Existen cada vez más evidencias de que el virus de la hepatitis C favorece el desarrollo de diabetes. Objetivos: 1.- Analizar la prevalencia de las alteraciones del metabolismo hidrocarbonado (diabetes y glucemia anómala en ayunas) en los pacientes con infección crónica por el VHC (n=498) y compararla con la que presentan los pacientes con otras enfermedades hepáticas (n=144), considerando el grado de lesión hepática (hepatitis crónica o cirrosis) y los genotipos del VHC en el análisis de los resultados. 2.- Evaluar los mecanismos etiopatogénicos por los que el VHC puede favorecer el desarrollo de diabetes (citocinas proinflamatorias, resistencia a la insulina, disfunción célula beta) mediante un estudio caso control en pacientes con hepatitis crónica no diabéticos (14 VHC (-) y 28 (+)) estrictamente equiparados por los factores relacionados con la aparición de diabetes.3.- Analizar si el aumento de ferritina que existe en los pacientes infectados por el VHC es debido a la propia infección o, si por el contrario, puede atribuirse a la mayor prevalencia de diabetes (enfermedad que también cursa con ferritina elevada) en estos pacientes.4.- Complementando al último objetivo, determinar mediante el análisis de los receptores solubles de la transferrina (sTfR), si la concentración de ferritina en los pacientes diabéticos tipo 2 es un buen indicador de los depósitos de hierro.Conclusiones:1.- Los pacientes con infección por el VHC presentan una elevada prevalencia tanto de glucemia anómala en ayunas como de diabetes en comparación con los pacientes con otras enfermedades hepáticas no atribuibles al VHC (17% vs. 7% y 15% vs. 5%, respectivamente). Este aumento de prevalencia se produce fundamentalmente en los pacientes con hepatitis crónica e incluso se objetiva en sujetos con transaminasas normales.2.- El análisis del genotipo no parece útil para identificar una población de pacientes infectados por el VHC con mayor riesgo para desarrollar alteraciones hidrocarbonadas.3.- La infección por el VHC debe consideradarse un factor de riesgo para el desarrollo de diabetes. Por tanto, es recomendable realizar un cribado sistemático de las alteraciones hidrocarbonadas en los pacientes infectados por el VHC.4.- En los pacientes infectados por el VHC la prueba de la sobrecarga oral de glucosa es el método de elección para realizar el diagnóstico de la diabetes.5.- En los pacientes infectados por el VHC que aún no han desarrollado una diabetes existe un hiperinsulinismo, tanto en situación basal como tras la estimulación con glucagón endovenoso o la ingesta de una comida estándar, lo que traduce un estado de insulinresistencia. 6.- El aumento de resistencia a la insulina en los pacientes infectados por el VHC se asocia a un incremento de citocinas proinflamatorias.7.- Los pacientes infectados por el VHC no diabéticos presentan concentraciones similares de ferritina que la población general. De ello puede deducirse que el aumento de los depósitos de hierro, evaluados mediante los niveles séricos de ferritina, no parece un elemento fundamental en la etiopatogenia de la diabetes asociada al VHC.8.- La diabetes mellitus es el principal factor relacionado con el aumento de las concentraciones séricas de ferritina observado en los pacientes con infección crónica por el VHC. Por tanto, la diabetes mellitus debe ser tenida en cuenta al evaluar el metabolismo del hierro en los pacientes infectados por el VHC.9.