Hepatitis: Boston

Wong JB. · Division of Clinical Decision Making, Department of Medicine, Tupper Research Institute, Tufts-New England Medical Center, Tufts University School of Medicine, 750 Washington Street, Boston, MA 02111, USA. · Hepatology. · Pubmed #12085373 No free full text.

This publication has no abstract.

Rodriguez-Manzanet R, DeKruyff R, Kuchroo VK, Umetsu DT. · Department of Neurology, Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. · Immunol Rev. · Pubmed #19426227 No free full text.

Abstract: SUMMARY: The T-cell immunoglobulin domain and mucin domain (TIM) family, including TIM-1, TIM-2, TIM-3, and TIM-4, is a relatively newly described group of molecules with a conserved structure and important immunological functions, including T-cell activation, induction of T-cell apoptosis and T-cell tolerance, and the clearance of apoptotic cells. TIM-1 costimulates T-cell activation and enhances cytokine production. In humans, TIM-1 also serves as a susceptibility gene for allergy and asthma. TIM-3, expressed on T cells and dendritic cells, regulates T-cell apoptosis and immune tolerance. By contrast, TIM-4, which is expressed primarily on antigen-presenting cells and which is a receptor for phosphatidylserine, regulates T-cell activation and tolerance, in part by mediating the uptake and engulfment of apoptotic cells. The TIM molecules thus have surprisingly broad activities affecting multiple aspects of immunology.

Vergidis PI, Falagas ME, Hamer DH. · Department of Medicine, Section of Infectious Diseases, Boston Medical Center, Dowling 3N, Boston, MA 02118, USA. · Infect Dis Clin North Am. · Pubmed #19393910 No free full text.

Abstract: Since the beginning of the epidemic, extensive research has been conducted in the field of HIV infection. Original research and subsequent meta-analyses have contributed to a better understanding of the disease. Epidemiologic research has shown, for example, that male circumcision reduces the risk of female-to-male transmission. Nevertheless, the question whether circumcision confers protection against HIV transmission in MSM remains open. Studies have shown a positive correlation between HIV and HSV-2 infection. However, a recent RCT found that suppressive antiherpes therapy did not affect rates of HIV acquisition. Meta-analytical studies have advanced the knowledge on the global prevalence of infection among MSM, and disparities among black and white MSM. They have also solidified the evidence that the prophylactic use of ARVs reduces the risk of MTCT. It has also been shown that prolonged ruptured of membranes increases the rates of vertical transmission, and that breastfeeding is associated with postnatal transmission. In addition, prognostic markers of disease progression have been identified. The introduction of ART has resulted in substantial improvements in morbidity and mortality for HIV-seropositive individuals. Several studies have defined recommended and alternative regimens. In a recent meta-analysis it was shown that in treatment naïve patients, NNRTI-based or boosted-PI-based regimens are superior to triple NRTI or unboosted PI-based regimens in terms of virologic suppression. Recent evidence has demonstrated that ART can be successfully used in Africa with better outcomes in those receiving free treatment. Regarding resistance testing in treatment-experienced patients with virologic failure, GRT offers a benefit of small magnitude and there is insufficient evidence to support the use of PRT, in contrast to current guidelines. Meta-analyses have also shown that interventions to improve adherence can be successfully implemented. Finally, the efficacy of the influenza and hepatitis vaccine in the setting of HIV infection has been analyzed. As our knowledge advances, further questions will inevitably arise and will need to be addressed in well-conducted trials.

Freedman K, Nathanson J. · Chief of Medicine, Lemuel Shattuck Hospital, Associate Clinical Professor of Medicine, Tufts University School of Medicine (TUSM), 170 Morton Street, Boston, MA 02130, USA. · Expert Rev Anti Infect Ther. · Pubmed #19344248 No free full text.

