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George N Dalekos

Publications and source records attributed to George N Dalekos.

8 recordsLinked to original sources
PubMed2006

Presence of high avidity anticardiolipin antibodies in patients with autoimmune cholestatic liver diseases.

We studied the prevalence and clinical significance of anticardiolipin antibodies (aCL) in primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) as similar data are missing. Ninety-nine PBC patients, 41 PSC, 228 HCV, 50 HBV, 111 with other non-viral and non-autoimmune liver disorders and 267 healthy were investigated. In order to evaluate the avidity of aCL, urea 2 M was used. IgG and/or IgM aCL were detected in 40% of PBC and PSC patients, in 26.2% of disease controls (P < 0.05) and 2.25% of healthy (P < 0.05). In PBC, IgG aCL associated with presence of cirrhosis, increased Mayo risk score and thrombocytopenia, while in PSC with longer disease duration and biochemical activity. Anti-beta2-GPI was detected in only three patients. Both in PBC and PSC, resistance of aCL to urea was high, similar to that observed in antiphospholipid syndrome (APS). We demonstrated a significantly higher prevalence of aCL in PBC and PSC compared to other liver diseases and healthy. aCL were associated with more severe disease in PBC and biochemical activity in PSC, but they rather seem to be "non-pathogenic" (co-factor-independent). However, their avidity was comparable with that of APS, indicating the need for prospective studies in order to address whether aCL in PBC and PSC may contribute to APS development or the progression of hepatic disease.

Adolescent↗
PubMed2006

Alterations of leptin during IFN-alpha therapy in patients with chronic viral hepatitis.

BACKGROUND/AIMS: Leptin has a particular profibrogenic role in the liver. We investigated whether IFN-alpha influences leptin production in patients with chronic hepatitis B (CHB) and C (CHC). Leptin was determined in serial samples from 63 CHB and 42 CHC IFN-alpha treated patients. Furthermore, we evaluated whether leptin alterations were associated with patients' characteristics. METHODS: Sera were investigated at serial time-points using an enzyme-linked-immunosorbent-assay. Controls consisted of 36 patients with autoimmune liver diseases and 44 healthy patients. RESULTS: Leptin levels before IFN-alpha administration were higher in CHB and CHC compared to healthy (P<0.004) and diseased controls (P=0.0001). In CHB patients, we observed a significant reduction of leptin during IFN-alpha treatment and lasting for up to 6 months after the end of treatment, followed by an increase reaching pretreatment levels at 1.5 years after stopping therapy. The pattern of leptin alterations was similar in CHC patients where leptin's decrease was more pronounced at 6 months after the end of treatment. Biochemical or virological response to treatment was not associated with leptin reduction in both groups. CONCLUSIONS: This study provides information on leptin kinetics during IFN-alpha treatment and follow-up in CHB and CHC patients and suggests IFN-alpha as a potential inhibitor of leptin production.

Adult↗
PubMed2006

Leptin receptor isoforms mRNA expression in peripheral blood mononuclear cells from patients with chronic viral hepatitis.

There is accumulating evidence that leptin has a pleiotropic role in hematopoiesis, immune response, fibrogenesis, and hepatocarcinogenesis. We investigated the expression of leptin and leptin receptor (OB-R) at the protein level by flow cytometry and also quantified by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) the two major leptin receptor isoforms (OB-Rl, OB-Rs) in peripheral blood mononuclear cells (PBMCs) of patients with hepatitis B (HBV; n = 31), hepatitis C (HCV; n = 34), and nonviral liver disease (n = 25), and healthy controls (n = 36), as well as in liver tissues of HBV (n = 8), HCV (n = 7), and healthy individuals (n = 6). Serum leptin levels were measured in all participants (N = 126). We observed significantly lower OB-Rl and OB-Rs mRNA levels in PBMCs of HBV and HCV patients compared with healthy controls and nonviral liver disease patients (P < 0.05). Flow cytometry analysis confirmed the real-time RT-PCR results. Expression of leptin and OB-Rl was significantly increased in viral hepatitis liver tissues compared with healthy tissues (P < 0.01). OB-Rl mRNA levels were not associated with hepatitis patients' clinical status (inactive, chronic hepatitis, or cirrhosis). We also found decreased serum leptin in HBV and HCV patients compared with healthy individuals and the nonviral liver disease group. Leptin was expressed in 3 of 34 HCV (8.8%) and 19 of 25 (76%) nonviral liver disease patients. Moreover, expression of OB-Rl and OB-Rs were associated when all individuals were grouped together (r = 0.78, P < 0.001). In conclusion, our findings may suggest the involvement of the leptin system in the immunopathology of chronic viral hepatitis.

Female↗
PubMed2005

Prevalence and clinical significance of anticardiolipin antibodies in patients with type 1 autoimmune hepatitis.

