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Fernando Alvarez

Publications and source records attributed to Fernando Alvarez.

At least 37 records · Page 2Linked to original sources
PubMed2004

Treatment of Autoimmune Hepatitis: Current and Future Therapies.

Autoimmune hepatitis is an uncommon liver disease affecting children and adults. Early diagnosis and start of treatment improve the response and long-term outcome. Initial treatment depends on patient's age and the clinical, laboratory, and histological features that allow the prediction of the response, as well as the presence or absence of associated extrahepatic disorders. In specialized centers, short-term cyclosporine is used safely and successfully to control the liver inflammatory process. Low doses of prednisone in association with azathioprine are sufficient to sustain the response. Maintenance treatment must be administered for several years, and withdrawal can be attempted after at least 4 years of a complete and sustained response. Future research should focus on the recovery of immune homeostasis in these patients by less aggressive means.

Journal Article↗
PubMed2004

Anti-LC1 autoantibodies in patients with chronic hepatitis C virus infection.

UNLABELLED: Various autoantibodies have been reported in patients chronically infected by hepatitis C virus. 2% to 10% of theses patients have anti-liver-kidney microsome type 1 (anti-LKM1) autoantibodies. In type 2 autoimmune hepatitis, anti-LKM1 autoantibodies are frequently associated with anti-liver-cytosol type 1 (anti-LC1) autoantibodies. AIMS: To determine the prevalence of anti-LC1 autoantibodies in a hepatitis C-positive population and characterize their reactivity. METHODS: 146 patients suffering from liver diseases, of which 99 were chronically infected by hepatitis C virus, were tested by Western blotting and immunoprecipitation to detect and characterize anti-LC1 autoantibodies. RESULTS: 12% of this hepatitis C population had anti-LC1 autoantibodies. LC1 positivity by Western blotting was 30% of LC1+ sera. Epitopes were found throughout the protein but linear epitopes were situated in the 395-541 amino acid region of formiminotransferase cyclodeaminase. Three putative conformational epitopes were identified by phage display. CONCLUSIONS: Anti-LC1 autoantibodies are as prevalent as anti-LKM1 autoantibodies in patients infected with hepatitis C virus and their production is not dependent of anti-LKM1 autoantibodies formation. Autoantibody reactivity against the anti-LC1 antigen is different in hepatitis C than in type 2 autoimmune hepatitis. Anti-LC1 autoantibodies can now be regarded as a serological marker of autoimmunity in chronic hepatitis C infection.

Adult↗
PubMed2004

Linkage disequilibrium between HLA class II region and autoimmune hepatitis in pediatric patients.

BACKGROUND/AIMS: Susceptibility HLA class II alleles associated with autoimmune hepatitis (AIH) were only described in case-control studies. METHODS: The transmission/disequilibrium test was used in 50 simplex families with AIH, to determine if affected offspring received the disease-associated allele more frequently than its alternate. HLA-DRB1 and DQB1 allele genotyping and autoimmune regulator (AIRE) polymorphisms located in exons 6, 8 and 10 were investigated by PCR-based methods. RESULTS: HLA-DRB1*03 allele was significantly transmitted from heterozygous parent to affected offspring (81.5%) with type 1 AIH compared to random expected frequency (50.0%; P=0.004) or to unaffected offspring (42.8%; P=0.03). HLA-DRB1*1301 allele showed an excess transmission to affected children (100%) than expected frequency (P<0.0001) or unaffected offspring (P=0.001). The transmission of DQB1*201 or DQB1*0603 alleles showed significant deviation in patients compared to random frequencies: (84.8%; P<0.0001 for DQB1*0201 or 100%; P<0.0001 for DQB1*0603). HLA-DQB1*0201 showed a strong association with type 2 AIH in children (100.0%, P=0.0005). CONCLUSIONS: HLA-DRB1 gene is the major genetic determinant in HLA class II region for children with type 1 AIH. Type 2 AIH is associated with the HLA-DQB1gene. Finally, AIRE gene abnormality does not contribute to the development of isolated AIH.

Adolescent↗
PubMed2004

Epidemiology of liver disease in cystic fibrosis: a longitudinal study.

