Hepatitis: Australia

Holz LE, McCaughan GW, Benseler V, Bertolino P, Bowen DG. · AW Morrow Gastroenterology and Liver Centre, Centenary Institute, Locked Bag No. 6, Newtown, NSW 2042, Australia. · Inflamm Allergy Drug Targets. · Pubmed #18473895 No free full text.

Abstract: In recent years it has become apparent that the liver holds a distinct immunological position. Previously described as a "graveyard" for T cells activated in the periphery, emerging evidence indicates that this organ may have a more active role in mediating tolerance. Attenuated immune responses in the liver can be beneficial in the transplantation setting, as liver transplants are more readily accepted than other organ allografts even in the absence of immunosuppressive drugs. However, the ability of the liver to induce immunological unresponsiveness could be exploited by some pathogens, such as the hepatitis C virus (HCV), to establish chronic infections with potentially fatal outcomes. Understanding the mechanisms controlling the balance between intrahepatic tolerance and immunity is critical in order to design new strategies to enhance acceptance of solid organ allografts and to promote efficient immune responses against HCV. In this article, we will review current knowledge of the mechanisms regulating intrahepatic immunity and discuss how these mechanisms might potentially be targeted to achieve advantageous clinical outcomes in transplantation and persistent hepatotropic infections.

Iser DM, Sasadeusz JJ. · Department of Gastroenterology, St. Vincent's Hospital, and Infectious Diseases Unit, Alfred Hospital, Melbourne, Victoria, Australia. · J Gastroenterol Hepatol. · Pubmed #18410604 No free full text.

Abstract: Coinfection with HIV and hepatitis B virus (HBV) has become a significant global health problem. Liver disease is now one of the leading causes of morbidity and mortality in individuals with HIV, particularly those with viral hepatitis. There are a number of agents available with dual activity against HIV and HBV, and effective treatment depends on understanding the potential advantages and pitfalls in using these agents. There are a number of unresolved issues in the management of HIV/HBV coinfection. These include the role of liver biopsy, the significance of normal aminotransferase levels, serum HBV DNA threshold for treatment, treatment end-points, and the treatment of HBV when HIV does not yet require treatment. Treatment of HBV should be considered in individuals with HIV/HBV coinfection with evidence of significant fibrosis (>/=F2), or with elevated serum HBV DNA levels (>2000 IU/mL). Sustained suppression of serum HBV DNA to below the level of detection by the most sensitive available assay should be the goal of therapy, and, at present, treatment of HBV in HIV/HBV coinfection is lifelong. If antiretroviral therapy is required, then two agents with anti-HBV activity should be incorporated into the regimen. If antiretroviral therapy is not required, then the options are pegylated interferon, adefovir or the early introduction of antiretroviral therapy. Close monitoring is necessary to detect treatment failure or hepatic flares, such as immune reconstitution disease. Further studies of newer anti-HBV agents in individuals HIV/HBV coinfection may advance treatment of this important condition.

Locarnini S, Warner N. · Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria, Australia. · Antivir Ther. · Pubmed #18284179 No free full text.

Abstract: The two key events in the life-cycle of the hepatitis B virus (HBV) involve (1) the generation from viral genomic DNA of the covalently closed circular DNA transcriptional template, and (2) the reverse transcription of the viral pregenomic RNA to form the HBV DNA genome. Diversity in the HBV genome is ensured by the low fidelity of the viral reverse transcriptase (rt). Particular selection pressures such as antiviral therapy readily select out escape mutants from this pre-existing quasispecies pool. Antiviral drug resistance in chronic hepatitis B can be caused by many factors, including the viral mutation frequency, the intrinsic mutability of the antiviral target site, the selective pressure exerted by the drug, the magnitude and rate of virus replication, the overall replication fitness of the mutant, the genetic barrier of the compound and the availability of replication space. In the setting of HIV coinfection, the rate of replication is increased by one to two orders of magnitude, accelerating the emergence of drug resistance in this setting. The HBV genome is arranged into frame-shifted and overlapping reading frames in such a manner that antiviral drug-resistance-associated changes in the rt can result in changes in the viral envelope protein. These HBV isolates with altered surface antigens exhibit reduced binding of specific and neutralizing antibody and so have diagnostic and public health implications, especially in the setting of HIV coinfection where the risk of transmission is increased. Thus, prevention of resistance requires the adoption of strategies that effectively control virus replication, including the use of combination chemotherapy.