There are few case reports on the association between autoimmune hepatitis (AIH) and anticardiolipin antibodies (anti-CLAbs) and/or antiphospholipid syndrome (APLS). We studied the anti-CLAbs prevalence in AIH and other hepatic diseases. We also investigated whether anti-CLAbs are co-factor dependent and which is their avidity since co-factor dependency or increased resistance is associated with APLS. Fifty-nine AIH patients, 228 HCV, 50 HBV, 123 with other non-viral and non-autoimmune liver disorders (nV-nALD) and 267 healthy people were investigated for anti-CLAbs and antibodies against beta-2-glycoprotein I (anti-beta2-GPI). Resistance of IgG anti-CLAbs was evaluated using 2 M urea. IgG anti-CLAbs detected in 39% of AIH, 19.7% of HCV (p=0.006), 14% of HBV (p=0.01), 8.1% of nV-nALD (p=0.000) and 1.1% of healthy (p=0.000). IgG anti-CLAbs were associated with the presence of cirrhosis and active AIH while their resistance to urea was high. Anti-beta2-GPI was detected in two AIH patients. We demonstrated a significantly higher prevalence of anti-CLAbs in patients with AIH compared to other diseases and healthy people. Anti-CLAbs were associated with AIH stage but no association was found with APLS clinical manifestations (thrombosis, pregnancy morbidity, thrombocytopenia). However, their avidity was comparable with that of APLS indicating the need for prospective studies in order to address whether anti-CLAbs in AIH may contribute to the progression of liver disease or APLS development.

Adolescent↗
PubMed2004

Autoantibodies and autoantigens in autoimmune hepatitis: important tools in clinical practice and to study pathogenesis of the disease.

Autoimmune hepatitis (AIH) is a chronic necroinflammatory disease of the liver characterized by hypergammaglobulinemia, characteristic autoantibodies, association with HLA DR3 or DR4 and a favorable response to immunosuppressive treatment. The etiology is unknown. The detection of non-organ and liver-related autoantibodies remains the hallmark for the diagnosis of the disease in the absence of viral, metabolic, genetic, and toxic etiology of chronic hepatitis or hepatic injury. The current classification of AIH and the several autoantibodies/target-autoantigens found in this disease are reported. Current aspects on the significance of these markers in the differential diagnosis and the study of pathogenesis of AIH are also stated. AIH is subdivided into two major types; AIH type 1 (AIH-1) and type 2 (AIH-2). AIH-1 is characterized by the detection of smooth muscle autoantibodies (SMA) and/or antinuclear antibodies (ANA). Determination of antineutrophil cytoplasmic autoantibodies (ANCA), antibodies against the asialoglycoprotein receptor (anti-ASGP-R) and antibodies against to soluble liver antigens or liver-pancreas (anti-SLA/LP) may be useful for the identification of patients who are seronegative for ANA/SMA. AIH-2 is characterized by the presence of specific autoantibodies against liver and kidney microsomal antigens (anti-LKM type 1 or infrequently anti-LKM type 3) and/or autoantibodies against liver cytosol 1 antigen (anti-LC1). Anti-LKM-1 and anti-LKM-3 autoantibodies are also detected in some patients with chronic hepatitis C (HCV) and chronic hepatitis D (HDV). Cytochrome P450 2D6 (CYP2D6) has been documented as the major target-autoantigen of anti-LKM-1 autoantibodies in both AIH-2 and HCV infection. Recent convincing data demonstrated the expression of CYP2D6 on the surface of hepatocytes suggesting a pathogenetic role of anti-LKM-1 autoantibodies for the liver damage. Family 1 of UDP-glycuronosyltransferases has been identified as the target-autoantigen of anti-LKM-3. For these reasons the distinction between AIH and chronic viral hepatitis (especially of HCV) is of particular importance. Recently, the molecular target of anti-SLA/LP and anti-LC1 autoantibodies were identified as a 50 kDa UGA-suppressor tRNA-associated protein and a liver specific enzyme, the formiminotransferase cyclodeaminase, respectively. Anti-ASGP-R and anti-LC1 autoantibodies appear to correlate closely with disease severity and response to treatment suggesting a pathogenetic role of these autoantibodies for the hepatocellular injury. In general however, autoantibodies should not be used to monitor treatment, predict AIH activity or outcome. Finally, the current aspects on a specific form of AIH that may develop in some patients with a rare genetic syndrome, the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) are also given. Autoantibodies against liver microsomes (anti-LM) are the specific autoantibodies detected in AIH as a disease component of APECED but also in cases of dihydralazine-induced hepatitis. Cytochrome P450 1A2 has been identified as the target-autoantigen of anti-LM autoantibodies in both APECED-related AIH and dihydralazine-induced hepatitis. The latter may indicate that similar autoimmune pathogenetic mechanisms can lead to liver injury in susceptible individuals irrespective of the primary defect. Characterization of the autoantigen-autoantibody repertoire continues to be an attractive and important tool to get access to the correct diagnosis and to gain insight into the as yet unresolved mystery of how hepatic tolerance is given up and AIH ensues.

Journal Article↗