After alignment of 300 HBV sequences randomly downloaded from GenBank, we found that the frequency of A1762T and G1764A mutations in genotype C was found as high as 64%, while 34% was found for other genotypes (A, B, D to H). Besides, recent clinical studies have also shown that A1762T/G1764A mutations occur frequently in HCC patients with genotype B infection (81%, 30 of 37 patients), but were relatively lower in asymptomatic carriers (43%, 22 of 51 patients). These indicate that the contribution of A1762T/G1764A mutations to liver cancer might not be limited to genotype C. As the double mutations are present within the region of HBV Enhancer II/Basal core promoter (BCP) and cause residue substitution of HBx (Lys130Met and Val131Ile); therefore, their effects on the promoter and HBx activities were examined. / Chronic infection of hepatitis B virus (HBV) increases the risk of hepatocellular carcinoma (HCC) by more than 100-fold. However, the underlying molecular mechanism of this process is not fully understood. Several recent studies have shown that A1762T and G1764A mutations of HBV were associated with the aggressiveness of liver disease, in which inactive carriers would develop active hepatitis, and eventually liver cirrhosis and HCC. In Asia, genotypes B and C are the predominant genotypes of HBV infections. Our longitudinal five-year follow-up study of 426 chronic hepatitis B patients in Hong Kong found that the genotype C HBV (normally with A1762T/G1764A mutations) was closely associated with higher risk of HCC than genotype B HBV (non-frequent mutations with A1762T/G1764A). / In this study, systemic site-directed mutagenesis studies, promoter assays, replication capacity assays and overexpression of HBx assays were carried out to demonstrate the molecular mechanisms of these mutations for the increases risk of HCC. Three conclusions were drawn from this study. (1) A1762T and/or G1764A mutations of HBV could reduce BCP activities in a synergistic manner with 1764A contributing more. Reversed T1762A and/or A1764G mutations increase the BCP activities also in a synergistic manner with 1764G contributing more; (2) HBx could increase HBV BCP activity, HBV replication and HBsAg expression. The Lys130Met and Val131Ile mutations of HBx could further increase the above abilities while the A1762T/G1764A double mutations in the BCP region could not affect the interaction of HBx and HBV BCP; (3) The G1677T/A1679C and T1706C mutations could increase the BCP activity; The ectopic expression of HBx could further increase the BCP activity while the mutated HBx (130Met and 131Ile) has less effect on these mutated promoters. / Dong, Qingming. / Adviser: Ming-Liang He. / Source: Dissertation Abstracts International, Volume: 70-09, Section: B, page: . / Thesis submitted in: December 2008. / Thesis submitted in: December 2008. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 132-154). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

A case-control study was previously carried out to identify HCC-associated genomic markers on HBV. Some of them are clustered at the preS1 and X promoter regions of HBV genotype B and core promoter of HBV subgenotype Cs. The functional significance of these markers to the virus was investigated in our study. Our result showed that one of those markers, the G1613A mutation on core promoter, can significantly increase the promoter activity in a genotype-dependent manner and the effect is reversible by the A-to-G back mutation. We have established an in vitro full-length HBV genome transfection system and the result suggested that the G1613A mutation suppressed the e antigen (HBeAg) secretion and enhanced virus DNA production by downregulating the precore (preC) mRNA transcription. In consistence to the clinical study, the mutation was associated to serum HBV DNA level higher than 6 log copies/1M in female HBV carriers in a univariate analysis. In addition, we demonstrated that the G1613A mutation is a hot spot mutation situated on the negative regulatory element (NRE) on the core promoter in an alignment analysis. To further investigate the molecular mechanism of the mutation, two unknown protein complexes had been shown to bind on the NRE. They showed different binding affinity to the G1613-wild-type and A1613-mutant NRE sequence. Moreover, we