BACKGROUND/AIMS: To describe the prevalence of liver disease in a cohort of 241 cystic fibrosis (CF) patients. METHODS: 241 CF patients were followed-up every 3 months with clinical and biological assessment, and every year with ultrasonography of the liver. The presence of liver disease was studied using a multivariate Cox's regression analysis including variables such as history of meconium ileus, pulmonary function, pancreatic insufficiency and CFTR gene mutations. RESULTS: The prevalence of liver disease was 18, 29, and 41% after 2, 5 and 12 years, respectively, and did not increase thereafter. In multivariate analysis, the probability of liver disease was independently associated with history of meconium ileus (P = 0.001) and pancreatic insufficiency (P = 0.004). CFTR mutations and severity of pulmonary disease were not associated with liver disease. Cirrhosis occurred in 19 (7.8%) patients at a median age of 10 years, and liver transplantation was required in five patients. CONCLUSIONS: This study shows that CF related-liver disease occurs mainly in the first decade of life with a prevalence of 41% of patients at 12 years of age. A history of meconium ileus and pancreatic insufficiency are predictive of liver disease. Preventive treatment with ursodesoxycholic acid could be considered in patients with meconium ileus.

Adolescent↗
PubMed2004

Anti-soluble liver antigen (SLA) antibodies in chronic HCV infection.

Hepatitis C infection is associated with autoimmune disorders, such as the production of autoantibodies. Anti-LKM1 and anti-LC1, immunomarkers of type 2 autoimmune hepatitis, have been previously associated with a HCV infection. Anti-Soluble-Liver-Antigen autoantibodies (SLA) are specifically associated with type 1 and type 2 autoimmune hepatitis and more closely related to patients who relapse after steroid therapy. The recent molecular cloning of the soluble liver antigen provides the opportunity to develop more specific tests for the detection of antibodies against it. The aim of this work is to characterize anti-soluble-liver autoantibodies in sera from patients chronically infected by HCV. A recombinant cDNA from activated Jurkat cells coding for the full length tRNP(Ser)Sec/SLA antigen was obtained. ELISA, Western Blot and immunoprecipitation tests were developed and used to search for linear and conformational epitopes recognized by anti-SLA antibodies in sera from patients chronically infected by HCV. Anti-soluble liver antigen antibodies were found in sera from 10.4% of HCV-infected patients. The prevalence was significantly increased to 27% when anti-LKM1 was also present. Most anti-SLA reactivity was directed against conformational epitopes on the antigen. The means titers by ELISA were lower than those obtained in type 2 AIH. The result of autoantibody isotyping showed a subclass restriction to IgG1 and also IgG4. This study shows the presence of anti-SLA antibodies in approximately 10% of HCV infected patients. The prevalence of SLA autoantibodies in HCV infected patients increases when LKM1 autoantibodies are also present. The relationship between the prevalence of this characteristic autoimmune hepatitis autoantibody and the implication of an autoimmune phenomenon in the liver injury of patients chronically infected by HCV needs further investigation.

Autoantibodies↗
PubMed2004

Pharmacokinetics of omeprazole in healthy adults and in children with gastroesophageal reflux disease.

Studies of the pharmacokinetics of omeprazole in children with gastroesophageal reflux disease (GERD) remain scarce despite the vast number of reports on its efficacy. The objectives of this study were to assess the pharmacokinetics of omeprazole in healthy adults and in children with GERD. Omeprazole (Losec, delayed-release capsules) was administered orally to 18 healthy adults (mean age 36.8 years) and 12 children with GERD (mean age 6.1 years). Blood samples were collected over 5 hours, and plasma concentrations were assessed using liquid chromatography. Population pharmacokinetic parameters were calculated using NONMEM. A 1-compartment model with zero-order absorption and a lag time was used. The population approach was well suited to the limited number of samples available, and residual variability was low. Oral clearance (CL/F) and apparent volume of distribution (V(ss)/F) in healthy adults (Mean +/- SD: 0.62 +/- 0.27 L/h/kg and 0.76 +/- 0.26 L/kg, respectively) were not significantly different than those in children with GERD (0.51 +/- 0.34 L/h/kg and 0.66 +/- 0.25 L/kg, respectively). Healthy adults displayed a statistically significantly longer delay in drug absorption (Lag time: 0.62 +/- 0.15 hours) as compared with that observed in children with GERD (0.12 +/- 0.03 hours, P < 0.05). On the basis of these findings, omeprazole dosings on a milligram-per-kilogram basis are recommended with no further adjustments for the treatment of GERD in children.

Adult↗
PubMed2004

Hallux valgus and first ray mobility: a cadaveric study.

