Histological analysis of liver biopsies was performed by two hepatopathologists blinded to the clinical data.. Ninety-one patients were analysed including 17 patients with CHB and 74 with CHC. CHC genotype 3, C-peptide, glucose and waist circumference were independent predictors of extent of Brunt steatosis grade, while CHC genotype 3, C-peptide and waist circumference were independent predictors of microvesicular steatosis grade. Alcohol intake and age were predictors of hepatic fibrosis. There was a trend toward a correlation between both Brunt steatosis and microvesicular steatosis grades and fibrosis progression rate in CHC genotype non-3.. Hepatic steatosis is common in chronic hepatitis B and C, and is associated with waist circumference, glucose, C-peptide and chronic hepatitis C genotype 3. Steatosis grade appears to relate to hepatic fibrosis progression rate in chronic hepatitis C genotype non-3.

Topics: Adult; Aging; Alcohol Drinking; Anthropometry; Blood Glucose; C-Peptide; Disease Progression; Fatty Liver; Female; Genotype; Hepacivirus; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Liver Cirrhosis; Male; Middle Aged

Diabetes mellitus (DM) is frequently observed in patients with chronic hepatitis caused by hepatitis C virus infection (CHC). The present study was designed to determine the pathogenic factors responsible for glucose intolerance in CHC patients.. A total of 131 patients with CHC were enrolled in this study. Insulin resistance and beta-cell function were determined after 75 g oral glucose tolerance tests.. Glucose intolerance was detected in 27.5% (36/131) of CHC patients; 10 had DM and 26 impaired glucose tolerance. HOMA-R [insulin 0xglucose 0/22.5] was greater in patients with both impaired glucose tolerance and DM than in those with normal glucose tolerance (P<0.01). Matsuda index [10(4)/ (square root) (mean insulinxmean glucosexglucose 0xinsulin 0)] was lower in diabetic patients than in those with normal glucose tolerance (P<0.05). The insulinogenic index [Deltainsulin 30-0/Deltaglucose 30-0] and DeltaC-peptide 30 [DeltaC-peptide 30-0/Deltaglucose 30-0] were significantly lower even in patients with impaired glucose tolerance than in patients with normal glucose tolerance (P<0.01).. Both insulin resistance and beta-cell dysfunction contribute to glucose intolerance in CHC patients.

Topics: Adult; C-Peptide; Female; Glucose Intolerance; Glucose Tolerance Test; Hepatitis C, Chronic; Humans; Insulin; Insulin Resistance; Insulin Secretion; Islets of Langerhans; Liver Cirrhosis; Male; Middle Aged; Prevalence

Type 1 diabetes mellitus (DM) is a frequent complication in patients with beta-thalassemia. It is believed to be due to the damage inflicted by iron overload of the pancreatic beta cells. Liver disorders and genetic influences seem to be additional predisposing factors.. To study the prevalence of diabetes and impaired glucose tolerance (IGT) in transfusion-dependent Egyptian beta-thalassemic patients and to evaluate the possible role of genotyping in the pathogenesis of diabetes associated with beta-thalassemia.. A total of 56 transfusion-dependent beta-thalassemic patients aged 10-31 (mean age=15.9 +/- 5.7 yr), 32 males and 24 females, including 48 thalassemia major and eight thalassemia intermedia; compared to 15 age- and sex-matched controls. All were subjected to history and examination, laboratory investigations: complete blood count (CBC), serum ferritin, liver function tests, hepatitis B and C markers, fasting blood glucose, oral glucose tolerance test (OGTT) and fasting C-peptide. Genotyping for 16 mutations was assessed in thalassemic patients with abnormal glucose tolerance.. The prevalence of diabetes was 10.4% (5 of 48) and IGT was 14.6% (7 of 48) among thalassemia major, whereas, none of thalassemia intermedia had abnormal glucose tolerance. Fasting C-peptide was lower in beta-thalassemic patients compared to controls (p <0.001); the level was significantly higher in patients complicated by diabetes or IGT compared with other thalassemic patients (p <0.001). Chronic hepatitis C was detected in all patients (100%) with abnormal glucose tolerance. Genotyping showed that IVS II nt 745 was detected in 77.7% of cases with abnormal glucose tolerance.. Abnormal glucose tolerance is common in multiply transfused beta-thalassemia major patients, which could be attributed to progressive and early loss of beta-cell mass, along with persistent insulin resistance. Chronic hepatitis C may play a role in the development of abnormal glucose tolerance. An association between diabetes and genotyping IVS II nt 745 was found. Patients with this particular genotype are advised to check their blood glucose every 6 months to detect early occurrence of diabetes.

