Assessment of Serum Vitamin D and Irisin Levels in Obese Patients.

Background: 25-hydroxyvitamin D and irisin have been found to be involved in the pathogenesis of obesity. The aim of the study is to assess the serum levels of 25-hydroxyvitamin D and irisin in obese patients and to determine the association of 25-hydroxyvitamin D and irisin levels with anthropometric parameters. Methods: The study was carried out on 300 obese patients in addition to 156 healthy age and gender matched subjects as a control group. Demographic data were collected from the studied cases. Body mass index, serum levels of insulin, total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, 25-hydroxyvitamin D, and irisin were measured. Results: 25-hydroxyvitamin D levels were significantly associated with obesity, the incidence of 25-hydroxyvitamin D deficiency (< 12 ng/mL) was 49.3% in obese patients, especially in females. A positive correlation was noted between 25-hydroxyvitamin D and age TC:HDL ratio. It was negatively correlated with BMI. Serum irisin levels were higher, but not significantly, in obese patients compared to controls. Irisin was positively associated with insulin levels and negatively correlated with total cholesterol. Conclusions: Obesity is associated with 25-hydroxyvitamin D deficiency and high serum levels of irisin. Body mass index and gender are predictors of 25-hydroxyvitamin D status. The positive correlation between serum irisin and insulin indicates that compensatory enhancement of irisin excretion can occur due to insulin resistance.

Evaluation of Biomarkers in Egyptian Patients with Different Grades of Nonalcoholic Fatty Liver Disease.

Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is a silent disease; its spectrum includes simple steatosis, nonalcoholic steatohepatitis and fibrosis. Pro- and anti-inflammatory cytokines play roles in the pathogenesis of NAFLD and insulin resistance (IR). Moreover, plasma cell antigen-1 (PC-1) is related to IR and associated with NAFLD progression. Therefore, we aimed to detect biomarkers, ultrasonographic and anthropometric findings capable of differentiating NAFLD grades, since most previous investigators were concerned more with NAFLD patients without classifying them into grades. Methods: A total of 87 NAFLD patients (31 with grade 1 (mild NAFLD), 26 with grade 2 (moderate NAFLD) and 30 with grade 3 (severe NAFLD) were included in the study, in addition to 47 controls (grade 0). All subjects underwent ultrasonographic examination for NAFLD diagnosis. Serum interleukin-10 (IL-10), plasma interleukin-18 (IL-18) and plasma PC-1 levels were determined using enzyme-linked immunosorbent assay. Results: Homoeostasis model assessment (HOMA)-IR was higher in different NAFLD grades than in controls. Ultrasonographic and anthropometric findings and lipid profile indices (except for high-density lipoprotein cholesterol, which was decreased) were increased with NAFLD progression. Grade 3 patients showed significant increase in levels of IL-18 and significant decrease in IL-10 and PC-1 levels when compared to grade 1 patients. Conclusion: Anthropometric and ultrasonographic findings were valuable in differentiating NAFLD grades. IR is very important in NAFLD pathogenesis. IL-18, HOMA-index and PC-1 levels could be used to differentiate between NAFLD grades, together with other measurements.

MTP genetic variants associated with non-alcoholic fatty liver in metabolic syndrome patients.

This study was performed for investigation the relationship between variants of MTP gene polymorphism and the development of NAFLD in patients with and without MS. The study was included 174 NAFLD patients (106 with MS and 68 without MS), and 141 healthy control subjects. The 493 G/T polymorphism of MTP gene was evaluated by PCR-RFLP method. The frequency of MTP TT genotype and T allele were significantly higher in NAFLD patients when compared to healthy controls. Moreover, a significant association in MTP gene polymorphism was observed in NAFLD patients with MS compared to NAFLD patients without MS and controls. Our study suggested that MTP 493 G/T gene polymorphism may act as susceptibility biomarker for NAFLD and MS.

Hepatobiliary Schistosomiasis.

Schistosomiasis is an ancient parasitic disease that has afflicted Egyptians since the time of the pharaohs. The disease is caused by lodged schistosome eggs in the host liver, evoking an immune response and leading in some patients to the development of hepatic granuloma and fibrosis. Here, we review the epidemiology, immunopathogenesis, and clinical profile of schistosomiasis. This information may aid in the development of more efficacious treatments and improved disease prognosis.

