The role of HLA-G molecule and HLA-G gene polymorphisms in tumors, viral hepatitis, and parasitic diseases

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Hepatitis C infection: challenges in dental management and diagnosis of extrahepatic manifestations

Hepatitis C is associated with autoimmune diseases, hepatocellular carcinoma,and extrahepatic manifestations that, in conjunction, may seriously compromise the patient's quality of life. We herein describe a case of chronic hepatitis C with oral manifestations and discuss some implications for diagnosis and treatment. A 63-year-old woman complaining of spontaneous bleeding of the oral mucosa presented with bilateral asymmetric ulcers surrounded by white papules and striae on the buccal mucosa. Her medical history revealed leucopenia, thrombocytopenia, and skin lesions associated with chronic hepatitis C. Propranolol and ranitidine had recently been prescribed. Lichen planus, lichenoid reaction, and erythema multiforme were considered in the differential diagnosis. Histopathological analysis revealed lymphocytic infiltrate in a lichenoid pattern. The lesions partially healed after 1 week and completely regressed after 6 months, despite the maintenance of all medications; no recurrence was observed. The final diagnosis was oral lichen planus associated with hepatitis C. Chronic hepatitis C may present oral manifestations, which demand adjustments in dental treatment planning. Medication side effects may interfere with the clinical presentation and course of the disease and should be accounted for in the differential diagnosis. The possibility of spontaneous remission of oral lichen planus should always be considered, especially when putative etiological factors of a lichenoid lesion are withdrawn in an attempt to differentiate oral lichen planus from lichenoid lesions. This case emphasizes the importance of recognizing the extrahepatic manifestations of hepatitis C as a cause of increased morbidity.

MTP -493G/T gene polymorphism is associated with steatosis in hepatitis C-infected patients

The reduction of hepatic microsomal transfer protein (MTP) activity results in fatty liver, worsening hepatic steatosis and fibrosis in chronic hepatitis C (CHC). The G allele of the MTP gene promoter, -493G/T, has been associated with lower transcriptional activity than the T allele. We investigated this association with metabolic and histological variables in patients with CHC. A total of 174 untreated patients with CHC were genotyped for MTP -493G/T by direct sequencing using PCR. All patients were negative for markers of Wilson’s disease, hemochromatosis and autoimmune diseases and had current and past daily alcohol intake lower than 100 g/week. The sample distribution was in Hardy-Weinberg equilibrium. Among subjects with genotype 1, 56.8% of the patients with fibrosis grade 3+4 presented at least one G allele versus 34.3% of the patients with fibrosis grade 1+2 (OR = 1.8; 95%CI = 1.3-2.3). Logistic regression analysis with steatosis as the dependent variable identified genotypes GG+GT as independent protective factors against steatosis (OR = 0.4, 95%CI = 0.2-0.8; P = 0.01). The results suggest that the presence of the G allele of MTP -493G/T associated with lower hepatic MTP expression protects against steatosis in our CHC patients.

Macrophage activating syndrome is associated with lobular hepatitis and severe bile duct injury with cholestasis

Macrophage activating syndrome (MAS) is a rare hematological disorder associated with uncontrolled systemic T-cell activation. Persistent fever, fatigue and hepatosplenomegaly are frequent clinical manifestations, whereas hyperferritinemia, elevated serum lactate dehydrogenase levels and cytopenia are key criteria for the diagnosis of MAS. The nature of liver pathology in MAS has been partially elucidated but destructive biliary lesions have been rarely described. This report illustrates four cases of MAS developing marked cholestasis, leading to one case of biliary cirrhosis necessitating liver transplantation. Histologically, liver involvement was characterized in all cases by acute lobular hepatitis, marked hepatocyte apoptosis and small bile duct injury similar to the vanishing bile duct syndrome. Immuno-histological studies showed that the inflammatory changes and bile duct lesions were dominated by the presence of activated macrophages and T-cells, in particular CD8+ lymphocytes, and in part NK-cells. These findings suggest that in MAS, various T-cell triggers such as infection, autoimmune disease and malignancy might result in the release of cytokines, which in turn activate macrophages to trigger a systemic acute phase response and local tissue damage. This communication suggests that a macrophage, T- and NK-cell network is operational in the pathogenesis of the cholangiocyte, hepatocyte and sinus endothelial cell damage in MAS.