Abstract: Hepatitis C infection in patients with mental illness and drug addiction is highly prevalent and infrequently treated. Over the past 5 years, a wealth of studies specifically focused on these groups have demonstrated comparable rates of sustained virological response, compliance and adverse events. Optimization of psychotropic and opioid-replacement therapy with integrated psychiatric/addiction treatment prior to and during IFN-alpha initiation produces optimal results. Experience in treating these populations demonstrates clinical outcomes comparable with those without these comorbidities. Patients with mental illness and drug addiction should have routine screening and treatment for HCV infection to prevent associated morbidity and mortality.

Alatrakchi N, Koziel M. · Infectious Diseases Division, BIDMC and Harvard Medical School, Boston, MA 02115, USA. · J Viral Hepat. · Pubmed #19222744 No free full text.

Abstract: Important questions remain on the role of T cells in progression of hepatitis virus-mediated liver pathogenesis: are T cells 'Good or Bad'? How could one maintain a beneficial balance, in which regulatory T-cell (Treg) populations might play an important role? Treg are a heterogeneous population of cells, including the classical CD4+CD25+ subset expressing the transcription factor Foxp3, CD4 T cells secreting IL-10 (Tr1) or TGF-beta (Th3), but also some CD8 T cells, double negative T cells and gammadelta T cells. The role of Treg in viral hepatitis, particularly HBV and HCV, seems to range from suppressing T-cell responses directed against hepatitis viruses to down-regulating the immune responses causing the liver damage. Questions also remain unresolved on which Treg populations are important and how to establish a beneficial balance, mostly due to the difficulties in studying the heterogeneous Treg populations but also due to the problem accessing liver, the principal target of hepatitis viruses. Here, we will review progress to date on understanding Treg populations in regard to viral hepatitis.

Jonas MM. · Children's Hospital Boston, Center for Childhood Liver Disease, Division of Gastroenterology, Boston, MA 02115, USA. · Liver Int. · Pubmed #19207977 No free full text.

Abstract: Hepatitis B infection during pregnancy presents a unique set of management issues. Aspects of care that must be considered include maternal and fetal effects of hepatitis B, effects of pregnancy itself on the course of hepatitis B infection and its complications, treatment of hepatitis B during pregnancy and prevention of perinatal infection. There are insufficient studies to date regarding these concerns; most are from the Far East, and many have important limitations, but some have yielded valuable data. Pregnant women with acute hepatitis B virus (HBV) infection typically have a course not very different from that in the general adult population, but the risk of transmission of HBV to neonates increases the later in gestation the acute infection occurs. Chronic HBV infection is usually mild in pregnant women, but may flare shortly after delivery. The risk of perinatal transmission is highest in women with high levels of viraemia; this may be a factor in the small but reproducible failure rate of current immunoprophylaxis strategies. Obstetrical policies must be assessed with respect to detection of maternal infection and liver disease, as well as with respect to perinatal transmission risk. In addition to the usual issues of drug efficacy and safety in the affected individuals, effects on the developing fetus must be considered. This paper reviews the current experience in each of these areas, and highlights the need for further investigation into this critical but often underestimated topic.

Demirjian A, Levy O. · Department of Medicine, Division of Infectious Diseases, Children's Hospital Boston, Boston, MA 02115, USA. · Eur J Immunol. · Pubmed #19089811 No free full text.

Abstract: Newborns have an immature immune system that renders them at high risk for infection while simultaneously reducing responses to most vaccines, thereby posing challenges in protecting this vulnerable population. Nevertheless, certain vaccines, such as BCG and Hepatitis B vaccine, do demonstrate safety and some efficacy at birth, providing proof of principal that certain antigen-adjuvant combinations are able to elicit protective neonatal responses. Moreover, birth is a major point of healthcare contact globally meaning that effective neonatal vaccines achieve high population penetration. Given the potentially significant benefit of vaccinating at birth, availability of a broader range of more effective neonatal vaccines is an unmet medical need and a public health priority. This review focuses on safety and efficacy of neonatal vaccination in humans as well as recent research employing novel approaches to enhance the efficacy of neonatal vaccination.

