Hepatitis: Baltimore

Azzam HS, Goertz C, Fritts M, Jonas WB. · Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, Baltimore, MD 21201-1596, USA. · Liver Int. · Pubmed #17241377 No free full text.

Abstract: BACKGROUND: Chronic hepatitis C virus (HCV) infection is a significant public health problem, with a worldwide prevalence of approximately 170 million. The standard of care for chronic HCV, a combination of alpha-interferon (IFN) and ribavirin, is only 50% effective, has serious side effects, and can be prohibitively expensive for low-income countries with a high prevalence of HCV. Many patients use natural products, including those who are not eligible for IFN/ribavirin, cannot afford treatment, or fail to respond to IFN. METHODS: Extensive literature searches were conducted in order to identify clinical trials and reviews of natural products used for treatment of chronic HCV. This review focuses on the composition, pharmacology and results of clinical trials of three natural products: Oxymatrine, TJ-108/schisandra/Gomisin A and lactoferrin. RESULTS: Several laboratory and human studies have been performed to evalaute these alternative treatments, but many of these studies are small, uncontrolled and have other important design flaws. While they do offer some safety and efficacy data, none of these studies is conclusive. CONCLUSION: Further research is needed on the effectiveness of these natural products for treatment of chronic HCV, including their preparation and standardization.

Verma S, Thuluvath PJ. · Section of Hepatology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Clin Gastroenterol Hepatol. · Pubmed #17222587 No free full text.

Abstract: There is an increase in the use of complementary and alternative medicine (CAM), especially herbal therapy, among patients with liver disease. The most commonly used herbal agent is silymarin. In animal models, many of the commonly used agents have shown anti-inflammatory and antifibrotic effects. Although many human studies have shown improvements in subjective symptoms (well being) and liver biochemistry, there are no convincing data to suggest a definite histologic and/or virologic improvement with most of these agents. Poorly designed studies, heterogeneous patient populations, lack of standardized preparations, and poorly defined nonobjective end points may partly explain the conflicting reports in the literature. Hepatotoxicity and drug interactions are common with many herbal medications, and therefore physicians need to be cognizant of known or occult use of CAM by their patients. Only well-designed, randomized, controlled trials will be able to ascertain whether CAM has any role in the management of patients with acute or chronic liver diseases. Until such time, the use of CAM cannot be recommended as a therapy for patients with liver disease.

Groopman JD, Johnson D, Kensler TW. · Johns Hopkins University, Bloomberg School of Public Health, Department of Environmental Health Sciences, 615 North Wolfe Street, Baltimore, MD 21205, USA. · Cancer Biomark. · Pubmed #17192028 links to  free full text

Abstract: The use of biomarkers in molecular epidemiology studies for identifying stages in the progression of development of the health effects of environmental agents has the potential for providing important information for critical regulatory, clinical and public health problems. Investigations of aflatoxins probably represents one of the most extensive data sets in the field and this work may serve as a template for future studies of other environmental agents. The aflatoxins are naturally occurring mycotoxins found on foods such as corn, peanuts, various other nuts and cottonseed and they have been demonstrated to be carcinogenic in many experimental models. As a result of nearly thirty years of study, experimental data and epidemiological studies in human populations, aflatoxin B(1) was classified as carcinogenic to humans by the International Agency for Research on Cancer. The long-term goal of the research described herein is the application of biomarkers to the development of preventative interventions for use in human populations at high-risk for cancer. Several of the aflatoxin specific biomarkers have been validated in epidemiological studies and are now being used as intermediate biomarkers in prevention studies. The development of these aflatoxin biomarkers has been based upon the knowledge of the biochemistry and toxicology of aflatoxins gleaned from both experimental and human studies. These biomarkers have subsequently been utilised in experimental models to provide data on the modulation of these markers under different situations of disease risk. This systematic approach provides encouragement for preventive interventions and should serve as a template for the development, validation and application of other chemical-specific biomarkers to cancer or other chronic diseases. This systematic approach provides encouragement for preventive interventions and should serve as a template for the development, validation and application of other chemical-specific biomarkers to cancer or other chronic diseases.