Interleukin 12 suppresses autoantibody production by reversing helper T-cell phenotype in hepatitis B e antigen transgenic mice.

Helper T (Th) cells are classified as Th1 or Th2 cells by virtue of cytokine secretion and function as mediators of cellular or humoral immunity, respectively. Cytokines also regulate the differentiation of Th cells. For example, interleukin (IL)-12 promotes Th1 and suppresses Th2 cell development, suggesting that IL-12 may be useful therapeutically in Th2-mediated autoimmune and allergic disorders. Therefore, the effect of systemic IL-12 treatment on in vivo autoantibody synthesis in hepatitis B e antigen (HBeAg)-expressing transgenic mice, which is dependent on self-reactive Th2 cells, was examined. Low-dose IL-12 significantly inhibited autoantibody production by shifting the Th2-mediated response toward Th1 predominance. Additionally, previous studies suggest that a predominance of HBeAg-specific Th2-type cells may contribute to chronicity in hepatitis B virus infection. Therefore, IL-12 may also prove beneficial in modulating the HBeAg-specific Th response to favor viral clearance in chronic hepatitis B virus infection.

Estimation on disease burden related to hepatitis B virus infection in Shandong province of China [山东省乙型肝炎病毒感染所致相关疾病的疾病负担研究]

Objective: To comprehensively measure the burden of hepatitis B, liver cirrhosis and liver cancer in Shandong province, using disability-adjusted life years (DALYs) to estimate the disease burden attribute to hepatitis B virus (HBV)infection. Methods: Based on the mortality data of hepatitis B, liver cirrhosis and liver cancer derived from the third National Sampling Retrospective Survey for Causes of Death during 2004 and 2005, the incidence data of hepatitis B and the prevalence and the disability weights of liver cancer gained from the Shandong Cancer Prevalence Sampling Survey in 2007, we calculated the years of life lost (YLLs), years lived with disability (YLDs) and DALYs of three diseases following the procedures developed for the global burden of disease (GBD) study to ensure the comparability. Results: The total burden for hepatitis B, liver cirrhosis and liver cancer were 211 616 (39 377 YLLs and 172 239 YLDs), 16 783 (13 497 YLLs and 3286 YLDs) and 247 795 (240 236 YLLs and 7559 YLDs) DALYs in 2005 respectively, and men were 2.19, 2.36 and 3.16 times as that for women, respectively in Shandong province. The burden for hepatitis B was mainly because of disability (81.39%). However, most burden on liver cirrhosis and liver cancer were due to premature death (80.42% and 96.95%). The burden of each patient related to hepatitis B, liver cirrhosis and liver cancer were 4.8, 13.73 and 11.11 respectively. Conclusion: Hepatitis B, liver cirrhosis and liver cancer caused considerable burden to the people living in Shandong province, indicating that the control of hepatitis B virus infection would bring huge potential benefits.

The adenine-rich tract in the 5ʹ-end of the hepatitis C virus ORF encodes a peptide regulating the binding of the C protein to RNA

Hepatitis C virus (HCV ) core (C) protein is thought to bind to viral RNA before it undergoes oligomerization leading to RNA encapsidation. Details of these events are so far unknown. The 5ʹ-terminal C protein coding sequence that includes an adenine (A)-rich tract is a part of an internal ribosome entry site(IRES). This nucleotide sequence but not the corresponding protein sequence is needed for proper initiation of translation of viral RNA by an IRES-dependent mechanism. In this study, we examined the importance of this sequence for the ability of the C protein to bind to viral RNA. Serially truncated C proteins with deletions from 10 up to 45 N-terminal amino acids were expressed in Escherichia coli, purified and tested for binding to viral RNA by a gel shift assay. The results showed that truncation of the C protein from its N-terminus by more than 10 amino acids abolished almost completely its expression in E. coli. The latter could be restored by adding a tag to the N-terminus of the protein. The tagged proteins truncated by 15 or more amino acids showed an anomalous migration in SDS-PAGE. Truncation by more than 20 amino acids resulted in a complete loss of ability of tagged C protein to bind to viral RNA. These results provide clues to the early events in the C protein - RNA interactions leading to C protein oligomerization, RNA encapsidation and virion assembly.