Harbour S, Sutton P. · Centre for Animal Biotechnology, School of Veterinary Science, University of Melbourne, Melbourne, VIC 3010, Australia. · Vet Immunol Immunopathol. · Pubmed #18243338 No free full text.

Abstract: The initial discovery that the human stomach is commonly infected by the bacterium Helicobacter pylori subsequently resulted in the identification of a whole new family of pathogenic bacteria. In less than 25 years, the Helicobacter genus has grown from obscurity to number at least 38 different species with many more awaiting classifications. These bacteria, many of which are either direct or opportunistic pathogens, are present in virtually every mammalian species examined, and have also now been identified in a number of birds. The pathogenesis associated with these infections is predominantly the result of a chronic inflammatory response mounted by the host against the infection. This is typically a Th1-driven response which can result in a range of conditions from hepatitis, through gallstones to cancer. In some cases the inflammatory response to these infections is normally well managed by the host and disease only results when there is a breakdown or misbalance in the immunoregulatory process, which for example can result in inflammatory bowel disease in experimental models. Understanding the disease association and pathogenic mechanisms of the different Helicobacter infections is clearly of potential significance not only from an animal welfare point of view but also from the growing realisation of how commonly transmission of Helicobacter occurs between different mammals, including pathogenic zoonotic infections of humans.

Viebahn CS, Yeoh GC. · School of Biomedical, Biomolecular and Chemical Sciences, The University of Western Australia, 35 Stirling Highway, M310, Crawley, WA 6009, Australia. · Int J Biochem Cell Biol. · Pubmed #18207446 No free full text.

Abstract: Liver progenitor cells (LPCs) play a major role in the regeneration process after chronic liver damage, giving rise to hepatocytes and cholangiocytes. Thus, they provide a cell-based therapeutic alternative to organ transplant, the current treatment of choice for end-stage liver disease. In recent years, much attention has focused on unravelling the cytokines and growth factors that underlie this response. Liver regeneration following acute damage is achieved by proliferation of mature hepatocytes; yet similar cytokines, most related to the inflammatory process, are implicated in both acute and chronic liver regeneration. Thus, many recent studies represent attempts to identify LPC-specific factors. This review summarises our current understanding of LPC biology with a particular focus on the liver inflammatory response being associated with the induction of LPCs in the liver. We will describe: (i) the pathways of liver regeneration following acute and chronic damage; (ii) the similarities and differences between the two pathways; (iii) the liver inflammatory environment; (iv) the unique features of liver immunology as well as (v) the interactions between liver immune cells and LPCs. Combining data from studies on the LPC-driven regeneration process with the knowledge in the field of liver immunology will improve our understanding of the LPC response and allow us to regulate these cells in vivo and in vitro for future therapeutic strategies to treat chronic liver disease.

Mackay IR, Leskovsek NV, Rose NR. · Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia. · J Autoimmun. · Pubmed #18194728 links to  free full text

