Hepatitis: Australia

Anonymous00371, McCaughan GW, Omata M, Amarapurkar D, Bowden S, Chow WC, Chutaputti A, Dore G, Gane E, Guan R, Hamid SS, Hardikar W, Hui CK, Jafri W, Jia JD, Lai MY, Wei L, Leung N, Piratvisuth T, Sarin S, Sollano J, Tateishi R. · Centenary Research Institute, AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, University of Sydney, NSW 2006, Australia. · J Gastroenterol Hepatol. · Pubmed #17444847 No free full text.

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Bell SJ, Lau A, Thompson A, Watson KJ, Demediuk B, Shaw G, Chen RY, Ayres A, Yuen L, Bartholomeusz A, Locarnini SA, Desmond PV. · Department of Gastroenterology, St. Vincent's Hospital, P.O. Box 2900, Fitzroy 3065, Australia. · J Clin Virol. · Pubmed #15653414 No free full text.

Abstract: BACKGROUND: Chronic hepatitis B infection (CHB) is a major health problem in Australia and worldwide. CHB is associated with significant long-term morbidity and mortality. Well tolerated treatment is now available, however the development of resistance is common and the optimal timing of treatment is yet to be determined. Identifying the factors that influence the natural history of CHB may help determine which patients need treatment and when to start it. OBJECTIVE: To determine the demographics, clinical features and virological profile of Australian patients infected with CHB and the influence of these factors on disease activity and severity. STUDY DESIGN: Review of prospectively collected demographic, clinical and virological features of all patients positive for hepatitis B surface antigen (HBsAg) for more than 6 months who were referred to St. Vincent's Hospital liver clinics. Age, sex and ethnicity were correlated with hepatitis B e antigen status (HBeAg), HBV replication status (ALT and HBV DNA), genotype and liver histology. RESULTS: 703 chronic hepatitis B surface antigen positive patients were identified. The patients were predominantly male with an average age of 44. Eighty two percent of patients were born overseas, primarily from Asian (65%) and Mediterranean countries (14%). Two thirds (426) had an elevated ALT (median 79) at presentation. HBeAg was positive in 37%. Active viral replication, defined as abnormal ALT or positive HBVDNA, was present in 74%, 48% of whom were HBeAg negative. In a subset of 103 patients genotyped, 8% had genotype A, 29% B, 41% C and 22% D. Genotype correlated with ethnicity; patients infected with genotypes A were predominantly Caucasian, B and C were Asian, and D were Mediterranean. Of 296 (42%) patients who underwent liver biopsy, 76 (27%) had advanced fibrosis. Advanced fibrosis was associated with increasing age and Mediterranean ethnicity. CONCLUSION AND RECOMMENDATIONS: Perinatal or early childhood transmission is predominant mode of infection in Australia. Two thirds of this cohort had active replication and were at increased risk of developing cirrhosis and/or hepatoma. Advanced disease was associated with age and ethnicity. HBeAg negative CHB accounts for almost half of all those with active viral replication. This parallels the rise in this form of CHB in Asia and the Mediterranean basin. Screening should be offered to people born in, or with parents born in areas of high endemnicity. To detect the development of active disease, patients with positive HBsAg but normal ALT should have liver function tests done 6 monthly and those with elevated ALT should be referred for consideration of therapy, irrespective of HBeAg status.

Madden A, Cavalieri W. · Australian Injecting and Illicit Drug Users' League, Canberra, Australia. <> · Int J Drug Policy. · Pubmed #17854719 No free full text.

This publication has no abstract.

Bowden S, Bartholomeusz A, Locarnini S. · Victorian Infectious Diseases Reference Laboratory, 10 Wreckyn Street, North Melbourne, Vic. 3051, Australia. · J Hepatol. · Pubmed #12663248 No free full text.

This publication has no abstract.

Farrell GC, Liaw YF. · Storr Liver Unit, Westmead Millennium Institute, University of Sydney at Westmead Hospital, New South Wales, Australia. · J Gastroenterol Hepatol. · Pubmed #10921372 No free full text.