Tai AW, Chung RT. · Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, WRN 1007, 55 Fruit Street, Boston, MA 02114, USA. · J Hepatol. · Pubmed #19070928 No free full text.

Abstract: Hepatitis C virus (HCV) has evolved remarkable mechanisms that favor viral persistence by interfering with host innate and adaptive immune responses. These same mechanisms are likely to contribute to resistance to exogenously administered interferon used for HCV treatment. We review the host innate and adaptive immune responses in the context of HCV infection as well as the strategies by which these responses are subverted by the virus. In addition, the contribution of host factors, such as race and insulin resistance, to interferon non-responsiveness is discussed. Our progress in understanding the molecular underpinnings of interferon treatment failure in HCV infection has resulted in several promising and novel treatment strategies for HCV treatment non-responders.

Bovier PA. · Department of Community and Primary Care Medicine, Geneva University Hospitals, Switzerland. · Expert Rev Vaccines. · Pubmed #18844588 No free full text.

Abstract: Over the last few decades, different types of inactivated hepatitis A virus (HAV) vaccines have been developed: several aluminum-adjuvanted vaccines and an aluminum-free, virosome-formulated vaccine. Both types of vaccines are whole-virus preparations that are produced by growth of HAV strains in human diploid cell cultures and are subsequently inactivated with formaldehyde. This review summarizes all published papers on a virosome-formulated vaccine, Epaxal, based on formalin inactivated HAV (strain RG-SB) adsorbed to the surface of special liposomes (virosomes), that replace aluminum hydroxide as the adjuvant principle. A single injection of virosomal HAV vaccine is well tolerated and highly immunogenic, with 88-97% of seroprotection 2 weeks after a first dose. HAV virosomal vaccine can be administered concomitantly with other vaccines, without inducing antigenic competition. Direct comparison with aluminum-adsorbed vaccine has shown that the immunogenicity was similar, but fewer local reactions were reported with Epaxal. Recent studies in children have demonstrated that Epaxal Junior is also an excellent HAV vaccine for mass vaccination programs.

Dienstag JL. · Gastrointestinal Unit (Medical Services), Massachusetts General Hospital, and Department of Medicine and Office of the Dean for Medical Education, Harvard Medical School, Boston 02114, USA. · N Engl J Med. · Pubmed #18832247 No free full text.

This publication has no abstract.

Sabharwal S, Delgado-Borrego A, Chung RT. · Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA. · Liver Transpl. · Pubmed #18825714 No free full text.

Abstract: 1. Insulin resistance is associated with hepatitis C virus infection and plays a role in the progression of hepatitis C virus-related liver disease and fibrosis. 2. Treating insulin resistance and achieving glycemic control will be important for improving post-liver transplant morbidity and mortality: control of the hepatitis C virus will help to accomplish this. 3. The main renal complication of hepatitis C virus is membranoproliferative glomerulonephritis, and this occurs most commonly in the setting of mixed cryoglobulinemia.

Balasubramanian A, Groopman JE, Ganju RK. · Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA. · J Addict Dis. · Pubmed #18681194 links to  free full text

Abstract: HCV and HIV infections are very common among injection drug users (IDUs). It is well known that 80-90% of HIV-infected IDUs are also infected with HCV. Furthermore, patients with HCV/HIV co-infection are at a higher risk of progressing to end-stage liver disease, namely cirrhosis. Even though there is increasing global awareness of HCV/HIV co-infection and extended therapeutic programs for this infected population, little is known about the HCV/HIV pathophysiology that mediates the rapid progression to hepatic disease. Liver disease caused by HCV/HIV co-infection is characterized by inflammation and cell-death. Recent reports suggest that the HIV and HCV envelope proteins may induce apoptosis and inflammation in hepatocytes via a novel pathway involving collaborative signaling. Moreover, HCV/HIV co-infection may also alter the cytokine production in vivo. Further studies to elucidate the molecular mechanisms of HCV and HIV-mediated pathogenesis will help in the development of therapeutic strategies against HCV/HIV co-infection in these patients.