Diagnostic value of fibronectin discriminant score for predicting liver fibrosis stages in chronic hepatitis C virus patients.

BACKGROUND: Several noninvasive predictive models were developed to substitute liver biopsy for fibrosis assessment. AIM: To evaluate the diagnostic value of fibronectin which reflect extracellular matrix metabolism and standard liver functions tests which reflect alterations in hepatic functions. MATERIAL AND METHODS: Chronic hepatitis C (CHC) patients (n = 145) were evaluated using ROC curves and stepwise multivariate discriminant analysis (MDA) and was validated in 180 additional patients. Liver biochemical profile including transaminases, bilirubin, alkaline phosphatase, albumin, complete blood count were estimated. Fibronectin concentration was determined using monoclonal antibody and ELISA. RESULTS: A novel index named fibronectin discriminant score (FDS) based on fibronectin, APRI and albumin was developed. FDS produced areas under ROC curves (AUC) of 0.91 for significant fibrosis and 0.81 for advanced fibrosis. The FDS correctly classified 79% of the significant liver fibrosis patients (F2-F4) with 87% sensitivity and 75% specificity. The relative risk [odds ratio (OR)] of having significant liver fibrosis using the cut-off values determined by ROC curve analyses were 6.1 for fibronectin, 4.9 for APRI, and 4.2 for albumin. FDS predicted liver fibrosis with an OR of 16.8 for significant fibrosis and 8.6 for advanced fibrosis. The FDS had similar AUC and OR in the validation group to the estimation group without statistically significant difference. CONCLUSION: FDS predicted liver fibrosis with high degree of accuracy, potentially decreasing the number of liver biopsy required.

Changes in adipocytokines and insulin sensitivity during and after antiviral therapy for hepatitis C genotype 4.

BACKGROUND: Hepatitis C virus (HCV) infection, especially genotypes 1 and 4, is associated with wide metabolic disarrangements. AIM: To assess whether host metabolic factors influence sustained virological response (SVR) in patients with chronic hepatitis C genotype 4 (HCV-4) treated with peginterferon / ribavirin and to evaluate the impact of antiviral therapy on insulin resistance (IR) and serum levels of adipocytokines. METHODS: Changes in levels of adiponectin, leptin, TNF-α and the homeostasis model assessment for insulin resistance (HOMA-IR) on antiviral combination in patients with HCV-4 were analyzed and effect on response was studied. RESULTS: 107 patients were included (M/F 86/21; mean age 41.4±5.6 years). Neither serum adipocytokines nor HOMA-IR was correlated with viral load. SVR was achieved by 57% of patients and was associated with fibrosis score (odds ratio: 6.5; P = 0.001) and adiponectin level (odds ratio: 1.3; P = 0.01). At the end of follow-up, HOMA-IR, adiponectin, leptin and TNF-α were reduced, all these changes unrelated to predicting the outcome of treatment. At follow-up, HOMA-IR and adiponectin continued to decrease in patients with SVR, but remained unchanged significantly in patients who did not response or relapse. CONCLUSIONS: Serum adiponectin at baseline appears to be an independent predictor for the achievement of SVR and can be utilized as an additional predictive marker. Changes of IR and adipocytokines occur under treatment which is more evident with the resolution of HCV infection, suggesting that HCV could have a direct role in these metabolic changes.

Insulin resistance impairs viral dynamics independently of ethnicity or genotypes.