showed that in vitro synthesized RFX1 protein could bind to the mutated NRE probe at a higher affinity than that to wild-type NRE probe. Overall, our result suggests that the G1613A mutation exerts its effect by differential binding to some proteins via the NRE region. Studying the mechanism of the mutations may provide insights to the viral pathogenesis and HBV-associated HCC, which has long been a health burden in Asia-Pacific countries. / Infection of hepatitis B virus (HBV) causes acute and chronic hepatitis and is closely associated with the development of cirrhosis and hepatocellular carcinoma (HCC). Approximately 60-80% of world's HCC is related to HBV, and it is the third most common cause of cancer death in Asia-Pacific region. Almost 400 million people are chronically infected with HBV and one-third was likely to die of complications of cirrhosis, including liver failure and HCC. As there is a shortage of effective curative treatments, detection and prognosis of the risk of cancer development will be essential to improve survival of patients with chronic HBV infection. / Li, Man Shan. / Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 198-210). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Submitted by Suzana Dias (suzana.dias@famerp.br) on 2018-10-19T20:56:33Z No. of bitstreams: 1 JaquelineCalçaAssis_dissert.pdf: 1656909 bytes, checksum: 0f9e5425c7d3ffa51b86c71d5b4b9687 (MD5) / Made available in DSpace on 2018-10-19T20:56:33Z (GMT). No. of bitstreams: 1 JaquelineCalçaAssis_dissert.pdf: 1656909 bytes, checksum: 0f9e5425c7d3ffa51b86c71d5b4b9687 (MD5) Previous issue date: 2016-11-07 / The presence of anti-HBc alone can have several meanings: false positive, healing immune window, delayed immunity or occult hepatitis B virus infection (OBI). In clinical practice, it is important and necessary to clarify the diagnosis to prevent transmission to the risk population such as hemodialysis patients, blood donors, transplant recipients and co-infected individuals with HIV and/or HCV. Objectives: The aim of the study was to determine the prevalence of anti-HBc alone and occult hepatitis B, respectively, in blood samples from Adolfo Lutz Institute - Regional Laboratory Center X - São José do Rio Preto (IAL - CLR X - SJRP) and patients from Municipal Ambulatory of Viral Hepatitis (AMHV) both from São José do Rio Preto city in the period from January 1st, 2009 to December 31st, 2014. Methods: The study population of IAL - CLR X - SJRP is from the region served by the 15th Health Regional Division (DRS), and the AMHV is a population screened for clarification, monitoring and treatment of viral hepatitis in the city. In this population with anti-HBc alone, patients were immunized against hepatitis B and the individuals without vaccine response were selected for the performance of HBV-DNA research for the diagnosis of occult hepatitis B. Results: During the study period, 6805 samples were evaluated without duplication in IAL - CLR X - SJRP, of these 624 samples had anti-HBc positive, and the prevalence of anti-HBc alone was 17.63% (110/624). In the AMHV, 940 patients anti-HBc isolated were evaluated, from these 816 (86.81%) were vaccinated and after the criterion of disregarding the vaccinated patients who did not have anti-HBs evaluated after vaccination (85 - 10.42%), 731 (89.58%) patients were considered for analysis of the vaccine response, and 568 (77.70%) presented seroconversion with anti-HBs positive and 163 (22.30%) non-seroconverted patients. The research of HBV-DNA was performed in 25.77% (42/163) patients without a vaccine response, finding a prevalence of occult hepatitis B (OBI) of 47.62% (20/42).The presence of antibodies to HIV and HCV was 25.40% and 13.25% in the blood samples IAL - CLR X - SJRP and in AMHV was 1.80% and 0.33%, respectively. Conclusion: The results show the occurrence of antiHBc alone in IAL - CLR X - SJRP and the need of monitoring this population. In AMHV, the vaccination was effective for most cases, which demonstrates the need of vaccine introduction as a routine in anti- HBc alone patients in the overall population. The occult hepatitis B was found in almost half of patients assessed without vaccine response. / A presença do anti-HBc isolado pode ter vários significados: falso positivo, janela imunológica de cura, imunidade