BACKGROUND: Several studies have demonstrated that patients with hallux valgus (HV) deformities have increased first ray sagittal mobility. However, the change in mobility that occurs after surgical correction of HV deformities has not been extensively evaluated. This study was done to determine if surgical realignment of the first ray in cadaver specimens with a proximal crescentic osteotomy and distal soft tissue reconstruction (DSTR) would reduce the first ray sagittal motion as measured with an external-type micrometer (the Klaue device). METHODS: Twelve fresh-frozen below-knee cadaver specimens with an HV deformity (HV angle > 15 degrees, 1-2 IM angle > 9 degrees) were used for the study. Standardized simulated weightbearing radiographs were obtained before and after the surgical correction of the deformity. The first ray sagittal motion was measured with an external micrometer (Klaue device) before correction of the HV deformity and after the procedure. All specimens had correction of the hallux valgus deformity with a DSTR and proximal crescentic osteotomy. Internal fixation was applied to secure the osteotomy site. RESULTS: The HV angle was corrected from a mean of 28.6 degrees to a mean of 11.0 degrees. The 1-2 IM angle was corrected from a mean of 12.9 degrees to a mean of 6.8 degrees. The average preoperative first ray sagittal motion was 11.0 mm (range, 8.5 mm to 13.5 mm). After the surgical repair, the mean sagittal first ray motion was significantly decreased (p <.0005) to a mean of 5.2 mm (range, 3.5 mm to 7.5 mm). CONCLUSION: After correction of HV deformities with a DSTR and a proximal crescentic osteotomy, first ray mobility in cadaver specimens was significantly reduced. The stabilization of first ray mobility that occurred immediately after surgical correction despite leaving the capsule of the first metatarsocuneiform (MC) joint undisturbed suggests that extrinsic anatomic features may play a role in first ray mobility. Additionally, stability of the first ray may be restored with a bunion procedure that does not sacrifice the first MC joint.

Aged↗
PubMed2003

Epstein-Barr virus (EBV) early-antigen serologic testing in conjunction with peripheral blood EBV DNA load as a marker for risk of posttransplantation lymphoproliferative disease.

Epstein-Barr virus (EBV) early-antigen (EA) serologic profile was examined in conjunction with peripheral blood EBV DNA load, to assess its value in evaluating the risk of developing posttransplantation lymphoproliferative disease (PTLD). The cohort included 26 pediatric recipients of solid-organ transplants, 6 of whom developed PTLD. All 6 patients had high peripheral blood EBV DNA loads. Of the remaining 20 patients who did not develop PTLD, 14 had high EBV DNA loads, and 6 had low EBV DNA loads. None of the patients who developed PTLD had significant EA immunoglobulin G (IgG) titers. However, all 14 patients with high EBV DNA loads and without PTLD had high EA IgG titers, either at the time of initial high EBV DNA load or during the ensuing weeks. Here, we report that EBV DNA load analysis, combined with EA serologic analysis, is a potentially useful prognostic marker for evaluating the risk of developing PTLD.

Adolescent↗
PubMed2003

Studying biological tissue with fluorescence lifetime imaging: microscopy, endoscopy, and complex decay profiles.

We have applied fluorescence lifetime imaging (FLIM) to the autofluorescence of different kinds of biological tissue in vitro, including animal tissue sections and knee joints as well as human teeth, obtaining two-dimensional maps with functional contrast. We find that fluorescence decay profiles of biological tissue are well described by the stretched exponential function (StrEF), which can represent the complex nature of tissue. The StrEF yields a continuous distribution of fluorescence lifetimes, which can be extracted with an inverse Laplace transformation, and additional information is provided by the width of the distribution. Our experimental results from FLIM microscopy in combination with the StrEF analysis indicate that this technique is ready for clinical deployment, including portability that is through the use of a compact picosecond diode laser as the excitation source. The results obtained with our FLIM endoscope successfully demonstrated the viability of this modality, though they need further optimization. We expect a custom-designed endoscope with optimized illumination and detection efficiencies to provide significantly improved performance.

Animals↗
PubMed2003

Characterization of the B cell response of patients with anti-liver cytosol autoantibodies in type 2 autoimmune hepatitis.

