The influence of high-density lipoprotein (HDL) and HDL subfractions on insulin secretion and cholesterol efflux in pancreatic derived ß-cells.

BACKGROUND: High-density lipoprotein (HDL) is considered a complex plasma-circulating particle with subfractions that vary in function, size, and chemical composition. We sought to test the effects of HDL, and HDL subfractions on insulin secretion and cholesterol efflux in the ß-cell line MIN-6. METHODS: We used total HDL and HDL subfractions 2a, 2b, 3a, 3b, and 3c, isolated from human plasma, to test insulin secretion under different glucose concentrations as well as insulin content and cholesterol efflux in the insulinoma MIN-6 cell line. RESULTS: Incubation of MIN-6 cells with low glucose and total HDL increased insulin release two-fold. Meanwhile, when high glucose and HDL were used, insulin release increased more than five times. HDL subfractions 2a, 2b, 3a, 3b, and 3c elicited higher insulin secretion and cholesterol efflux than their respective controls, at both low and high glucose concentrations. The insulin content of the MIN-6 cells incubated with low glucose and any of the five HDL subclasses had a modest reduction compared with their controls. However, there were no statistically significant differences between each HDL subfraction on their capacity of eliciting insulin secretion, insulin content, or cholesterol efflux. CONCLUSIONS: HDL can trigger insulin secretion under low, normal, and high glucose conditions. We found that all HDL subfractions exhibit very similar capacity to increase insulin secretion and cholesterol efflux. This is the first report demonstrating that HDL subfractions act both as insulin secretagogues (under low glucose) and insulin secretion enhancers (under high glucose) in the MIN-6 cell line.

Association between rs662 (A > G) and rs854560 (A > T) polymorphisms in PON1 gene and the susceptibility for psoriasis in mestizo population of Western Mexico.

Psoriasis is a chronic, autoimmune skin disease. In psoriasis, PON1 activity is diminished and peroxidation biomarkers are elevated. The most studied PON1 polymorphisms are rs662 (A > G) and rs854560 (A > T), which have been associated with the antioxidant activity of PON1, risk of cardiovascular diseases and psoriasis development. The aim of this study, was to determine the association of rs662 (A > G) and rs854560 (A > T) PON1 polymorphisms with psoriasis susceptibility in Western Mexico population. In this case-control study, we included 104 psoriasis patients and 124 control subjects. The genotyping of polymorphisms rs662 (A > G) and rs854560 (A > T) of PON1 was carried out by PCR-RFLPs. The lipid profiles were quantified by enzymatic colorimetric method, and PON1 activity was determined by spectrophotometry. The lipid profile levels, except HDL-C and atherogenic index, were higher in patients vs. controls. Patients presented lower paraoxonase and arylesterase activity. The G allele of rs662 (A > G) is associated with risk for psoriasis, while the T allele of rs854560 (A > T) is associated with low susceptibility to psoriasis. The AG haplotype was more frequent within the patient group (p < 0.05). The AA and AG genotypes of rs662 (A > G) and TT and AA genotypes of rs854560 (A > T) are associated with lower PONase and ARE activity in patients vs. controls. Patients with the G allele of rs662 (G > A) and T alleles of rs854560 (A > T) show significant differences in the lipid levels in comparison to controls. These results suggest that carriers of G allele of rs662 (A > G) present a greater susceptibility to psoriasis.

R230C but not - 565C/T variant of the ABCA1 gene is associated with type 2 diabetes in Mexicans through an effect on lowering HDL-cholesterol levels.

