Asociación entre polimorfismos en los genes PNPLA3 y TM6SF2 y presencia de fibrosis en pacientes con infección crónica por virus hepatitis C / The association between polymorphisms in the genes PNPLA3 and TM6SF2 and the presence of fibrosis in patients with chronic hepatitis C virus infection

Hepatitis C virus (HCV) is a globally prevalent pathogen and a leading cause of death and morbidity. The most recent estimates of disease burden show an increase in seroprevalence over the last 15 years to 2.8 percent, equating to >185 million infections worldwide. Persistent hepatitis C infection is associated with the development of liver cirrhosis, hepatocellular cancer, liver failure and death. The magnitude of disease progression in chronic infection varies significantly among individuals. Several factors have been recognized as being associated with the progression of HCV-related liver fibrosis and with clinical outcomes. As liver fibrosis progression remains variable between individuals with similar environmental or virological risks, host genetic predispositions have been suggested as another critical determinant. The single nucleotide polymorphisms in Patatin-like phospholipase domain-containing 3 (PNPLA3) and Transmembrane 6 Superfamily Member 2 (TM6SF2) genes are genetic determinants of nonalcoholic fatty liver disease, in terms of inflammation and fibrosis. The possible action of the PNPLA3 and TM6SF2 polymorphisms on fibrosis development in chronic hepatis C is being studied, with controversial results.

Interferones lambdas (IFNs-lambda) en infección con virus hepatitis C / Lamba interferons in infection with hepatitis C virus

The current standard therapy for patients chronically infected with hepatitis C virus (HCV) is the administration of pegylated interferon-alpha (PEG-IFN) plus ribavirin (RBV), eliminating the virus in only about half of patients infected with the genotype most common in Chile and the world (genotype 1), being higher for genotypes 2 and 3. Genotyping of the HCV is a strong predictor of treatment response, and it defines the treatment duration (48 weeks for genotype 1 and 24weeks for genotypes 2 and 3). Genome studies revealed the association of polymorphisms (SNPs) close to IL28B gene with increased spontaneous and treatment-inducing clearance for HCV, which are now evaluated as a strong predictor of treatment response. These SNPs are close to genes coding for type III IFNs family, known as IFNs lambda (IFNs lambda), composed by IFN lambda1 (IL29), IFN lambda2 (IL28A) and IFN lambda3 (IL28B). It has been shown that these cytokines are highly involved in antiviral immune responses, including HCV, playing IFN lambda1 a central role. Today, there is an ongoing study where pegylated IFN alpha1 was administrated in chronic HCV patients as alternative to IFN lambda therapy, seeking for a more specific response to infected hepatocytes and with fewer adverse effects.

Variabilidad genética del virus hepatitis B y su significado clínico / Genetic variability hepatitis b virus, the clinical meaning

The Hepatitis B virus (HBV) is the prototype member of the Hepadnaviridae family, which can cause acute or chronic hepatic illness. The virus has a partially double-stranded DNA genome of3.2 kb. Molecular variations and change in the genome over time have resulted in the emergence of at least eight genotypes and multiple subgenotypes. The distribution of HBV genotypes varies widely across geographic regions, been the genotype F the most prevalent in Chile. In recent years, substantial progress has been made toward understanding the epidemiology and virologic significance of HBV variants. Actually, accumulating evidence suggests that hepatitis B genotypes and subgenotypes can influence the severity, course and likelihood of complications, and response to treatment of HBV infection and possibly vaccination against the virus.

[Thiopurine S-methyltransferase gene polymorphism in Chilean blood donors]. / Polimorfismo del gen de la tiopurina S-metiltransferasa en donantes de sangre de un hospital universitario.

