Serum autoantibodies in chronic hepatitis C: influence on disease profile

Non-organ-specific autoantibodies [NOSAs] are commonly detected in chronic hepatitis C [CHC] bat their significance remain on debate. To determine the prevalence of anti-nuclear [ANA], anti-smooth muscle [ASMA] and anti-liver kidney microsomes type 1 [anti-LKM1] antibodies and assess their association with patient demographics, biochemical and histological parameters of disease activity and response to antiviral therapy. One hundred and thirty naive chronic hepatitis C [CHC] patients were included. Clinical demographic and laboratory data at the time of liver biopsy were obtained. All cases were screened for autoantibodies by an enzyme linked immanosorbent assay [ELISA]. A pathologist reviewed all pathologic specimens using the modified histological activity index [HAL] of Ishak. All patients received combined antiviral therapy in the form of Pegylated Interferon alpha 2a-l60 micro g plus Ribavirin. Non-organ-specific autoantibodies [NOSAs] were observed in 38 patients [29.23%]: ANA in 25 [19.23%], ASMA in 18 [13.85%] and anti-LKM1 was the rarest occurring in only two CHC patients [1.54%]. Concomitant positivity for ANA and ASMA was observed in 7 of these 38 cases [5.38%]. The presence of NOSAs was associated with higher aspartate trasaminase [AST], alanine trasaminase [ALT] and gamma-globulin. There was a significant association between seropositivity of NOSAs and higher histological activity score of inflammation and hepatocellubr injury [P=0.024] and with increased plasma cell infiltrate [P=0.000]. In contrast, no differences were observed regarding age, gender, viral load, stage of fibrosis and response to combined antiviral therapy. The presence of non-organ-specific autoantibodies [NOSAs] in CHC is associated with more necroinflammatory grade without increased degree of fibrosis or failure of combined antiviral therapy

Assessment of serum hyaluronic acid and N-acetylglucosamine levels in chronic hepatitis C patients

Knowledge of the stage of liver fibrosis is essential for prognosis and decisions on antiviral treatment. Liver biopsy is currently the gold standard in assessing the liver histology. There is an increasing desire for non-invasive tests to assess the stage of liver fibrosis or cirrhosis. Serum hyaluronic acid [SHA] and N-acetylglucosamine [NAG] could be a hope for clinicians to diagnose or exclude fibrosis and cirrhosis. Therefore, the present study was done to assess SHA and NAG levels in chronic hepatitis C [CHC] patients and to determine the cut off values of these markers to predict fibrosis or cirrhosis. The present study was conducted on 89 subjects [20 controls and 69 CHC patients]. The HCV infection was diagnosed based on positive HCV antibodies and positive HCV-RNA. Percutaneous-ultrasoundassisted liver biopsies were done for all patients and assessed by the METAVIR scoring system. According to the results of the liver biopsy, the patients were classified into 3 groups. Group I included 15 patients without fibrosis [F0]. Group II included 35 patients with significant fibrosis [F1-F3]. Group III included 19 patients with cirrhosis [F4]. SHA levels were determined using enzyme-linked binding protein assay Kits and NAG levels were assayed by reverse phase-high performance liquid chromatography [RP-HPLC]. There were highly significant elevations of SHA and NAG in patient group when compared to the control group. Moreover levels of SHA and NAG increase with the extent of fibrosis. SHA with cut off value of less than 25 ng/ml was used to exclude fibrosis or cirrhosis with a sensitivity of 68% and specificity of 58%. SHA with cut off value of more than 200 ng/ml was used to detect significant fibrosis with sensitivity of 93% and specificity of 95%. SHA with cut off value of more than 350 ng/ml was used to detect cirrhosis with sensitivity of 92% and specificity of 100%. NAG with cut off value of less than 25 ng/ml was used to exclude fibrosis or cirrhosis with sensitivity of 60%, specificity of 55%. NAG with cut off value of more than 40 ng/ml was used to detect significant fibrosis with sensitivity of 90% and specificity of 92%. NAG with cut off value of more than 55 ng/ml was used to detect cirrhosis with sensitivity of 90% and specificity of 86%. SHA and NAG were correlated negatively with serum albumin, prothrombin concentrations and platelet count and positively with the degree of fibrosis. Serum hyaluronic acid and N-acetylglucosamine are highly valuable and informative in detection of significant fibrosis and cirrhosis while they are of limited value in exclusion of minimal fibrosis

Pulse pressure and inflammatory markers in subjects with type 1 diabetes mellitus