Kim AY, Timm J. · Partners AIDS Research Center, Massachusetts General Hospital/Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA. · Expert Rev Anti Infect Ther. · Pubmed #18662114 No free full text.

Abstract: Recent advances in our understanding of the HCV life cycle and the functions of virally encoded proteins enabled the development of specifically targeted antiviral therapies for HCV, which directly inhibit HCV replication. Early clinical trials show great efficacy; however, from the first trials it became evident that, similar to HIV and HBV, selection of resistant variants will be problematic. Error-prone replication of HCV, resulting in a complex quasispecies population within each infected individual, enables rapid adaptation to changing environments. In this review, the evolutionary mechanisms involved in the selection process resulting in drug resistance are discussed. We give an overview of the resistance profiles to recently developed HCV protease and polymerase inhibitors and discuss potential implications for future treatment developments.

Bassett IV, Farel C, Szmuilowicz ED, Walensky RP. · Division of Infectious Disease, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. · Clin Infect Dis. · Pubmed #18643759 links to  free full text

Abstract: AIDS [Acquired Immunodeficiency Syndrome] Drug Assistance Programs, operating within the larger Ryan White Program, are state-based, discretionary programs that provide a drug "safety net" for low-income and uninsured individuals infected with human immunodeficiency virus (HIV). Although the AIDS Drug Assistance Programs and the primary care system that provides care for patients with HIV infection are already financially stressed, the Centers for Disease Control and Prevention recently issued guidelines recommending universal HIV testing to help identify the estimated 300,000 individuals in the United States who are unaware that they are infected with HIV. As the number of people living with HIV/AIDS who are coinfected with hepatitis C virus has grown and the cost and complexity of care have increased, the sustainability of the current HIV care system requires a reevaluation in light of the new testing guidelines. We examine the current state of the AIDS Drug Assistance Programs, discuss the implications of the Centers for Disease Control and Prevention guidelines for the already overstretched Ryan White Program, and consider a federally supported national program to ensure high-quality, efficient HIV care for low-income HIV-infected Americans.

Liang SL. · Harvard Medical School, Boston, MA, USA. · MLO Med Lab Obs. · Pubmed #18630096 No free full text.

This publication has no abstract.

Kanayama G, Hudson JI, Pope HG. · Biological Psychiatry Laboratory, McLean Hospital/Harvard Medical School, 115 Mill Street, Belmont, MA 02478, United States. · Drug Alcohol Depend. · Pubmed #18599224 No free full text.

Abstract: BACKGROUND: The problem of anabolic-androgenic steroid (AAS) abuse has recently generated widespread public and media attention. Most AAS abusers, however, are not elite athletes like those portrayed in the media, and many are not competitive athletes at all. This larger but less visible population of ordinary AAS users began to emerge in about 1980. The senior members of this population are now entering middle age; they represent the leading wave of a new type of aging former substance abusers, with specific medical and psychiatric risks. METHODS: We reviewed the evolving literature on long-term psychiatric and medical consequences of AAS abuse. RESULTS: Long-term use of supraphysiologic doses of AAS may cause irreversible cardiovascular toxicity, especially atherosclerotic effects and cardiomyopathy. In other organ systems, evidence of persistent toxicity is more modest, and interestingly, there is little evidence for an increased risk of prostate cancer. High concentrations of AAS, comparable to those likely sustained by many AAS abusers, produce apoptotic effects on various cell types, including neuronal cells--raising the specter of possibly irreversible neuropsychiatric toxicity. Finally, AAS abuse appears to be associated with a range of potentially prolonged psychiatric effects, including dependence syndromes, mood syndromes, and progression to other forms of substance abuse. However, the prevalence and severity of these various effects remains poorly understood. CONCLUSIONS: As the first large wave of former AAS users now moves into middle age, it will be important to obtain more systematic data on the long-term psychiatric and medical consequences of this form of substance abuse.