Pham PA, Gallant JE. · Johns Hopkins University School of Medicine, Division of Infectious Diseases, 1830 E. Monument St. #443, Baltimore, MD 21287, USA. · Expert Opin Drug Metab Toxicol. · Pubmed #16863446 No free full text.

Abstract: Tenofovir disoproxil fumarate is a nucleotide analogue reverse transcriptase inhibitor approved by the FDA for the treatment of HIV infection. It is a potent agent with a long intracellular half-life that allows for once-daily dosing. It has been well tolerated in clinical trials, without evidence of the mitochondrial toxicity that has been associated with long-term treatment of some of the nucleoside analogue reverse transcriptase inhibitors. Because of its demonstrated efficacy and favourable safety profile, tenofovir disoproxil fumarate has quickly become a favoured nucleoside component of antiretroviral regimens for both treatment-naive and -experienced patients.

Abougergi MS, Rai R, Cohen CK, Montgomery R, Solga SF. · The Good Samaritan Hospital, Baltimore, MD, USA. · Prog Transplant. · Pubmed #16676671 No free full text.

Abstract: Adult-to-adult living donor liver transplantation is an increasingly important option for 17000 patients awaiting liver transplantation in the United States. However, adult-to-adult living donor liver transplantation volumes peaked in 2001 (N = 518), and have gradually fallen in 2002 (N = 362), 2003 (N = 321), and 2004 (N = 323). Recent concerns about donor safety and ethical considerations have made careful analysis of donor availability and selection criteria critically important. We conducted a retrospective review of our active liver transplant recipient registry (N = 251) and compared it to our living donor registry (N = 231), which included all potential living donors before the selection process. Fifteen percent of recipients accounted for the majority (53%) of donor evaluations, whereas 42% of recipients did not have even a single donor evaluation. Recipient diagnosis appears to have a significant impact on donor availability, with donors rarely evaluated for patients with alcoholic cirrhosis. Careful and stringent selection criteria rule out 67% of potential donors.

Strickland GT. · Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, Baltimore 21201, USA. · Hepatology. · Pubmed #16628669 No free full text.

Abstract: In Egypt, schistosomiasis was traditionally the most important public health problem and infection with Schistosoma mansoni the major cause of liver disease. From the 1950s until the 1980s, the Egyptian Ministry of Health (MOH) undertook large control campaigns using intravenous tartar emetic, the standard treatment for schistosomiasis, as community-wide therapy. This commendable effort to control a major health problem unfortunately established a very large reservoir of hepatitis C virus (HCV) in the country. By the mid-1980s, the effective oral drug, praziquantel, replaced tartar emetic a s treatment f o r schistosomiasis in the entire country.This both reduced schistosomal transmission and disease and interrupted the "occult" HCV epidemic. It was evident when diagnostic serology became available in the 1990s that HCV had replaced schistosomiasis as the predominant cause of chronic liver disease. Epidemiological studies reported a high prevalence and incidence of HCV, particutarly within families in rural areas endemic for schistosomiasis. Clinical studies showed 70% to 90% of patients with chronic hepatitis, cirrhosis, or hepatocellular carcinoma had HCV infections. Co-infections with schistosomiasis caused more severe liver disease than infection with HCV alone. Schistosomiasis was reported to cause an imbalance in HCV-specific T-cell responses leading to increased viral load, a higher probability of HCV chronicity, and more rapid progression of complications in co-infected persons. As complications of HCV usually occur after 20 years of infection, the peak impact of the Egyptian outbreak has not yet occurred. Efforts have been initiated by the Egyptian MOH to prevent new infections and complications of HCV in the estimated 6 million infected persons.

Dumler JS. · Division of Medical Microbiology, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. · Ann N Y Acad Sci. · Pubmed #16481544 No free full text.