This publication has no abstract.

Iser DM, Lewin SR. · Department of Medicine, The University of Melbourne, St Vincent's Hospital, Melbourne, Victoria, Australia. · Antivir Ther. · Pubmed #19430090 No free full text.

Abstract: There are many potential reasons for increased liver-related mortality in HIV-hepatitis B virus (HBV) coinfection compared with either infection alone. HIV infects multiple cells in the liver and might potentially alter the life cycle of HBV, although evidence to date is limited. Unique mutations in HBV have been defined in HIV-HBV-coinfected individuals and might directly alter pathogenesis. In addition, an impaired HBV-specific T-cell immune response is likely to be important. The roles of microbial translocation, immune activation and increased hepatic stellate cell activation will be important areas for future study.

McCaughan GW, Shackel NA, Bertolino P, Bowen DG. · AW Morrow Gastroenterology and Liver Centre, Centenary Institute, Royal Prince Alfred Hospital and Sydney University, Sydney, Australia. · Transplantation. · Pubmed #19384153 No free full text.

Abstract: Hepatitis C virus (HCV)-related liver disease postliver transplantation is associated with an accelerated course in comparison with that observed in the nonimmunosuppressed individual. Outcomes in transplantation for this indication have, therefore, been a major area of clinical interest in the field of liver transplantation. The factors underlying the rapid progression of HCV-related liver disease posttransplantation are complex and multifactorial. Nevertheless, recent data indicate a range of parameters assessable early posttransplantation that may be useful in the prediction of outcome of transplantation for this condition. This overview, therefore, concentrates on the early events occurring postliver transplantation in the HCV-infected patient, and the implications of these recent observations for the pathogenesis of the various forms of HCV-related allograft injury.

Patterson SJ, Angus PW. · Victorian Liver Transplant Unit, Austin Health, Studley Road, Heidelberg, Victoria 3084, Australia. · Curr Opin Organ Transplant. · Pubmed #19373086 No free full text.

Abstract: PURPOSE OF REVIEW: The established gold standard for prophylaxis against hepatitis B virus (HBV) recurrence post-liver transplant is combination hepatitis B immune globulin (HBIG) and lamivudine. This therapy reduces the risk of recurrence to less than 5% at 5 years; however, the cost of HBIG has led to the investigation of alternatives. This paper reviews the HBIG-sparing alternatives achieved with lamivudine and the prospects for the newer anti-HBV agents in post-liver transplant prophylaxis. RECENT FINDINGS: When used with lamivudine as part of combination prophylaxis, low-dose intramuscular HBIG is equivalent to high-dose intravenous HBIG. There is recent evidence that in patients receiving HBIG/lamivudine, HBIG can be replaced with adefovir dipivoxil at 6-12 months post-liver transplant without precipitating recurrence. Furthermore, a recent study showed that primary prophylaxis with combination adefovir/lamivudine therapy without the use of long-term HBIG was effective and well tolerated as primary prophylaxis. SUMMARY: Although there are few studies of potent newer anti-HBV agents such as entecavir or tenofovir being used as HBV prophylaxis, the properties of these drugs suggest that they should replace lamivudine within HBV prophylaxis regimes.

Farrugia A, Evers T, Falcou PF, Burnouf T, Amorim L, Thomas S. · Blood and Tissues Unit, Office of Devices, Blood and Tissues, Therapeutic Goods Administration, Woden, ACT 2606, Australia. · Biologicals. · Pubmed #19289290 No free full text.

Abstract: Procurement and processing of human plasma for fractionation of therapeutic proteins or biological medicines used in clinical practice is a multi-billion dollar international trade. Together the private sector and public sector (non-profit) provide large amounts of safe and effective therapeutic plasma proteins needed worldwide. The principal therapeutic proteins produced by the dichotomous industry include gamma globulins or immunoglobulins (including pathogen-specific hyperimmune globulins, such as hepatitis B immune globulins) albumin, factor VIII and Factor IX concentrates. Viral inactivation, principally by solvent detergent and other processes, has proven highly effective in preventing transmission of enveloped viruses, viz. HBV, HIV, and HCV.

