Thesis (Ph. D.)--University of Queensland, 2002. / Includes bibliographical references.

Hepatitis C Virus (HCV) is the most common blood borne infection in the United States and frequently develops into a chronic disease, which can lead to serious health complications including liver damage, cirrhosis, cancer, and death. Due to vague symptomology associated with HCV, half of people with chronic HCV are unaware of their condition. New HCV infections are most common in persons who inject drugs (PWID) and chronic infection is currently most prevalent in baby boomers (birth age 1945 to 1965). The purpose of this project was to increase health care professionals? comfort level and knowledge regarding HCV screening guidelines per USPSTF as well as to improve HCV screening rates for the PWID cohort and baby boomer cohort. This project was implemented when risk-based HCV screening was recommended. Many eligible patients do not undergo screening as nationally screening rates are low at 12.8%. Lack of time and knowledge deficit are common documented barriers that health care professionals identified throughout the literature that negate screening uptake. This project was implemented by a multidisciplinary team utilizing the PDSA method. Two one-hour educational sessions were developed and provided to all health care professionals at two federally qualified health center primary care clinics in the Midwest region. The presentations were conducted by an infectious disease physician, a pharmacist who specializes in viral hepatitis, and the co-investigator in October 2019. Academic detailing occurred to follow-up and support health care professionals. A voluntary, post-implementation survey was distributed to participants after the educational sessions and an abbreviated survey two months later. PWID and baby boomer and pre- and post-implementation screening rates were computed through the facility?s established process. After this project, HCV screening rates increased by 16% for the baby boomer cohort and 5.5% for the PWID cohort. Health care professionals? knowledge and confidence in HCV screening guidelines was enhanced through this intervention. With new updated universal HCV screening guidelines, continued efforts to screen for HCV is essential.

Hepatitis C virus (HCV) infection is a major global health burden affecting 1-2% of the world’s population. The majority of infected individuals will develop chronic infection and are at risk of cirrhosis and hepatocellular carcinoma. There is currently no preventative vaccine available for HCV. In the developed world, the highest HCV incidence and prevalence rate is amongst intravenous drug users (IDU). The duration, frequency of IDU, and sharing of drug injecting equipment contribute to particularly high rates of HCV infection in this population. Individuals at high risk of recurrent exposure to HCV infection from long term IDU have been recruited in Plymouth, UK, from 2003 onwards and if they remain negative for HCV infection are termed exposed uninfected (EU). Understanding the factors that prevent HCV infection in this cohort could give valuable insight into the mechanisms of natural resistance to HCV infection. The EU cohort was previously shown to have characteristics attributable to the activation of both the adaptive and the innate arms of the immune system with no known dominant, immune or non- immune, mechanism of HCV protection. The aim of this thesis was to attempt and identify this mechanism and for that purpose a comparative transcriptional profile study was initially performed between 3 groups: EU, individuals who spontaneously cleared HCV infection (SR) and patients with chronic HCV infection (CHCV). Of the differentially regulated genes, the association with resistance to HCV was strongest for Interleukin-27 (IL-27) which was significantly upregulated in EU compared to the 2 other groups and C X C motif chemokine 7 (CXCL7) which was significantly upregulated in EU relative to the CHCV group. The CD28 mediated T-helper cell signalling pathway was significantly upregulated in SR relative to the 2 other groups. We attempted to corroborate the above findings and we demonstrated that IL-27 is overexpressed in EU, compared to SR and CHCV. The possible role of IL-27 in natural protection from HCV infection remains to be elucidated and requires further study.