Prenatal Vitamin D deficiency induces an early and more severe experimental autoimmune encephalomyelitis in the second generation

In a previous study, we demonstrated that mouse adult F(1) offspring, exposed to a vitamin d deficiency during pregnancy, developed a less severe and delayed Experimental Autoimmune Encephalomyelitis (EAE), when compared with control offspring. We then wondered whether a similar response was observed in the subsequent generation. To answer this question, we assessed F(2) females whose F(1) parents (males or females) were vitamin d-deprived when developing in the uterus of F(0) females. Unexpectedly, we observed that the vitamin d deficiency affecting the F(0) pregnant mice induced a precocious and more severe EAE in the F(2) generation. This paradoxical finding led us to assess its implications for the epidemiology of Multiple Sclerosis (MS) in humans. Using the REFGENSEP database for MS trios (the patient and his/her parents), we collected the parents' dates of birth and assessed a potential season of birth effect that could potentially be indicative of the vitamin d status of the pregnant grandmothers. A trend for a reduced number of births in the Fall for the parents of MS patients was observed but statistical significance was not reached. Further well powered studies are warranted to validate the latter finding.

Hepatitis B knowledge, testing, and vaccination among Chinese and Vietnamese adults in Australia

Hepatitis B is a significant public health challenge within some subpopulations in Australia, including Chinese and Vietnamese migrants. There has been limited research on hepatitis B knowledge and actions in these communities. The authors conducted a self-administered survey among 442 Chinese and 433 Vietnamese in Brisbane. Generally, the knowledge is best described as “moderate.” One in 2 could not identify the sexual transmission risk and less than one third knew that sharing foods or drinks did not spread the disease. The majority of Vietnamese (80%) and 60% of Chinese respondents indicated prior testing. Vaccination was reported in 60% of the Vietnamese and in 52% of the Chinese. Knowledge was better among Chinese people who had been tested and vaccinated compared with those who were nontested and nonvaccinated. Only 3.5% of the Chinese, but 11.6% of the Vietnamese, indicated having a positive test result hepatitis B virus. This study helps identify strategies for programs targeting both communities and practitioners.

Support for patients with hepatitis C : An exploratory qualitative study of medical specialists’ perceptions

Objective: To explore the range of meanings about the role of support for patients with hepatitis C by examining medical specialists' perceptions. Method: The study employed a qualitative, open-ended interview design and was conducted in four major teaching hospitals in Adelaide, South Australia. Eight participants (three infectious disease physicians, four gastroenterologists, one hepatologist), selected through purposive sampling, were interviewed about general patient support, their role in support provision, the role of non-medical support and their reasons for not using support services. Results: Main themes included a focus on support as information provision and that patient education is best carried out by a medical specialist. The use of support services was defined as the patient's decision. Participants identified four key periods when patients would benefit from support; during diagnosis, failure to meet treatment criteria, during interferon treatment and following treatment failure. Conclusions: It was concluded that while barriers exist to the establishment of partnerships between specialists and other support services, this study has identified clear points at which future partnerships could be established. Implications: A partnership approach to developing support for patients with hepatitis C offers a systematic framework to facilitate the participation of health professionals and the community in an important area of public health.