Richmond J, Dunning P, Desmond P. · Gastroenterology Department, St. Vincent's Hospital, Melbourne, Victoria. · Aust Nurs J. · Pubmed #19149457 No free full text.

Abstract: Hepatitis C has reached epidemic proportions in Australia. Because of its association with injecting drug use, which is a main transmission mode, hepatitis C is a highly stigmatising health condition. In fact, the stigma attached to hepatitis C means hepatitis C is not just a medical diagnosis, but also a social diagnosis. The limited available research indicates hepatitis C-related discrimination is most likely to occur in health care settings. A strategic and evidenced-based approach is required to combat the social impact of hepatitis C.

Post J, Ratnarajah S, Lloyd AR. · Department of Infectious Diseases, Prince of Wales Hospital, Randwick, NSW 2031, Australia. · Cell Mol Life Sci. · Pubmed #19011759 No free full text.

Abstract: Individuals infected with hepatitis C virus (HCV) have two possible outcomes of infection, clearance or persistent infection, determined by a complex set of virus-host interactions. The focus of this review is the host mechanisms that facilitate clearance. Strong evidence points to characteristics of the cellular immune response as the key determinants of outcome, with evidence for the coordinated effects of the timing, magnitude, and breadth, as well as the intra-hepatic localisation of CD4+ and CD8+ T cell responses being critical. The recent discovery of viral evasion strategies targeting innate immunity suggests that interferon-stimulated gene products are also important. A growing body of evidence has implicated polymorphisms in both innate and adaptive immune response genes as determinants of viral clearance in individuals with acute HCV.

van der Poorten D, George J. · Storr Liver Unit, Westmead Millennium Institute, Westmead NSW, Australia. · Clin Liver Dis. · Pubmed #18984468 No free full text.

Abstract: Our mechanistic understanding of liver fibrosis has increased dramatically in recent years for all liver diseases and for hepatitis C and nonalcoholic steatohepatitis (NASH) in particular. Hepatitis C causes liver injury and fibrosis through direct cytopathic means, direct and indirect interactions with hepatic stellate cells, and activation of the immune system. Steatosis and insulin resistance, which are intrinsic deficits in NASH, are also of great importance in hepatitis C and may be induced by viral or host metabolic factors. For NASH, the key mediators of damage include oxidative stress, fat compartmentalization, visceral fat, apoptosis, and adipokine derangement. This article explores in depth the disease-specific mechanisms of fibrosis in hepatitis C and NASH, with a focus on recent developments.

Huynh W, Cordato DJ, Kehdi E, Masters LT, Dedousis C. · Department of Neurology, Liverpool Hospital, Liverpool, New South Wales, Australia. · J Clin Neurosci. · Pubmed #18976924 No free full text.

Abstract: Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system that is usually considered a monophasic disease. ADEM forms one of several categories of primary inflammatory demyelinating disorders of the central nervous system including multiple sclerosis, optic neuropathy, acute transverse myelitis, and neuromyelitis optica (Devic's disease). Post-infectious and post-immunisation encephalomyelitis make up about three-quarters of cases, where the timing of a febrile event is associated with the onset of neurological disease. Post-vaccination ADEM has been associated with several vaccines such as rabies, diphtheria-tetanus-polio, smallpox, measles, mumps, rubella, Japanese B encephalitis, pertussis, influenza, hepatitis B, and the Hog vaccine. We review ADEM with particular emphasis on vaccination as the precipitating factor. We performed a literature search using Medline (1976-2007) with search terms including "ADEM", "acute disseminated encephalomyelitis", "encephalomyelitis", "vaccination", and "immunisation". A patient presenting with bilateral optic neuropathies within 3 weeks of "inactivated" influenza vaccination followed by delayed onset of ADEM 3 months post-vaccination is described.