tardia ou infecção oculta pelo vírus da hepatite B (IOB). Na prática clínica é importante e necessário o esclarecimento diagnóstico para evitar transmissão em populações de risco como pacientes hemodialisados, doadores de sangue, transplantados e indivíduos coinfectados com HIV e/ou HCV. Objetivo: O objetivo do estudo foi determinar a prevalência de anti-HBc isolado e hepatite B oculta, respectivamente, em amostras de sangue do Instituto Adolfo Lutz - Centro de Laboratório Regional X - São José do Rio Preto (IAL - CLR X - SJRP) e pacientes do Ambulatório Municipal de Hepatites Virais (AMHV) ambos da cidade de São José do Rio Preto, no período de 01 de janeiro de 2009 a 31 de dezembro de 2014. Casuística e Métodos: A população estudada do IAL - CLR X - SJRP é proveniente da região atendida pela Divisão Regional de Saúde (DRS) XV e a do AMHV é uma população triada para esclarecimento, acompanhamento e tratamento das hepatites virais do município. Nesta população com anti-HBc isolado os pacientes foram imunizados contra hepatite B e os indivíduos sem resposta vacinal foram selecionados para realização da pesquisa de HBV-DNA para diagnóstico da hepatite B oculta. Resultados: Durante o período de estudo, foram avaliadas 6805 amostras, sem duplicação, no IAL - CLR X - SJRP, destas, 624 amostras apresentavam anti-HBc reagente, sendo a prevalência de anti-HBc isolado 17,63% (110/624). No AMHV foram analisados 940 pacientes com anti-HBc total isolado destes 816 (86,81%) foram vacinados e depois de aplicado o critério de desconsiderar os pacientes vacinados que não tiveram o anti-HBs avaliado após a vacinação (85 - 10,42%), 731 (89,58%) pacientes foram considerados para análise da resposta vacinal, sendo que 568 (77,70%) apresentaram soroconversão com anti-HBs positivo e 163 (22,30%) pacientes não soroconverteram. A pesquisa do HBV-DNA foi realizada em 25,77% (42/163) dos pacientes sem resposta vacinal, encontrando uma prevalência de hepatite B oculta (IOB) de 47,62% (20/42). A presença de anticorpos contra HIV e HCV foi de 25,40%, 13,25% nas amostras do IAL - CLR X - SJRP e no AMHV foi de 1,80%, 0,33%, respectivamente. Conclusão: Os resultados obtidos demonstram a ocorrência de anti-HBc isolado nas amostras do IAL - CLRX - SJRP e a necessidade de acompanhamento dessa população. No AMHV a vacinação esclareceu a maioria dos casos, o que demonstra a necessidade da introdução da vacina como rotina em pacientes anti-HBc isolado na população geral. A hepatite B oculta foi encontrada em quase metade dos pacientes não respondedores vacinais avaliados.

Submitted by admin tede (tede@pucgoias.edu.br) on 2018-05-28T19:39:54Z No. of bitstreams: 1 Marina Brandão Braz Albuquerque.pdf: 605500 bytes, checksum: 1405379cffb1283fb04eb721d76cc92a (MD5) / Made available in DSpace on 2018-05-28T19:39:54Z (GMT). No. of bitstreams: 1 Marina Brandão Braz Albuquerque.pdf: 605500 bytes, checksum: 1405379cffb1283fb04eb721d76cc92a (MD5) Previous issue date: 2018-03-27 / The use of hepatic biopsy to assess the stay of the level of fibrosis continues to be gold standard but may present some risks during the procedure and high cost. Given that the WHO suggested the use of APRI and FIB-4 indexes to evaluate hepatic fibrosis in patients with chronic hepatitis C, because they are low-cost exams that can replace the use of hepatic biopsy. Objectives: Assess the level of hepatic fibrosis before and after treatment of hepatitis C by means of APRI and FIB 4 methods. Methods: This is a cross-descriptive study, carried out by reviewing medical records of patients attending the STD/AIDS and Viral Hepatitis clinics in the period from March 2016 to December 2017. The level of fibrosis was defined according to PCDT 2015 in significant fibrosis values of APRI > 1.5 and FIB-4 > 3.25; and absence of fibrosis APRI ≤ 0.5 and FIB-4 ≤ 1.5. Patients who did not fit within the triage were defined as indeterminate. The correlation between the improvement of fibrosis and the variables was performed: gender, age and genotype. Results: 45 selected patients were assisted in the clinic, 23 of them (51.1%) were male. The average age of the patients was 57.13. The infection by genotype 1a was more prevalent n = 19 (42.2%). Among the 45 patients, 28 were within the classifications between absence and advanced by the APRI before