Abstract: Human and animal infections by Anaplasmataceae are increasingly recognized as important and potentially fatal arthropod-transmitted diseases. Since the first recognition and implementation of diagnostic methods for human infection by Ehrlichia chaffeensis and Anaplasma phagocytophilum, the incidence of infections has linearly increased. Moreover, diagnostic and epidemiological testing indicates that "ehrlichia" infections are globally distributed and suggests that additional agents of human and veterinary "ehrlichiosis" will be identified. With increasing disease identification has come recognition that the infections can be severe, with approximately one-half of patients requiring hospitalization for complications including respiratory distress, myocarditis, neurological complications, hepatitis, a septic or toxic shock-like disease, opportunistic infections, and death in 0.5 to 3.0%. An understanding of the diseases, pathophysiology, pathogenesis, control, and management will best be developed through fundamental investigations. Advances in comprehension as to the separate contributions of bacteria and host are crucial since most data now suggest that alterations in host neutrophil function and protection from innate and adaptive immunity also contribute to disease manifestations. It is reasonable to operate from the hypothesis that these host cell functional changes ultimately benefit bacterial survival while inadvertently eliciting clinical disease in poorly adapted hosts. A firmer basis for the scientific understanding of Anaplasmataceae biology will allow logical and rational approaches toward infection control, prevention, and treatment.

Thomas DL. · Johns Hopkins School of Medicine, Baltimore, MD 21231, USA. · Hepatology. · Pubmed #16447263 No free full text.

Abstract: Liver disease is a growing problem in HIV-infected persons. In those who are able to take antiretroviral therapy, the forms of liver disease have changed and their relative importance has increased. This review focuses on liver disease in HIV-infected persons, caused by hepatitis C virus, hepatitis B virus, or treatment of HIV infection.

Angelino AF, Treisman GJ. · Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. · Int Rev Psychiatry. · Pubmed #16401545 No free full text.

Abstract: More than 4 million people are currently infected with Hepatitis C an RNA virus that may ultimately result in complete hepatic failure and is often a silent infection until late in the course of disease. Hepatitis C patients have increased rates of major depression (as well as substance abuse) and treatment of hepatitis with interferon, the current standard treatment, provokes episodes of depression in as many as a third of patients treated. Immune-dysfunction mediated mechanisms for the depression in these patients have been proposed and have increasing experimental support. The resulting depression has interfered with treatment for many patients, but several standard treatments for depression have been shown to be effective in patients with interferon-associated depression, suggesting that this should not be a barrier to effective treatment. In this paper, we review the evidence for associations between depression and Hepatitis C and interferon treatment, as well as the evidence supporting an immune mechanism for the association, and finally the data showing effective treatment and recommendations for prophylactic use of anti-depressants.

Sulkowski MS. · Johns Hopkins Medical Institutions, 1830 East Monument Street, Room 319, Baltimore, MD 21287-0003, USA. · J Hepatol. · Pubmed #16360232 No free full text.

Abstract: In the era of highly effective antiretroviral therapy (ART), HCV-related liver disease has emerged as a significant cause of morbidity and mortality. Accordingly, expert panels have recommend that coinfected patients undergo medical evaluation for HCV-related liver disease, consideration for HCV treatment and, if indicated, orthotopic liver transplantation. While the treatment of such patients is complicated by medical, and psychiatric comorbidities, HIV disease, and concurrent antiretroviral therapy, randomized controlled trials support the safety, tolerability and efficacy of HCV treatment with peginterferon alfa (PEG-IFN) plus ribavirin (RBV) in HIV-infected persons. Although, the available data has led to consensus among experts regarding the need to medically manage HCV disease in HIV-infected persons, uncertainty remains regarding the best treatment algorithm for coinfected patients.

Thomas DL. · Johns Hopkins School of Medicine, 1503 East Jefferson Street, Baltimore, MD 21231, USA. · J Hepatol. · Pubmed #16356578 No free full text.