Angus PW, Patterson SJ. · Victorian Liver Transplant Unit, Austin Health, Heidelberg, Victoria, Australia. · Liver Transpl. · Pubmed #18825721 No free full text.

Abstract: 1. Prophylaxis using the combination of lamivudine and high-dose intravenous hepatitis B immunoglobulin (approximately 10,000 IU monthly) reduces the long-term risk of recurrence of hepatitis B in hepatitis B surface antigen-positive transplant recipients to 5% to 10%. However, this therapy is expensive and inconvenient for patients. 2. Recent studies have shown that similar results can be obtained, at far less cost, with much lower doses of intramuscular hepatitis B immune globulin (400-800 IU monthly) in combination with pretransplant and posttransplant lamivudine therapy. 3. The development of lamivudine resistance pre-transplant can lead to hepatic decompensation and increases the risk of posttransplant recurrence in patients receiving hepatitis B immune globulin/lamivudine prophylaxis. Newer nucleos(t)ide analogues with lower resistance rates such as entecavir, adefovir, and tenofovir should therefore replace lamivudine in hepatitis B prophylaxis. 4. Combination therapy with these newer agents and low-dose intramuscular hepatitis B immune globulin is likely to be the most cost effective hepatitis B immune globulin-containing regimen for the prevention of hepatitis B recurrence post-transplant. 5. Some form of hepatitis B virus prophylaxis needs be continued indefinitely post-transplant. However, the use of antivirals with very low rates of drug resistance will make it possible to stop hepatitis B immune globulin therapy in many patients currently receiving hepatitis B immune globulin/nucleos(t)ide combination therapy.

Menzies R, Turnour C, Chiu C, McIntyre P. · National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases, Australia. · Commun Dis Intell. · Pubmed #18711998 No free full text.

Abstract: This, the second report on vaccine preventable diseases and vaccination coverage in Aboriginal and Torres Strait Islander people, brings together the relevant sources of routinely collected data on vaccine preventable diseases--notifications, hospitalisations, deaths, and childhood and adult vaccination coverage. As a result of continued improvements in the collection of data on Indigenous status, this second report is considerably more comprehensive, with data available from more jurisdictions, and more detailed presentation, including time trends and vaccination coverage by jurisdiction. Vaccination coverage data provide evidence of successful program delivery and highlight some areas for improvement. For universally funded vaccines in children, coverage is similar in Indigenous and non-Indigenous children by 24 months of age. However, delayed vaccination is more common in Indigenous children, with 6%-8% fewer children fully vaccinated at 12 months of age. More timely vaccination, particularly within the first six months of life, is particularly important in reducing the disproportionate burdens of disease due to pertussis and Haemophilus influenzae type b (Hib). For vaccination programs targeted specifically at Aboriginal and Torres Strait Islander children and adults, coverage is substantially lower than for those programs targeted at all Australians. This is true for hepatitis A and polysaccharide pneumococcal vaccine for children, and influenza and polysaccharide pneumococcal vaccine for adults. Targeted vaccination programs present a particular challenge for health services in urban areas. Nevertheless, the impact of vaccination programs in preventing disease and reducing the disparity of disease burden between Aboriginal and Torres Strait Islander and non-Indigenous people has been substantial. This is evident in data on notifications, hospitalisations and deaths. Diseases which, in the past, have had devastating and often disproportionately high impact on Indigenous people, such as diphtheria, measles, poliomyelitis, smallpox and tetanus, are now completely or almost completely absent from Australia. Hepatitis B infection, another disease responsible for high levels of infection and substantial serious illness and death in the pre-vaccine era, is also now well controlled in age groups eligible for vaccination. Although invasive Hib disease is now rare in Australia since the introduction of vaccination in 1993, higher rates of disease persist in Aboriginal and Torres Strait Islander children. More research is needed into the contribution of environmental factors, delayed vaccination and vaccine failure to this continued disparity. Hepatitis A has disproportionately affected Aboriginal and Torres Strait Islander children in the past. Vaccination programs in north Queensland and in various other countries have been very successful in reducing the burden of hepatitis A. It is too early to assess the impact of the vaccination program for Aboriginal and Torres Strait Islander children that commenced in regions outside north Queensland in November 2005. For some other diseases the situation is more complicated. The substantial impact of the national meningococcal C vaccination program since 2003 is evident in this report, although the higher proportion of non-vaccine preventable serotype B disease in Aboriginal and Torres Strait Islander people underlines the need for a new vaccine to cover this serotype. Pneumonia remains the most important communicable disease contributor to premature mortality in Aboriginal and Torres Strait Islander people of all ages. In young Indigenous adults, the eightfold higher rate of hospitalisation compared with their non-Indigenous peers, and the 11-fold higher rate of invasive pneumococcal disease, suggest the need for more widespread use of influenza and pneumococcal vaccines in this age group. Current coverage for Indigenous 15-49 year olds, where influenza and pneumococcal vaccines are funded only for those with risk factors, is low even though some 70% of this age group have one or more risk factors. Overall, the data presented in this report provide powerful evidence for the impact of vaccines in reducing disease in Aboriginal and Torres Strait Islander people, and also point to areas for further improvement. Immunisation programs are an example of how preventive health programs in general can be enhanced to close the gap in morbidity and mortality between Indigenous and non-Indigenous Australians.