PURPOSE: Type 2 diabetes (T2D) and low serum concentration of high-density lipoprotein cholesterol (HDL-c) are common coexisting metabolic disorders. ABCA1 variants have been shown to be associated to these conditions. We sought to test the combined effect of two ABCA1 gene common variants, rs2422493 (- 565C > T) and rs9282541 (R230C) on HDL-c levels and T2D risk. METHODS: Path analysis was conducted in 3,303 Mexican-mestizos to assess the specific contributions of rs2422493 and rs9282541 ABCA1 variants, insulin resistance, waist-to-height ratio (WHtR), and age on HDL-c levels and T2D risk. Participants were classified into four groups according to their ABCA1 variants carrier status: (i) the reference group carried wild type alleles for both ABCA1 variants (-/-), (ii) +/- were carriers of rs2422493 but non-carriers of rs9282541, (iii) -/+ for carriers of rs9282541 but not carriers of rs2422493 and (iv) carriers of minor alleles for both SNPs (+/+). Principal components from two previous genome-wide association studies were used to control for ethnicity. RESULTS: We identified significant indirect effects on T2D risk mediated by HDL-c in groups -/+ and +/+ (ß = 0.04; p = 0.03 and ß = 0.06; p < 0.01, respectively) in comparison to the -/- reference group. Low concentrations of HDL-c were directly and significantly associated with increased T2D risk (ß = -0.70; p < 0.01). WHtR, male gender, age, and insulin resistance were also associated with T2D risk (p < 0.05). There was no significant direct effect for any of the ABCA1 groups on T2D risk: p = 0.99, p = 0.58, and p = 0.91 for groups +/-, -/+, and +/+ respectively. CONCLUSIONS: The ABCA1 rs9282541 (R230C) allele is associated with T2D in Mexicans through its effect on lowering HDL-c levels. This is the first report demonstrating that HDL-c levels act as an intermediate factor between an ABCA1 variant and T2D.

[Demographic and clinical features of diagnosed individuals of enterobiasis in the southern Gran Canaria: sampling assessment]. / Características clínico-demográficas de la población del Sur de Gran Canaria con diagnóstico de enterobiasis: valoración de la toma de muestras.

OBJECTIVE: Enterobius vermicularis, also known as pinworn, is the responsible agent for Human Enterobiasis. It is one of the most prevalent, but underrated, parasitic disease in children population. Diagnosis involves demonstration of either eggs or adult worms by Graham test. The aim of this study is to describe the clinical, demographic and microbiological features of patients with suspected diagnosis of Enterobiasis in southern Gran Canaria. METHODS: Descriptive and prospective study of perianal samples evaluated by Graham test in the Microbiology Department of `Insular de Gran Canaria´ University Hospital between November 2014 and November 2015. Descriptive analysis to evaluate the correlation between clinical and demographic variables and the results of Graham test microbiological observation. RESULTS: 1,128 samples were analyzed. E. vermicularis was found in 11.4% of the samples. Among the positives samples, 88.4% belonged to children under 14 years, and 53.5% were male. Abdominal pain (18.6%), anal itching (11.6%), eosinophilia (8.5%) and intestinal parasitosis suspicion (7.8%) were the reasons of parasitological investigation request in positive samples. Nevertheless, a high proportion of the requests was not founded in a suspicious diagnosis or was unrelated to Enterobiasis. CONCLUSIONS: Enterobiasis is a common disease in primary health care and is of great importance in Gran Canaria. Quality in sample collection as well as diagnosis suspicious information are necessary for a good microbiological analysis.

Correlation of IL-12, IL-22, and IL-23 in patients with psoriasis and metabolic syndrome. Preliminary report.

BACKGROUND: Psoriasis is an autoimmune skin disease characterised by proliferation of keratinocytes, primarily due to cytokines Th1 and Th17. This profile is involved in pathogenesis of metabolic syndrome, a frequently found comorbidity in patients with psoriasis. OBJECTIVE: In this study we determine the correlation of levels of pro-inflammatory cytokines TNF-α, IL-23, IL-12, and IL-22 in patients with psoriasis with and without metabolic syndrome and clinically healthy controls. METHODS: We included 55 patients with plaque psoriasis: 30 with metabolic syndrome (PPMS), 25 without metabolic syndrome (PP), 15 healthy subjects (HS) and 15 with metabolic syndrome (MS). Quantification of serum levels of IL-12, TNF-α, IL-22, and IL-23 was done by ELISA. RESULTS: We observed that serum levels of IL-12 were more elevated in PP group, while the lowest levels of TNF-α were seen in HS group. IL-22 was found to be higher in PP than in PPMS (p<0.05). PP patients with PASI scores rating as severe showed higher levels of IL-12. TNF-α level analysis showed significant differences in HS group compared with the others; levels of this cytokine were lower in patients with PP and moderate PASI scores than in MS group (p<0.05). We found no correlation between cytokine levels and psoriasis or between cytokines and PASI scores. In PP group, a positive correlation was observed between IL-23 and fasting glucose (r=0.432, p<0.05), as well as a negative correlation between IL-23, IL-22, and IL-12 versus waist circumference (r=-0.504, r=-0.556 and r=-0.511, respectively; p<0.05). CONCLUSIONS: Psoriasis is not just a skin disorder, but rather a condition with systemic implications, with intervention of pro-inflammatory cytokines that contribute to metabolic syndrome and other comorbidities, which in turn increases the risk of developing cardiovascular disease.