Abstract: Irrespective of whether a patient has HIV infection, the optimal treatment for hepatitis C virus (HCV) infection is peginterferon alpha and ribavirin. In both HIV-infected and uninfected persons, sustained virologic response (SVR) rates are higher for genotype 2 and genotype 3 HCV infection and for patients with lower pre-treatment HCV RNA levels. HIV-infection does not alter either the reality that persons who fail to achieve a 2log(10) reduction in HCV RNA level after 12 weeks of therapy rarely achieve a SVR, or the theoretical benefits of maintenance therapy in those without viral responses. The same adverse treatment effects can occur in HIV-infected and uninfected persons, but treatment of HIV-infected persons is complicated by interactions between ribavirin and antiretroviral medications and effects of HCV treatment on the course of HIV. The optimal treatment doses and durations are not known for HIV-infected persons, who are also less likely to achieve a SVR. A final difference is that the benefits of HCV treatment breakthroughs are usually realized in patients without HIV years before those with HIV. Future research must focus both on improving outcomes with currently available medications and rapidly evaluating the safety and efficacy of forthcoming antiviral compounds in HIV/HCV coinfected persons.

Rodríguez-Pla A, Stone JH. · Division of Molecular and Clinical Rheumatology, The Johns Hopkins School of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, USA. · Curr Opin Rheumatol. · Pubmed #16344618 No free full text.

Abstract: PURPOSE OF REVIEW: In recent years, many investigators have focused on potential associations between infections and vascular inflammation. We review the principal pathogenic mechanisms that have been implicated for possible roles in the vascular inflammation initiated by infectious agents. We also summarize the most important literature related to this topic. RECENT FINDINGS: A novel theory known as autoantigen complementarity suggests that an infectious agent could trigger antineutrophil cytoplasmic antibody-associated vasculitis. Several recent studies investigating the presence of parvovirus B19 and herpesviruses in temporal arteries with giant cell arteritis have yielded contradictory results. A recent study has identified higher frequency of a novel human virus, the 'New Haven coronavirus', in respiratory secretions of children with Kawasaki disease. Many case reports have suggested potential relationships between human pathogens and vasculitis. SUMMARY: There remains considerable interest in the possibilities of primary vasculitic syndromes caused in some fashion by infection. With the exception of a few well sustained associations - for example hepatitis B or C with known vasculitic syndromes - most of the purported links between microbial agents and primary vasculitides remain speculative.

Sulkowski MS. · Viral Hepatitis Center, Johns Hopkins Medical Institutions, Baltimore, MD 21287-0003, USA. · Nat Clin Pract Gastroenterol Hepatol. · Pubmed #16265205 No free full text.

Abstract: Infection with HCV is common in HIV-infected patients and is an increasingly important public health problem. The medical management of hepatitis C in HIV-infected patients is complicated by immune suppression, potential drug interactions and toxicities, and the relative paucity of health-care providers with expertise in the management of both diseases. Nonetheless, there are now data to support the safety, tolerability and efficacy of hepatitis C treatment with peginterferon plus ribavirin in HIV-infected patients, and the impetus to treat these patients is, therefore, strong. Although the standard of care for the treatment of hepatitis C in HIV-infected patients has been more clearly defined, the delivery of care for hepatitis C remains inconsistent in many settings. The development and implementation of single-center multidisciplinary programs that combine the expertise of HIV specialists, hepatologists, gastroenterologists, psychiatrists, and addiction specialists, are needed to improve hepatitis C treatment outcomes in HIV-infected patients. This review considers the management of HCV infection in HIV-infected patients.

Sulkowski MS, Thomas DL. · Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0003, USA. · AIDS. · Pubmed #16251833 No free full text.

This publication has no abstract.

Goldberg RW. · Division of Services Research, Department of Psychiatry, University of Maryland, Baltimore, MD 21201, USA. · AIDS. · Pubmed #16251821 No free full text.

Abstract: This paper presents a multi-faceted supported rehabilitation and health management model to inform the development of interventions for mentally ill adults who are HIV/hepatitis C virus co-infected. The model, referred to as 'supported medical care' (SMC), calls for the combination of chronic illness self-management skills training and enhanced case management. Illustrative examples of each SMC intervention component are provided. Integrated delivery of these intervention components shows promise for improving the coordination of psychiatric and medical care. Research and related policy challenges regarding ongoing quality improvement efforts are also discussed.