the treatment and 17 were defined as indeterminate. In the FIB-4, 26 patients were classified between absence and advanced fibrosis and 19 defined as indeterminate. After the treatment 25 patients were classified by APRI and 20 by FIB- 4. Only the FIB-4 index had significant correlation (P < 0.05) with age and improvement in fibrosis. Conclusions: Both tests can be used to verify the staging of hepatic fibrosis and assist in daily practice, but some results may be in the indeterminate zone. In these cases, it is necessary to carry out complementary tests to better define the degree of fibrosis. / O uso da biópsia hepática para avaliar o estadiamento do grau de fibrose continua sendo padrão-ouro, contudo pode apresentar alguns riscos durante o procedimento, além de elevado custo. Diante disso, a OMS sugeriu o uso dos índices APRI e FIB-4 para avaliar a fibrose hepática em pacientes portadores de hepatite C crônica, visto que os exames têm baixo custo e podem substituir a biópsia hepática. Objetivos: Avaliar o grau de fibrose hepática pelos métodos APRI e FIB 4 antes e após tratamento de hepatite C. Métodos: Trata-se de estudo descritivo transversal, realizado por meio da revisão de prontuários médicos de pacientes atendidos no Ambulatório de DST/AIDS e Hepatites Virais em Aparecida de Goiânia no período de março de 2016 a dezembro de 2017. O grau de fibrose foi assim definido conforme PCDT 2015: fibrose significativa com valores de APRI >1,5 e FIB-4 >3,25; ausência de fibrose com APRI ≤0,5 e FIB-4 ≤1,5. Os pacientes que não se enquadravam na classificação foram definidos como indeterminados. Foi realizada a correlação entre a melhora da fibrose e as variáveis: gênero, idade e genótipo. Resultados: Foram selecionados para o estudo 45 pacientes atendidos na unidade, dos quais 23 (51,1%) eram do sexo masculino. A média de idade dos pacientes foi de 57,13 anos. A infecção pelo genótipo 1a foi mais prevalente, n= 19 (42,2%). Dos 45 pacientes, 28 estavam inseridos nas classificações entre fibrose ausente e avançada pelo APRI antes do tratamento e 17 foram definidos como indeterminados. No FIB-4, 26 pacientes foram classificados entre ausência e fibrose avançada e 19 foram definidos como indeterminados. Após o tratamento, 25 pacientes foram classificados pelo APRI e 20 pelo FIB-4. Apenas o índice FIB-4 mostrou correlação significativa (p<0,05) entre idade e melhora na fibrose. Conclusões: Ambos os testes podem ser utilizados para verificar o estadiamento da fibrose hepática e auxiliar na prática diária, porém alguns resultados podem estar na zona indeterminada. Neste caso é necessária a realização de testes complementares para definir melhor o grau de fibrose.

<p>Hepatitis E virus (HEV) je uzročnik akutne hepatis E infekcije kod ljudi. HEV se prenosi putem zagaĎene vode i odgovoran je za nastanak mnogobrojnih epidemija velikih razmera u zemljama u razvoju Azije i Afrike. Hepatitis E je prvi put kod svinja izolovan 1997. godine, a kasnije je dokazan i kod ostalih ţivotinjskih vrsta, kao &scaron;to su: divlje svinje, jelen, zečevi, pacovi, ptice i ostalo.<br />Prva istraţivanja prisustva HEV infekcije kod domaćih i divljih svinja u Srbiji sprovedena su 2008. godine. HEV RNK je dokazana u 30% uzoraka fecesa i 45% uzoraka organa (Petrovic et al., 2008). Analizom uzoraka krvnih seruma svinja u individualnim gazdinstvima ustanovljena je seroprevalencija od 34,6% (Lupulovic et al, 2010). Cilj ovog istraţivanja je ispitivanje ra&scaron;irenosti HEV infekcije kod svinja na farmama na teritoriji Vojvodine, kao i ispitivanje HEV seroprevalencije kod ljudi u Vojvodini.<br />Od metoda za istraţivanje kori&scaron;ćene su: nekomercijalni ELISA test (in-house ELISA), komercijalni ELISA test, Western-blot metod, real-time RT -PCR i imunohistohemijska metoda za detekciju HEV antigena.<br />Materijal za ispitivanje su bili uzorci krvi svinja (300) sa 3 farme na teritoriji Juţne Bačke i Srema i uzorci krvi ljudi (294), kao i uzorci fecesa, ţuči, jetre i mesa sakupljeni u klanicama od 95 tovljenika i 50 prasadi.<br />Prisustvo specifičnih antitela IgG klase protiv hepatitis E virusa dokazano je kod svinja na sve tri ispitujuće farme. Primenom in house ELISA testa ustanovljena je seroprevalencija od 37% na farmi A, 31% na farmi B i 54% na farmi C, dok je primenom komercijalnog ELISA testa utvrĎeno 40% seropozitivnih svinja na farmi A, 41% na fami B i 65% na farmi C. Uporednom analizom rezultata dobijenih sa oba ELISA testa, ustanovljena je prosečna seroprevalencija od 40,66% in house ELISA testom, odnosno 48,66% komercijalnim ELISA testom.