BACKGROUND: Thiopurine S-methyltransferase (TPMT) is a cytosolic enzyme that catalyzes the S-methylation of 6-mercaptopurine and azathioprine. Low-activity phenotypes are correlated with polymorphism in the TPMT gene. Patients with low or undetectable TMPT activity could develop severe myelosuppression when they are treated with standard doses of thiopurine drugs. Since ethnic differences in the TPMT gen polymorphism have been demonstrated worldwide, its assessment in the Chilean population is worthwhile. AIM: To investigate the TMPT gene polymorphism in a Chilean blood donor individuals. SUBJECTS AND METHODS: The frequency of four allelic variants of the TPMT gene, *2 (G238C), *3A (G460A and A719G), *3B (G460A) and *3C (A719G) were analyzed in 210 Chilean blood donors, using polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) and allele-specific PCR-based assays. RESULTS: TPMT variants associated to low enzymatic activity, were detected in 16 subjects (8%), who had a heterozygous genotype (*3A in 12; *3C in three and *2 in one subject). No TPMT*3B allelic variant was found. The normal allele (wild-type) was found in 92% of studied individuals. CONCLUSIONS: The allele TPMT*3A, is the most prevalent in this group of Chilean blood donors, as in Caucasian populations.

Polimorfismo del gen de la tiopurina S-metiltransferasa en donantes de sangre de un hospital universitario / Thiopurine S-methyltransferase gene polymorphism in Chilean blood donors

Background: Thiopurine S- methyltransferase (TPMT) is a cytosolic enzyme that catalyzes the S-methylation of 6-mercaptopurine and azathioprine. Lowactivity phenotypes are correlated with polymorphism in the TPMT gene. Patients with low or undetectable TMPT activity could develop severe myelosuppression when they are treated with standard doses of thiopurine drugs. Since ethnic differences in the TPMT gen polymorphism have been demonstrated worldwide, its assessment in the Chilean population is worthwhile. Aim: To investigate the TMPT gene polymorphism in a Chilean blood donor individuals. Subjects and Methods: The frequency of four allelic variants of the TPMT gene, *2 (G238C), *3A (G460A and A719G), *3B (G460A) and *3C (A719G) were analyzed in 210 Chilean blood donors, using polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) and allele-specific PCR-based assays. Results: TPMT variants associated to low enzymatic activity, were detected in 16 subjects (8%), who had a heterozygous genotype (*3A in 12; *3C in three and *2 in one subject). No TPMT*3B allelic variant was found. The normal allele (wild-type) was found in 92% of studied individuals. Conclusions: The allele TPMT*3A, is the most prevalent in this group of Chilean blood donors, as in Caucasian populations.

Prevalencia de la infección por helicobacter pylori según ensayo de la ureasa en pacientes derivados a la Unidad de Endoscopía del Hospital Clínico de la Universidad de Chile / Prevalence of infection by helicobacter pylori by urease test in patients derivates to the endoscopic section of Hospital Clínico de la Universidad de Chile

Helicobacter pylori is a pathogenic bacterium that infects a significant number of individuals. In Chile about 79 percent of the population is colonized. Aims: This study evaluate the prevalence of the H. pylori infection in symptomatic outpatients. Materials and Methods: 276 non selected patients were enrolled from Endoscopic Unit of Clinical Hospital of the University of Chile. The bacterium was detected by urease test. Results: H. pylori infection was found in 44,9 percent patients. Infection was higher in younger patients, 53,8 percent between 21-60 years, and was lower in older patients, 25,6 percent in older than 60 years. The risk of being H. pylori carrier is twofold higher in persons younger than 60 years as compared to those older than 60 years. Conclusion: The age would be modifier factors for H. pylori infection risk.

Dirección de las mutaciones factor V Leiden y protrombina G20210A en pacientes con trombosis venosa / Direction of the mutations factor V Leiden and Prothrombin G20210A in patients with venous thrombosis

El tromboembolismo venoso es una condición patológica de origen multifactorial, incluyendo causas adquiridas o genéticas. De estas últimas, las mutaciones puntuales factor V Leiden y Protrombina G20210A representan etiologías más frecuentes de trombosis hereditaria. Para el diagnóstico de estos efectos genéticos en pacientes con trombosis venosa, se realizan las técnicas de biología molecular de reacción en cadena de la polimerasa y polimorfismo del tamaño de los fragmentos de restricción. Desde febrero del 2001hasta diciembre de 2005 se realizaron 565 exámenes para la detección del factor V Leiden, encontrándose un 6,19 por ciento de prevalencia (35 pacientes). Esta cifra contrasta con algunos estudios y esta en concordancia con otros. En el mismo periodo se realizaron 557 exámenes para la detección de Protrombina G20210A, encontrándose un 6,1 por ciento de prevalencia (34 pacientes), valor que es muy similar a la mayoría de las series clínicas descritas.

