Gamma-glutamyl transpeptidase and alpha-fetoprotein: are they predictors of treatment response in patients with chronic hepatitis C?

Hepatitis C virus is a leading cause of chronic liver disease. Elevated serum alpha-fetoprotein [AFP] has been used as a marker for hepatic regeneration after the destruction of hepatocyte in viral hepatitis. Recently, gamma-glutamyl transpeptidase [GGT] has also been taken into account in the evaluation of patients with chronic hepatitis C [CHC]. This study aimed to examine the association between serum AFP and serum GGT levels, and treatment outcome in patients with CHC treated with pegylated interferon and ribavirin. We examined the association between AFP and GGT levels and sustained virological response [SVR] in 150 patients with CHC in whom antiviral therapy was initiated. Serum AFP, GGT, and hepatitis C virus RNA were tested for patients completing 48 weeks of treatment and patients who responded to treatment after 6 months. AFP and GGT levels were lesser in patients who achieved SVR than in those who did not achieve a response. The logistic regression model [univariate analysis] of factors associated with SVR showed a significant increase in SVR when AFP ranged from 2.8 to 9.9 micro g/ml, GGT less than or equal to 50 U/l, and Ishak fibrosis score less than or equal to F2. Serum AFP and GGTwere strongly correlated in multivariate analysis; only GGT less than or equal to 50 U/l and AFP from 2.8 to 9.9 micro g/ml were independent predictors of SVR, whereas Ishak score of fibrosis was a dependent predictor for SVR. AFP and GGT can be used as independent predictors of treatment response in patients with CHC receiving pegylated interferon and ribavirin

Role of pro-inflammatory cytokines, and matrix metalloprotinases in the pathogenesis of heart failure

Extracellular matrix remodeling is thought to play an important role in the progression of heart failure [HF]. Matrix metalloproteinases [MMPs] and tissue inhibitors of metalloproteinases [TIMPs] are matrix-degrading enzymes that have been demonstrated to influence left ventricular properties and serve as targets of potential anti-remodeling agents. It has been reported that MMPs concentration and activity are upregulated in the failing human heart. However, there are few reports describing the role of elevated level of circulating MMPs in severe congestive heart failure [CHF] patients. This study examined whether circulating MMPs are also related to the pathogenesis of CHF. The study involved 50 patients with severe CHF and 20 apparently healthy subjects, with matched age and sex were selected as a control group. Two Dimensional echocardiography, Doppler and colour flow mapping were done for the patients. Left ventricular dimensions [LVD] and cardiac size were measured. LV mass [LVM] was calculated from Interventricular septum [IVS], Left ventricular end diastolic dimensions [LVEDd], Left ventricular wall thickness [LVWT] and Left ventricular end systolic dimension [LVESd]. The serum levels of MMP-2, MMP-9 and TIMP-l as well as IL-18, TNF-alpha as pro-inflammatory cytokines were measured in patients with CHF and control subjects. The serum levels of MMP-2, MMP-9, TIMP-1, IL-18 and TNF-alpha were significantly higher in the CHF patients than control group. Moreover, MMP-2, MMP-9 and TIMP-1 serum levels were positively correlated with the levels of IL-8, TNF-alpha, cholesterol, triglyceride and CRP. Furthermore, MMP-2, MMP-9 andTIMP-1 were positively coffelated with LVM, LVED[d] and LVWT. We conclude that, the increasing serum levels of MMP-2, MMP-9 and TIMP-l were associated with increased LV diastolic dimensions and increased wall thickness in patients with CHF. These observations indicate that MMPs and TIMP- I serum levels may be markers for cardiac extracellular matrix degradation, a process involved in LV remodelling. These findings may open a new avenue for therapy that ameliorating heart failure especially high risk patients

Effect of alfa-fetoprotein on monocytes expression of CD86 and secretion of tumour necrosis factor-alpha in patients with hepatocellular carcinoma

