Angiotensin converting enzyme-2 and transforming growth factor beta-1 are over-expressed during fibrogenesis in liver tissue of patients with chronic hepatitis C virus infection

Hepatitis C virus [HCV] infection leads to chronic hepatitis which may eventually progress to cirrhosis and hepatocellular carcinoma. A significant relationship between inheritance of hightened expression of angiotensin II [A-2] and transforming growth factor beta [TGF-beta] and the development of progressive hepatic fibrosis has been noted. Recent studies have revealed that the renin angiotensin system [RAS] and the local RAS components are implicated in liver fibrogenesis and carcinogenesis. TGF-beta1 is a key cytokine in inflammation that regulates the production and deposition of extracellular matrix, directly stimulates angiogenesis and plays an important role in tumorigenesis. In this study we aimed to investigate the expression of angiotensin converting enzyme-2 [ACE-2] and TGF-beta1 in liver biopsies from patients with HCV infection alone or with hepatocellular carcinoma [HCC] on top of HCV cirrhosis. Liver biopsies from 40 patients with HCV infection and 20 patients with HCC on top of HCV-cirrhosis were included in this study. Semiquantitative immunohistochemical analyses were performed using ACE-2 and TGF-beta1 antibodies on paraffin embedded liver sections. Immunohistochemical results revealed that the immunoreactive score of ACE-2 and TGF-beta1 correlated significantly with the stage of fibrosis [p=0.05, p=0.001 respectively] and that TGF-beta1 correlated also with the histological activity index [p=0.05]. Liver tissue from HCC demonstrated enhanced and differential expression of both ACE-2 and TGF-beta1. Our data provide evidence for the implication of ACE.-2 and TGF-beta1 in liver fibrogenesis and carcinogenesis; a finding that might be of prognostic and therapeutic value

Clinical evaluation of son invasive biomarkers for monitoring liver fibrosis and disease progression

Liver biopsy is the gold standard for assessment of hepatic fibrosis. However, it is invasive with possible complications, costly and prone to sampling errors. Many non-invasive markers of liver fibrosis have been recently proposed and assessed in the clinical setting as surrogates of liver biopsy. Although several non invasive markers of liver fibrosis have been developed in the last decade their implementation in clinical practice has been slow and is still limited. This study aimed to describe the different non invasive markers and methods that have been proposed for the assessment of liver fibrosis, to discuss their advantages and limits and to suggest a rational use in clinical practice. This study included 40 patients with chronic liver disease, 21 of chronic hepatitis C [CHC] as group I, and 19 patients with liver cirrhosis [group 11] as well as 20 healthy subjects with age and sex matched was enrolled as control group. Serum levels of tissue inhibitor of metalloproteinase- 1 [TIMP-I], laminin and cystatin C were measured and correlate with laboratory and histological findings. This study revealed that, significantly elevated serum level of cystatin C in CHC [group I] and cirrhotic patients [group II] than healthy controls [p<0.001] for each. Moreover, cystatin C concentrations were significantly higher in patients with liver cirrhosis [p<0.01] than in patients with CHC. Furthermore, serum cystatin C levels correlated significantly with the stage of liver fibrosis [p<0.01] but revealed no significant difference with the grade of necroinflammation of the disease process [p>0.05]. However, serum TIMP-1 values showed a significant increase in group I and 11 patients than in controls. Serum TIMP-1 levels correlated significantly with both the stage of fibrosis [p<0.05] and the grade of activity [p<0.01]. Serum larninin levels showed significant increase in patients with chronic hepatitis and liver cirrhosis than controls [p<0.001]. While, no significant difference of on comparing chronic hepatitis patients with control group [p>0.05]. Also, serum laminin levels showed a significant correlation with fibrosis stage [p<0.001] but not with inflammatory grade [p>0.05]. Based on available evidence, it can be anticipated that non-invasive markers of liver fibrosis [cystatin C, TIMP-1 and laminin] and their combined use will soon become a most useful tool in the clinical management of many forms of chronic liver disease. However, their implementation is expected to reduce, but not to completely eliminate, the need for liver biopsy

Helicobacter associated chronic gastritis and thrombotic risk

Helicobacter pylori [H.pylori] infection is now recognized to be of major etiological importance in peptic ulcer disease and gastric cancer. More recently, interest in the possible association be- tween H pylori infection and thrombotic events has developed. This study aimed to evaluate the relationship between plasma levels and gastric mucosal concentrations of tumor nemesis factor-a [TNF-alpha] and interleukin-8 [IL-8] as pro-inflammatory cytokines and plasma levels of prothrombin fragments 1+2 [PF1+2] and fib- rinogen in H. pylori positive patients before and after successful eradication therapy. Forty-two patients proven to have chronic gastritis were enrolled in this study. They were divided into 2 groups based on histopathological examination of gastric antral biopsies. Group I: included 28 H. pylori positive patients, and group II: 14 H. pylori negative patients' chronic gastritis. Plasma levels and antral mucosal concentrations of TNF-alpha and IL- 8 as well as plasma levels of fibrinogen and PF1+2 were assessed in all patients. A triple eradication therapy for H. pylori was given for Group I. Eradication was histopathologically evaluated 2 months post-therapy together with estimation of plasma levels of fibrinogen, PF1+2, TNF-alpha and IL-8. The results showed that, group I of patients had significantly increased plasma fibrinogen and PF1+2 as well as mucosal and plasma levels of TNF-alpha and IL-8 compared with group II. Furthermore, in-group I, positive correlations were found between plasma level of PF1+2 and gastric mucosal concentrations of TNF-alpha and IL-8. While in-group II [H pylori negative chronic gastritis], no significant correlations were detected between the studied parameters. A significant reduction in the mean value of plasma levels of TNF-alpha IL-8 and PF1+2 were observed in those with infection eradication. In conclusion, the present study showed a close relationship between plasma levels of PF1+2, plasma and mucosal levels of TNF-alpha and IL-8 in H. pylori associated chronic gastritis patients. These findings suggest that H. pylori may represent a trigger factor for clotting system activation through persistent inflammatory stimulation, cytokine production. Therefore, H. pylori eradication may reduce the risk of hypercoagulable state and thrombotic events in those patients