Matthews GV, Dore GJ. · Viral Hepatitis Program, National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, New South Wales, Australia. · J Gastroenterol Hepatol. · Pubmed #18707597 No free full text.

Abstract: The significant burden of HIV/hepatitis C virus (HCV) coinfection is increasingly recognized worldwide, and in particular within the Asia-Pacific region. Individuals who are coinfected with both viruses are at risk from accelerated liver disease and consequently cirrhosis, liver failure, and hepatocellular carcinoma. In addition, coinfected individuals may have altered immunological responses to HAART and are at increased risk of highly active antiretroviral therapy (HAART)-related hepatotoxicity. Treatment for HCV infection in HIV-infected individuals is with standard pegylated interferon and ribavirin therapy, and all HIV/HCV coinfected subjects should undergo suitability for HCV treatment assessment. Response rates to HCV therapy are generally 10-15% lower than in HCV monoinfection, and therapy may be complicated by issues of drug interactions and significant toxicity. However, greater understanding of baseline factors can contribute to better prediction of treatment outcome, and monitoring of on-treatment virological responses increasingly allows individualization of therapy. Where possible, treatment of HCV is often advisable before HAART is required to avoid the issues of drug interactions on HCV therapy and the risk of HAART-related hepatotoxicity. Early diagnosis of both HIV and HCV infection is essential to most effectively manage HIV-HCV-coinfected individuals. New therapies, including HCV protease and polymerase inhibitors, are in development and may widen therapeutic options for HIV-HCV-coinfected individuals into the future.

Danta M, Dusheiko GM. · St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Australia. · Curr Pharm Des. · Pubmed #18673193 No free full text.

Abstract: HCV/HIV co-infection is a major public health problem with between 10-25% of HIV-positive individuals infected with HCV. Following the introduction of effective HIV therapies, HCV has become a leading cause of morbidity and mortality in the HIV population. Since the early 2000s, there has been a marked rise in the diagnosis of acute HCV in HIV-positive populations. Cohorts have been reported in Europe, USA and Australia. Molecular studies have revealed multiple HCV variants circulating within the HIV-positive men who have sex with men (MSM) population. There is also evidence of a large international transmission network, particularly in Europe. Significantly, permucosal rather than percutaneous risk factors related to high-risk traumatic sexual and drug factors have been associated with transmission. This has important implications for public health interventions aimed at mitigating the spread of HCV. HIV also impacts the early cell-mediated immunological responses to HCV, leading to higher rates of persistence. Data now exists supporting early treatment of these individuals with combination pegylated interferon and ribavirin. This epidemic has come about as a result of significant change in patient behavioural risk factors and these factors need to be the focus of a concerted effort on the part of public health specialist, clinicians and HIV-positive individuals themselves at a national and international level. Acute HCV in HIV-positive individuals differs significantly from acute HCV mono-infection in its epidemiology, natural history, immunology and virology and is becoming an increasingly significant problem in the HIV community. This will be the focus of this review article.

