Among the estimated 210,000 Australians living with the hepatitis C virus, over 80% will go on to live with chronic hepatitis C and its debilitating effects. Patients with chronic hepatitis C who have active inflammatory changes on liver biopsy may undergo combination therapy with interferon and ribavirin. Adverse effects of combination therapy can be variable in their nature, intensity and severity. They may be mild, reversible, moderate, or serious and life threatening. For some patients the adverse effects are so severe that it places enormous stress on partner relationships. Through a phenomenological approach using purposive sampling and semi-structured interviews of five patients and their partners, this study aimed to explore the issues surrounding chronic hepatitis C, combination therapy and personal relationships. The purpose of the study was to enhance understanding of the experiences of people living with the illness and undergoing treatment. The complexities that hepatitis C and treatment brings into the personal lives of people have led me to this study because there is a need to understand their impact on the personal relationships of patients and their partners. Through deeper understanding of their experiences, nurses can move beyond the medical oriented approach to treatment towards a holistic approach. The findings from this study revealed that chronic hepatitis C and combination therapy had an enormous impact on the lives of the patients, their partners and families. Both had significant physiological effects that impacted on quality of life, however, the social and psychological consequences of living with a highly stigmatised disease with an unknown course and outcome cannot be underestimated. The participants’ narratives provided a rich description of their experiences and offered insight into the life world of people living with chronic hepatitis C and combination therapy, and their partners. The themes that emerged from the study were: experiencing illness and treatment; keeping a secret; sharing the experience; and enduring struggle. Nurses play a significant role in educating patients with chronic hepatitis C, advocating for them and helping them to achieve a reasonable state of well being. Nurses also have the important role of providing partners with information and support that will assist them as caregivers. The results of this study lend support to the effectiveness of providing equitable services to persons diagnosed with chronic hepatitis C. However, additional research is needed to explore gender, socioeconomic, sexual-orientation, transmission, cultural and religious differences within this group to better address their needs. / Master of Nursing (Honours)

The human hepatitis B virus (HBV) is a small hepatotropic virus, which affects approximately 350 million chronic sufferers worldwide. It has a compact 3.2 kbp dsDNA genome encoding four major overlapping genes namely core, polymerase, surface and X required for its replication. The virus synthesises a pregenomic RNA (pgRNA) which functions both as an RNA intermediate for reverse transcription into the DNA genome and as the mRNA for the translation of the core (C) and polymerase (P) proteins. The core overlaps the polymerase gene and is translated at a 10 to 1 ratio. The polymerase gene translated from the P AUG codon is preceded by at least 4 upstream AUG codons (uAUGs), namely C AUG, C1 AUG, J AUG and C2 AUG. Various mechanisms have been implicated in the synthesis of the polymerase protein. This led to the currently accepted model which involves leaky scanning and a reinitiation mechanism in polymerase synthesis. However, multiple sequence alignment of the pgRNA revealed a short upstream open reading frame (uORF) highly conserved at the nucleotide level in all HBV subtypes and mammalian hepadnaviruses. This previously unreported uORF, designated as C0 ORF in this study is also conserved in its position and length. Past studies have either omitted this uORF in their test constructs or ignored its potential role. The C0 ORF has a conserved weak initiation context and is located within the epsilon structure within the 5' leader of the pgRNA, required for viral encapsidation. Importantly, the C0 ORF precedes and overlaps the core ORF, which may suggest an alternative model in which the core and polymerase may be translated and coordinately regulated. Fusion of the C0 ORF to luciferase showed for the first time that this uORF is translated through the detection of reporter activity (~20% of C) and also visualisation of the fusion protein via western analysis using anti-C0 and anti-luciferase antibodies. Subsequent removal of the C0 ORF implicated a role in repressing downstream core fusion protein synthesis in HepG2 cells. A similar repression was observed on J expression. To study the effect of C0 on downstream polymerase translation, a pgRNA-like DNA construct was made and subsequent mutations introduced. Mutation of the C0 AUG led to an increase in initiation at the downstream P AUG. Alteration of the existing weak initiation context to an optimal context which favours stronger initiation consistently showed a potential role for C0 ORF in facilitating reinitiation at certain downstream initiation codons including P AUG. Mutations of other uAUGs preceding the P AUG were also done to better understand their roles in regulating polymerase synthesis. The removal of the C AUG markedly increased expression from the P AUG. This study revealed other internal uAUGs in-frame to the C AUG, namely the C1 and C2 AUGs are also effectively translated, further reducing availability of translating ribosomes to downstream P AUG. Indeed the removal of the C1 and C2 AUGs led to a corresponding increase in initiation from the P AUG. Initiation at the internal J AUG was also reported and its removal showed a significant decrease in expression from the P AUG, consistent with the previous model implicating reinitiation at the P initiation site after translation of the short J ORF. The inhibitory role of the 5 uAUGs prior to the P AUG were confirmed when all were removed, giving rise to translation almost equal to that at C AUG. Taken together, these results suggest a new model in which the HBV C0 ORF plays a key role in controlling core and polymerase synthesis by repressing core translation and making available more ribosomes to downstream AUGs possibly facilitating translation reinitiation. In addition, the translation of the C0 ORF across the [epsilon] region may also preclude encapsidation, potentially acting as a switch discriminating the pgRNA template between encapsidation and translation. Therefore, the highly conserved [epsilon] region and C0 ORF present an excellent target for molecular based antiviral drugs (antisense oligonucleotides, aptamers, ribozymes) potentially providing new anti HBV drugs.