Evidence for adaptive divergence of thermal responses among Bemisia tabaci populations from tropical Colombia following a recent invasion.

There is an increasing evidence that populations of ectotherms can diverge genetically in response to different climatic conditions, both within their native range and (in the case of invasive species) in their new range. Here, we test for such divergence in invasive whitefly Bemisia tabaci populations in tropical Colombia, by considering heritable variation within and between populations in survival and fecundity under temperature stress, and by comparing population differences with patterns established from putatively neutral microsatellite markers. We detected significant differences among populations linked to mean temperature (for survival) and temperature variation (for fecundity) in local environments. A QST  - FST analysis indicated that phenotypic divergence was often larger than neutral expectations (QST  > FST ). Particularly, for survival after a sublethal heat shock, this divergence remained linked to the local mean temperature after controlling for neutral divergence. These findings point to rapid adaptation in invasive whitefly likely to contribute to its success as a pest species. Ongoing evolutionary divergence also provides challenges in predicting the likely impact of Bemisia in invaded regions.

Estudio de la producción de jarabes glucosados a partir de maltodextrinas empleando dos enzimas comerciales / Study of glucose syrup production from maltodextrines using two comercial enzymes

El almidón hidrolizado con alto equivalente de dextrosa tiene amplio uso en la industria de alimentos y como fuente de azúcares fermentables. Para mejorar el rendimiento de este proceso se desarrollan continuamente enzimas más eficientes. La enzima Dextrozyme GA® (DGA) ha salido recientemente al mercado pretendiendo substituir a la enzima AMG 300L ® (AMG). En este trabajo se evaluaron los rendimientos y velocidades de conversión en función de concentraciones de enzima entre 0,188-0,75 AGU/mL y maltodextrinas entre 60-180 g/L. La enzima DGA permitió desarrollar velocidades de reacción 26 veces superiores a las observadas con AMG 300L ®. Así mismo generó conversiones de hasta el 95% en tiempos de tratamientos menores a 60 minutos, en comparación con conversiones del 50% en 8 h para AMG. En el rango de valores de sustrato y enzima evaluados, se encontró que una concentración de sustrato de 130,2 g/L y de enzima de 0,55 AGU/mL fueron los valores óptimos. DGA presentó inhibición por producto del tipo anticompetitivo, mayor a bajos niveles de enzima. Un modelo matemático tipo Michaelis-Menten con inhibición permitió simular los datos experimentales. Estos resultados podrían ser usados para el diseño de reactores donde se lleven a cabo procesos de obtención enzimática de jarabes glucosados.

Hydrolyzed starch with a high-dextrose equivalent is extensively used in the food industry and as a source of fermentable sugars. In order to obtain a better yield in this process more efficient enzymes had been continuously developed. Dextrozyme GA ® (DGA) has been released recently in the market to replace AMG 300L ® (AMG) enzyme. In this paper yields and hydrolysis rates were evaluated as a function of maltodextrin concentration between 60 and 180 g/L and enzymes concentration between 0.188 and 0.75 AGU/mL. DGA allows enhancing hydrolysis rates up to 26 times more than those using AMG. Also DGA generates conversion of maltodextrin up to 95% in less than 60 minutes, in comparison with AMG which produces conversions up to 50% in 8 h. Among the values of substrate and enzyme concentration studied it was found that a substrate concentration of 130.2 g/L and enzyme concentration of 0.55 AGU/mL were optimal values. DGA is inhibited by uncompetitively product and is highly affected at a low enzyme concentration. We developed a mathematical model that successfully reproduces the experimental data. These results could be used in reactors design for syrup glucose enzymatic production.

Receptor for advanced glycation end products in donor lungs is associated with primary graft dysfunction after lung transplantation.