Sitas F, Parkin DM, Chirenje M, Stein L, Abratt R, Wabinga H. · Research Division, The Cancer Council New South Wales, Australia. · Lancet Oncol. · Pubmed #18672214 No free full text.

Abstract: Africa has contributed substantial knowledge to the understanding of certain risk factors for cancer, such as the role of several infectious agents (eg, viruses, bacteria, and parasites), aflatoxins, and certain lifestyle factors. Although the relative importance of many lifestyle factors is becoming better understood in developed countries, more work is needed to understand the importance of these factors in different African settings. In view of the substantial genetic diversity in Africa, it would be prudent not to generalize too widely from one place to the next. We argue that risks for several exposures related to certain cancers differ from the patterns seen in developed countries. In this paper, we review the current knowledge of causes of some of the leading cancers in Africa, namely cancers of the cervix, breast, liver, prostate, stomach, bladder, and oesophagus, Kaposi's sarcoma, non-Hodgkin lymphoma, and tobacco-related cancers. There are no comprehensive cancer-control programmes in Africa and provision of radiotherapy, chemotherapy, and palliation is inadequate. Certain cost-effective interventions, such as tobacco control, provision of antiretroviral therapy, and malarial and bilharzial control, can cause substantial decreases in the burden of some of these cancers. Vaccinations against hepatitis B and oncogenic human papilloma viruses can make the biggest difference, but very few countries in Africa can afford these vaccines without substantial subsidization.

Wang L, Coppel RL. · Department of Microbiology, Monash University, Clayton, Victoira 3800, Australia. · Expert Rev Vaccines. · Pubmed #18665772 No free full text.

Abstract: Vaccination is an efficient and cost-effective form of preventing infectious diseases. However, most currently available vaccines are delivered by injection, which makes mass immunization more costly and less safe, particularly in resource-poor developing countries. Oral vaccines have several attractive features compared with parenteral vaccines, but studies on their use have been limited almost exclusively to protection against mucosally transmitted pathogens. Their potential for controlling non-mucosally transmitted diseases has not yet been appreciated in general. In this article, we provide evidence that oral immunization is a feasible alternative for preventing infections transmitted through non-mucosal routes, including infections such as malaria, Japanese encephalitis and hepatitis B. Although there are still hurdles to overcome before such approaches can be deployed widely, recent progress in the oral vaccination field and the availability of a range of delivery systems offers hope for the development of a larger number of oral vaccines.

Jonsson JR, Purdie DM, Clouston AD, Powell EE. · School of Medicine, Southern Division, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland, Australia. · Mol Diagn Ther. · Pubmed #18652517 No free full text.

Abstract: Infection with hepatitis C virus (HCV) is a major cause of chronic liver disease. Hepatic fibrosis may develop in subjects with chronic HCV infection, culminating in cirrhosis and an increased risk of hepatocellular carcinoma. The rate of development of fibrosis varies substantially between individuals; while it is influenced by a number of demographic and environmental factors, these account for only a small proportion of the variability.There are no clinical markers or tests that predict the rate of fibrosis progression in an individual subject. Thus, there has been increasing interest in the influence of host genetic factors on the rate of disease progression, and whether a genetic signature can be developed to reliably identify individuals at risk of severe disease. Numerous case-control, candidate gene, allele-association studies have examined the relationship between host single nucleotide polymorphisms or other genetic mutations and fibrosis in patients with chronic HCV infection. However, these studies have generally been irreproducible and disappointing. As seen with genetic studies for other diseases, small study cohorts and poor study design have contributed to limited meaningful findings. The successful determination of genetic signatures for fibrosis progression in chronic HCV will require multicenter collaborations using genome-wide association studies, with large, phenotypically well-defined sample sets. While these studies will require a significant financial commitment, a successful outcome offers the potential for personalized therapy and better patient management.