Abstract: In April 2007, an international Colloquium bridging scientific and clinical disciplines was held to discuss the role of cellular and tissue damage in the initiation, development and persistence of autoimmune disease. Five potential etiologic and pathophysiologic processes fundamental to autoimmune disease (i.e. inflammation, infection, apoptosis, environmental exposure and genetics) were the focus of the presentations and integrative discussions at the Colloquium. The information presented on these topics is condensed in this review. Inflammation has close clinico-pathologic associations with autoimmunity, but future analyses will require better definition and metrics of inflammation, particularly for the earliest cellular and molecular components dependent on recruitment of elements of innate immunity. Although infection may be associated with increased levels of autoantibodies, most infections and virtually all vaccinations in humans lack well-established links to autoimmune diseases. Further application of well-designed, long-term epidemiologic and population-based studies is urgently needed to relate antecedent exposures with later occurring stigmata of autoimmunity with a goal of discerning potentially susceptible individuals or subpopulations. Suspect infections requiring closer interrogation include EB virus (SLE and other diseases), HCV (autoimmune hepatitis), beta hemolytic streptococci (rheumatic carditis) and Helicobacter pylori (autoimmune gastritis) among others. And even if a micro-organism was to be incriminated, mechanisms of initiation/perpetuation of autoimmunity continue to challenge investigators. Plausible mechanisms include potentiation and diversion of innate immunity; exposure or spillage of intracellular autoantigens; or provision of autoantigenic mimics. Integrity of apoptosis as a critical safeguard against autoimmunity was discussed in the contexts of over-reactivity causing autoantigens to gain enhanced exposure to the immune system, or under-reactivity producing insufficient elimination of autoreactive clones of lymphocytes. Although environmental agents are widely believed to serve as necessary "triggers" of autoimmune disease in genetically predisposed individuals, only a few such agents (mainly drugs and some nutrients) have been clearly identified and their mechanism of action defined. Finally an essential genetic foundation underlies all these hazards for autoimmunity in the form of risk-associated polymorphisms in immunoregulatory genes. They may be predictive of future or impending disease.

Leggat PA, Kedjarune U, Smith DR. · Anton Breinl Centre for Public Health and Tropical Medicine, James Cook University, Townsville, Queensland, Australia. · Ind Health. · Pubmed #18057804 links to  free full text

Abstract: Despite numerous technical advances in recent years, many occupational health problems still persist in modern dentistry. These include percutaneous exposure incidents (PEI); exposure to infectious diseases (including bioaerosols), radiation, dental materials, and noise; musculoskeletal disorders; dermatitis and respiratory disorders; eye injuries; and psychological problems. PEI remain a particular concern, as there is an almost constant risk of exposure to serious infectious agents. Strategies to minimise PEI and their consequences should continue to be employed, including sound infection control practices, continuing education and hepatitis B immunisation. As part of any infection control protocols, dentists should continue to utilise personal protective measures and appropriate sterilisation or other high-level disinfection techniques. Aside from biological hazards, dentists continue to suffer a high prevalence of musculoskeletal disorders (MSD), especially of the back, neck and shoulders. To fully understand the nature of these problems, further studies are needed to identify causative factors and other correlates of MSD. Continuing education and investigation of appropriate interventions to help reduce the prevalence of MSD and contact dermatitis are also needed. For these reasons, it is therefore important that dentists remain constantly informed regarding up-to-date measures on how to deal with newer technologies and dental materials.

Frazer IH, Lowy DR, Schiller JT. · Diamantina Institute for Cancer Immunology and Metabolic Medicine, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia. · Eur J Immunol. · Pubmed #17972339 No free full text.

Abstract: Persistent infection by several microbial agents is responsible for at least 15% of cancer globally, including most cancers of the liver, stomach, and cervix. The recent development of vaccines that can prevent infection and premalignant disease caused by human papillomaviruses (HPV), which cause virtually all cases of cervical cancer as well as some other cancers, has focused renewed attention on infection control as a means of reducing the global cancer burden. For vaccines to prevent cancer-causing infection with hepatitis C virus, Helicobacter pylori, or Epstein Barr virus, new vaccine technologies to induce more effective protective responses are required. For the two available cancer control vaccines, designed to prevent infection with HPV and hepatitis B virus, the major challenge is to promote effective vaccine deployment through education programs and increased affordability/accessibility for underserved populations, particularly in the developing world, where the cancer burden attributable to infection by these two viruses is greatest.

Poumbourios P, Drummer HE. · Viral Fusion Laboratory, Macfarlane Burnet Institute for Medical Research and Public Health Limited, Melbourne, Australia. · Antivir Chem Chemother. · Pubmed #17907376 No free full text.