Topics: Adolescent; Adult; beta-Thalassemia; Blood Transfusion; C-Peptide; Child; Diabetes Mellitus; Egypt; Female; Genotype; Glucose Intolerance; Hepatitis C, Chronic; Humans; Male

This study aimed at elucidating the effects of interferon (IFN)-alpha on glucose metabolism in patients with chronic hepatitis B and C infections. Twenty-eight biopsy-proven patients with chronic hepatitis B (ten cases) and hepatitis C (18 cases) were given IFN-alpha for a total of 24 weeks. The patients received a 75 g oral glucose tolerance test (OGTT), glucagon stimulation test, tests for type 1 diabetes-related autoantibodies and an insulin suppression test before and after IFN-alpha therapy. Ten of the 28 patients responded to IFN-alpha therapy. Steady-state plasma glucose of the insulin suppression test decreased significantly in responders (13.32+/-1.48 (S.E.M.) vs 11.33+/-1.19 mmol/l, P=0.0501) but not in non-responders (12.29+/-1.24 vs 11.11+/-0.99 mmol/l, P=0.2110) immediately after completion of IFN-alpha treatment. In the oral glucose tolerance test, no significant difference was observed in plasma glucose in either responders (10.17+/-0.23 vs 10.03+/-0.22 mmol/l) or non-responders (10.11+/-0.22 vs 9.97+/-0.21 mmol/l) 3 Months after completion of IFN-alpha treatment. However, significant differences were noted in C-peptide in both responders (2.90+/-0.13 vs 2.20+/-0.09 nmol/l, P=0.0040) and non-responders (2.45+/-0.11 vs 2.22+/-0.08 nmol/l, P=0.0287) before vs after treatment. The changes of C-peptide in an OGTT between responders and non-responders were also significantly different (P=0.0028), with responders reporting a greater reduction in C-peptide. No case developed autoantibodies during the treatment. In patients who were successfully treated with IFN-alpha, insulin sensitivity improved and their plasma glucose stayed at the same level without secreting as much insulin from islet beta-cells.

Topics: Adult; Alanine Transaminase; Analysis of Variance; Autoantibodies; Blood Glucose; C-Peptide; Chi-Square Distribution; Diabetes Mellitus, Type 1; DNA, Viral; Female; Glucagon; Glucose Tolerance Test; Hepatitis B e Antigens; Hepatitis B, Chronic; Hepatitis C, Chronic; Homeostasis; Humans; Insulin; Insulin Resistance; Insulin Secretion; Interferon-alpha; Islets of Langerhans; Male; Middle Aged

We report a case of chronic hepatitis C presenting insulin-dependent diabetes mellitus (IDDM) associated with various autoantibodies including possible anti-insulin receptor antibody (AIRA) during interferon (IFN) therapy. A 57-year-old man having chronic hepatitis C virus (HCV) infection with chronic thyroiditis received IFN therapy. The thyroid function was well-controlled by administration of thyroid hormone, although thyroid autoantibodies were positive. At 15 weeks after starting IFN (reaching 530 million units of total dose), marked thirst happened, with increased fasting plasma glucose level (488 mg/dl) and decreased daily urinary C peptide immunoreactivity level (less than 4.2 microg/day). IDDM occurred with anti-nuclear antibody (ANA), anti-DNA antibody and possible AIRA, and thyroid autoantibodies titers increased, but without pancreatic islet cell antibody and anti-glutamic acid decarboxylase antibody. Administration of IFN was stopped and insulin treatment was started, but plasma glucose level was not controlled well. AIRA became negative 2 months later, however, insulin antibody (IA) was positive when tested after 18 months. Serum HCV RNA has been negative, and a normal level of serum transaminase has been observed since IFN therapy. It is likely that IFN therapy induced the immunological disturbance and resulted in occurrence of various autoantibodies and IDDM in the patient.

Topics: Antibodies, Antinuclear; Antiviral Agents; Autoantibodies; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Glutamate Decarboxylase; Glycated Hemoglobin; Hepatitis C, Chronic; Humans; Hypothyroidism; Insulin; Insulin Antibodies; Interferon alpha-2; Interferon-alpha; Male; Middle Aged; Receptor, Insulin; Recombinant Proteins; Thyroid Hormones; Transfusion Reaction