Mehta SH, Thomas DL, Sulkowski MS, Safaein M, Vlahov D, Strathdee SA. · Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD, USA. · AIDS. · Pubmed #16251816 No free full text.

Abstract: Treatment for hepatitis C virus (HCV) is rarely received by injection drug users (IDU), particularly those co-infected with HIV. We propose a framework for understanding factors that affect utilization and adherence to HCV therapy among HCV mono-infected and HIV/HCV-co-infected IDU. Provision of treatment requires calculation of risks and benefits including evaluation of a number of time-varying factors that collectively determine a gradient of treatment eligibility, advisability and acceptability, the relative importance of which may differ in co-infected and mono-infected IDU. Treatment eligibility is determined by a number of non-modifiable and modifiable contraindications, the latter of which can change over time rendering patients who were once ineligible eligible. Among those eligible, treatment need can be assessed by liver biopsy and therapy may be deferred in those with no liver disease and started in those with significant liver disease. Among those with moderate disease, further consideration of treatment advisability (medical factors that affect treatment response) and acceptability (individual, provider and environmental barriers) is needed before treatment decisions are made. These factors are dynamic and thus should be continually evaluated even among those who may not initially appear to be ready for treatment. An evaluation of this framework is needed to determine applicability and feasibility. Until then, treatment decisions should be made on an individual basis after careful consideration of these issues by provider and patient and efforts to develop novel strategies for identifying IDU who need treatment most (alternatives to liver biopsy) and multidimensional approaches to deliver treatment for HCV while addressing other factors including HIV infection, depression and drug use should be continued.

Lambert JS. · University of Maryland Institute of Human Virology, Baltimore, USA. · Paediatr Drugs. · Pubmed #16220994 No free full text.

Abstract: The interruption of HIV transmission from mother to child is important. Prevention strategies, including antiretroviral agents administered to the mother and/or child, can successfully prevent such transmission. Avoidance of breastfeeding or the administration of antiretroviral agents to the mother while she continues breastfeeding is another strategy. Based on the successful model of hepatitis B prevention by treatment of the newborn, research protocols have been designed to prevent mother-to-child transmission of HIV by the administration of passive HIV-specific antibody preparations and HIV vaccines to the mother and/or child. A number of animal studies using active and passive products have shown efficacy in similar settings, providing hope that a similar strategy will work in humans.Clinical trials conducted through the US National Institutes of Health AIDS Clinical Trials Programs have focused on such an approach. This article summarizes the results of a number of these trials, including AVEG (AIDS Vaccine Evaluation Group) 104, a phase I study of active immunization of HIV-infected pregnant women with an HIV gp120 subunit vaccine, and PACTG (Pediatrics AIDS Clinical Trial Group) 185, a phase III efficacy trial of HIV immunoglobulin administered to HIV-infected pregnant women and their newborns. A number of HIV vaccine trials have been performed in HIV-exposed and -infected children. These include PACTG 218, a vaccine immunotherapy phase I trial of HIV subunit vaccines administered to asymptomatic HIV-infected children, and two phase I vaccine trials in HIV-exposed children, PACTG 230 and 326. While the results of PACTG 230 were encouraging, the gp120 subunit vaccines were not capable of generating cytotoxic T-cell (CTL) responses. A subsequent phase I study, PACTG 326, utilized a canarypox vectored HIV vaccine (ALVAC vCP205, Sanofi Pasteur), which was previously shown to generate CTL responses in HIV-uninfected adults. The vaccines were safe but the immunogenicity was poor when compared with results of adult studies. Specifically, no antibody responses were found, lymphoproliferative responses to HIV-specific antigens were found in <50% of vaccinees, and CTL responses, modest in nature, were seen in approximately 50% of vaccinees.Future planned vaccine studies are focused on prime-boost approaches, using live recombinant vectors or DNA vaccines combined with subunit vaccines to stimulate both cellular and antibody responses. HIV vaccines may have special utility in newborns, in infants who continue to breastfeed, and in pre-adolescent children before they become sexually active. However, to date, candidate HIV vaccines capable of generating robust immunologic responses in these populations have been disappointing.