Longworth DL. · Department of Medicine, Tufts University School of Medicine, USA. · Cleve Clin J Med. · Pubmed #18595548 links to  free full text

Abstract: Key studies on the prevention of human papillomavirus and hepatitis A published during the past year found that: A quadrivalent vaccine against human papillomavirus prevents cervical intraepithelial neoplasia, vulvar and vaginal intraepithelial neoplasia, and anogenital disease in young women. The vaccine is likely cost-effective when given to girls, but perhaps not when given to boys. Although hepatitis A immune globulin is modestly better than hepatitis A vaccine for postexposure prophylaxis against hepatitis A, both are highly effective. Hepatitis A vaccine is now recommended by the Advisory Committee on Immunization Practices as the preferred agent in healthy individuals between the ages of 2 and 40.

Ishii S, Koziel MJ. · Infectious Disease Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. · Clin Immunol. · Pubmed #18514579 No free full text.

Abstract: Hepatitis C virus (HCV) induces persistent infection and causes chronic liver disease in most infected patients. Vigorous HCV-specific CD4+ and CD8+ T cell responses against HCV multiple epitopes are necessary for spontaneous viral clearance during the acute phase, but the virus appears to have multiple strategies to evade these defenses. There are relatively few studies on the role of immune responses during the chronic phase of infection. CD4+ T cell responses appear to protect against liver injury and may be important to clearance during interferon and ribavirin based therapy. Classic cytotoxic T cells (CTL) may primarily damage the liver in chronic HCV, but there may be subpopulations of T cells that protect against liver inflammation. Resolution of these outstanding questions is important to the development of a prophylactic vaccine as well as improving therapeutic options for those with chronic infection.

Ge Z, Schauer DB, Fox JG. · Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. · Cell Microbiol. · Pubmed #18489725 No free full text.

Abstract: Multiple pathogenic Gram-negative bacteria produce cytolethal-distending toxins (CDTs). CDT is typically composed of three subunits: the catalytic subunit CdtB has DNase I-like activity, whereas CdtA and CdtC are binding proteins for delivering CdtB into target cells. Translocation of CdtB to the nucleus induces genotoxic effects on host DNA, triggering DNA repair cascades that lead to cell cycle arrest and eventual cell death. Several lines of evidence indicate that this toxin contributes to the pathogenicity of CDT-producing bacteria in vivo. Helicobacter hepaticus and Campylobacter jejuni CDTs are essential for persistent infection of the gastrointestinal tract and increase the severity of mucosal inflammation or liver disease in susceptible mouse strains. Haemophilus ducreyi CDT may contribute to the pathogenesis of chancroid in rabbits. Recently, H. hepaticus CDT has been shown to play a crucial role in promoting the progression of infectious hepatitis to pre-malignant, dysplastic lesions via activation of a pro-inflammatory NF-kappaB pathway and increased proliferation of hepatocytes, providing the first evidence that CDT has carcinogenic potential in vivo. Thus, both in vitro and in vivo data indicate that CDT is a bacterial virulence factor.

Afdhal N, McHutchison J, Brown R, Jacobson I, Manns M, Poordad F, Weksler B, Esteban R. · Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA. · J Hepatol. · Pubmed #18433919 No free full text.

Abstract: Thrombocytopenia (platelet count <150,000/microL) is a common complication in patients with chronic liver disease (CLD) that has been observed in up to 76% of patients. Moderate thrombocytopenia (platelet count, 50,000/microL-75,000/microL) occurs in approximately 13% of patients with cirrhosis. Multiple factors can contribute to the development of thrombocytopenia, including splenic platelet sequestration, bone marrow suppression by chronic hepatitis C infection, and antiviral treatment with interferon-based therapy. Reductions in the level or activity of the hematopoietic growth factor thrombopoietin (TPO) may also play a role. Thrombocytopenia can impact routine care of patients with CLD, potentially postponing or interfering with diagnostic and therapeutic procedures including liver biopsy, antiviral therapy, and medically indicated or elective surgery. Therapeutic options to safely and effectively raise platelet levels could have a significant effect on care of these patients. Several promising novel agents that stimulate TPO and increase platelet levels, such as the oral platelet growth factor eltrombopag, are currently in development for the prevention and/or treatment of thrombocytopenia. The ability to increase platelet levels could significantly reduce the need for platelet transfusions and facilitate the use of interferon-based antiviral therapy and other medically indicated treatments in patients with liver disease.