Hepatitis C in the workplace : a survey of women’s occupational health and safety in the beauty therapy industry

Objective: To examine current knowledge and practice of occupational health and safety (OH&S) regarding hepatitis C in beauty therapy practice. Methods: A questionnaire was sent to all beauty therapy practices identified through the Telstra Yellow Pages and distributed via beauty therapy product agencies. Results: 119 questionnaires were completed by employers and employees in 99 beauty therapy practices in metropolitan Adelaide. Beauty therapists reported carrying out many practices that had exposed them to blood in the past. More than 80% of the procedures carried out by beauty therapists in the previous week were reported to have led to exposure to blood. 39.5% of respondents had not received information about OH&S practices related to blood spills and 77.5% of respondents had received no OH&S information about hepatitis C. Knowledge of hepatitis C and its transmission was poor, with 62% of respondents incorrectly identifying the prevalence of hepatitis C and respondents incorrectly identifying sneezing (28%), kissing (46%) and sharing coffee cups (42%) as a modes of transmission. 80% of beauty therapy practices had no OH&S representative. Conclusion: Beauty therapy practice can expose both operator and client to blood and is therefore a potential site for the transmission of blood-borne diseases including hepatitis C. OH&S information is inadequate in this industry and knowledge of hepatitis C is poor.

Hepatitis C : a socio-cultural perspective on the effects of a new virus on a community’s health

Since the emergence of diagnostic medical tests in Australia in 1990, hepatitis C (HCV) has been shown to account for over 90 percent of all non-A non-B hepatitis, revealing it to be a widespread and major public health problem. The diagnosis of HCV involves a diverse range of issues for affected persons, introducing identity and lifestyle changes, which are commonly articulated through psychological concepts. In this article we argue that it is important to examine the broader social and cultural contexts that contribute to the experiences of persons affected by HCV. The thematic analysis of qualitative data from six individuals diagnosed with HCV is included to exemplify some of the processes that are involved in the changing identity of a person following a positive diagnosis. The theoretical framework for the interpretation of these processes is interpretive interactionism. In this research, we are attempting to extend the understanding of the effects of HCV diagnoses beyond internal, psychological processes by examining how these diagnoses transform some of the processes of self-formation and expression. The participants’ experiences indicate that there are at least four dimensions of self that were significant to their changing sense of self: relationship of self to others; the emotional self; self-stories and identity; and self-scrutiny and relationships. We conclude that a socio-cultural perspective contributes to the explanation of the transition period following a HCV-positive diagnosis and the redefinition of self towards a HCV status.

Hepatitis C and policy implementation : ethics as a dialogic process for resource allocation

Hepatitis C, which was first identified in 1988, has become an important issue for public health as epidemiological and clinical evidence has emerged. These disciplines have highlighted the extent of infection and its medical consequences. Now, governments at both the state and federal levels are sifting through this evidence and are attempting to create structures to deal with the problem of hepatitis C. These structures have generally taken the form of expert committees and working parties organised from established medical, scientific and public health bodies...

Unravelling the maze : Hepatitis C, psychosocial factors and access to antiviral therapy

In this paper we present an examination of the literature on the psychosocial aspects of hepatitis C (HCV), and ask what are the implications for patients and clinicians regarding access to treatment? Hepatitis C (HCV) is a blood-borne communicable disease that was identified in 1988. In Australia, an estimated 217,000 people live with HCV. The virus causes serious liver inflammation, can lead to liver cirrhosis and a small percentage of sufferers will develop hepatocellular carcinoma. Reports about the psychosocial aspects of HCV appeared from around 1994 indicating a similar set of societal responses to people with HIV; stigmatisation and discrimination. A number of calls were made for the establishment of counselling and support services to address the specific mental health needs of people with HCV. We conducted a systematic review of the literature between 2002-2012 about the psychosocial aspects of HCV and its relationship to access to treatment and identified a number of key issues that suggest the anticipated progress in this area has not been made. The majority of people with HCV already experience marginalisation, and the diagnosis of HCV further compounds their marginalisation through stigma and discrimination and complicates clinical decision-making around treatment. We conclude that the need for mental health services that are capable of addressing the complexities of the psychosocial aspects of HCV remains. Concomitantly, primary care clinicians require greater clarity and consistency about the clinical guidelines for HCV to meet the increasing expectations on them to deliver comprehensive patient management within primary care. (248 words)