Venous thromboembolism is a pathological condition of multifactorial origin, including acquired and genetic causes. The point mutation factor V Leiden and Prothrombin G2021OA are the most frequent etiologies of hereditary thrombosis. To diagnose these genetic defects in patients with venous thrombosis, the molecular biological technique of polymerase chain reaction – restriction fragment length polymorphism (PCR-RFLP) is used. In this study, 565 exams for the detection of factor V Leiden were carried out from February, 2001 through December, 2005, finding a prevalence of 6.19 percent (35 patients). This rate contradicts some studies and agrees with others. In the same period, 557 exams for the detection of prothrombin G2021OA were performed, finding a prevalence of 6.1 percent (34 patients), a very similar value to the prevalence reported in the majority of the published clinical series.

Estudio de reproducibilidad del examen de cuantificación de VIH-1 por la técnica Nuclisens HIV-1 QT en muestras de plasma de pacientes infectados con VIH-1 / Reproducibility of a quantification assay, nuclisens HIV-1 QT in HIV positive plasma samples

La cuantificación (carga viral) del virus de inmunodeficiencia humana (VIH) en los pacientes infectados por este agente ha demostrado ser un valioso examen para la predicción del progreso de la infección y el monitoreo de la respuesta al tratamiento antiviral. Se evaluó la reproducibilidad de la técnica Nuclisens HIV-1 QT, recientemente introducida en nuestro país, comparando diferentes volúmenes de plasma en 11 pacientes infectados con VIH. Cada muestra fue analizada al menos en duplicado, realizándose un total de 29 determinaciones. Se encontró una mayor reproducibilidad al utilizar un volumen inicial mayor o igual a 500 µl de plasma (precisión promedio de 0,18 log y un coeficiente de variación promedio de 20 por ciento). La variación intra e inter-ensayo fue de 0,19 y 0,07 log respectivamente. La buena reproducibilidad encontrada en este estudio, asociada a la facilidad de manipulación de esta metodología en un laboratorio de biología molecular, la hace altamente recomendable para su uso rutinario en el estudio de la carga viral de los pacientes con infección por VIH

Inmunoglobulina A ¿un predictor de daño hepático crónico por alcohol? / Immunoglobulin A: predictor of alcoholic chronic liver damage?

La relación entre etiología, severidad del daño hepático y niveles aumentados de IgA ha sido motivo de controversia. Nuestros objetivos fueron a) analizar el efecto del alcohol sobre la concentración sérica de IgA en pacientes con cirrosis alcohólica, b) estudiar la relación entre IgA y severidad del daño hepático y c) evaluar el efecto de la suspensión del consumo de alcohol sobre sus niveles. Se estudiaron 48 pacientes cirróticos, 30 alcohólicos y 18 no alcohólicos. En todos se midieron inmunoglobulinas séricas (IgA, IgG, IgM) y se determinó la puntuación de Child-Pugh. En 16 pacientes alcohólicos se realizó una segunda determinación de inmunoglobulinas luego de al menos 7 meses de abstinencia. Los valores de la IgA fueron significativamente mayores en pacientes alcohólicos y cifras más elevadas se observaron en la medida que aumentó el grado de insuficiencia hepática, de acuerdo a los niveles de Child-Pugh. No se observó relación entre los valores de IgA y transaminasas. Estos valores aumentados de IgA se mantienen más allá de los seis meses

Hepatitis colestásica por piroxicam: caso clínico / Cholestatic hepatitis associated to piroxicam use: report of one case

Most nonsteroidal antiinflammatory drugs can produce hepatotoxicity. We report a 22 years old female who presented with an acute cholestatic hepatitis after a prolonged period of piroxicam use. Hepatitis was attributed to this drug since all markers for hepatitis virus (A, B, C, E, Epstein Barr, Cytomegalovirus and Herpex Simplex) were negative, autoimmune markers were negative, serum iron and ceruloplasmin were normal, there was a temporal relationship between the administration of piroxicam and the hepatitis, the histological picture was compatible with this etiology and the patient had a favorable evolution after the discontinuance of the drug. This type of hepatotoxicity is not common but it must be born in mind when patients must receive nonsteroidal antiinflammatory drugs for prolonged periods