- El aumento de la ferritina en los pacientes diabéticos no se acompaña de un descenso recíproco de los niveles de sTfR, lo que sugiere que es un reflejo del estado inflamatorio crónico de baja intensidad característico de la DM tipo 2.10.- La determinación de la concentración sérica de ferritina no es un marcador útil de los depósitos de hierro en los pacientes con DM tipo 2. / There is growing evidence to suggest an association between hepatitis C virus infection and type 2 diabetes mellitus. Objetives: 1.- To compare the prevalence of both diabetes and impaired fasting glucose between hepatitis C virus (HCV)-infected patients (n=498) and patients with other liver diseases but not HCV (n=144), taking into account the degree of liver damage (chronic hepatitis and cirrhosis) and the different HCV genotypes. 2.- To explore the specific mechanisms responsible for the development of diabetes in HCV infected patients (proinflammatory cytokines, insulin resistance and beta-cell function) in a case-control study with nondiabetic noncirrhotic patients (14 anti-HCV negative and 28 anti-HCV positive) carefully matched for the main items related with diabetes development.3.- To investigate if the high ferritin levels observed in HCV-infected patients are related with HCV infection itself or could be associated with the higher prevalence of diabetes (also related with hyperferritinemia) in HCV infected patients.4.- To determine circulating transferrin receptor levels (sTfR) to evaluate if serum ferritin reflects iron body stores in type 2 diabetic patients.Conclusions:1.- Both impaired fasting glucose and diabetes were more prevalent among patients with HCV infection than among anti-HCV negative patients. This finding was mainly due to the group of patients with chronic hepatitis, and it was also present among patients with normal transaminases.2.- No differences in the prevalence of either impaired fasting glucose or diabetes among HCV genotypes were observed.3.- HCV infected patients must be considered as a high risk group for type 2 diabetes development, and testing for glucose abnormalities should be mandatory in these patients.4.- The high percentage of new cases of diabetes detected using postload hyperglycemia in the subset of patients with chronic hepatitis suggests that the oral glucose tolerance test (OGTT) should be recommended as the primary screening test for diabetes in these patients.5.- In HCV nondiabetic noncirrhotic patients an hyperinsulinemia is detected, both basal and after stimulation tests (intravenous administration of 1 mg of glucagon and the standard food intake test), suggesting an insulin resistance state. 6.- This state of insulin resistance, before the development of glucose abnormalities, is accompanied with a marked increase of proinflammatory cytokines.7.- Serum ferritin levels in anti-HCV positive nondiabetic patients were similar to those in the control group, suggesting that iron deposition is not one of the main mechanisms linking HCV infection and diabetes. 8.- The increase in ferritin levels detected in HCV patients was closely related to the presence of diabetes. So, diabetes should be taken into consideration when evaluating iron metabolism in HCV-infected patients.9.- Serum ferritin levels are increased in Type 2 diabetic patients in the absence of a reciprocal decrease of sTfR. This finding suggest that elevated ferritin levels in Type 2 diabetic patients are mainly as a result of inflammatory mechanisms rather than iron overload.10.- Serum ferritin levels may not be a reliable tool for evaluating iron deficiency anaemia in Type 2 diabetes.