Anti-liver cytosol type 1 (LC1) autoantibody is detected in 30% of sera from patients with type 2 autoimmune hepatitis (AIH), and is the only circulating autoantibody in 10% of cases. Human formiminotransferase cyclodeaminase (FTCD) has been shown to be the specific liver antigen recognized by anti-LC1 autoantibodies. The aim of this study was to identify the dominant epitope on human FTCD and to analyze antigenic-site sequences for clues on the development of AIH. Recombinant proteins and peptides covering the entire cDNA of human FTCD were tested against anti-LC1 autoantibodies. Conformational epitopes were found throughout the protein but linear epitopes were found exclusively in the C-terminal 146 amino acids. Two groups of sera with different reactivities were found: 69%of the sera recognized two specific linear epitopes at positions 428-434 (NTPEEKD) and 440-447 (LQEGLRRA) of human FTCD; others reacted only with a discontinuous epitope between the amino acids at position 395 and 528. FTCD autoantibody production is thus a polyclonal-antigen-driven B cell response. Autoantibodies against conformational or discontinuous epitopes were found in all patients and two-thirds also recognized linear epitopes on human FTCD.

Ammonia-Lyases↗
PubMed2003

Subtalar arthroereisis for posterior tibial tendon dysfunction: a preliminary report.

BACKGROUND: The purpose of this study was to evaluate preliminary results with Kalix subtalar arthroereisis in sinus tarsi for stage II posterior tibial tendon dysfunction. METHODS: Twenty-one patients with stage II posterior tibial dysfunction, according to Johnson and Storm, underwent surgical treatment between July 1999 and December 2000. All patients were evaluated clinically using the America Orthopaedic Foot and Ankle Society (AOFAS) hindfoot-ankle score. We performed a tendon repair depending on the type and location of the injury and implanted a Kalix endorthesis in the sinus tarsi. RESULTS: Nineteen patients attended for clinical review with an average follow-up of 27.31 months (range, 19-36). AOFAS scale improved from a preoperative average of 47.2 to an average of 81.6 at revision. The most important improvement was observed in pain (16.3 preoperative to 31.6 postoperative). Two cases required removal of the endorthesis for pain, probably because the endorthesis was too big, without any loss of correction. Patient satisfaction was "satisfied" or "very satisfied" in 17/19. All except three patients would have elected to undergo the same procedure. CONCLUSIONS: Subtalar arthroereisis by means of implantation of a Kalix endorthesis in the sinus tarsi, with prior correction of the deformity and tendon repair, offers an alternative to bone operations such as calcaneal osteotomies, lengthening the external column, or arthodesis in patients with stage II posterior tibial dysfunction.

Adult↗
PubMed2002

DNA vaccination breaks tolerance for a neo-self antigen in liver: a transgenic murine model of autoimmune hepatitis.

Understanding the pathogenesis of autoimmune hepatitis requires an animal model in which chronic progressive immune injury develops spontaneously or with minimal manipulations. The new transgenic mouse model proposed in this study is based on the hypothesis that infectious agents have the potential to initiate autoreactivity through molecular mimicry. A transgenic mouse expressing lymphocytic choriomeningitis virus nucleoprotein (NP) in a H-2(b) background developed liver injury when vaccinated with plasmids expressing NP as an intracellular or a secretory protein. Coinjection of plasmids coding for NP and IL-12 facilitated the induction of a Th1 phenotype as detected by a specific B lymphocyte response characterized by a predominance of IgG2 subclass anti-NP Abs. CTLs activated in peripheral lymphoid organs by DNA vaccination migrated to the periportal and lobular areas of the liver. Their presence was associated with a significant degree of cytolysis, as evidenced by elevated transaminases several weeks after immunization. As activated specific T lymphocytes proliferated in the periphery and caused cytolysis of target cells, this study suggests that autoimmune hepatitis can be triggered by molecular mimicry, and that local injury may not be essential to initiate autoreactivity in the liver.

Animals↗
PubMed2002

Centrilobular fibrosis in long-term follow-up of pediatric liver transplant recipients.