Abstract: Improvements to antiviral therapies for the treatment of hepatitis C virus (HCV) infections will require the use of multiple drugs that target viral proteins essential for replication. The discovery of anti-HCV compounds has been severely hampered by the lack of cell culture replication systems. Since the late 1990s, the advent of sub-genomic replicons that model the intracellular events leading to HCV genome replication have enabled the discovery of HCV protease and polymerase inhibitors, but did not allow the study of HCV entry or entry inhibitors. More recently, retroviral pseudotyping of the viral glycoproteins and the development of a cell culture-based system that recapitulates the entire HCV replication cycle were achieved. These new experimental systems have enabled a rapid advance in our knowledge of how HCV glycoproteins, E1 and E2, mediate receptor binding and viral entry. These systems have facilitated the discovery of a range of viral receptors. Evidence is emerging that CD81, scavenger receptor class B type I, claudin-1 and the low-density lipoprotein receptor are involved in viral entry. In addition, DC-SIGN and L-SIGN may function to internalize virus into dendritic or endothelial cells, facilitating the transport of virions to sites of infection such as the liver. This review focuses on the interaction between the HCV glycoproteins and cellular receptors, and our current understanding of the viral entry pathway. In addition, key questions on the role that these receptors play in viral entry are raised and potential avenues for the discovery of new antiviral agents are highlighted.

Hickman IJ, Macdonald GA. · Diamantina Institute for Cancer, Immunology and Metabolic Medicine, Princess Alexandra Hospital, Brisbane, Queensland, Australia. · Am J Med. · Pubmed #17904449 No free full text.

Abstract: The prevalence of type 2 diabetes is higher in patients who have liver diseases, such as nonalcoholic fatty liver disease, chronic viral hepatitis, hemochromatosis, alcoholic liver disease, and cirrhosis. The development of diabetes in patients with cirrhosis is well recognized, but evidence is emerging that the development of chronic liver disease and progression to cirrhosis may occur after the diagnosis of diabetes and that diabetes plays a role in the initiation and progression of liver injury. This article provides an overview of the evidence for an increased prevalence of diabetes in a range of liver diseases; the effect of diabetes on the severity of disease; the potential mechanisms whereby coexistent diabetes exacerbates progression of hepatic fibrosis; and the impact of obesity, insulin resistance, and type 2 diabetes on clinical outcomes.

Lubel JS, Testro AG, Angus PW. · Victorian Liver Transplant Unit, Department of Gastroenterology, Austin Health, Heidelberg, Victoria, Australia. · Intern Med J. · Pubmed #17894766 No free full text.

Abstract: It is well known that immunosuppressive drugs or cancer chemotherapy can stimulate replication of hepatitis B virus (HBV) and precipitate severe flares of HBV infection. The risk of this syndrome of 'reactivation hepatitis B' is highest in haematopoietic stem cell or solid organ transplant recipients and in those undergoing chemotherapy for haematological malignancies; however, it has been described following almost any form of immunosuppressive treatment. Fortunately, it can be largely prevented by prophylactic therapy with oral anti-HBV nucleoside/nucleotide analogues. Importantly, chronic HBV infection is usually asymptomatic, and most patients at risk are likely to be unaware that they carry the infection. Thus, the key to avoiding this potentially fatal complication of immunosuppressive treatment is to ensure that all patients at risk of chronic HBV infection are screened for the disease before commencing immunosuppressive treatment or chemotherapy.