The human hepatitis B virus (HBV) is a small hepatotropic virus, which affects approximately 350 million chronic sufferers worldwide. It has a compact 3.2 kbp dsDNA genome encoding four major overlapping genes namely core, polymerase, surface and X required for its replication. The virus synthesises a pregenomic RNA (pgRNA) which functions both as an RNA intermediate for reverse transcription into the DNA genome and as the mRNA for the translation of the core (C) and polymerase (P) proteins. The core overlaps the polymerase gene and is translated at a 10 to 1 ratio. The polymerase gene translated from the P AUG codon is preceded by at least 4 upstream AUG codons (uAUGs), namely C AUG, C1 AUG, J AUG and C2 AUG. Various mechanisms have been implicated in the synthesis of the polymerase protein. This led to the currently accepted model which involves leaky scanning and a reinitiation mechanism in polymerase synthesis. However, multiple sequence alignment of the pgRNA revealed a short upstream open reading frame (uORF) highly conserved at the nucleotide level in all HBV subtypes and mammalian hepadnaviruses. This previously unreported uORF, designated as C0 ORF in this study is also conserved in its position and length. Past studies have either omitted this uORF in their test constructs or ignored its potential role. The C0 ORF has a conserved weak initiation context and is located within the epsilon structure within the 5� leader of the pgRNA, required for viral encapsidation. Importantly, the C0 ORF precedes and overlaps the core ORF, which may suggest an alternative model in which the core and polymerase may be translated and coordinately regulated. Fusion of the C0 ORF to luciferase showed for the first time that this uORF is translated through the detection of reporter activity (~20% of C) and also visualisation of the fusion protein via western analysis using anti-C0 and anti-luciferase antibodies. Subsequent removal of the C0 ORF implicated a role in repressing downstream core fusion protein synthesis in HepG2 cells. A similar repression was observed on J expression. To study the effect of C0 on downstream polymerase translation, a pgRNA-like DNA construct was made and subsequent mutations introduced. Mutation of the C0 AUG led to an increase in initiation at the downstream P AUG. Alteration of the existing weak initiation context to an optimal context which favours stronger initiation consistently showed a potential role for C0 ORF in facilitating reinitiation at certain downstream initiation codons including P AUG. Mutations of other uAUGs preceding the P AUG were also done to better understand their roles in regulating polymerase synthesis. The removal of the C AUG markedly increased expression from the P AUG. This study revealed other internal uAUGs in-frame to the C AUG, namely the C1 and C2 AUGs are also effectively translated, further reducing availability of translating ribosomes to downstream P AUG. Indeed the removal of the C1 and C2 AUGs led to a corresponding increase in initiation from the P AUG. Initiation at the internal J AUG was also reported and its removal showed a significant decrease in expression from the P AUG, consistent with the previous model implicating reinitiation at the P initiation site after translation of the short J ORF. The inhibitory role of the 5 uAUGs prior to the P AUG were confirmed when all were removed, giving rise to translation almost equal to that at C AUG. Taken together, these results suggest a new model in which the HBV C0 ORF plays a key role in controlling core and polymerase synthesis by repressing core translation and making available more ribosomes to downstream AUGs possibly facilitating translation reinitiation. In addition, the translation of the C0 ORF across the [epsilon] region may also preclude encapsidation, potentially acting as a switch discriminating the pgRNA template between encapsidation and translation. Therefore, the highly conserved [epsilon] region and C0 ORF present an excellent target for molecular based antiviral drugs (antisense oligonucleotides, aptamers, ribozymes) potentially providing new anti HBV drugs.