BACKGROUND: Centrilobular fibrosis after liver transplant in adults is caused mainly by viral hepatitis, chronic rejection, and azathioprine toxicity. The aim of this study was to investigate possible etiologies and the long-term outcome of this lesion in children. METHODS: We identified centrilobular fibrosis in 12 of 117 pediatric liver transplant recipients who were investigated for persistent elevations in aminotransferases. Etiologic factors, histologic features on serial biopsies, and clinical and biochemical changes over time were noted for 8 recipients in whom a readily identifiable cause was not apparent. RESULTS: Centrilobular fibrosis developed a mean of 1.7 years (range: 30 days-3.6 years) posttransplantation in patients receiving cyclosporine, azathioprine, and prednisone. Centrilobular fibrosis was always associated with portal fibrosis and, in six recipients, with persistent, low-grade, cellular rejection. None demonstrated chronic cholestasis, ductopenia, or identifiable vasculopathy. Ischemic, viral, and autoimmune etiologies were excluded. Discontinuing azathioprine did not lead to biochemical or histological improvement. After changing to tacrolimus, aminotransferases normalized in three recipients and repeat biopsies in six were unchanged during a further 2 years of follow-up. CONCLUSIONS: Centrilobular fibrosis may develop in a small number of pediatric liver transplant recipients, resulting in considerable difficulties in biopsy interpretation. It is not associated with viral hepatitis nor with classical features of chronic rejection. The prognostic significance of centrilobular fibrosis is uncertain, although no child has required retransplantation in up to 12 years of follow-up. A role for a low-grade, chronic form of cellular rejection heralded by persistent, variable, and otherwise unexplained elevations in aminotransferases is suggested.

Adolescent↗
PubMed2002

Hepatic artery pseudoaneurysm following laparoscopic cholecystectomy.

The authors describe a hepatic pseudoaneurysm following laparoscopic cholecystectomy in a child. It arose from a hepatic artery that was ligated during surgery and was supplied by collaterals from the superior right branch. Because of the risk of hepatic infarction and recanalization of the pseudoaneurysm by new collaterals, the authors decided not to occlude the superior right branch, but to embolize the aneurysm itself with cyanoacrylate. Since the intra-arterial approach was not feasible, a transhepatic puncture was successfully performed.

Aneurysm, False↗
PubMed2002

Long-term follow-up of chronic hepatitis B virus infection in children of different ethnic origins.

The natural history of chronic hepatitis B in children is influenced by mode of transmission and varies with regional endemicity. Seroconversion rates were studied in 174 hepatitis B e antigen (HBeAg)-positive children who were of different ethnic origins and living in Canada. Overall, 40.2% became anti-HBeAg positive, and 8.6% were hepatitis B surface-antigen positive during a mean follow-up of 4.5 years. Spontaneous seroconversion rates were lower in Asian-born, mainly vertically infected, children, versus those born either in Canada or where horizontal transmission predominates (24% vs. 44%, P=.015). Kaplan-Meier analysis showed that the cumulative persistence of HBeAg after 13 years was 25% in Asian-born children, versus 6% in all others (P<.05). Treatment of 27 children accelerated seroconversion by 3 years, without influencing the proportion seroconverting over time. Thus, although Asian-born children seroconvert more slowly, a large proportion will seroconvert before adulthood. Because treatment appears to accelerate anti-HBe seroconversion, longitudinal studies are required in order to assess the long-term benefits of early treatment.

Adolescent↗
PubMed2002

Autoantibody detection in type 2 autoimmune hepatitis using a chimera recombinant protein.

Autoantibodies against cytochrome P450 2D6 (CYP2D6), known as anti-liver/kidney microsome type 1 (LKM1) and/or anti-human formiminotransferase cyclodeaminase, formally known as anti-liver cytosol type 1 (LC1) define type 2 autoimmune hepatitis (AIH). The aims of this work are to develop a sensitive and specific test to detect anti-LKM1 and/or anti-LC1 autoantibodies and to establish the prevalence of anti-LC1. Sera from children with type 2 AIH (n=48) and those from a control group (n=100) were evaluated for anti-LKM1 and anti-LC1 by Enzyme-Linked Immunosorbent Assay (ELISA) and Western blotting. Each serum sample was assayed for reactivity against formiminotransferase cyclodeaminase and CYP2D6 alone or as part of a recombinant chimera protein. By ELISA with recombinant chimera protein, 50 serum samples were positive, 48 from patients with type 2 AIH and 2 from patients with chronic hepatitis C. Twenty-five of 48 (52%) patients studied were positive for both CYP2D6 and LC1 autoantibodies. Anti-LC1, either as the only marker or associated with anti-LKM1, was positive in 34/48 (71%). By Western blotting, anti-LC1 was found in 27/48 (56%) patients. This ELISA technique has proven to be antigen-specific and more sensitive than Western blot for the detection of anti-LC1 and anti-LKM1 autoantibodies. The prevalence of anti-LC1 (71%) confirms it as an important immunomarker in type 2 AIH.

Autoantibodies↗