Sulkowski MS. · Viral Hepatitis Center, Johns Hopkins University School of Medicine, 600 North Wolfe Street, 1830 Building, Room 448, Baltimore, MD 21287, USA. · Clin Liver Dis. · Pubmed #16207566 No free full text.

Abstract: Consensus guidelines are in place for treating chronic hepatitis C virus infection. This article highlights some of the hematologic complications of hepatitis C therapy. Management options are presented.

Thio CL, Sulkowski MS, Thomas DL. · Department of Medicine, Johns Hopkins University, Baltimore, MD, USA. · Clin Infect Dis. · Pubmed #16142671 No free full text.

This publication has no abstract.

Sulkowski MS. · Division of Infectious Diseases, Johns Hopkins Medical Institutions, 1830 East Monument Street, Room 319, Baltimore, MD 21287, USA. · Curr HIV/AIDS Rep. · Pubmed #16091233 No free full text.

Abstract: Because of shared routes of transmission, hepatitis C and HIV coinfection is common in the United States, affecting 15% to 30% of HIV-infected individuals. In the era of highly effective antiretroviral therapy, hepatitis C virus (HCV)-related liver disease has emerged as a significant cause of morbidity and mortality. Accordingly, the Infectious Diseases Society of America and the American Association for the Study of Liver Disease guidelines for the management of HCV recommend that patients with HIV/HCV undergo medical evaluation for HCV-related liver disease and consideration for HCV treatment and, if indicated, orthotopic liver transplantation. However, the treatment of patients with HIV/HCV is complicated by the relatively high prevalence of medical and psychiatric comorbidities and the challenges of anti-HCV therapy in the setting of HIV disease and antiretroviral therapy. Nonetheless, recently completed randomized controlled trials provide evidence of the safety, tolerability, and efficacy of HCV treatment with pegylated interferon-alpha plus ribavirin in HIV-infected individuals. This review focuses on the epidemiology, natural history, and management of HCV in the HIV-infected patient.

Thomas DL, Seeff LB. · Johns Hopkins School of Medicine, 1503 E. Jefferson Street, Baltimore, MD 21231, USA. · Clin Liver Dis. · Pubmed #16023972 No free full text.

Abstract: Fifteen years after the discovery of the hepatitis C virus, a substantial amount of information has been learned about the natural history of infection. Testing for viral nucleic acid made it possible to accurately diagnose chronic infection and provided a more precise estimate of the overall frequency of viral persistence. Although cirrhosis and hepatocellular carcinoma can arise in persons with chronic hepatitis C, these outcomes do not always occur. The cirrhosis risk is greater in those who are infected at older ages, those who drink >50 g of alcohol each day, and persons coinfected with HIV. However, much of the person-to-person variability in progression of chronic hepatitis C remains unexplained. The ability to detect persons at highest risk of progression remains incomplete and represents an important future challenge in the understanding of the natural history of hepatitis C.

Groopman JD, Kensler TW. · Department of Environmental Health Sciences, The Johns Hopkins University, Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA. · Toxicol Appl Pharmacol. · Pubmed #15967201 No free full text.

Abstract: The use of biomarkers in molecular epidemiology studies for identifying stages in the progression of development of the health effects of environmental agents has the potential for providing important information for critical regulatory, clinical and public health problems. Investigations of aflatoxins probably represent one of the most extensive data sets in the field and this work may serve as a template for future studies of other environmental agents. The aflatoxins are naturally occurring mycotoxins found on foods such as corn, peanuts, various other nuts and cottonseed and they have been demonstrated to be carcinogenic in many experimental models. As a result of nearly 30 years of study, experimental data and epidemiological studies in human populations, aflatoxin B(1) was classified as carcinogenic to humans by the International Agency for Research on Cancer. The long-term goal of the research described herein is the application of biomarkers to the development of preventative interventions for use in human populations at high-risk for cancer. Several of the aflatoxin-specific biomarkers have been validated in epidemiological studies and are now being used as intermediate biomarkers in prevention studies. The development of these aflatoxin biomarkers has been based upon the knowledge of the biochemistry and toxicology of aflatoxins gleaned from both experimental and human studies. These biomarkers have subsequently been utilized in experimental models to provide data on the modulation of these markers under different situations of disease risk. This systematic approach provides encouragement for preventive interventions and should serve as a template for the development, validation and application of other chemical-specific biomarkers to cancer or other chronic diseases.