Mackay IR. · Department of Biochemistry and Molecular Biology, Monash University, Clayton Victoria 3800, Australia. · World J Gastroenterol. · Pubmed #18528926 links to  free full text

Abstract: Autoimmune hepatitis (AIH), initially known as chronic active or active chronic hepatitis (and by various other names), first came under clinical notice in the late 1940s. However, quite likely, chronic active hepatitis (CAH) had been observed prior to this and was attributed to a persistently destructive virus infection of the liver. An earlier (and controversial) designation in 1956 as lupoid hepatitis was derived from associated L.E. cell test positivity and emphasized accompanying multisystem features and immunological aberrations. Young women featured prominently in early descriptions of CAH. AIH was first applied in 1965 as a descriptive term. Disease-characteristic autoantibodies were defined from the early 1960s, notably antinuclear antibody (ANA), smooth muscle antibody (SMA) and liver-kidney microsomal (LKM) antibody. These are still widely used diagnostically but their relationship to pathogenesis is still not evident. A liver and disease specific autoantigen has long been searched for but unsuccessfully. Prolonged immunosuppressive therapy with predisolone and azathioprine in the 1960s proved beneficial and remains standard therapy today. AIH like many other autoimmune diseases is associated with particular HLA alleles especially with the "ancestral" B8, DR3 haplotype, and also with DR4. Looking forwards, AIH is one of the several enigmatic autoimmune diseases that, despite being (relatively) organ specific, are marked by autoimmune reactivities with non-organ-specific autoantigens. New paradigms are needed to explain the occurrence, expressions and pathogenesis of such diseases.

Cook IF. · University of Newcastle, Discipline of General Practice, School of Medical Practice and Population Health University Drive Callaghan, NSW 2308, Australia. · Vaccine. · Pubmed #18524433 No free full text.

Abstract: It has been contended that limited data exist on sex-difference in immune response with vaccines in humans. However, a comprehensive search of the literature retrieved 97 studies with 14 vaccines influenza (7 studies), hepatitis A (15 studies), hepatitis B (50 studies), pnuemococcal polysaccaride (4 studies), diphtheria (4 studies), rubella (3 studies), measles (2 studies), yellow fever (3 studies), meningococcal A (1 study), meningococcal C (1 study), tetanus (1 study), brucella (1 study), Venezuelan equine encephalitis (1 study) and rabies (4 studies), with sex-difference in humoral (antibody) response. These differences are associated with sex-difference in the clinical efficacy of influenza, hepatitis A, hepatitis B, pneumococcal polysaccharide and diphtheria vaccines and significant adverse reactions with rubella, measles and yellow fever vaccines. The genesis of these differences is uncertain but not entirely related to gonadal hormones (differences are seen in pre-pubertal and post-menopausal subjects not on hormone replacement therapy) or female sex (males had greater serological response for pneumococcal, diphtheria, yellow fever, Venezuelan equine encephalitis and in some studies with rabies vaccine. As sex-difference in humoral immune response was seen with most vaccines which cover the spectrum of mechanisms by which infectious agents cause disease (mucosal replication, viral viraemia, bacterial bacteraemia, toxin production and neuronal invasion), it is mandatory that vaccine trialists recruit a representative sample of females and males to be able to assess sex-differences which may have clinical implications.

Desmond CP, Bartholomeusz A, Gaudieri S, Revill PA, Lewin SR. · Department of Gastroenterology, Alfred Hospital, Melbourne, Australia. · Antivir Ther. · Pubmed #18505168 No free full text.