viii, 122 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (M.D.)--University of Adelaide, Dept. of Medicine, 1974

No description available.

About 10% of the world population suffers from chronic virus infections such as infections with hepatitis B virus, hepatitis C virus, and human immunodeficiency virus. Chronic virus infection is associated with the loss of functional cytotoxic T cells. Recent studies uncovered several mechanisms that play a central role in T cell exhaustion and thus development of chronic infections. The role of the innate immune system in the development of chronic virus infections remains unclear. Here we show that type I interferons trigger not only inhibition of virus replication but also immunoregulatory functions. The antiviral effects of type I interferons in the liver were dependent on the presence of macrophages. Macrophage depletion led to excessive virus replication and the development of chronic infection. Moreover, specific deletion of the type I interferon receptor on macrophages led to a decreased innate immune response. The regulatory functions of type I interferons were carried out by natural killer cells. Activated natural killer cells inhibited the virus specific cytotoxic T cell response and therefore delayed virus control. Depletion of natural killer cells prevented development of chronic infections and immunopathology. Moreover, type I interferons acted directly on the cytotoxic T cell response. Treatment with interferon 3 lead to increased T cell function. This resulted in induction of autoimmune diabetes in transgenic mice. In conclusion, the nature of the innate immune response triggers the development of chronic virus infection. These results uncover new mechanisms that might provide the foundation for new therapeutic approaches for patients with chronic infections.

La hepatitis C en hemodiálisis es un problema de salud que no ha sido estudiado a largo plazo en el hospital Alberto Sabogal Sologuren, por lo cual decidí realizar un estudio seroepidemiológico de la hepatitis C, de tipo prospectivo, descriptivo y trasversal, en la Unidad de Hemodiálisis, entre los meses de enero y mayo del 2,002, al considerársele a esta patología como la complicación hepática más frecuente a largo plazo entre los pacientes en hemodiálisis, para así poder conocer nuestra realidad y compararla con la de otros países para intercambiar información y lograr una mejora mutua. Durante el lapso de estudio, se presentaron 89 pacientes con IRCT en programa de hemodiálisis. Se encontró una prevalencia de la hepatitis C del 63% (N° 56 pacientes) y una incidencia del 17%, con una tasa de seroconversión del 0.64%. Teniendo en cuenta el tiempo de permanencia de 90 días en hemodiálisis, la prevalencia fue del 58% y la incidencia del 12%. La tasa de seroconversión fue 0.51%. Fueron cuatro pacientes los que tenía menos de 90 días de recibir terapia de reemplazo de la función renal a través de la hemodiálisis, todos ellos presentaron seroconversión durante el estudio. Las causas más frecuentes de IRCT en los pacientes con hepatitis C en orden de frecuencia fueron: la diabetes mellitus, la hipertensión arterial, glomerulonefritis difusa crónica y las uropatías obstructivas. El tiempo promedio en hemodiálisis entre los pacientes con hepatitis C fue de 42.5 meses. El promedio de edad fue de 59 años (24 a 82 años). El 61% de los pacientes con hepatitis C fueron mujeres y el 39% varones. Los factores de riesgo importantes en esta población estuvieron dados, por la creación del acceso vascular (100%), los procedimientos odontológicos (89%), las transfusiones sanguíneas (86%), la promiscuidad heterosexual (88%). Antecedentes familiares de hepatopatía viral (82%). Dada la alta prevalencia e incidencia de hepatitis C en la Unidad de Hemodiálisis del Hospital Sabogal, y conociendo los factores de riesgo, es necesario reforzar las normas de bioseguridad existentes, para evitar la transmisión de dicha infección por la vía horizontal y por productos hemáticos a los pacientes con IRCT en hemodiálisis que no tienen hepatitis C, al personal de salud y a los familiares de los pacientes con hepatitis C.