Romero V, Azocar J, Zúñiga J, Clavijo OP, Terreros D, Gu X, Husain Z, Chung RT, Amos C, Yunis EJ. · Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA. · Mol Immunol. · Pubmed #18289678 links to  free full text

Abstract: Natural killer cells are important in innate defense against viral infections. The interplay between stimulatory and inhibitory natural killer cell receptors and their corresponding human leukocyte antigen ligands are known to influence the outcome of acute Hepatitis C virus infection. Frequencies of NK receptor genes (8 inhibitory, 6 activating and 2 pseudogenes) and HLA class II alleles (DRB1, DQB1) were analyzed in 160 Puerto-Rican American drug users with Hepatitis C virus infection; 121 had chronic viremia (CV) and 39 were spontaneous clearance (SC). We further ruled out genetic stratification using short tandem repeats. Interaction between KIR gene receptor 2DL3/2DL3 and its ligand, C1/C1 of HLA-Cw alleles and spontaneous clearance was confirmed (p=0.03, OR=3.05). We also found a new interaction between the KIR receptor gene 2DL3 with HLA-DRB1*1201 (p=0.0001, OR=22) associated with SC, and an association of HLA DQB1*0501 (p=0.05, OR=0.30) with CV. Our findings suggested a role for MHC class II alleles in Hepatitis C virus peptide presentation to T cells together with NK ligand interaction involving pathways that will be useful for the development of immunotherapeutic interventions.

McGovern BH. · Division of Infectious Diseases, Tufts University School of Medicine, Boston, MA, USA. · Antivir Ther. · Pubmed #18284178 No free full text.

Abstract: Approximately 350 million people have chronic hepatitis B infection, a leading cause of cirrhosis and hepatocellular carcinoma (HCC). Patients who are infected through parenteral or sexual transmission are also at risk for acquisition of HIV. Concomitant HIV infection can lead to an increased risk of morbidity and mortality from hepatitis B virus (HBV)-related cirrhosis, end-stage liver disease and HCC. This review will focus on the epidemiology, natural history and prevention of HBV infection and the modulating effect of HIV on the clinical expression of HBV disease.

Kim SY, Goldie SJ. · Program in Health Decision Science, Department of Health Policy and Management, Harvard School of Public Health, Boston, MA 02115, USA. · Pharmacoeconomics. · Pubmed #18282015 No free full text.

Abstract: Cost effectiveness is becoming an increasingly important factor for stakeholders faced with decisions about adding a new vaccine into national immunization programmes versus alternative use of resources. Evaluating cost effectiveness, taking into account the relevant biological, clinical, epidemiological and economic factors of a vaccination programme, generally requires use of a model. This review examines the modelling approaches used in cost-effectiveness analyses (CEAs) of vaccination programmes.After overviewing the key attributes of models used in CEAs, a framework for categorising theoretical models is presented. Categories are based on three main attributes: static/dynamic; stochastic/deterministic; and aggregate/individual based. This framework was applied to a systematic review of CEAs of all currently available vaccines for the period of 1976 to May 2007.The systematic review identified 276 CEAs of vaccination programmes. The great majority (83%) of CEAs were conducted in the setting of high-income countries. Only a few vaccines were widely studied, with 57% of available CEAs being focused on the varicella, influenza, hepatitis A, hepatitis B or pneumococcal vaccine. Several time trends were evident, indicating that the number of vaccine CEAs being published is increasing; the main health outcome measures are moving away from the number of cases prevented towards quality-adjusted and unadjusted life-years gained, and more complex models are beginning to be used.The modelling approach was often not adequately described. Of the 208 CEAs that could be categorized according to the framework, around 90% were deterministic, aggregate-level static models. Although a dynamic transmission model is required to account for herd-immunity effects, only 23 of the CEAs were dynamic. None of the CEAs were individual based.To improve communication about the cost effectiveness of vaccination programmes, we believe the first step is for analysts to be more transparent with each other. A clear description of the model type using consistent terminology and justification for the model choice must begin to accompany all CEAs. As a minimum, we urge modellers to provide an explicit statement about the following attributes: static/dynamic; stochastic/deterministic; aggregate/individual based; open/closed. Where relevant, time intervals (discrete/continuous) and (non)linearity should also be described. Enhanced methods of assessing model performance and validity are also required.Our results emphasize the need to improve modelling methods for CEAs of vaccination programmes; specifically, model choice, construction, assessment and validation.

