Serum amyloid a and leptin levels and insulin resistance in relation to steatosis in chronic hepatitis C patients

Chronic hepatitis C [CHC] was found to be closely related to insulin resistance [IR] and may increase risk of liver steatosis and fibrosis. Several mechanisms have been proposed to explain HCV-induced IR; including obesity, steatosis, leptin hormone and serum amyloid -A [SAA]. The aim of the present work was to assess serum amyloid -A and leptin levels and insulin resistance in normal weight and obese patients with chronic hepatitis C, and their relation to the steatotic changes and grade of inflammation and fibrosis according to Metavir scoring system. The present study was earned out on thirty patients with chronic hepatitis C [Group II], and thirty male-control subjects of matched age and body built [Group I]. Both groups were further divided according to body mass index [BMI] into normal-weight [Ia and IIa] and over-weight and obese [Ib and IIb] subgroups. All studied subjects were subjected to full history taking, thorough clinical examination and ultrasound of the abdomen. Percutaneous ultrasound assisted tru cut needle liver biopsy was done to HCV patients and assessed for tile grade of the necro-inflammatory changes and fibrosis, according to Metavir scoring system, and steatosis. Laboratory investigations included the evaluation of fasting serum amyloid-A, leptin, glucose and insulin levels and insulin resistance index [assessed by HOMA equation]. In addition; HBs-Ag, HCV-antibodies, and HCV-RNA by PCR and serum anti-sehistosomal antibodies were also evaluated. All patients and controls were negative for HBs-Ag and schistosomal antibodies. It was found that SAA was significantly higher in the patients group [subgroups Ia, IIb] than controls. Fasting serum amyhoid-A, leptin, glucose and insulin levels and HOMA, were significantly higher in the obese subjects [subgroups Ib and IIb] than in normal weight subjects [subgroups Ia and IIa]. There was a significant positive correlation between HOMA and both serum amyloid-A and leptin levels in obese subjects. Moreover, serum amyloid-A, leptin and insulin were positively correlated with increased BMI and waist/hip ratio in obese subjects [subgroups Ib and IIb]. Steatotic changes were significantly higher in obese patients [group IIb] than in normal weight patients [groups IIa]. Steatosis and necroinflammatory grades in CHC patients showed a positive significant correlation with serum amyloid-A, leptin and HOMA. Moreover steatosis was significantly correlated with fasting serum glucose, while necroinflammatory grade was significantly correlated with fasting serum insulin level. From the present work, it could be concluded that - Serum amyloid A, leptin hormone and insulin resistance were significantly correlated with both steatosis and the severity of Metavir necroinflammatory grade in CHC patients. - SAA is a feature of obesity in both HCV patients and controls as an inflammatory marker. Also, it seems to be altered by viral factors as it was significantly increased in CHC patients than controls. Thus, SAA might be a missing link between enhanced adipose tissue mass, low grade inflammatory state and insulin resistance in CHC patients. Therefore it is recommended for CHC patients to undergo weight reduction programs and follow up investigations including SAA and leptin levels

Study of serum osteoprotegrin [OPG], tumor necrosis factor-related apoptosis-inducing ligand [Trail] and fetuin-A in patients with chronic renal failure

Vascular and valvular calcifications are strong prognostic markers of cardiovascular disease mortality in chronic kidney disease [CKD] patients especially those on hemodialysis. It has been demonstrated that CKD patients with osteodystrophy have increased atherosclerosis and, more recently, increased coronary artery calcification. Was to evaluate the link between renal failure, atherosclerosis, vascular calcification and inflammation by determining the role of serum osteoprotegrin [OPG], tumor necrosis factor-related apoptosis-inducing ligand [TRAIL], and Fetuin A in the development of vascular calcification in patients with End stage renal failure disease [ESRD]. The study included, thirty patients on maintenance hemodialysis [HD] and fifteen patients with conservatively managed chronic renal failure [CRF] for whom dialysis was not performed. Both groups were compared to fifteen age and sex matched healthy individuals who constituted the control group. To all the subjects clinical examination, and 12 lead electro-cardiography were done. To all subjects the following investigations were performed: routine biochemical analysis, serum OPG, Fetuin A and plasma TRAIL Also serum parathyroid hormone [PTH], Calcium [total and ionized], phosphorus [Ph], and C- reactive protein [CRP] were measured. Finaly carotid ultra sonography of the pelvis and hand, and calculation of vascular calcification score were done. Carotid intima media thickness [CIMT] was found to be significantly higher in both undialyzed [CRF] patients and dialyzed [HD] patients when compared to controls [p<0.001 leach]. Also the difference between both groups of patients was statistically significant [p: 0.014]. Calcification score was found to be significantly higher in CRF and HD patients when compared to controls [p: 0.047 and < 0.001 respectively] Serum OPG level was significantly higher in both undialyzed CRF and dialyzed HD patients when compared to the control group [p: 0.041 and < 0.001 respectively].The level was also found to be significantly higher in the HD group when compared to CRF patients [p< 0.001]. Serum fetuin A level was found to be significantly lower in both CRF and HD patients when compared to the control group [p: 0.02, 0.05 respectively]. As regards TRAIL levels, no significant difference was found between the three studied groups. The level of the PTH was significantly higher in CRF undialyzed and HD patients when compared to control group [p: 0.021 and < 0.001 respectively]. CRP level was significantly higher in both patients groups when compared to controls [p< 0.001, 0.04 respectively].In the total patients group: there was a positive significant correlation between VC score and both PTH and AP. There was a positive significant correlation between OPG and [CIMT, Fetuin, AP and total Ca]. There was also a positive significant correlation between Fetuin A and both TRAIL and Albumin. By performing multiple logistic regression, only serum PTH was significant independent predictor of vascular calcification [p=0.006] and serum OPG was significant independent predictor of inflammation. [p=0.029]. The only parameter with significant ROC curve was PTH. It could be finally concluded that the increased level of OPG in CRF and HD patients might be a compensatory self defensive response against other factors that promote vascular calcification, or may possess potentially damaging properties, while the decreased level of Fetuin A reflects an inadequate response against the development of VC. Also the increase level of CRP denotes an ongoing inflammatory state and this causes down regulation of fetuin A which may represent the essential link between chronic inflammation and vascular calcification. PTH was found to be the best diagnostic marker of VC of all studied parameters, and was also the most independent predictor of VC, while OPG was the most independent predictor of inflammation