Abstract: BACKGROUND: The immune response to hepatitis B virus (HBV) is important for both viral control and disease pathogenesis. A detailed understanding of the HBV-specific T-cell responses may potentially lead to novel therapeutic strategies for HBV. METHODS: All English language journal articles (including articles in press) up to October 2007 were retrieved using searches of MEDLINE, EMBASE and the Cochrane Controlled Trial Registry. An extensive database of HBV sequences (SeqHepB) and GenBank were used to assess the degree of sequence variation in each epitope. The new standardized nomenclature for HBV amino acid position number was applied to all previously defined epitopes. RESULTS: Forty-four HBV-specific human leukocyte antigen (HLA) class I restricted and 32 HBV-specific HLA class II restricted epitopes have been defined and have been identified in all HBV genes. The majority of HLA class I restricted epitopes have been defined in HLA-A2-positive individuals in the setting of acute HBV infection. There is significant sequence variation of these epitopes within and between HBV genotypes. Newer HBV immunotherapeutics appear promising but are still in early phases of development. CONCLUSIONS: Identification of HBV-specific epitopes in non-HLA-A2-positive individuals and recognition of genotypic variation across epitopes are important for the future development of novel immunotherapeutic strategies for the management of chronic HBV infection.

Urosevic N, Martins RN. · Sir James McCusker Alzheimer Disease Research Unit, School of Psychiatry and Clinical Neurosciences, The University of Western Australia, Australia. · J Alzheimers Dis. · Pubmed #18487850 No free full text.

Abstract: Microorganisms, bacteria and viruses may infect and cause a range of acute and chronic diseases in humans dependent on the genetic background, age, sex, immune and health status of the host, as well as on the nature, virulence and dose of infectious agent. Late onset Alzheimer's disease (AD) is a progressive neurodegenerative illness of broad aetiology with a strong genetic component and a significant contribution of age, sex and life style factors. Both infectious diseases and AD are characterised by an increased production of an array of immune mediators, cytokines, chemokines and complement proteins by the host cells as well as by changes in the host lipid metabolism. In this review, we re-examine a dangerous liaison between several viral and bacterial infections and the most significant genetic factor for AD, APOE epsilon4, and the possible impact of this alliance on AD development. This connection was discussed in the broader context of lipid metabolism and in the light of different capacity of various infectious agents, their toxic lipophilic products and host lipoprotein particles for binding to cell receptor(s).

Farrell GC, Teoh NC, McCuskey RS. · Gastroenterology and Hepatology Unit, and Australian National University Medical School, The Canberra Hospital, Garran, Australia. · Anat Rec (Hoboken). · Pubmed #18484615 links to  free full text

Abstract: Nonalcoholic fatty liver disease (NAFLD), the most common cause of steatosis, is associated with visceral obesity and insulin resistance. With more severe risk factors (obesity, type 2 diabetes [T2D], metabolic syndrome), steatosis may be complicated by hepatocellular injury and liver inflammation (steatohepatitis or NASH). NASH can lead to perisinusoidal fibrosis and cirrhosis. Fat-laden hepatocytes are swollen, and in steatohepatitis, further swelling occurs due to hydropic change (ballooning) of hepatocytes to cause sinusoidal distortion, as visualized by in vivo microscopy, reducing intrasinusoidal volume and microvascular blood flow. Involvement of other cell types (sinusoidal endothelial cells, Kupffer cells, stellate cells) and recruitment of inflammatory cells and platelets lead to dysregulation of microvascular blood flow. In animal models, the net effect of such changes is a marked reduction of sinusoidal space (approximately 50% of control), and a decrease in the number of normally perfused sinusoids. Such microvascular damage could accentuate further liver injury and disease progression in NASH. The fatty liver is also exquisitely sensitive to ischemia-reperfusion injury, at least partly due to the propensity of unsaturated fatty acids to undergo lipid peroxidation in the face of reactive oxygen species (ROS). This has important clinical consequences, particularly limiting the use of fatty donor livers for transplantation. In this review, we discuss available data about the effects of steatosis and steatohepatitis on the hepatic microvascular structure and sinusoidal blood flow, highlighting areas for future investigation.