Immunomodulatory therapy in chronic hepatitis C infection

The imbalance of Th1 and Th2 cytokine production may play an important role in immunopathogenesis of persistent HCV infection and disease progression. BCG vaccine induces TNF gamma, causing Th1 type immune response. This study aimed to demonstrate the immunomodulatory effect of BCG vaccine on the progression of Hepatitis C viral infection. Forty patients with chronic hepatitis C were included [Group I] as well as 10 healthy controls [Group II]. All participants were subjected to: clinical examination, laboratory investigations, HCV antibodies by ELISA, quantitative PCR for HCV, HBsAg, HBcAb, serum IL-4, serum IL-2, tuberculin test and BCG vaccine [patients only]. Tuberculin positive, diabetic and bilharzial patients were excluded. The previous work-up was repeated only to group I at 12 weeks after BCG vaccine. Showed significant statistical elevation of both IL-2 and IL-4 pre vaccination compared to controls. Significant statistical elevation in levels of IL-2 and lowering in levels of IL-4 at 12 weeks post vaccination occured in patients. Levels of IL-4 were still significantly higher than those of controls. A significant lowering of viremia as detected by quantitative PCR also occurred BCG vaccine could be considered a new line of immune therapy based on its immunomodulatory action on chronic hepatitis C patients

Relationship between insulin resistance, liver fibrosis and steatosis in non-diabetic non-obese chronic hepatitis C patients

Relationship between HCV and DM was documented in several studies. HCV through pro-inflammatory cytokines causes insulin resistance. Steatosis in HCV is a well known pathological feature. Interest in the last decade was turned into the possible link between insulin resistance and Steatosis and their effect on fibrosis progression was to study relationships between fibrosis, inflammation, Steatosis and insulin resistance in HCV patients. This study was conducted on 80 patients with HCV and 20 healthy controls. Participants were subjected to clinical examination, laboratory investigations [liver and kidney function tests, hepatitis markers, fasting glucose, insulin, and serum lipids], HOMA score estimation, BMI calculation and abdominal ultrasonography. Patients underwent liver biopsy and qualitative PCR for HCV RNA. showed higher HOMA score and fasting insulin levels in HCV patients than controls. A strong positive correlation was found between insulin resistance, fasting insulin levels and liver fibrosis in HCV patients. No correlation was found between insulin resistance and neither BMI nor age of patients. Prevalence of Steatosis in HCV patients biopsies was 93.75%. Significant correlation was found between fibrosis and Steatosis, and between insulin resistance and Steatosis. detection and treatment of insulin resistance in chronic hepatitis C patients are recommended to improve outcome of patients and decrease rate of progression of fibrosis

Evaluation of plasma thrombomodulin in patients with type II diabetes mellitus

Thrombumodulin is an important endothelial anticoagulant protein that decreases thrombin activity and activates protein C. Increased plasma concentrations of various markers of endothelial damage especially thrombomodulin, have been observed in type I diabetic patients particularly in those with microangiopathy. So we aimed in this study to evaluate the significance of plasma thrombomodulin as a biochemical marker for early detection of microvascular complication such as diabetic nephropathy in patients with Type II diabetes mellitus Thirty diabetic patients fulfilled the WHO criteria for type II diabetes-were included in this study together with 10 normal volunteers as normal control.-The type II diabetic patients were classified into three groups according to the level of microalbuminuria in 24hours urine: Group I: included 10 diabetic patients [without nephropathy] microalbumin/24 hours urine<30 mg, Group II included 10 diabetic patients with [incipient diabetic nephropathy] microalbomin/24 hours urine ranged from 30 to 300 mg, and Group III included 10 diabetic patients with [overt diabetic nephropathy], microalbuminl24 hours urine>300mg. For all patients and control the following were done serum creatinine, glycated hemoglobin [HbAlc] Plasma thrombomodulin [TM] and 24 hours urinary micro-albuminuria-In this study we found that, TM were highly significantly elevated in diabetic patients with microalbominuria [group II] and with macroalbuminuria [group III] as compared to the control group [P<0.01] [Table 2]. Also group III showed highly significant elevation in TM than group II [P<0.0 1]. TM showed highly significant correlation with albumin concentration in 24 hours urine HbAlc, and duration of diabetes [P<0.01] [tables]. Because plasma TM level was strongly affected by kidney function. TM index [TM[FU/ml]/serum creatinine [mg%] was used as an endothelial marker. TM index showed a highly significant elevation in diabetic patients [p<0.01] especially in patients with macroalbuminurea [group III] as compared to normal control [p<0.01] [Table 2] also its level was significantly higher in group III than both group I and group II [p<0.01] while no significant difference was found between neither group I nor group II and control group [p>0.05]. TM index showed a highly significant positive correlation with duration of diabetes, but it showed no significant correlation with HbAlc [P>0.05] [Table 6]. These results suggested that a generalized vascular endothelial damage occurs in diabetic nephropathy including the microalbuminuric stage, and TM could be used as a marker for early detection of diabetic microvascular complications

Bronchial mucosal changes in patients with chronic hepatitis C virus infection

Hepatitis C virus [HCV], being both a hepatotropic and lymphotropic virus represents a chronic stimulus for the immune system. So, various extra hepatic immunologic abnormalities have been shown to occur frequently in patients with chronic hepatitis C virus. Among the systemic manifestations of chronic HCV infection, lung involvement has been described. Also the possibility that HCV infects extra hepatic cells has been widely discussed. So we aimed in this study to detect HCV antigen in the bronchial mucosa and broncho-alveolar lavage [BAL]. Together with, the study of histopathological changes in the bronchial biopsy and the cellular content of the BAL in patients with chronic HCV infection.Our study included 50 patients suffering from chronic liver disease due to Hepatitis C virus infection complaining of recurrent cough with negative clinical chest finding and normal X-ray chest.The patients were subdivided into: three groups according to Child-pugh classification.Bronchoalveolar lavage and bronchial biopsy were obtained through the use of fibre optic bronchoscopy. And detection of HCV antigen in the BAL and biopsy using immunohistochemistry was done. Alsostudy of the histopathological changes of bronchial biopsy and lavage were performed

In our results, HCV in bronchial biopsy and BAL fluid was detected in 42% [21/50] of our patients. And BAL showed increase in the neutrophils and lymphocytes percentage especially in patients in group II "Child B".Pulmonary permeability is mostly affected in cases of HCV infection, noticed by increase of the albumin level in the BAL of patient of Child "C" [group III]. Also Variable degrees of pathological changes have been noticed in the bronchial mucosa of the patients. These variations are affected by the severity of liver disease.So we conclude that the presence of inflammatory cell infiltration together with pathological changes of the bronchial mucosa may induce bronchial inflammation as a sequel of HCV infection which could explain the occurrence of the recurrent cough in our patients, and may lead to progressive fibrosingalveolitis