Diabetes worsening of hepatitis C cirrhosis: are alterations in monocytic tissue factor (CD 142) is the cause?

BACKGROUND & AIM. The mechanisms by which type 2 diabetes mellitus (T2DM) worsen liver function are not yet established. Tissue factor (TF) is a protein that participates in hemostatic, immune and inflammatory processes. To test the hypothesis that T2DM contributes to clinical outcome through changes of TF expression on monocytes and to investigate the association between antidiabetic therapies and monocytic TF expression in HCV-related cirrhotic patients with T2DM. MATERIAL AND METHODS. In HCV-related cirrhotic patients (139 diabetics and 130 non diabetics) compared with 100 matched diabetic patients and 100 Controls; the flowcytometric analysis of CD14, TF (CD142), costimulatory molecules; CD86 and HLA-DR on monocytes were determined. RESULTS. Cirrhotic patients with T2DM have increase in the expression of monocytic TF and CD86 in comparison with cirrhotic non-diabetic, diabetic and healthy control; which increase significantly with increase of the stage of the Child-Pugh score. The expression of HLA-DR is significantly lower in cirrhotic patients than controls. Albeit, there were no significant differences in the HbA1c levels between the three groups, the use of exogenous insulin were associated with significantly higher monocytic TF expression than those in sulphonylurea and insulin sensitizer group (P < 0.03 for both). CONCLUSIONS. The monocytic TF as a significant link connecting inflammatory and immunological phenomena can partially explain a lot of events in HCV- related cirrhotic patients with T2DM. The use of exogenous insulin was associated with significantly higher TF expression than sulphonylurea and insulin sensitizer. Future target therapy against TF may be beneficial for T2DM cirrhotic patients.

Hepatopulmonary syndrome: prevalence and predictors in Egyptian cirrhotic patients.

BACKGROUND: The reported prevalence of hepatopulmonary syndrome (HPS) in cirrhotic patients is heterogeneous. Although the prevalence of chronic liver diseases is high in Egypt, however, scanty data is available about HPS. AIM: To assess the frequency of HPS and factors predictive of diagnosis of HPS in Egyptian patients with liver cirrhosis. METHODS: Fifty cirrhotic patients were evaluated for the presence of HPS. Orthodeoxia was measured by arterial blood gas test. The patients positive for diagnostic criteria of HPS (the presence of A-a O2 > or = 15 mmHg and pulmonary vascular dilatation assessed by contrast enhanced echocardiography) were defined as clinical HPS cases and those manifesting with intrapulmonary arterial dilation but no other criteria were defined as subclinical HPS cases. RESULTS: Subclinical HPS and clinical HPS was observed in 10 (20%) and 17 (34%) of the patients, respectively. The presence of HPS was significantly associated with severity of liver disease assessed by the Child-Pugh score (CP) or MELD score. Portal vein diameter (mm) (OR 3.3; 95% C.I 1.3-8.2; p=0.01) was the only independent predictor for HPS; the specificity of orthodeoxia for diagnosis of HPS was 100%. CONCLUSIONS: HPS and intrapulmonary vein dilation are relatively frequent in patients with liver cirrhosis and occur in 34% and 20% of cirrhosis patients, respectively. They are associated with disease severity according to the MELD and CP score. Alveolar arterial oxygen gradient is the most valuable negative and positive diagnostic predictor for presence of HPS in cirrhotic patients.