BACKGROUND AND AIM: Data concerning the influence of insulin resistance (IR) and ethnicity on early phases of viral kinetics after initiation of peginterferon plus ribavirin in treatment-naive, chronic hepatitis C (CHC) patients are limited. METHODS: A total of 263 nondiabetic CHC patients treated with peginterferon plus ribavirin were enrolled for analysis from an Egyptian and Spanish center. IR was evaluated by homeostasis model assessment (HOMA)-IR. Hepatitis C virus (HCV) RNA levels were measured at baseline, 48 hours, 2, 4, and 12 weeks after treatment initiation. Sustained virological response (SVR) was examined 24 weeks after therapy discontinuation. RESULTS: Baseline HOMA-IR strongly influenced 48 hours viral dynamics. HCV-RNA decay observed at 48 hours after the first injection of peginterferon was significantly lower (0.91±0.51 log) in patients with HOMA ≥2 compared with those with HOMA <2 (1.8±0.95 log, P=0.005) this effect was independent of stage of liver fibrosis, HCV genotype, and ethnicity. These differences remained with several cutoffs such as HOMA >3 or HOMA >4. Multivariate analysis identified baseline insulin levels as the main independent variable affecting the 48-hour response in addition to baseline HCV-RNA. The difference in early viral kinetics between patients with HOMA ≥2 or <2 is associated with a significant difference in the percentage of patients achieving both rapid virological response and SVR. CONCLUSIONS: IR is a major determinant of the early viral kinetic response to peginterferon plus ribavirin, which has a great impact on subsequent rapid virological response and SVR in CHC patients. This suggests that strategies to improve IR may have a positive effect on SVR and may be early monitored.

Serum lipids and chronic hepatitis C genotype 4: interaction and significance.

BACKGROUND & AIM: Metabolic abnormalities are common in chronic hepatitis C infection (CHC). However, the genotypic differences of these disarrangements in patients infected with CHC genotype 4 (HCV-4) and its association with liver histology and viral loads remain unknown. MATERIAL AND METHODS: We consecutively enrolled 183 HCV-4 patients and 106 healthy matched controls; to compare metabolic profiles and assess pattern of association of HCV RNA levels as well as histological factors with the serum lipid profile. RESULTS: HCV-4 infection is associated with higher homeostasis model assessment of insulin resistance (HOMA-IR) index, despite that, a favourable lipid pattern, consisting of an elevation in HDL- C and a reduction in serum cholesterol (TC), LDL-C and triglyceride (TG) levels, in comparison with normal matched adults. Significant fibrosis was independently associated with HOMA-IR, portal/periportal inflammation grade, serum cholesterol and age. Univariate association was elucidated between lower LDL-C and TC and Metavir activity score and between higher TG and TC and steatosis. In multivariate analysis, severe hepatitis activity, milder hepatic fibrosis, and triglyceride levels are associated with higher HCV RNA levels. CONCLUSION: HCV-4 is associated with wide metabolic changes. A proportional relationship is found between serum lipid profiles and hepatitis C viral load and liver histology in patients with HCV-4.

Effects of PEG-interferon-alpha-2A on Schistosoma mansoni infection in mice.

In some regions of the world, co-existence of schistosomiasis and hepatitis C (HCV) infection is common. Because the morbidity in human schistosomiasis is primarily due to host cell-mediated immune response, it was of interest to determine the effects on Schistosoma mansoni infection of an immune stimulator used in the standard treatment of HCV infection. Schistosoma mansoni -infected mice were treated with PEG-interferon-alpha-2a (PEG-IFN-alpha) by subcutaneous injection. Groups 1, 2, and 3 received 0.2 microg, 0.6 microg, and 1 microg PEG-IFN-alpha/wk, respectively, while group 4 received saline. The total worm burden was lower in all treated groups, with a maximal reduction of 35% after 9 wk of treatment with 1 microg PEG-IFN-alpha. Interferon treatment also increased the proportion of single worms over pairs. Ova counts in intestine and liver, as well as the number of liver granulomas, were greatly decreased at all time points for all treated groups. PEG-IFN-alpha also had inhibitory effects on the size of granulomas after 4 wk of treatment. The results suggest that PEG-IFN-alpha may be worth investigating for the treatment of human schistosomiasis when standard oral agents cannot be used, or when rapid inhibition of granuloma formation may be a priority.

Pioglitazone improves virological response to peginterferon alpha-2b/ribavirin combination therapy in hepatitis C genotype 4 patients with insulin resistance.