Hepatocellular carcinoma [HCC] constitutes a major health problem in Egypt due to the high prevalence of Hepatitis C virus [HCV]. Alfa-fetoprotein [AFP] is a tumour-associated antigen [Ag], and its serum level is elevated in patients with HCC. In vitro, AFP induces functional impairment of monocytes cells. This was demonstrated by the down-regulation of CD86 and tumour necrosis factor-a [TNF-alpha]. This study aimed to evaluate the effect of AFP level on monocytes function as a source of TNF-alpha and the expression of surface co-stimulatory molecule CD86 in patients with histopathologically proven HCC. This study comprised 23 patients. They were classified into group I [comprised 13 patients with AFP level >200 ng/ml] and group II [comprised 10 patients with API level<200ng/m1] in addition 10 cirrhotic patients with AFP level <200 ng/ml [group III] and 10 apparantely healthy individuals as a control group [group IV] were also included in this work. Serum AFP, CD86 and TNF-alpha were measured in all subjects using Enzyme Immunoassay [EIA], flow cytometery and Enzyme Linked Immunosorbent Assay [ELISA] respectively. CD86 and TNF-alpha were significantly reduced in patients of group I than those of groups II, III and IV [P<0.001]. Serum AFP level had a significant negative correlation with TNF-alpha level and CD86 expression in patients with HCC. On the other hand liver transaminases and total bilirubin level were significantly increased in groups I, II and III when compared to control group IV. The percent of patients infected with HCV was significantly higher in patients groups [I, II, III] when compared to control group while there was no significant difference between them as regard the percent of HBV infection. Serum albumin level in patients groups was significantly decreased when compared with control group. It can be concluded that AFP markedly impairs the function of monocytes, in addition, the ability of antigen presenting cells [APCS] of patients with HCC and high level of serum AFP to produce proinflammatory cytokines is reduced. Although the number of patients in this study was small, it provides a new insight into understanding the mechanisms underlying the suppression of immune recognition of tumour in patients with HCC. Further studies are needed to correlate these finding, with the clinical outcome of patients with HCC

Blood lead level in full-term and pre-term delivering women and their neonates

Lead toxicity causes hematological, gastrointestinal and neurological dysfunction in children and adults. This work aimed to determine whole blood lead level in full- and pre-term mothers and their neonates, to find the relation between maternal and neonatal blood lead level and to correlate it with some biochemical and hematological parameters. One hundred delivering women and their neonates were subjected to this study, fifty women were full-term and fifty were pre-term. In addition to whole blood lead level and complete blood picture which provides measurement of RBCs, Hb, Ht and MCV, determination of serum iron, total iron binding capacity [TIBC], ferritin and calcium was done for the mothers and their neonates. The blood lead level was> or= 200 micro g/L in 59% of mothers and 47% of neonates. The level was significantly higher in full-term mothers [273.5 +/- 112 micro g/L] and their neonates [215.5 +/- 90.2 micro g/L] than in pre-term ones [218 +/- 109.2 and 191.4 +/- 96.6 micro g/L]. There was non-significant differences between full- and pre-term mothers or their neonates regarding serum iron, TIBC, calcium, Hb, Ht and MCV [p > 0.05]. A significant statistical difference in serum iron, TIBC, Ferritin, Hb, Ht and MCV was found between mothers and their neonates in full- and pre-term groups [p < 0.05] whereas no significant differences were found as regards serum calcium and RBCs. There was significant correlation between blood lead level and each of serum iron, RBCs, Hb and MCV whereas no significant correlation was found between blood lead level and each of serum TIBC, ferritin, calcium and Ht in full-term mothers and their neonates. There was significant correlation between blood lead level and each of serum iron, TIBC, RBCs, Hb and MCV and non-significant correlation with serum ferritin, calcium and Ht in pre-term neonateSoThe blood lead level was higher in frequent Kohl users [338 micro g/L] than in infrequent users [209 micro g/L] and non-users [142 micro g/L]. The blood lead level was statistically higher in mothers having smoking husbands and their neonates [259 and 210 micro g/L respectively] than in those with non- smoking husbands [181 and 154 micro g/L respectively]. In conclusion, this study found high blood lead levels in delivering women and their neonates suggesting that lead exposure would be a major health problem which deserves special attention if possible future healthy pregnancy outcomes are to be considered