Development of primary graft dysfunction (PGD) is associated with poor outcomes after transplantation. We hypothesized that Receptor for Advanced Glycation End-products (RAGE) levels in donor lungs is associated with the development of PGD. Furthermore, we hypothesized that RAGE levels would be increased with PGD in recipients after transplantation. We measured RAGE in bronchoalveolar lavage fluid (BALf) from 25 donors and 34 recipients. RAGE was also detected in biopsies (transbronchial biopsy) from recipients with and without PGD. RAGE levels were significantly higher in donor lungs that subsequently developed sustained PGD versus transplanted lungs that did not display PGD. Donor RAGE level was a predictor of recipient PGD (odds ratio = 1.768 per 0.25 ng/mL increase in donor RAGE level). In addition, RAGE levels remained high for 14 days in those recipients that developed severe graft dysfunction. Recipients may be at higher risk for developing PGD if they receive transplanted organs that have higher levels of soluble RAGE prior to explantation. Moreover, the clinical and pathologic abnormalities associated with PGD posttransplantation are associated with increased RAGE expression. These findings also raise the possibility that targeting the RAGE signaling pathway could be a novel strategy for treatment and/or prevention of PGD.

Mutations in E2-PePHD, NS5A-PKRBD, NS5A-ISDR, and NS5A-V3 of hepatitis C virus genotype 1 and their relationships to pegylated interferon-ribavirin treatment responses.

Mutations in several subgenomic regions of hepatitis C virus (HCV) have been implicated in influencing the response to interferon (IFN) therapy. Sequences within HCV NS5A (PKR binding domain [PKRBD], IFN sensitivity-determining region [ISDR], and variable region 3 [V3]) were analyzed for the pretreatment serum samples of 60 HCV genotype 1-infected patients treated with pegylated IFN plus ribavirin (1b, n = 47; 1a, n = 13) but with different treatment outcomes, those with sustained virologic responses (SVR; n = 36) or nonresponders (NR; n = 24). Additionally, the sequence of the PKR/eIF-2alpha phosphorylation homology domain (E2-PePHD) region was determined for 23 patients (11 SVR and 12 NR). The presence of > 4 mutations in the PKRBD region was associated with SVR (P = 0.001) and early virologic responses (EVR; 12 weeks) (P = 0.037) but not rapid virologic responses (4 weeks). In the ISDR, the difference was almost statistically significant (68% of SVR patients with mutations versus 45% without mutations; P = 0.07). The V3 region had a very high genetic variability, but this was not related to SVR. Finally, the E2-PePHD (n = 23) region was well conserved. The presence of > 4 mutations in the PKRBD region (odds ratio [OR] = 9.9; P = 0.006) and an age of < or = 40 years (OR = 3.2; P = 0.056) were selected in a multivariate analysis as predictive factors of SVR. NS5A sequences from serum samples taken after 1 month of treatment and posttreatment were examined for 3 SVR and 15 NR patients to select treatment-resistant viral subpopulations, and it was found that in the V3 and flanking regions, the mutations increased significantly in posttreatment sera (P = 0.05). The genetic variability in the PKRBD (> 4 mutations) is a predictive factor of SVR and EVR in HCV genotype 1 patients treated with pegylated IFN and ribavirin.

Producción de enzimas ligninolíticas con hongos basidiomicetos cultivados sobre materiales lignocelulósicos / Production of ligninolytic enzimes from basidiomycete fungi on lignocellulosic materials

Los hongos de podredumbre blanca de la madera tienen la capacidad de producir un complejo enzimático con actividad oxidativa contra una amplia variedad de sustancias tóxicas recalcitrantes como plaguicidas, tintes, hidrocarburos poliaromáticos, explosivos, etc., que contaminan suelos y cuerpos de agua. Su propagación sobre suelos contaminados, la producción de enzimas ligninolíticas y la biodegradación de contamimantes, se favorece cuando estos hongos se inoculan en el suelo mezclados con materiales lignocelulósicos que les suministran la fuente de carbono necesaria para sotener su crecimiento e inducir la producción del complejo enzimático. Este trabajo muestra la capacidad para producir las enzimas ligninolíticas manganeso peroxidasa (MnP) y lignino peroxidasa (LiP) en cultivos de los hongos Bjerkandera adusta y Phanerochaete chrysporium sobre tres materiales lignocelulósicos: viruta de madera, carozo de maíz y compost de jardinería. De estos materiales, la viruta de madera permitió alcanzar los mayores títulos de la enzima MnP, con valores de 5.0 U/g de material seco cuando se cultiva con Bj. adusta y de 1.3 U/g de material seco con P. chrysosporium, mientras que con carozo de maís se obtienen las mejores actividades de LiP. Estos materiales se mostraron adecuados para favorecer la producción de enzimas ligninolíticas y para ser empleados como soportes en la inoculación de hongos sobre suelos contaminados