Benson J, Donohue W. · Health in Human Diversity Unit, Discipline of General Practice, University of Adelaide, and Migrant Health Service, Tullawon Health Service Yalata Community and Parklands Medical Practice, South Australia, Australia. · Aust Fam Physician. · Pubmed #17885706 links to  free full text

Abstract: BACKGROUND: The World Health Organisation estimates that 2 billion people have been infected with hepatitis B and about 180 million people infected with hepatitis C worldwide. More than 350 million have chronic hepatitis B and 130 million have chronic hepatitis C infection. Most infections of hepatitis B and C are from unsafe injection practices, both medical and nonmedical; from household contacts; or, in the case of hepatitis B, from 'vertical' transmission from mother to child. OBJECTIVE: This article discusses screening and management of hepatitis B and C in refugees who settle in Australia. DISCUSSION: Most people carrying hepatitis will be asymptomatic with infection detected by screening. Refugees need counselling, education and support to come to terms with the implications of hepatitis B and C for both themselves and their families. In Australia both viruses can be treated in those with active infection and general practitioners can be involved in diagnosis, follow up and shared care management.

Batey RG. · Drug and Alcohol Clinical Services, Hunter New England Area Health Services, Newcastle, New South Wales, Australia. · World J Gastroenterol. · Pubmed #17696244 links to  free full text

Abstract: Discovered in 1989, the hepatitis C virus (HCV) continues to cause significant morbidity and mortality world-wide despite a huge research commitment to defining and understanding the virus and the disease it causes. This paper discusses a number of areas where progress in the management of the HCV have not kept pace with the scientific understanding of the HCV. It is suggested that in the fields of HCV prevention and providing access to treatment, practice falls short of what could be achieved. The role of alcohol in the pathogenesis of HCV liver injury is discussed. Discrimination against those with HCV infection and particularly those in prison settings fails to match good clinical practice. The complicated processes of sharing information between specialty groups is also discussed in an attempt to optimise knowledge dissemination in this field.

Bowden DS, Berzsenyi MD. · Victorian Infectious Diseases Reference Laboratory, and Department of Microbiology, Monash University, Clayton, Carlton South, Victoria, Australia. · Future Microbiol. · Pubmed #17661689 No free full text.

Abstract: Chronic hepatitis C virus (HCV) infection is a worldwide public health problem with a global prevalence of 2%. A high proportion of those infected are at risk of developing cirrhosis and hepatocellular carcinoma and modeling data predicts that the burden of disease could soon increase substantially. The liver disease associated with chronic infection has led investigators to look for correlates between viral properties and disease progression, severity of disease and the response to antiviral therapy. HCV has been classified into six genotypes but genotype does not appear to influence disease presentation or severity of disease. However, genotype has been identified as a major predictor of response to interferon-based antiviral therapy. Antiviral regimens have been optimized for infections with HCV genotypes 1-4, although treatment strategies for genotypes 5 and 6 have yet to be developed. The molecular basis for the differences in response of HCV genotypes has yet to be determined.

Duggan JM, Duggan AE. · Princeton Medical Centre, Newcastle, New South Wales, Australia. · Med J Aust. · Pubmed #17605704 links to  free full text

Abstract: Although early studies of hepatitis C indicated this is a serious disease, more recent evidence shows it can be relatively benign. A major determinant of hepatitis C prognosis is alcohol consumption. Promotion of alcohol abstinence among people with hepatitis C could result in substantial reductions in morbidity, mortality and treatment costs.

Clements AC, Pfeiffer DU, Martin V, Otte MJ. · Epidemiology Division, Department of Veterinary Clinical Sciences, Royal Veterinary College, University of London, Hatfield, Hertfordshire, United Kingdom. · Prev Vet Med. · Pubmed #17570545 No free full text.

Abstract: Rift Valley fever (RVF) epidemics have serious consequences for human and animal health and the livestock trade. Recent epidemics have occurred in previously unaffected regions, increasing concerns that the geographical range of RVF will continue to expand. We conducted an extensive, systematic review of the literature to obtain serological data for RVF in Africa, collected between 1970 and 2000 from human, livestock and wild ungulate populations. Aims were to calculate sub-national estimates of RVF infection prevalence and to define areas where no information was available. We presented the data (aggregated at the first administrative level of countries) using a geographical information system. Data from 71 publications were used to build a spatially explicit Bayesian logistic-regression model, with spatial and non-spatial random effects, allowing us to identify clusters of high and low RVF seroprevalence, and fixed effects that described the disparate nature of the survey subjects and methods. Significant high-prevalence clusters encompassed areas that had experienced epidemics during the late 20th century and significant low-prevalence clusters were located in contiguous areas of Western and Central Africa.