Spector J, Fernandez WG. · Boston Medical Center, Department of Emergency Medicine, Boston University School of Medicine, Boston, MA 02118, USA. · Emerg Med Clin North Am. · Pubmed #18249260 No free full text.

Abstract: Chemical or radiant energy injuries to the eyes are considered ocular burns. The majority of these injuries are occupation-related. Chemical burns are by far more common and represent a true emergency. Thermal and UV injuries are associated with severe pain, but often result in less long-term sequelae than chemical injuries do. The term "biologic exposure" refers to an exposure to human blood or other body fluid. This article describes patterns of these injuries and exposures, with particular emphasis on emergent management and including acute diagnostic and treatment considerations.

Gordon CE, Uhlig K, Lau J, Schmid CH, Levey AS, Wong JB. · Division of Nephrology, Institute for Clinical Research and Health Policy Studies, Tufts-New England Medical Center, Boston, MA 02111, USA. · Am J Kidney Dis. · Pubmed #18215704 No free full text.

Abstract: BACKGROUND: Hepatitis C virus (HCV) infection is prevalent in patients undergoing hemodialysis and is associated with greater mortality. We determined the efficacy and harms of interferon (IFN) and pegylated IFN (PEG-IFN) treatment of hemodialysis patients with chronic HCV infection and identified factors associated with these outcomes. STUDY DESIGN: Meta-analysis and meta-regression of randomized controlled trials, uncontrolled trials, and prospective observational studies. SETTING & POPULATION: Hemodialysis patients with chronic HCV infection. SELECTION CRITERIA FOR STUDIES: MEDLINE indexed studies since 1966, sample size greater than 10. INTERVENTION: IFN-based treatment, including PEG-IFN with and without ribavirin. OUTCOMES: Sustained virological response (SVR) 6 months after treatment, rate of treatment discontinuation caused by adverse events, and factors associated with these outcomes. RESULTS: 20 studies of 459 IFN-treated patients, 3 studies of 38 PEG-IFN-treated patients, and 2 studies of 49 PEG-IFN and ribavirin-treated patients met inclusion criteria. The overall SVR rate was 41% (95% confidence interval [CI], 33 to 49) for IFN and 37% (95% CI, 9 to 77) for PEG-IFN. Treatment discontinuation rates were 26% (95% CI, 20 to 34) for IFN and 28% (95% CI, 12 to 53) for PEG-IFN. SVR was higher with 3 million units (MU) or higher of IFN 3 times weekly, with lower mean HCV RNA, and with lower rates of cirrhosis, HCV genotype 1 or elevated transaminase, but these findings were not statistically significant. Treatment discontinuation rates were greater in studies using larger doses. LIMITATIONS: Publication bias, few randomized controlled trials, and limitations in generalizability to all hemodialysis patients. CONCLUSION: IFN treatment of hemodialysis patients results in an SVR rate of 41%. Higher dose, lower mean HCV RNA level, and lower rates of cirrhosis, transaminase level increase, and HCV genotype 1 may be associated with greater SVR rates, but additional studies using individual patient data are needed.