Estudio de la replicación del virus de la hepatitis C y del virus de la hepatitis G en suero, hígado y células mononucleares de sangre periférica / Genomic and antigenomic chains of hepatitis C virus and hepatitis G virus in serum, liver and peripheral blood mononuclear cells

Objetivo: determinar los lugares de replicación del VHC y del VHG en pacientes con hepatitis crónica C y estudiar la interacción de ambos virus. Pacientes: se estudió el ARN-VHG en 272 pacientes con hepatitis crónica C. De éstos, 35 fueron positivos (grupo I). Se seleccionaron 23 pacientes con hepatitis crónica C y no coinfectados con el VHG (grupo II). Resultados: se estudiaron las cadenas genómica y antigenómica del VHC en los dos grupos y del VHG en el grupo I en muestras de suero, células mononucleares de sangre periférica y tejido hepático. En el grupo I se observó la genómica del VHC y VHG en un 86 y 100 por ciento respectivamente (ns) en las muestras de suero (n=35), y la antigenómica en un 17 y 23 por ciento (ns). En las muestras de células mononucleares (n=15), el 100 por ciento presentaba la cadena genómica del VHC y el 60 por ciento la del VHG (p<0,05); las antigenómicas se detectaron en un 13 y 33 por ciento respectivamente (ns). En hígado (n=25) las cadenas genómicas se observaron en un 100 y 12 por ciento respectivamente (p<0,001); la antigenómica del VHC se detectó en un 76 por ciento mientras que la del VHG no estaba presente (p<0,001). En el grupo II la cadena genómica del VHC se encontraba en un porcentaje muy elevado en todas las muestras, mientras que la antigenómica apareció en un 13 por ciento en suero y células mononucleares y en un 89 por ciento en hígado. Conclusiones: el VHC y el VHG tienen lugares distintos de replicación: mientras que el VHC se replica principalmente en el hígado, el VHG no es hepatotropo. Las células mononucleares podrían representar un lugar de replicación para el VHG y menos importante para el VHC. Por último, el VHG no modifica la replicación viral del VHC. (AU)

Genomic and antigenomic chains of hepatitis C virus and hepatitis G virus in serum, liver and peripheral blood mononuclear cells.

OBJECTIVE: To determine HCV and HGV replication sites in patients with chronic hepatitis C and to study interaction between these two viruses. PATIENTS: HGV RNA was studied in 272 patients with chronic hepatitis C. Of these, 35 were positive (group I). Twenty-three patients with chronic hepatitis C not co-infected with HGV were selected (group II). RESULTS: Genomic and antigenomic chains of HCV were studied in both groups and those of HGV in group I in serum samples, peripheral blood mononuclear cells and liver tissue. In group I genomic chains of HCV and HGV were observed in 86 and 100%, respectively (ns), in serum samples (n = 35), and antigenomic chains in 17 and 23%, respectively (ns). In mononuclear cell samples (n = 15) 100% presented the genomic chain of HCV and 60% presented that of HGV (p < 0.05). Antigenomic chains were detected in 13 and 33%, respectively (ns). In liver tissue (n = 25) genomic chains were observed in 100 and 12%, respectively (p < 0.001); the antigenomic chain of HCV was detected in 76% while that of HGV was not present (p < 0.001). In group II genomic chains of HCV were found to be present in a very high percentage in all samples, while antigenomic chains appeared in 13% of serum and mononuclear cell samples and 89% of liver samples. CONCLUSIONS: HCV and HGV have different sites of replication: whereas HCV replicates mainly in the liver, HGV is not hepatotropic. Mononuclear cells could represent a replication site for HGV but they are less important for HCV. Lastly, HGV does not modify the viral replication of HCV.

