Lack of association of hepatic estrogen receptor-alpha expression with histopathological and biochemical findings in chronic hepatitis C

Estrogens exert a protective effect against hepatic steatosis and fibrosis. Loss of estrogen receptor-alpha (ER-α) in the liver is associated with hepatic steatosis and inflammation in animal models. We conducted a study in order to investigate the presence and extent of ER-α expression in HCV infection, and its relationship with histological and biochemical findings. Ninety biopsy-proven chronic hepatitis C (CHC) patients were enrolled in the study. Liver biopsy specimens were immunohistochemically stained for ER-α expression. Nuclear ER-α expression percentage was calculated. ER-α was positive in 69 of the patients (76%). ER-α positive and negative groups were not significantly different in terms of age, gender, necroinflammatory activity, fibrosis, steatosis, serum levels of AST, ALT, ALP, GGT, and bilirubin. ER-α expression percentage was not correlated with fibrosis, steatosis, necroinflammatory activity and biochemical findings. Although estrogens are known to be protective against fibrosis and steatosis in animal models, we did not find any significant correlation between ER-α expression and histopathological and biochemical findings in CHC patients. These findings should be verified in further large scale studies.     

Estrogen Receptor Alpha Expression and Liver Fibrosis in Chronic Hepatitis C Virus Genotype 1b: A Clinicopathological Study

Background:

Hepatic damage due to chronic hepatitis C virus (HCV) genotype 1b infection varies widely.

Objectives:

We aimed to investigate whether estrogen receptor alpha (ERα) plays a role in liver fibrosis in patients infected with HCV genotype 1b.

Patients and Methods:

All the consecutive patients who received the same standard treatment protocol for HCV genotype 1b were subdivided into two subgroups according to their fibrosis scores as fibrotic stages < 2 in mild fibrosis group and fibrotic stages ≥ 2 in advanced fibrosis group, depending on the presence of septal fibrosis. ERα was stained in liver biopsy specimens. Demographics and clinical properties were compared between the groups. Multivariate logistic regression analysis was performed to predict advanced fibrosis.

Results:

There were 66 patients in the mild fibrosis group and 24 in the advanced fibrosis group. Among the mild and advanced fibrosis groups, 65.1% and 50%were female, respectively (P = 0.19). There was an inverse correlation between ERα and fibrotic stage (r: -0.413; P < 0.001). Age, platelet counts, neutrophil counts, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transferase (GGT) and ERα were statistically significant in the univariate analysis. In multivariate logistic regression analyses, ERα expression continued to be an independent predicting factor of liver fibrosis in patients infected with chronic HCV genotype 1b (OR: 0.10; 95% CI: 0.018-0.586; P < 0.001).

Conclusions:

ERα expression in liver was inversely correlated with liver fibrosis among patients infected with chronic HCV genotype 1b.     

Dobutamine stress echocardiography and left ventricular mass changes of mechanical aortic valve replacement in four years follow-up

AIM: The aim of this study was to investigate the differences in cardiac response to stress according to the size of the prosthetic valve in patients who underwent aortic valve replacement (AVR) and to evaluate the relationship between the size of the prosthetic valve and cardiac recovery-remodeling after the operation. METHODS: Thirty patients who had undergone AVR (12 patients) or double valve replacement (18 patients) underwent dobutamine-stress echocardiography 4.2 years after the operation to evaluate response to stress . They were divided into 2 groups according to valve prosthesis size. The small-size AVR group (group 1, n=17) had prosthetic aortic valves 21 pounds mm; the large-size AVR group (group 2, n=13) had valves >21 mm. Response to stress and preoperative and postoperative echocardiographic findings were compared. Pulsed and continuous-wave Doppler studies were performed at rest and at the end of each stage. Peak and mean aortic gradients, left ventricular diastolic and systolic functions were measured for each group. RESULTS: Dobutamine stress increased heart rate and blood pressure in both groups. Peak pressure gradient across the aortic valve prostheses was 42.1 mm Hg in group 1 and 20.9 mm Hg in group 2 (P<0.05) at rest. After dobutamine infusion, the peak pressure gradient across the aortic valve prostheses increased to 85.1 mm Hg in group 1 and 54 mm Hg in group 2 (P<0.05). Isovolumetric relaxation time returned to normal in both groups following dobutamine infusion; this decrease was significant only in group 1. Patients achieved a decrease in left atrium and left ventricular diameters and volumes, as evidence of remodeling following AVR. Left ventricular mass index (LVMI) decreased from 127.6+/-47.6 to 98.1+/-36.9 and from 159.9+/-16.1 to 125.3+/-10.1 in groups 1 and 2, respectively, but this decline was not statistically significant. CONCLUSIONS: Smaller valves have higher gradients and this significant difference increases under stress. Significant improvement in echocardiographic diameters, cardiac filling volumes and LVMI reflects the benefit of the operation. Cardiac remodeling is independent of valve size, although high transprosthetic gradients occur during stress conditions.     

Immunohistochemical detection of transforming growth factor-alpha, epidermal growth factor, and vascular endothelial growth factor expression in hyperstimulated rat ovary

OBJECTIVE: The aim of the present study is to figure out the immunohistochemical expression of transforming growth factor-alpha (TGF-alpha), epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF) in hyperstimulated rat ovaries. METHODS: Twenty Wistar-Albino adult female rats (250-300 g) were taken into the study. The animals were randomly divided into two groups, each containing 10 rats: (i) stimulation group and (ii) control group. In the stimulation group, a stimulation regimen was administered to induce follicular maturity and ovarian hyperstimulation syndrome (OHSS) at the end using a 30-IU follicle-stimulating hormone that was administered subcutaneously for 4 consecutive days, followed by a 30-IU human chorionic gonadotropin on day 5 to induce ovulation. The rats, in the control group, received 0.2 ml of 0.9% NaCl for 5 consecutive days to mimic the conditions of the study animals. At the end of the treatment period, all rats underwent ovariectomy and the sections of ovaries were stained for the TGF-alpha, EGF, and VEGF. RESULTS: The expression of TGF-alpha, EGF, and VEGF in the endothelium, the stroma, the granulosa cells, and the corpus luteum was found to be significantly higher in the stimulated group, compared to that in the control group ( p < 0.05). CONCLUSION: TGF-alpha, EGF, and VEGF are found to have increased in the hyperstimulated ovaries and this finding seems to be involved in the OHSS pathogenesis.