Motivado por conocer las características de la hepatitis autoinmune en nuestro pais, se lleva acabo una evaluación retrospectiva en el Hospital Nacional Guillermo Almenara Para ello se revisaron las historias clínicas de los pacientes evaluados por el Servicio de Gastroenterología, con el diagnostico de enfermedad hepática de presunto origen autoinmune entre Enero de 1998 y Enero del 2001, incluyéndose aquellas que cumplieran los criterios preestablecidos según el Grupo Internacional para el estudio de la enfermedad. Ventiseis pacientes cumplieron los puntajes diagnósticos , de ellos 21 fueron de sexo femenino conservando la relación de 4.2,, la edad media fue de 38.81 años (DS 16.74). la presentación mas común fue como hepatopatia crónica, existiendo un de presentación aguda en un 23.1%. la presentación como cirrosis predominó en la edad pediátrica. Se encontraron enfermedades autoinmunes concomitantes en 8 casos, la fatiga y la ictericia fueron los principales síntomas y signos, se presentó transaminasemia marcada en un 57.7% y positividad a autoanticuerpos un 100% de casos. De acuerdo a los criterios del grupo internacional 17 fueron catalogados como casos definitivos, y 9 como probables: 16 de ellos reunieron condiciones clínicas bioquímicas e histológicas para iniciar tratamiento inmunosupresor con prednisona sola o en asociación con Azatioprina Conclusión: la Hepatitis Autoinmune en el Hospital Nacional Guillermo Almenara se presenta afectando predominantemente mujeres, de edad media, con comorbilidad de otras enfermedades autoinmunes, transaminasemia e hipergamaglobulinemia.

No description available.

Objetivo: Determinar cuál fue la incidencia y la distribución de los factores de riesgo para hepatitis C entre los militares en actividad en el Hospital Militar Central durante el periodo Enero 2004 – Diciembre 2005. Material y métodos: Se utilizó un diseño observacional, descriptivo, trasversal, retrospectivo, identificándose todos los pacientes militares en actividad que acudieron a consulta sea por examen médico de rigor, hemodonadores o que acudieron o fueron referidos al Hospital Militar Central para descarte de hepatitis, que resultaron Ac-VHC+ y ARN-VHC+ (PCR+), para luego determinar la incidencia anual del servicio y la presencia de factores de riego para hepatitis C. / Objective: To assess incidence and risk factors distribution of hepatitis C between the active military at the Central Military Hospital during the January 2004 - December 2005 period. Method: A retrospective, cross-sectional, descriptive, observational design was used, identifying all the active military patients who went to ambulatory consultation by regular medical examination, as blood-donors or were referred to the Central Military Hospital for hepatitis discarding, that were Ac- HCV+ and RNA-HCV+ (CPR+), to determine the annual incidence and the presence absence of hepatitis C risk factors between them.