Estudio multicéntrico retrospectivo de la respuesta al interferón en la hepatitis crónica por VHB / Multicenter retrospective study of response to interferon in choric hepatitis B

OBJETIVO: el fármaco más ampliamente utilizado en el tratamiento de la hepatitis crónica B ha sido el interferón alfa, con unas tasas de respuesta del 25-40 por ciento. Los objetivos a corto plazo del tratamiento son inducir la eliminación de los marcadores de replicación viral en suero, reducir los niveles de transaminasas y mejorar la histología hepática. Son factores predictores de respuesta unos niveles elevados de transaminasas, una concentración baja de DNA-VH13 y signos de actividad histológica fundamentalmente. Los objetivos de este estudio han sido conocer de forma retrospectiva la respuesta al INF-a en pacientes con hepatopatía crónica por VHB, de forma global y según el HBeAg, así como analizar los factores predictores de respuesta al mismo. PACIENTES Y MÉTODOS: hemos realizado un estudio multicéntrico retrospectivo de la respuesta al interferón alfa en 132 pacientes con hepatopatía crónica por el virus B, tanto de forma global como teniendo en cuenta el HBeAg y analizado los factores predictores de respuesta al mismo. RESULTADOS: globalmente, 59 pacientes (45 por ciento) tuvieron respuesta completa mantenida al INF, 61 (46 por ciento) no respondieron y 12 (9 por ciento) recidivaron. Ninguno negativizó el HBsAg. En los pacientes HBeAg+, 30 pacientes respondieron de forma mantenida (46 por ciento), 22 no respondieron (49 por ciento) y tres (5 por ciento) recidivaron, siendo similar en los casos HBeAg- (43, 43 y 14 por ciento, respectivamente). De todos los parámetros estudiados sólo las transaminasas sirvieron para predecir la respuesta global, observando en los pacientes con respuesta completa mantenida unas cifras significativamente más altas que en los no respondedores. En los HBeAg+ sólo la edad fue predictora de respuesta y en los HBeAg- la histología. El sexo, el antecedente epidemiológico, tipo de IFN, dosis, tiempo de tratamiento y tipo de virus no tuvieron influencia en la respuesta. CONCLUSIONES: hemos observado una respuesta mantenida global al IFN del 45 por ciento con una tasa de seroconversión (AU)

[Coinfection with hepatitis G virus in chronic hepatitis C. Response to treatment with interferon alpha]. / Estudio de la coinfección por el virus de la hepatitis G en la hepatitis crónica C. Respuesta al tratamiento con interferón alfa.

BACKGROUND: It is thought that the cytopathic effect of HGV is not important. Nevertheless, the cytopathic effect on liver is less known in the cases of co-infection with HCV. The aim was to study the prevalence of co-infection in patients with chronic hepatitis C (CHC) and to analyse the clinical-epidemiological and histological data and the interferon (IFN) response. PATIENTS AND METHODS: We included 180 patients with CHC and the HGV-RNA was determined. RESULTS: The prevalence of co-infection was 12.2% (n = 22). No statistical differences were observed between the non co-infected and co-infected groups with regard to the age, sex, mechanism of transmission and alcohol abuse. Also, there were no differences in the hepatic biochemical, no organ-specific antibodies, histological lesions and Knodell index. The HCV biochemical response (BR) and virological response (VR) after 6 months post-IFN were the same in both groups (HGV negative: BR = 29%, VR = 12%; HGV positive: BR = 22%, VR = 18%). HGV was determined after 6 months posttreatment in the co-infected group (first cycle of IFN, n = 22; second cycle of IFN, n = 9): 12 (55%) were HGV-RNA negative and 5 (23%) HCV-RNA negative, (p = 0.021). When we compared the BR vs VR in this group, there were 12 HGV-RNA negative but only two had BR (NS). On the contrary, the BR was related to HCV-RNA negative (p = 0.023). CONCLUSION: The prevalence of HGV co-infection is important in our area (12.8%). The HGV does not increase the pathogenicity of HCV and does not change the IFN response, although the HGV is more IFN sensible than HCV. The determination of HGV is not necessary in patients with HCV.

Multicenter retrospective study of response to interferon in chronic hepatitis B.