Phillips CB, Benson J. · Social Foundations of Medicine, Medical School, College of Medicine and Health Sciences, Australian National University, Australia. · Aust Fam Physician. · Pubmed #17565403 links to  free full text

Abstract: BACKGROUND: Many newly arrived refugees come from countries with fragile primary health infrastructure. As a result they may have had patchy primary immunisation against vaccine preventable diseases. OBJECTIVE: This article outlines key considerations in developing an effective catch up immunisation program for refugees. DISCUSSION: The potential challenges include knowing which vaccines to give to provide catch up vaccination, access to appropriate vaccines through public health units, and adequate follow up to support completion of immunisation courses. The most useful immunisations for adolescent and adult refugees are adult diphtheria/tetanus, measles/mumps/rubella, inactivated polio, and hepatitis B vaccines. Immunisation programs for refugees require cooperation between primary health care practitioners and health policy makers to ensure that good primary health care is available to the most vulnerable groups arriving in Australia.

Clouston AD, Jonsson JR, Powell EE. · School of Medicine, Southern Division, The University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland, Australia. · Clin Liver Dis. · Pubmed #17544978 No free full text.

Abstract: As obesity prevalence rises, there is evidence that fatty liver disease can act synergistically with other chronic liver diseases to aggravate parenchymal injury. This is characterized best in chronic hepatitis C, where steatosis is caused by viral and metabolic effects. There is evidence that steatosis and its metabolic abnormalities also exacerbate other diseases, such as alcoholic liver disease, hemochromatosis, and, possibly, drug-induced liver disease. The pathogenesis seems related to increased susceptibility of steatotic hepatocytes to apoptosis, enhanced oxidative injury, and altered hepatocytic regeneration. Data suggest that active management of obesity may improve liver injury and decrease the progression of fibrosis in patients who have other chronic liver diseases.

Dixon JB. · Australian Centre for Obesity Research and Education, Monash University, Alfred Hospital, Melbourne, Victoria, Australia. · Clin Liver Dis. · Pubmed #17544976 No free full text.

Abstract: Non-alcoholic steatohepatitis (NASH) in obese and severely obese populations is associated with the metabolic syndrome, with features of the syndrome predicting those who will have NASH rather than simple steatosis, a more benign form of non-alcoholic fatty liver disease. Substantial weight loss is proving the most effective therapy for obesity-related conditions. Improvements have seen the development of less invasive procedures. There is growing evidence that laparoscopic adjustable gastric banding and roux-en-Y gastric bypass provide effective therapy.

London RM, George J. · Westmead Millennium Institute, Storr Liver Unit, Westmead, NSW 2145, Australia. · Clin Liver Dis. · Pubmed #17544972 No free full text.

Abstract: The incidence of non-alcoholic steatohepatitis, a disorder linked to visceral adiposity, insulin resistance, dyslipidemia, and type 2 diabetes mellitus, is increasing with the rise in the prevalence of the metabolic syndrome. This review focuses on animal models of steatohepatitis currently used to study (1) the mechanisms regulating hepatic lipid, glucose, and cholesterol homeostasis and (2) inflammatory recruitment and fibrogenesis in the steatotic liver. The ultimate aim of this research is to gain insights into the role of hepatic lipid, inflammation, and fibrosis in human non-alcoholic fatty liver disease.

Bhola K, McGuire W. · Department of Paediatrics and Child Health, Australian National University Medical School, Canberra, Australia. · Arch Dis Child. · Pubmed #17376949 No free full text.

This publication has no abstract.

Matthews G. · Viral Hepatitis Clinical Research Program, National Centre in HIV Epidemiology and Clinical Research, Sydney, New South Wales, Australia. · Curr Opin Infect Dis. · Pubmed #17197877 No free full text.