Sulkowski MS, Thomas DL. · Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA. · Clin Infect Dis. · Pubmed #15768333 No free full text.

Abstract: Effective methods to diminish the burden of hepatitis C virus (HCV) infection among injection drug users (IDUs) require consideration of the epidemiology and natural history of both hepatitis C and drug use. Most HCV infections are due to injection drug use, and most IDUs have HCV infection. In addition, HCV infection often occurs with other medical problems, such as human immunodeficiency virus infection and depression, which may complicate its recognition and management. Infection with HCV can be fatal, but usually not until years later, and persons may be unaware of the infection, allowing an individual to infect many others. Effective treatment is available for HCV infection; however, the therapy is prolonged, involving both weekly injections and daily oral medication, and is typically associated with significant adverse effects, such as fatigue, depression, and, rarely, life-threatening complications. Although clearly some IDUs want their HCV infection to be treated, many are unwilling or unable to initiate or sustain treatment with currently available therapies, and IDUs who are treated require considerable, multidimensional support. Solutions to the problem of HCV infection among IDUs must account for these facts.

Klein HG. · Department of Medicine and Pathology, The Johns Hopkins School of Medicine, Baltimore, MD, USA. · J Intern Med. · Pubmed #15715679 No free full text.

Abstract: The calculated residual infectious risk of HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) from blood transfusion is extremely low. However, the risk of bacterial contamination remains and a variety of other agents including emerging viruses, protozoa and tick-borne agents threaten blood supplies and undermine public confidence in blood safety. Traditional methods of donor screening and testing have limited ability to further reduce disease transmission and cannot prevent an emerging infectious agent from entering the blood supply. Pathogen inactivation technologies have all but eliminated the infectious risks of plasma-derived protein fractions, but as yet no technique has proved sufficiently safe and effective for traditional blood components. Half-way technologies can reduce the risk of pathogen transmission from fresh frozen plasma and cryoprecipitate. Traditional methods of mechanical removal such as washing and filtration have limited success in reducing the risk of cell-associated agents, but methods aimed at sterilizing blood have either proved toxic to the cells or to the recipients of blood components. Several promising methods that target pathogen nucleic acid have recently entered clinical testing.

Kensler TW, Egner PA, Wang JB, Zhu YR, Zhang BC, Lu PX, Chen JG, Qian GS, Kuang SY, Jackson PE, Gange SJ, Jacobson LP, Muñoz A, Groopman JD. · Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, Maryland 21205, USA. · Gastroenterology. · Pubmed #15508099 No free full text.

Abstract: Hepatocellular carcinoma is one of the most common cancers worldwide. Infection with hepatitis B virus and exposure to aflatoxins in the diet act synergistically to amplify risk. From a public health perspective, hepatitis virus vaccination programs and efforts to both reduce aflatoxin exposures and to attenuate the toxicological consequences of unavoidable exposures should have major impacts on the global incidence of this disease. Experimentally, aflatoxin-induced hepatocarcinogenesis can be inhibited by over a score of different chemopreventive agents with multiple mechanisms of action. One agent, oltipraz, is a potent inducer of phase 2 enzymes involved in the detoxication of carcinogens including aflatoxin. A second agent, chlorophyllin, impedes the bioavailability of carcinogens by forming molecular complexes and enhances their elimination in the fecal stream. This review highlights the findings of recent randomized clinical trials with oltipraz and chlorophyllin conducted in individuals exposed to dietary aflatoxins and at high risk for development of liver cancer. Both chemopreventive agents modulated levels of aflatoxin biomarkers in the study participants in manners consonant with protection. Although pharmacological approaches establish proof of principle and help identify key molecular targets for interventions, food-based approaches that also use these molecular targets may be the most practical for widespread application in high-risk populations.