AIM: The only agent known to have a lasting beneficial effect in chronic hepatitis B is interferon alpha, which achieves long-term remission in 25-40% of the patients. The goals of treatment are to induce clearance of HBV DNA from serum, to return serum aminotransferases to normal, and to improve histological findings in the liver. The most important factors predictive of response to treatment are high serum aminotranferases levels, low serum HBV DNA concentrations, and active histologic changes on liver biopsy. The aim of this study was to assess the response to interferon alpha in patients with chronic hepatitis B and to analyze the factors predictive of response. METHODS: We conducted a multicenter retrospective study to investigate the effect of interferon treatment in 132 patients with chronic hepatitis B in overall terms and based on HBeAg, and factors predictive of response. RESULTS: A overall sustained response was noted in 59 of 132 interferon-treated patients (45%) and 61 patients were nonresponders (46%). 12 patients relapsed (9%). None of the patients had negative HBsAg. No difference was observed in the response rate between the two treatment groups (HBeAg-positive and HBeAg-negative patients). Overall, high initial levels of serum AST and ALT predicted a good response. Age and liver biopsy findings were factors predictive of response in HBeAg-positive and HBeAg-negative patients respectively. Sex, epidemiological factors, treatment and type of virus did not correlate with the response to interferon. CONCLUSIONS: A sustained response to interferon alpha was observed in 45% of the patients with chronic hepatitis B. HBeAg seroconversion was found in up to 50% of HBeAg-positive patients. None of the patients had negative HBsAg. Overall, the response rate was higher in patients with high pretreatment serum aminotransferase levels. Age was the predictive factor in HBeAg-positive patients, and histological features were predictive in the HBeAg-negative group. However, further studies in a larger patient population are necessary to obtain well-substantiated conclusions.

Interferon versus ribavirin plus interferon in chronic hepatitis C previously resistant to interferon: a randomized trial.

BACKGROUND: More than 70% of patients with chronic hepatitis C are resistant to interferon therapy. Ribavirin, in association with interferon, has been demonstrated as effective, at a dose of 800-1200 mg/day, but the efficacy of a lower dose has not been established. METHODS: We assessed the effectiveness of the combination of 600 mg/day of ribavirin plus 3 MU of interferon over a period of 6 months, in a group of patients previously resistant to interferon. Sixty-two patients with chronic hepatitis C with serum and hepatic HCV RNA relapsers or non-responders to interferon, were randomly divided into two groups: group A received 3 MU of interferon alpha-2b, three times a week for 6 months; group B was given the same dose plus 600 mg per day of ribavirin for 6 months. Two patients from each group dropped from therapy. One patient from group A and two from group B withdrew from treatment because of adverse effects. RESULTS: Mean alanine aminotransferase levels were similar in both groups throughout the study. A sustained response was observed in 7% and 7.4% of groups A and B with short-term response in 39% and 59%, and no response in 54% and 34% from both groups respectively (non-significant). At 12 months, 4 and 7 patients from groups A and B respectively, cleared serum HCV RNA however, only one sustained responder from each group cleared HCV RNA from peripheral blood mononuclear cells. At 18 months, 3 patients remained serum HCV RNA negative. Adverse effects were similar. Only haemoglobin values were lower in group B in the first month of therapy (p<0.05). CONCLUSION: In conclusion, the combination of 3 MU of interferon plus 600 mg of ribavirin is not effective in chronic hepatitis C resistant to interferon.

Epidemiology and prevalence of seropositivity for hepatitis C virus in pregnant women in Granada.

OBJECTIVES: To study personal and familial antecedents of risk and prevalence of infection by HCV in pregnant women in the south area of Granada. PATIENTS AND METHODS: We included in the study 3003 pregnant women of the south area of Granada during the period from January 1993 to December 1995. Anti-HCV was detected in the third trimester of pregnancy by second and third generation ELISA, and positive results were confirmed by RIBA 3. We also determined HCV-RNA and genotype. Finally, we analyzed ALT levels in 1171 (39%) pregnant women. We carried out an epidemiological survey of all pregnant women, which included the following personal antecedents: transfusion, intravenous drug use, liver diseases, risk profession and sexually transmitted diseases. We studied the same antecedents in the parents, husbands and other relatives. RESULTS: Prevalence of anti-HCV was 0.63% (19 cases) with ELISA and 0.53% with RIBA. HCV-RNA was positive in 14 (74%) genotype 1b (57%) being the most frequent. ALT was increased in 52 (4.4%) pregnant women, 7 (13.5%) of whom were anti-HCV positive, versus 12 women (1%) in the normal ALT group (p < 0.001). In the epidemiological study we observed statistically significant differences in: a) housing characteristics [2125 (71%) anti-HCV negative pregnant women living in occupant-owned housing versus 7 (36%) in anti-HCV-positive group, p < 0.001]; b) personal antecedents of transfusion, chronic or acute hepatitis, or intravenous drug use (p < 0.001) (these factors were confirmed in the multivariable analysis), and c) familial antecedents of the husband (p < 0.05). CONCLUSIONS: In this study we demonstrated that 0.53% of the pregnant women were infected by HCV; most of them were HCV-RNA positive and was genotype 1b was the most frequent. The risk factors most frequently associated with infection were antecedents of transfusion, intravenous drug use and acute or chronic hepatitis.