<br />Sprovedena su i istraţivanja prisustva specifičnih antitela IgG klase protiv HEV u krvnim serumima dobrovoljnih davalaca krvi i kod pacijenata. Primenom in house ELISA testa utvrĎena je<br />seroprevalencija od 15% kod dobrovoljnih davalaca krvi, dok su uzorci krvi pacijenata bili seronegativni. Testiranjem komercijalnim ELISA testom kod dobrovoljnih davalaca krvi pozitivan serolo&scaron;ki nalaz je ustanovljen kod 17,86% dobrovoljnih davalaca krvi (pregledani su serumi koji su u in house testu dali pozitivan ili sumnjiv nalaz, kao i odreĎen broj seronegativnih uzoraka), a kod pacijenata 2,12%.<br />Kao tzv. &bdquo;zlatni standard&ldquo; za definisanje rezultata sa sumnjivim serolo&scaron;kim nalazom čije su ekstinkcije bile blizu cut off vrednosti u in house ELISA testu, kori&scaron;ćen je Western blot metod. Pozitivan rezultat je potvrĎen kod 6 od ukupno pregledanih 11 uzoraka krvi svinja, odnosno od ukupno pregledanih 11 uzoraka seruma ljudi, pozitivan nalaz je ustanovljen kod 7 uzoraka.<br />Uzorci sa klanica pregledani su real-time RT- PCR metodom, a HEV RNK je dokazana u u fecesu (54%), ţuči (26%), jetri (16%) i mesu (10%) prasadi. Kod tovljenika prisustvo HEV RNK je potvrĎeno samo u fecesu (7,27%), dok su svi uzorci tkiva bili negativni.<br />Patahistolo&scaron;kim pregledom dokazane su mikroskopske lezije II stepena kod 3 uzorka (11,53%) jetri prasadi od ukupno pregledanih 26 uzoraka sa pozitivnim RT-PCR. Imunohistohemijskim pregledom uzoraka jetre prasadi nije dokazano prisustvo antigena hepatitis E virusa.<br />Definisani su protokoli laboratorijskog ispitivanja hepatitis E infekcije kod svinja i ljudi, kao i u uzorcima mesa i jetri svinja u klanicama</p> / <p>Hepatitis E virus (HEV) is the causative agent of acute hepatitis E infection in humans. HEV is transmitted through contaminated water and is responsible for the outbreaks of many large-scale epidemics in the developing countries of Asia and Africa. Swine HEV was first isolated in 1997, and was later detected in other animal species, such are: wild boar, deer, rabbits, rats, birds and more.<br />The first investigations of HEV infection in domestic and wild pigs in Serbia were carried out in 2008. HEV RNA was detected in 30% of faecal samples and 45% of the tissue samples (Petrovic et al., 2008). Analysing the blood samples of beckyard pigs, the seroprevalence of 34,6% was determined (Lupulovic et al, 2010). The aim of this study was to investigate the prevalence of HEV infection in pigs on farms in Vojvodina, as well as testing the HEV seroprevalence in humans.<br />The methods used for this study were: non-commercial ELISA (in house ELISA), the commercial ELISA, Western blot method, real-time RT-PCR and immunohistochemical method for the detection of HEV antigen.<br />Material for the study were: blood samples of pigs (300) from 3 farms on the territory of South Backa and Srem and blood samples of people (294), as well as faeces, bile, liver and meat collected in slaughterhouses from 95 fatteners and 50 piglets.<br />The presence of specific IgG antibodies against the hepatitis E virus in pigs has been detected on all three examinated farms. Upon the application of in house ELISA, the seroprevalence of 37% was establised on farm A, 31% in farm B and 54% on farm C, while using a commercial ELISA , 40% of seropositive pigs were detected on farm A, 41% of fami B and 65% Farm C. The comparative analysis of the results obtained with both ELISA, determined the average seroprevalence of 40,66% by in house ELISA and 48,66% by commercial ELISA.<br />The research of the presence of specific IgG antibodies against HEV in the serum of blood donors and patients were also conducted. Upon the application of in house ELISA, the seroprevalence of 15% were recorded in blood donors, while blood samples of patients were seronegative. Testing by commercial ELISA, positiv serological findings were diagnosed in 17,86% of blood donors (serums with positive or suspicious results in in house ELISA and a number of seronegative samples were tested), and in patients 2, 12%.<br />As so-called &quot;gold standard&quot; for defining the serological results with suspiciousserological findings, which extinctions were close to cut off values in in house ELISA, we used the Western</p>

