Serum and tissue levels of transforming growth factor-B1 in Egyptian patients with chronic hepatitis C genotype 4: correlation with steatosis, and fibrosis

Activation of hepatic stellate cells [HSC] and transforming growth factor-b [TGF-bl] signaling are one of the important events at the beginning of fibrosis. Steatosis is present in liver biopsy in approximately 50% of patients with hepatitis C and its association with stage of fibrosis has been reported. The aim of this work is to study the relation between TGF-beta 1, steatosis, and fibrosis and hepatitis C genotype 4. We studied 47 patients [33 males, 14 females, mean age 43.46 +/- 13.54 years] with chronic HCV infection. Serum TGF-beta 1 was determined in all participants. Hepatitis C virus RNA was detected in patients' sera by reverse transcriptase-polymerase chain reaction [RT-PCR]. Liver biopsies were taken to evaluate steatosis, fibrosis, and tissue level of TGF-pL. Serurn levels of TGF-B1 [p < 0.001] were significantly higher in chronic hepatitis C patients compared with controls. Aspartate aminotransferase [AST], alanine aminotransferase [ALT] [p < 0.001], were significantly higher in chronic hepatitis C patients compared with controls. There was a significant difference between chronic hepatitis subgroups [as regard degree of steatosis] grading and staging [p< 0.001]. There was a significant correlation between steatosis grading and tissue level of TGF-Bl but not with serum level of TGF-B1. There was a significant correlation between fibrosis staging and tissue level of TGF-B1. Also, serum level of TGF-B1 was significantly correlated with advance of fibrosis. HCV-genotype 4 infection is associated with a significant higher serum level of TGF-B1 than those of normal subjects. We have confirmed that steatosis is associated with increased fibrosis and necroinflammation in chronic HCV biopsies

Active human cytomegalovirus infection in newly diagnosed patients with ulcerative colitis in Tanta University Hospitals

Cytomegalovirus infection is common throughout the world; 40%-100% of adults in different populations are infected by the fourth decade. Early studies suggested that CMV infection initiates some cases of ulcerative colitis [UC], plays a role in UC exacerbation, causes self-limited colitis, and increases the incidence of complications, emergency surgery or death in patients with UC. Thirty-seven patients with first-time diagnosed ulcerative colitis were selected retrospectively and included in this study from attendance Tanta University Hospitals. Patients were classified into two groups, group I ulcerative colitis patients infected with CMV; group II ulcerative colitis patients not infected with CMV Severity of UC was assessed clinically using Montreal classification of severity of ulcerative colitis, colonoscopicaly using Montreal classification of extent of ulcerative colitis. Histologically diagnosis and severity was graded using microscopic scores for the assessment of disease activity in UC. Patients were comparable with controls according to age and sex. Clinical and laboratory parameters showed no statistically significant differences except for reduced serum albumin and hemoglobin in group I [p <0.05]. The highest sensitivity was achieved in immunohistochemistry, while the lowest one was achieved in detection of inclusion bodies in H and E-stained biopsy for detection of infection with CMV in patients with UC As regards assessment of severity in patients with UC with or without CMV infection, no significant differences between both groups were detected. CMV infection in patients with UC may be common and is often underestimated. This has definite clinical significance and therefore should not be ignored

HFE mutations, serum iron indices, and hepatic iron: impact on fibrosis severity and steatosis in patients with chronic hepatitis C genotype 4

Iron overload may cause or contribute to hepatic injuiy and fibrosis. Mutations in tbr HFE gene may influence development or progression of chronic liver disease by increasing iron stores or modulating immune responses. The aim of this work was to assess the influence of HFE mutations and serum and hepatic measures of iron status on fibrosis severity and steatosis in patients with chronic hepatitis C genotype 4. We studied 47 patients [33 males, 14 females, mean age 43.46 +/- 13.54 years] with chronic HCV infection. Serum iron indices were determined in all participants. Hepatitis C virus RMA was detected in patients' sera by reverse transcriptase-polymerase chain reaction [RT-PCR]. Liver biopsies were taken to evaluate steatosis, fibrosis, and hepatic iron depositions. We used the method of polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] to analyze the HFE mutations. Twenty-three patients 23/47 [48.936%] had increased serum iron stores and only eleven patients 11/47 [23.40%] had positive hepatic iron stain. There was a significant difference between hepatic steatosis subgroups as regards inflammatory grading and fibrosis staging [p <0.001]. Ferritin level was significantly correlated with fibrosis severity and steatosis grading. Hepatic iron deposition was significantly correlated only with steatosis grading but not with fibrosis severity. Heterozyosity for H63D allele was noted to be five patients 5/47 [10.638%] in CHC patients. Our data demonstrated no significant difference in the prevalence of HFE mutations between the HCV patients with increased serum iron store and others without Also, the same results were noticed in patients with and without hepatic iron deposition. Ferritin level should be better considered as a surrogate marker of severe fibrosis in chronic hepatitis C. The prevalence of HFE mutations associated with hereditary hemochromatosis is not increased in the patients with CHC. The HFE mutations may not contribute to iron accumulation in the CHC patients even when serum iron overload is observed in these patients

Rantes in rheumatic pulmonary hypertension: a target for therapeutic decisions

Pulmonary arterial hypertension [PAH] is an important risk factor for morbidity and mortality in patients with mitral valve disease. Recent studies highlighted the possible influence of inflammatory mechanisms in several types of PAH but data about PAH in rheumatic heart disease [RHD] are lacking. The aim of this study was to investigate the circulating level of the chemokine regulated upon activation, normal T-cell expressed and secreted [RANTES] and the cytokine interleukine-6 [IL-6] in patients with rheumatic mitral valve disease associated with pulmonary hypertension. Serum'level of [RANTES] and [IL-6] were measured by enzyme-linked immunosorbent assay [ELISA] in 18 patients with mitral valve disease and 10 matched healthy subjects [control group], All patients had PAH and 7 only [38.9%] had severe pulmonary hypertension. The serum level of RANTES in the patients' group was not statistically different from that in the control group. However, patients with severe pulmonary hypertension have a mean serum level of RANTES of [6138.6 +/- 1572.5 pg/ml] that is significantly greater than that of patients without severe pulmonary hypertension [1818.2 +/- 153,6 pg/ml] [p=0.029]. On the other hand, the serum level of lL-6 in the patients was statistically different from that-of the control [378 +/- 12.7 vs. 262 +/- 28.6 respectively, p<0.005]. Comparison of IL-6 serum level in patients with and without severe pulmonary hypertension showed that the level is higher in patients with severe pulmonary hypertension but without statistical significance [410 +/- 5.77 vs. 370 +/- 15.1 pg/ml respectively p=0.71]. Clarification of the role of inflammatory mediators in the pathobiology of pulmonary hypertension in RHD is required in other studies on a wide scale. Despite of the multifactorial nature and complex mechanisms of pulmonary hypertension in RHD, RANTES and IL-6 should be investigated as potential therapeutic targets in the control of rheumatic severe pulmonary hypertension