En aquesta tesi s'estudia una població de pacients seropositius al VHC i en ells se'ls ha investigat els factors de risc que poden afavorir el patir aquesta infecció i a un grup se'ls ha practicat biòpsia hepàtica per via transjugular amb estidi posterior dels paràmetres histològics i factors que es relacionen amb un major mal hepàtic.S'estudia també l'evolució i pronòstic de la infecció pel VHC en aquests pacients, així com l'evolucióde la malaltia hepàtica en el posttrasplantament. / En esta tesis se estudia una población de pacientes seropositivos al VHC y en ellos se los ha investigado los factores de riesgo que pueden favorecer el padecer esta infección y a un grupo se los ha practicado biopsia hepática por vía transjugular con estidio posterior de los parámetros histológicos y factores que se relacionan con uno mayor mal hepático. Se estudia también la evolución y pronóstico de la infección por el VHC en estos pacientes, así como la evolución de la enfermedad hepática en el posttrasplante.

Tzukuan is an HBV-, HCV-, HDV- endemic township in southern Taiwan. Based on a mass screening on 2909 residents age of 45 years or more in 1997, the prevalence rates of HBsAg and anti-HCV were 12.8% and 41.6% respectively. Of HBsAg carriers, 15.3% were positive for anti-HDV. Tzukaun was divided into coastal area and inland area. The prevalence of anti-HCV of coastal area was two times higher than that of inland area (61.4% v.s. 29.1%) and genotype 1b and 2a are the main two subtypes. We wish to find the causes of discrepancy in these nearby areas by phylogenetic analysis. Stratified by the living areas, coastal or inland, 27 samples were picked up (ingroup). HCV sequence of NS5B region could be detected by RT-PCR then a nested PCR in eight males and ninteen females with mean age of 54.8 years old (range: 45-70). None of these 27 residents came from the same family. Another 10 HCV infected persons whose living townships also in southern Taiwan but other than Tzukuan were enrolled as local controls. From GenBank, 30 different HCV isolates were included. Phylogenic analysis unequivocally confirmed the simultaneous spread of two different HCV strains in this township clusters according to their subtypes were noted. A trend of the spreading from coastal to land area or an ultra-aggregation phynomenon which according to their living area, as we suspected, were not noted between Tzukuan¡¦s residents. In ingroup, the short genetic distance between the isolates of C hepatitis virus which came from different villages might be caused from the wide-spreading of HCV in this endemic area (the maximal and minimal genetic distance in 1b or 2a isolates are 0.0869 vs. 0.0098 and 0.0996 vs. 0.0334). Besides, according to the contacting history to foreigner by our aborigine tribes, from genebank, all isolates from different countries were included and three possible origins of HCV genotype 1b were noted in Tzukuan. All these findings might be caused from frequently HCV inflow in this endemic area and wide-spreading of HCV between different countries.

Tez (Tıpta Uzmanlık) - Süleyman Demirel Üniversitesi, Tıp Fakültesi, Tıbbi Mikrobioloji Anabilim Dalı, 2009. / Kaynakça var.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2009. / Härtill 6 uppsatser.

Düsseldorf, University, Thesis (doctoral), 2000.

Thesis (doctoral)--Universität, Münster (Westfalen).

published_or_final_version / Clinical Oncology / Doctoral / Doctor of Philosophy

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

The hepatitis C virus (HCV) disproportionately affects the prison population. Studies demonstrate that healthcare provider knowledge of HCV risk factors is insufficient and many individuals are not aware that they are HCV positive. Early identification of HCV status can prompt early treatment and avoidance of complications that contribute to poor outcomes resulting in chronic disease progression. This doctor of nursing practice (DNP) project addresses provider identification of HCV risk factors at initial inmate intake to prison and whether providers obtained HCV testing based on guidelines from the Centers for Disease Control and Prevention (CDC). The principal investigator (PI) conducted a retrospective medical record review at Arizona State Prison Complex (ASPC) Lewis focusing on initial inmate intake forms identifying two of the CDC risk factors for HCV: drug abuse and tattoos; and ascertaining if a providers ordered a HCV test if inmates had one or both of these risk factors. The PI reviewed 51 randomly selected medical records; 40 records met inclusion criteria of 1) inmates who had an initial inmate intake evaluation occurring from 1 October 2013 to 1 October 2014 and 2) documentation of positive HCV risk factors. Analysis of the records showed a mean inmate age of 26.78 years with a variable racial distribution. The risk factor of tattooing was present in 37 (92.5%) of records reviewed and the risk factor of intravenous drug use (IVDU) was present in 7 (17.5%). Only 4 (10%) records of inmates with positive risk factors had a HCV test ordered by the provider: One physician (n=2) and one nurse practitioner (n=2). This project demonstrated a gap in HCV testing in the presence of risk factors in the inmate population at ASPC Lewis which is consistent with studies in the general population. This study does not identify any reasons for this consistency, but raises questions for future studies focused on provider knowledge, education and the institution of HCV testing protocols. This DNP project provides the foundation for a future full quality improvement Plan-Do-Study-Act based project aimed at educating providers about HCV testing according to CDC (2013a) guidelines and subsequently re-evaluating their HCV test ordering practices.