Wong, Yee Man Melody. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 148-174). / Abstract also in Chinese. / Abstract --- p.i / Acknowledgements --- p.iv / Abbreviations --- p.v / Review of the literature --- p.1 / Overview of liver fibrosis --- p.2 / Pathophysiology of liver fibrosis --- p.3 / Histological classification of liver fibrosis --- p.4 / Gold standard for fibrosis assessment - Liver biopsy --- p.6 / Biomarker in blood - non-invasive method for assessing diseases --- p.7 / Significance of non-invasive markers of liver fibrosis --- p.9 / Biomarkers of liver fibrosis --- p.10 / Direct markers --- p.10 / Indirect markers --- p.11 / Proteomics / Why proteomics? --- p.16 / Clinical values of proteomics in biomarker discovery --- p.17 / Challenges in proteomics --- p.18 / Current proteomics technologies in biomarker discovery --- p.21 / Gel based --- p.21 / Gel free approach - MS based --- p.23 / Quantitative proteomics --- p.29 / Application of proteomics to discovery of biomarkers for diagnosis of liver fibrosis --- p.33 / Rationale and Objectives of the Project --- p.35 / Chapter Section 1 --- Method development of magnetic beads-based proteomic profiling for quantitative proteomic profiling and micro- purification in parallel --- p.36 / Chapter 1.1 --- Introduction --- p.36 / Chapter 1.2 --- Materials and methods --- p.38 / Chapter 1.3 --- Results / Chapter 1.3.1 --- Serum proteome profiles obtained with different types of chromatographic magnetic beads --- p.46 / Chapter 1.3.2 --- Performance of PCS 4000 ProteinChip reader --- p.49 / Chapter 1.3.3 --- Reproducibility of magnetic beads-based serum proteomic profiling --- p.54 / Chapter 1.3.4 --- Gel electrophoresis of the eluted proteins --- p.58 / Chapter 1.3.5 --- Identification of the protein peaks --- p.58 / Chapter 1.4 --- Discussion --- p.60 / Chapter 1.5 --- Conclusion --- p.64 / Chapter Section 2 --- Development of a proteome-based fingerprinting model for detecting liver fibrosis in patients with chronic hepatitis B infection --- p.65 / Chapter 2.1 --- Introduction --- p.65 / Chapter 2.2 --- Materials and methods --- p.68 / Chapter 2.3 --- Results / Chapter 2.3.1 --- Patients characteristics --- p.75 / Chapter 2.3.2 --- Correlation between biochemical/serological markers and the degrees of liver fibrosis --- p.81 / Chapter 2.3.3 --- Serum proteomic profiling by linear MALDI-TOF MS --- p.81 / Chapter 2.3.4 --- Correlation of proteomic features with Ishak score --- p.81 / Chapter 2.3.5 --- Correlation of significant proteomic features with serological markers --- p.89 / Chapter 2.3.6 --- Construction of diagnostic model in detecting liver fibrosis and cirrhosis --- p.91 / Chapter 2.3.7 --- Cross-validation of the diagnostic model using pre- treatment samples in detecting liver fibrosis and cirrhosis --- p.91 / Chapter 2.3.8 --- Independent validation of the diagnostic model using post-treatment samples in detecting liver fibrosis and cirrhosis --- p.95 / Chapter 2.3.9 --- Comparison against other non-invasive models in detecting liver fibrosis and cirrhosis --- p.98 / Chapter 2.4 --- Discussion --- p.103 / Chapter 2.5 --- Conclusion --- p.112 / Chapter Section 3 --- Identification of proteomic features to form diagnostic fingerprint for the detection of liver fibrosis in patients with chronic hepatitis B infection --- p.113 / Chapter 3.1 --- Introduction --- p.113 / Chapter 3.2 --- Materials and methods --- p.115 / Chapter 3.3 --- Results --- p.121 / Chapter 3.3.1 --- Protein identification of the protein marker in the diagnostic model --- p.121 / Chapter 3.3.2 --- Immunodepletion of apolipoprotein C-III --- p.125 / Chapter 3.3.3 --- Serum levels of apolipoprotins and their association with liver fibrosis --- p.127 / Chapter 3.4 --- Discussion --- p.130 / Chapter 3.5 --- Conclusion --- p.139 / General discussion --- p.141 / Reference --- p.148 / Original Data --- p.175