Response of chronic hepatitis C to interferon-alpha treatment and relationship with iron metabolism.

AIM: to prospectively analyze the influence of iron metabolism of the response to interferon-alpha therapy in chronic hepatitis C. METHODS: ninety-two patients with chronic hepatitis C treated with recombinant alpha-interferon were included. Basal serum levels of iron, ferritin and transferrin saturation were compared in responding and nonresponding patients. Additional epidemiologic, histologic and biochemical variables were studied as predictors of response to interferon-alpha therapy. RESULTS: we studied 57 men (62%) and 35 women (35%) with a mean age of 40 years. Biopsy specimens were classified as having chronic active hepatitis (63%), chronic persistent hepatitis (33.8%) or cirrhosis (3.2%). The basal serum levels of iron and ferritin were significantly higher in non responders (126 +/- 9.1 mu/dL and 222.7 +/- 31.9 eta g/dL respectively; p < 0.05) than in responders (101 +/- 5.7 micrograms/dL and 136 +/- 24.1 eta g/dL). Mean transferrin saturation was also higher in nonresponders (29.7% +/- 2.7% vs 26% +/- 2.02%) although this difference was not significant. Younger age, absence of cirrhosis and parenteral transmission were associated with an improved response to interferon therapy. No relationship was found between the presence of iron in the hepatic parenchyma and response to interferon treatment. CONCLUSIONS: elevated serum levels of iron, ferritin, or both may be associated with a worse response to interferon-alpha therapy.

[Retrospective multicenter study of the efficacy of interferon alpha in chronic hepatitis C]. / Estudio multicéntrico retrospectivo de la eficacia del interfeón alfa en la hepatitis crónica C.

BACKGROUND: Until very recently, interferon (INF) in Spain was authorized in chronic hepatitis C (C-HCV) at a dosis of 3 megaunits (mu) for 6 months. Nonetheless, the rate of maintained complete response is lower than that obtained with more prolonged treatments. The first aim of this study was to retrospectively know the effectiveness of alpha INF in patients treated for 6 or 12 months with a dosis of 3 or 5-6 MU. The second was to analyze the characteristics of the patients who achieved a maintained complete response. PATIENTS AND METHODS: Patients with C-HCV treated in 9 hospitals in Andalucía, Spain who fulfilled the following conditions were retrospectively analyzed: liver biopsy prior to treatment, positive test for anti HCV and a follow up of at least 6 months after alpha INF treatment. A total of 344 patients were studied: 267 treated with alpha INF-2b, 51 with alpha INF-2a and 26 with lymphoblastoid INF. One hundred ninety-five patients were treated for 6 months and 149 for 12 months. RESULTS: Seventy-seven (22%) of the patients presented maintained complete response, 170 (50%) did not respond and 97 (28%) relapsed. On comparing the three types of interferon used over 6 months, no significant differences were observed. Neither were differences found on comparing the dosis of 3 mu versus 5 or 6 mu. On analyzing the treatments of 6 and 12 months, the following was observed, respectively: maintained complete response 15% vs 32%, relapse 29% vs 30% and non responders 57% vs 38% (p < 0.001). Multivariate analysis demonstrated that the patients who responded the best to INF were those who presented the following characteristics: female sex, age under 40 years last, history of transfusion or IVDA, basal GPT level higher than 145 IU/I, GGT less than 55 IU/I, less evolved histologic lesions and duration of treatment over 12 months. CONCLUSIONS: Of the different treatments analyzed with alpha interferon in chronic hepatitis C, the best was found to be that with 3 mu during 12 months.