Se realizó un estudio retrospectivo de casos y controles para evaluar los factores predictivos de eficacia del tratamiento combinado con interferón pegilado alfa (Peg IFN) y ribavirina (RBV) contra la hepatitis C crónica en un hospital de Lima Perú, años 2006-2011. Se incluyó 34 casos consecutivos de sujetos con Respuesta Virológica Sostenida (RVS) y 36 controles temporales sin RVS, entre quienes se determinó 16 variables epidemiológicas, clínicas y de tratamiento. Se utilizó el análisis univariado de regresión logística a través del programa estadístico Epi Info. Los hallazgos fueron: ninguno de los factores epidemiológicos, como edad, género, procedencia e ingesta alcohólica se relacionó con la RVS; de los factores clínicos evaluados, como: IMC, score Child-Pugh, índice MELD, transaminasemia y grado de fibrosis, solo el estadío Child A (OR=9,45; p<0,05) se relacionó con RVS; y de los factores de tratamiento, la carga viral ≤ 600 mil UI/mL (OR=2,68; p<0,05), la Respuesta Virológica Rápida (RVR; OR=58,4; p<0,01), y la Respuesta Virológica Precoz (RVP; OR=14,5; p<0,05) se asociaron con la RVS. En conclusión, los factores predictores de la RVS en los pacientes con terapia para VHC fueron: la enfermedad hepática compensada (Child-Pugh A), la RVP, y sobretodo, la RVR. Palabras Claves: Hepatitis C crónica (HCC), Virus de hepatitis C (VHC), Respuesta Virológica Sostenida (RVS). / --- We performed a retrospective study of cases and controls to assess predictors of efficacy of combination therapy with pegylated interferon alpha (Peg IFN-) and ribavirin (RBV) for hepatitis C infection in a hospital in Lima Peru, years 2006 2011. It included 34 consecutive cases of patients with Sustained Virological Response (SVR) and 36 controls without SVR, among whom was determined 16 variables epidemiological, clinical and treatment. We used univariate logistic regression analysis through statistical program Epi Info. The findings were: none of the epidemiological factors such as age, gender, origin and alcohol intake, were associated with SVR; clinical factors evaluated, as: BMI, Child-Pugh score, MELD index, transaminasemia and degree of fibrosis; only stage Child A (OR = 9,45; p <0.05) was associated with SVR, and treatment factors, the load viral ≤ 600 000 IU/mL (OR = 2,68; p <0.05), Rapid Virological Response (RVR; OR = 58.4; p <0.01), and Early Virological Response (EVR; OR = 14,5 ; p <0.05) were associated with SVR. In conclusion, predictors of SVR in patients with HCV therapy were: the compensated liver disease (Child-Pugh A), the RVP, and above all, the RVR. Keywords: Hepatitis C Chronic (HCC), Hepatitis C Virus (HCV), Sustained Virological Response (SVR).

Diss. (sammanfattning) Örebro : Örebro universitet, 2009. / Härtill 4 uppsatser.

The cost effectiveness of using novel HCV treatment option, telaprevir and boceprevir, should depend on patients’ respond to conventional PEG-INFα and ribavirin therapy. The study of pharmacogenomics, interleukin-28B (IL-28B) polymorphisms, accompanied with the information of HCV genotypes are suggested to have the strongest predictive value of treatment outcomes and prognosis of disease in individuals infected with HCV who are undergoing conventional PEG-INFα and ribavirin therapy. It is extremely valuable in HCV/HIV co-infected patients as these groups of patients require a complex treatment regimen and demonstrate poor sustained viral response (SVR) rate. The development of a fast and promising IL-28B genotyping assay is urgently needed. A total of 47 blood samples randomly selected from HCV and HIV co-infected patients were used in this investigation. The aims of this study are to evaluate and compare the performance of newly developed IL-28B HybProbe real-time PCR assay using LightCycler® system against Sanger Sequencing method in determining IL-28B polymorphisms on rs12979860 and rs8099917 and to estimate the prevalence of IL-28B polymorphisms among HCV/HIV co-infected patients in Hong Kong. In addition, the genotypic distribution of HCV among the same patient group is identified by using in-house Sanger Sequencing method. It was found that the newly developed IL-28B real-time HybProbe assay resulted in 100% concordance with the traditionally used Sanger Sequencing method. The allele frequencies of C and T were 96% and 4% in rs12979860 and T and G were 97% and 3% in rs8099917 respectively. The CC and TT wild type are predominating in rs12979860 and rs8099917 with frequencies of 93.62% and 95.74% respectively. The most favorable compound genotype CC/TT with both homozygous wild types on both SNPs was the most predominant type with a high prevalence of 93.61%. Among all the samples, 50% samples were found to be HCV genotype 1, 41.18% were genotype 6 and 8.82% were genotype 3. A simple and efficient IL-28B real-time HybProbe assay was developed in this study and proved to show excellent performance on IL-28B genotyping although further optimization is suggested before it can be applied in the clinical setting. The favourable wild type genotypes of rs12979860 and rs8099917 accounted for the most predominant genotypes which is similar to other findings obtained from an Asian population. A comparatively high prevalence of HCV genotype 6 was found in the HCV/HIV co-infected group. Future study with the information of treatment outcomes (HCV viral load) can further evaluate the predictive value of IL-28B polymorphisms on SVR in different HCV genotypes. / published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.

Bochum, Universiẗat, Diss., 2004.

No description available.