Type 1 diabetes is associated with excessive cardiovascular risk and earlier age-related Increase in pulse pressure [PP]. Inflammation and PP are predictors of cardiovascular disease. However few data suggested that PP may stimulate inflammation. Therefore. the present study aimed to determine the levels of some inflammatory markers [tumour necrosis factor alpha. interleukln-6 and C-reactive protein] and to study the relation between PP and these markers in normotensive subjects with type I diabetes mellitus with and without microvascular complications. The present study included 50 normotensive subjects [<130/85 mmHg] with type I diabetes meliltus [T1DM], 24 of them with microvascular complications [mean age 39.6 +/- 5.4 years] and 26 of them without microvascular complications [mean age 29.7 +/- 6.9 years] 20 healthy subjects [mean age 33.3 +/- 8.5 years] were selected as a control group. Recorded data Included age, sex, duration of diabetes, body mass index [DMI]. waist-to-hip ratio [WHR], systolic blood pressure [SBP], diastolic blood pressure [DBP]. pulse pressure [PP]. mean arterial blood pressure [MAP], microvascular complications, lipid profile. HbAlc. estimated glucose disposal rate [eGDR] and serum concentration of tumour necrosis factor-alpha [TNT-alpha]. interleukin-6 [IL-6] and C-reactive protein [CRP]. Compared with control subjects, diabetic patients with and without microvascular complications had higher PP [47 +/- 3 and 41 +/- 4 vs 37 +/- 4. P<0.001 and P<0.01 respectively], CRP [6.04 +/- 0.6 and 4.11 +/- 0.64 vs 2.59 +/- 0.57, P<0.001. both], 1L6 [31.66 +/- 3.3 and 21.38 +/- 36.2 vs 11.5 +/- 2.81, P<0.001 both], and TNT-alpha [66.45 +/- 12.66 and 37.26 +/- 8.17 vs 32.05 +/- 6.3, P<0.001 and P<0.05 respectively]. PP CRP. IL-6 and TNF-alpha were elevated [P<0.001 all] in diabetic patients with versus those without microvascular complications. CRP. IL-6 and TNF-alpha levels were higher in diabetic patients with macroalbuminuria compared to those with microalbuminuria [P<0.05 and P=0.012 and P<0.001 respectively]. PP in diabetic patients showed significant correlation with micro and macrovascular complications [P<0.0001]. CRP. IL-6 and TNF-alpha in diabetic patients had significant correlation with PP [r=0.722, P<0.0001 and r=0.770, P<0.0001 and r=0.775. P<0.0001 respectively] and diabetic micro and macrovascular complications [P<0.0001]. In normotensive subjects with type I diabetes mellitus. Inflammatory markers and PP are increased and have significant relation with each other and with diabetic microvascular complications. So. lowering of both PP and Inflammation might be helpful to optimize therapeutic management of vascular disease in type diabetes

Transforming growth factor beta 1 in children with systemic lupus erythematosus

Systemic lupus erythematosus [SLE] is a disease characterized by loss of immunologic tolerance to self-antigens. About two thirds of children with SLE develop renal involvement during the course of their disease. Transforming growth factor beta 1 [TGF-beta 1] has an inhibitory effect on the immune system and it plays a central role in the pathogenesis of renal diseases. To assess plasma and urinaly TGF beta1 levels in children with active SLE and its possible role in the pathogenesis of the disease. Plasma and urinary [latent and active] TGF-beta 1 levels were assessed-by ELISA-in 32 children with active SLE and compared to 15 healthy controls of matched age and sex. Plasma latent and active TGF-beta 1 levels in children with active SLE were significantly lower than controls [median [IQR]=9.75 [9-27.6] Vs 18.9 [16-30] ng/mI,=0.004 and 0.38 [0.3-0.4] Vs 0.9 [0.8-1] ng/ml, p<0.001; respectively]. Plasma active TGF-beta 1 correlated negatively with Systemic Lupus Erythematosus Disease Activity Index [r=-0.38, P=0.03]. On the contrary; urinary latent and active TGF-beta 1 levels in children with active SLE were significantly higher than controls [median [IQR]=2.1[1.9-6.4] Vs 1.1[0.9-1.9] ng/mg creatinine, p<0.001 and 1.2 [1.07-1.53] Vs 0.7 [05-1] ng/mg creatinine, p=0.003; respectively]. Urinary active TGF-beta 1 levels correlated positively with Anti-ds DNA titer [r=0.42, p=0.015] and negatively with serum C3 levels [r=-0.48, p=0.005]. Patients with symptomatic nephritis had significantly elevated active urinary TGF-beta 1 levels in comparison to children with silent nephritis [P=0,008].In children with active SLE, lowered plasma TGF-beta 1 levels may be a feature of systemic immune dysfunction, which may have a role in the pathogenesis of the disease. On the other hand; increased renal production of TGF-beta 1 plays an important role in the pathogenesis and clinical presentation of lupus nephritis