Further functional investigation revealed that knockdown of GRP78 expression by RNA interference resulted in a significant increase of both intracellular and extracellular HBV virions in the transient HBV-producing HepG2 cells, concomitant with enhanced levels of hepatitis B surface antigen and e antigen in the culture medium Conversely, overexpression of GRP78 in HepG2 cells led to HBV suppression concomitant with induction of the positive regulatory circuit of GRP78 and interferon-beta 1 (IFN-beta1). In this connection, IFN-beta1-mediated 2', 5'-oligoadenylate synthetase (OAS) and ribonuclease L (RNase L) signaling pathway was noted to be activated in GRP78-overexpressing HepG2 cells. Moreover, GRP78 was significantly down-regulated in the livers of chronic hepatitis B patients after effective anti-HBV treatment (p= 0.019) as compared with their counterpart pre-treatment liver biopsies. / Hepatitis B virus (HBV) infection is a global public health problem, which plays a crucial role in the pathogenesis of chronic hepatitis, cirrhosis and hepatocellular carcinoma. Although considerable progress has been made over the past decade, the pathogenesis of HBV infection and the mechanisms of host-virus interactions are still elusive. / In conclusion, the present study demonstrates for the first time that GRP78 functions as an endogenous anti-HBV factor via IFN-beta1-OAS-RNase L pathway in hepatocytes. Induction of hepatic GRP78 may provide a novel therapeutic approach in treating HBV infection. / In this study, we applied a two-dimensional gel electrophoresis and mass spectrometry-based comparative proteomic approach to globally analyze the host early response to HBV by using an inducible HBV-producing cell line HepAD38. Twenty-three proteins were identified as differentially expressed, with glucose-regulated protein 78 (GRP78) as one of the most significantly up-regulated proteins induced by HBV replication. This induction was further confirmed in both HepAD38 and HepG2 cells transfected with HBV-producing plasmids by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, as well as in HBV-infected human liver biopsies by immunohistochemistry. / Ma, Yan. / Adviser: Ming-Liang He. / Source: Dissertation Abstracts International, Volume: 72-01, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 111-129). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Lau, Chi Chiu. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 133-142). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Zhu, Ranxu. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 123-142). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Determina el nivel de cobertura de inmunización contra el HBV en hijos nacidos de madres portadoras de la infección en el Hospital de apoyo de Huanta, Ayacucho, entre los años 2014 y 2018. Se realizó un estudio observacional de tipo descriptivo y retrospectivo. En el estudio se incluyó a los hijos nacidos de madres portadoras de la infección por HBV, cuyos nacimientos fueron registrados en el Hospital de Apoyo de Huanta, Ayacucho, entre enero de 2014 y diciembre de 2018. No se contó con criterios de exclusión. Se utilizó fuentes de información secundarias (Libro de Nacimientos del Hospital de Apoyo de Huanta y bases de datos otorgadas por la Unidad Ejecutora Red de Salud Ayacucho Norte Sede Huanta). Este estudio fue aprobado por el Instituto de Ética de la Facultad de Medicina de la Universidad Nacional Mayor de San Marcos. En el análisis estadístico se utilizó medidas de frecuencia y porcentaje. Se encontró que la cobertura total de inmunización contra el HBV de 64.47%, siendo la cobertura de la dosis de nacimiento de la vacuna contra el HBV de 100%, la cobertura de aplicación de la Inmunoglobulina de 77.78%, y la cobertura de la aplicación de la tres dosis de la vacuna pentavalente fue 97.61%, 93.90% y 80.26% respectivamente. Se concluye que se encontró una cobertura total de inmunización contra el HBV por debajo de lo esperado según las recomendaciones de la OMS. Individualmente se encontró una cobertura adecuada de la dosis de nacimiento y de la primera dosis de la vacuna contra el HBV incluida en la vacuna pentavalente, mas no en la segunda y tercera dosis de la misma ni en la aplicación de Inmunoglobulina. Se recomienda realizar futuros estudios en donde se lleve a cabo el seguimiento de la población y se utilice fuentes de información preferentemente primarias, además de complementar y reforzar el plan de eliminación de transmisión madre - hijo del HBV en el Perú. / Tesis