BACKGROUND & AIM: Insulin resistance (IR) affects sustained virological response (SVR). The use of insulin-sensitizing agents has been proposed to improve therapy outcome. The safety and efficacy of pioglitazone on insulin sensitivity and SVR in treatment-naïve patients with chronic hepatitis C (CHC) genotype 4 with IR receiving standard antiviral therapy were evaluated in a randomized-controlled study. METHODS: Ninety-seven previously untreated patients with CHC and IR [homeostasis model assessment (HOMA>2)] were randomly assigned into two arms; (arm A; n=48) were given pioglitazone 30 mg/day combined with peginterferon (Peg-IFN)-alpha-2b/ribavirin (RBV) for 48 weeks, and (arm B; n=49) were given standard of care (Peg-IFN-alpha-2b/RBV for 48 weeks); HOMA index and hepatitis C virus RNA (HCV RNA) levels were measured at baseline, during therapy and follow-up. Treatment was stopped in patients without an early virological response or those who were HCV RNA positive at 24 weeks. RESULTS: Baseline data of both groups were comparable, with no significant statistical differences. The percentages of rapid virological response (RVR) and SVR were significantly higher in patients given triple therapy compared with standard of care (27.08 vs. 6.1%; P=0.006 and 60.4 vs. 38.7%; P=0.04 respectively); patients in arm A showed a greater decrease in the HOMA index than those in arm B (-1.8 +/- 0.3, -2.1 +/- 0.3 vs. -1.1 +/- 0.6, -1.3 +/- 0.7) at week 24 and at the end of follow-up (P=0.001 at both time points). The triple therapy was well tolerated. CONCLUSIONS: A combination of pioglitazone, Peg-IFN-alpha-2b and ribavirin increased RVR, SVR and decreased IR, compared with patients given Peg-IFN plus ribavirin without an increase in adverse events.

Host susceptibility to schistosomes: effect of host sera on cell proliferation of Schistosoma mansoni schistosomula.

To determine effects of the sera on cell proliferation, schistosomula of Schistosoma mansoni (20-days-old) were incubated in medium containing fetal calf serum plus hamster (highly susceptible host) portal or peripheral venous serum, or rat (poorly susceptible host) portal or peripheral venous serum in the presence of bromodeoxyuridine (BrdU). Compared with schistosomula cultured in presence of control medium containing fetal calf serum alone, BrdU labeling indices (BLIs) were increased by 39% in the presence of portal, but not in peripheral, serum of hamsters. In contrast, no significant differences were observed in the BLIs in rat portal, or peripheral, sera or in control media. In vivo BrdU labeling results revealed that there was no detectable cell proliferation in S. mansoni schistosomula (6 days old) in the lungs. However, cell proliferation was detected in schistosomula beginning at 17 days. The results indicated that portal venous serum from a highly susceptible host, but not from a poorly susceptible host, stimulated schistosome cell proliferation in vitro. The timing of the increase in cell proliferation in terms of development corresponded to liver portal-mesenteric localization of schistosomula. Together, the data support the conclusion that in susceptible hosts, portal serum may play a role in schistosome cell proliferation, possibly resulting in termination of schistosome migration. This may explain the colocalization of adults, and the known organ selectivity of disease.

Immunodetection of collagen types I, II, III, and IV for differentiation of liver fibrosis stages in patients with chronic HCV.

The current study is aimed at evaluating serum collagens and other serum biochemical markers as useful, non-invasive markers of hepatic fibrosis associated with chronic hepatitis C virus (HCV). Collagen types I, II, III, and IV were detected in serum using ELISA and Western blot techniques. The ELISA levels of collagen I, II, III, and IV increased significantly with the progression of fibrosis staging. Based on receiver-operating characteristic (ROC) curve analysis, the collagen type III (70 kDa) and type IV (200 kDa) were more useful than other serum bio-markers for differentiating severe fibrosis from mild fibrosis. Multivariate discriminant analysis (MDA) selected a fibrosis discriminant score (FDS) = [2.345 + Collagen III (microg/mL) x 1.923 + Collagen IV (microg/mL) x 1.544 + ALT (U/mL) x 0.005] - [albumin(g/L) x 0.046]. The FDS correctly classified 87% of the severe fibrosis patients at a cut-off score = 2.2 (i.e., more than 2.2 indicated severe fibrotic liver and less than 2.2 indicated mild fibrotic liver) with specificity of 97%. In a validation study, the FDS was applied to the second cohort of patients and the results were reproduced without significant difference. In conclusion, the developed four-parameter based FDS is useful for identifying severe liver fibrosis in patients with chronic HCV infection.