Abstract: PURPOSE OF REVIEW: Coinfection with HIV and hepatitis B virus has a significant impact on the natural history of hepatitis B disease with faster rates of progression to cirrhosis and end stage liver disease. An increasing number of hepatitis B virus active drugs are now available, many of which have dual anti-HIV activity. This review highlights the most important recent developments in the management of HIV and hepatitis B virus coinfection. RECENT FINDINGS: Natural history studies continue to confirm the increased rate of liver-related mortality in coinfected individuals and the importance of hepatocellular carcinoma in this population. The most recent studies of adefovir and tenofovir in open label use in coinfected individuals are discussed and new data on the activity of emtricitabine, entecavir and pegylated interferon are presented. Strategies for use of these new options for anti-hepatitis B virus therapy in coinfected individuals are discussed. SUMMARY: Prevention of end stage liver disease and hepatocellular carcinoma in the coinfected population is vital and the increasing availability of drugs with potent anti-hepatitis B activity is encouraging. Appropriate diagnosis and monitoring of hepatitis B, coupled with better understanding of the mechanisms of drug resistance, will enable clinicians to manage coinfection more effectively.

Ritter A, Cameron J. · Australian National University, Canberra, Australian Capital Territory, Australia. · Drug Alcohol Rev. · Pubmed #17132577 No free full text.

Abstract: Harm reduction is both a policy approach and used to describe a specific set of interventions. These interventions aim to reduce the harms associated with drug use. Employing a strict definition of harm reduction, evidence for the efficacy and effectiveness of alcohol, tobacco and illicit drug harm reduction interventions were reviewed. Systematic searches of the published literature were undertaken. Studies were included if they provided evaluation data (pre-post, or control group comparisons). More than 650 articles were included in the review. The majority of the literature concerned illicit drugs. For alcohol, harm reduction interventions to reduce road trauma are well-founded in evidence. Otherwise, there is limited research to support the efficacy and effectiveness of other alcohol harm reduction interventions. For tobacco, the area is controversial but promising new products that reduce the harms associated with smoking are being developed. In the area of illicit drugs there is solid efficacy, effectiveness and economic data to support needle syringe programmes and outreach programmes. There is limited published evidence to date for other harm reduction interventions such as non-injecting routes of administration, brief interventions and emerging positive evidence for supervised injecting facilities. There is sufficient evidence to support the wide-spread adoption of harm reduction interventions and to use harm reduction as an overarching policy approach in relation to illicit drugs. The same cannot be concluded for alcohol or tobacco. Research at a broad policy level is required, especially in light of the failure by many policy makers to adopt cost-effective harm reduction interventions.

Chang JJ, Lewin SR. · Department of Microbiology and Immunology, University of Melbourne, Melbourne, Victoria, Australia. · Immunol Cell Biol. · Pubmed #17130898 No free full text.

Abstract: Hepatitis B virus (HBV) infection is a non-cytopathic hepatotropic virus that can lead to severe liver disease including acute hepatitis, cirrhosis and hepatocellular carcinoma. Successful clearance of the virus as well as the establishment of liver disease is largely driven by a complex interaction between the virus and the host immune response. In this review, the immunological events, including both the innate and adaptive immune response are discussed in the setting of both acute and chronic HBV infection and liver disease.

Lloyd AR, Jagger E, Post JJ, Crooks LA, Rawlinson WD, Hahn YS, Ffrench RA. · Centre for Infection and Inflammation Research, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia. · Immunol Cell Biol. · Pubmed #17130897 No free full text.

Abstract: Individuals infected with hepatitis C virus (HCV) have two possible outcomes of infection, clearance or persistent infection. The focus of this review is the host mechanisms that facilitate clearance. The interaction between HCV viral components and the immune system ultimately determines the balance between the virus and host. Strong evidence points to the aspects of cellular immune response as the key determinants of outcome. The recent discovery of viral evasion strategies targeting innate immunity suggests that the interferon-alpha/beta induction pathways are also critical. A growing body of evidence has implicated polymorphisms in both innate and adaptive immune response genes as determinants of viral clearance in individuals infected with HCV.